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Conserved domains on  [gi|568905969|ref|XP_006495851|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 isoform X3 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PI-PLCc_GDPD_SF super family cl14615
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
289-641 1.17e-160

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.


The actual alignment was detected with superfamily member cd08631:

Pssm-ID: 472694 [Multi-domain]  Cd Length: 258  Bit Score: 466.73  E-value: 1.17e-160
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08631    1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKLRtievdkeeee 448
Cdd:cd08631   81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKIR---------- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08631      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttiMCPDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08631  151 -----LSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYN 225
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08631  226 PQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PLN02228 super family cl31849
Phosphoinositide phospholipase C
207-784 1.04e-77

Phosphoinositide phospholipase C


The actual alignment was detected with superfamily member PLN02228:

Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 261.89  E-value: 1.04e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 207 EIEEIFEDFSSDkQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEpsENGRLLH--VLSKDGFLKYLCSKdgniFNSD 284
Cdd:PLN02228  25 SIKRLFEAYSRN-GKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVK--HHNVFHHhgLVHLNAFYRYLFSD----TNSP 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 285 cLP----IYQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDG-EPVVYHGHTLTSRIL 359
Cdd:PLN02228  98 -LPmsgqVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHED 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 360 FKDVLATLAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGllVDSMPSPEQLRGKILVKGKklrt 439
Cdd:PLN02228 177 LQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSES--TKHFPSPEELKNKILISTK---- 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 440 ievdkeeeeeeeeeelekdegpdldPASPELDTQPQPETQgqaagnkkerkkkvmkCPMsclliCGHVMAQAPSSIPESI 519
Cdd:PLN02228 251 -------------------------PPKEYLESKTVQTTR----------------TPT-----VKETSWKRVADAENKI 284
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 520 LLSKQflLLSSTTIMCPDLSALVVYLRTVPFCSFTHSKENYHIYdiSSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSG 599
Cdd:PLN02228 285 LEEYK--DEESEAVGYRDLIAIHAANCKDPLKDCLSDDPEKPIR--VSMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKG 360
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 600 LRTDSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEFLRDTQSSFNPERPISLykAQILVVQVI 679
Cdd:PLN02228 361 TRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPI--KTTLKVKIY 438
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 680 SGQ----QLPKvDKTKETTVVDPLVKVELYGVPEDTKEQETsHVENNGINPYWG-ETFYFRLQVPELAMLRFVVKDYSRK 754
Cdd:PLN02228 439 TGEgwdlDFHL-THFDQYSPPDFFVKIGIAGVPRDTVSYRT-ETAVDQWFPIWGnDEFLFQLRVPELALLWFKVQDYDND 516
                        570       580       590
                 ....*....|....*....|....*....|
gi 568905969 755 SRNNFIGQYTLPWTCMKQGYRHVSLLSRDG 784
Cdd:PLN02228 517 TQNDFAGQTCLPLPELKSGVRAVRLHDRAG 546
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
18-133 3.41e-52

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13363:

Pssm-ID: 473070  Cd Length: 117  Bit Score: 177.13  E-value: 3.41e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  18 MQEGTMMRKVRTKSWKKLRYFRLQNDGMTVWHGSQPESMP-KPTFSISDVERIRKGQDSELLRYLVEEFPLEQGFTVVFH 96
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKKTRSNsKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568905969  97 GRRPNLDLVANSVEEAQIWMRGLQLLVDLVASMDHQE 133
Cdd:cd13363   81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117
EF-hand_10 super family cl24052
EF hand;
153-202 1.33e-14

EF hand;


The actual alignment was detected with superfamily member pfam14788:

Pssm-ID: 405477  Cd Length: 50  Bit Score: 68.60  E-value: 1.33e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568905969  153 RMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKAL 202
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50
 
Name Accession Description Interval E-value
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
289-641 1.17e-160

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 466.73  E-value: 1.17e-160
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08631    1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKLRtievdkeeee 448
Cdd:cd08631   81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKIR---------- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08631      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttiMCPDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08631  151 -----LSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYN 225
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08631  226 PQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
292-434 2.42e-84

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 264.75  E-value: 2.42e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  292 MTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQYA 371
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568905969  372 FQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDsMPSPEQLRGKILVKG 434
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTE-LPSPEDLKGKILIKG 142
PLN02228 PLN02228
Phosphoinositide phospholipase C
207-784 1.04e-77

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 261.89  E-value: 1.04e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 207 EIEEIFEDFSSDkQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEpsENGRLLH--VLSKDGFLKYLCSKdgniFNSD 284
Cdd:PLN02228  25 SIKRLFEAYSRN-GKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVK--HHNVFHHhgLVHLNAFYRYLFSD----TNSP 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 285 cLP----IYQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDG-EPVVYHGHTLTSRIL 359
Cdd:PLN02228  98 -LPmsgqVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHED 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 360 FKDVLATLAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGllVDSMPSPEQLRGKILVKGKklrt 439
Cdd:PLN02228 177 LQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSES--TKHFPSPEELKNKILISTK---- 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 440 ievdkeeeeeeeeeelekdegpdldPASPELDTQPQPETQgqaagnkkerkkkvmkCPMsclliCGHVMAQAPSSIPESI 519
Cdd:PLN02228 251 -------------------------PPKEYLESKTVQTTR----------------TPT-----VKETSWKRVADAENKI 284
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 520 LLSKQflLLSSTTIMCPDLSALVVYLRTVPFCSFTHSKENYHIYdiSSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSG 599
Cdd:PLN02228 285 LEEYK--DEESEAVGYRDLIAIHAANCKDPLKDCLSDDPEKPIR--VSMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKG 360
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 600 LRTDSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEFLRDTQSSFNPERPISLykAQILVVQVI 679
Cdd:PLN02228 361 TRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPI--KTTLKVKIY 438
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 680 SGQ----QLPKvDKTKETTVVDPLVKVELYGVPEDTKEQETsHVENNGINPYWG-ETFYFRLQVPELAMLRFVVKDYSRK 754
Cdd:PLN02228 439 TGEgwdlDFHL-THFDQYSPPDFFVKIGIAGVPRDTVSYRT-ETAVDQWFPIWGnDEFLFQLRVPELALLWFKVQDYDND 516
                        570       580       590
                 ....*....|....*....|....*....|
gi 568905969 755 SRNNFIGQYTLPWTCMKQGYRHVSLLSRDG 784
Cdd:PLN02228 517 TQNDFAGQTCLPLPELKSGVRAVRLHDRAG 546
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
139-277 6.06e-67

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4.


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 218.17  E-value: 6.06e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD 218
Cdd:cd16219    2 IRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSAD 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568905969 219 KQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16219   82 GQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
292-435 4.43e-65

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 213.30  E-value: 4.43e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   292 MTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQYA 371
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568905969   372 FQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLvDSMPSPEQLRGKILVKGK 435
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSL-EVLPSPEQLRGKILLKVR 143
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
18-133 3.41e-52

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) consists of three family members, delta 1, 2, and 3. PLC-delta1 is the most well studied. PLC-delta is activated by high calcium levels generated by other PLC family members, and functions as a calcium amplifier within the cell. PLC-delta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. The PH domain binds PIP2 and promotes activation of the catalytic core as well as tethering the enzyme to the plasma membrane. The C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. The PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Its leucine-rich nuclear export signal (NES) in its EF hand motif, as well as a Nuclear localization signal within its linker region allow PLC-delta 1 to actively translocate into and out of the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270169  Cd Length: 117  Bit Score: 177.13  E-value: 3.41e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  18 MQEGTMMRKVRTKSWKKLRYFRLQNDGMTVWHGSQPESMP-KPTFSISDVERIRKGQDSELLRYLVEEFPLEQGFTVVFH 96
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKKTRSNsKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568905969  97 GRRPNLDLVANSVEEAQIWMRGLQLLVDLVASMDHQE 133
Cdd:cd13363   81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
198-282 7.49e-46

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme.


Pssm-ID: 401279 [Multi-domain]  Cd Length: 85  Bit Score: 158.56  E-value: 7.49e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  198 FYKALTKRTEIEEIFEDFSSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80

                  ....*
gi 568905969  278 GNIFN 282
Cdd:pfam09279  81 GSIFN 85
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
673-779 6.13e-24

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 96.79  E-value: 6.13e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   673 ILVVQVISGQQLPKVDKTketTVVDPLVKVELYGVPEdtKEQETSHVENNGiNPYWGETFYFRLQVPELAMLRFVVKDYS 752
Cdd:smart00239   1 TLTVKIISARNLPPKDKG---GKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKD 74
                           90       100
                   ....*....|....*....|....*..
gi 568905969   753 RKSRNNFIGQYTLPWTCMKQGYRHVSL 779
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101
EF-hand_10 pfam14788
EF hand;
153-202 1.33e-14

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 68.60  E-value: 1.33e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568905969  153 RMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKAL 202
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
143-238 4.78e-12

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 64.13  E-value: 4.78e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 143 FQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALT-KRTEIEEIFEDF--SSDK 219
Cdd:cd16201    6 FYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTRRRGELGFDDFAQLYHKLMfDQKIIEDFFKKYsySSDG 85
                         90
                 ....*....|....*....
gi 568905969 220 QKLTLLEFVDFLRKEQKEK 238
Cdd:cd16201   86 QTVTLEDFQRFLLEEQKEP 104
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
130-233 1.10e-09

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 57.11  E-value: 1.10e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 130 DHQEQMDQMLNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKAL-TKRTEI 208
Cdd:COG5126   26 DFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALgVSEEEA 105
                         90       100
                 ....*....|....*....|....*.
gi 568905969 209 EEIFEDFSSDKQ-KLTLLEFVDFLRK 233
Cdd:COG5126  106 DELFARLDTDGDgKISFEEFVAAVRD 131
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
17-124 1.94e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.63  E-value: 1.94e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969    17 LMQEGTMMRKVRT--KSWKKlRYFRLQNDGMTVW--HGSQPESMPKPTFSISDVErIRKGQDSEllrylveEFPLEQGFT 92
Cdd:smart00233   1 VIKEGWLYKKSGGgkKSWKK-RYFVLFNSTLLYYksKKDKKSYKPKGSIDLSGCT-VREAPDPD-------SSKKPHCFE 71
                           90       100       110
                   ....*....|....*....|....*....|..
gi 568905969    93 VVfHGRRPNLDLVANSVEEAQIWMRGLQLLVD 124
Cdd:smart00233  72 IK-TSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
17-123 2.81e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 52.18  E-value: 2.81e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   17 LMQEGTMMRKV--RTKSWKKlRYFRLQNDGMTVW--HGSQPESMPKPTFSISDVERIRKGQDsellrylvEEFPLEQGFT 92
Cdd:pfam00169   1 VVKEGWLLKKGggKKKSWKK-RYFVLFDGSLLYYkdDKSGKSKEPKGSISLSGCEVVEVVAS--------DSPKRKFCFE 71
                          90       100       110
                  ....*....|....*....|....*....|...
gi 568905969   93 VVFHGRRPN--LDLVANSVEEAQIWMRGLQLLV 123
Cdd:pfam00169  72 LRTGERTGKrtYLLQAESEEERKDWIKAIQSAI 104
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
665-784 3.97e-04

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 43.98  E-value: 3.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  665 PISLYK-AQILVVQVISGQQLPKVDKTKETtvvDPLVKVELYGvpedtKEQETSHVENNGINPYWGETFYFRLQVPELAM 743
Cdd:COG5038  1032 PVEMVEnSGYLTIMLRSGENLPSSDENGYS---DPFVKLFLNE-----KSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDV 1103
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568905969  744 LRFVVKDYSRKSRNNFIGQYTLPWTCMKQGYRHVSLLSRDG 784
Cdd:COG5038  1104 LTINVNDWDSGEKNDLLGTAEIDLSKLEPGGTTNSNIPLDG 1144
 
Name Accession Description Interval E-value
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
289-641 1.17e-160

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 466.73  E-value: 1.17e-160
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08631    1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKLRtievdkeeee 448
Cdd:cd08631   81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKIR---------- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08631      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttiMCPDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08631  151 -----LSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYN 225
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08631  226 PQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
289-641 7.62e-159

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.


Pssm-ID: 176535 [Multi-domain]  Cd Length: 257  Bit Score: 462.19  E-value: 7.62e-159
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLvDSMPSPEQLRGKILVKGKKLRtievdkeeee 448
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVL-TALPSPEELKGKILVKGKKLK---------- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08593      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttiMCPDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08593  150 -----LAKELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYD 224
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08593  225 PQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
289-641 1.21e-132

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.


Pssm-ID: 176501 [Multi-domain]  Cd Length: 226  Bit Score: 393.35  E-value: 1.21e-132
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08558    1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVdSMPSPEQLRGKILVKGKKlrtievdkeeee 448
Cdd:cd08558   81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPV-QLPSPEQLKGKILIKGKK------------ 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08558      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttimcpdlsalvvylrtvpfcsfthskenyhiYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08558  148 ----------------------------------YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYN 193
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08558  194 PQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
289-641 3.99e-113

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.


Pssm-ID: 176567 [Multi-domain]  Cd Length: 258  Bit Score: 344.31  E-value: 3.99e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08630    1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKLRtievdkeeee 448
Cdd:cd08630   81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKLQ---------- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08630      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttiMCPDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08630  151 -----ISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYS 225
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08630  226 PQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
290-641 9.24e-113

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 176539 [Multi-domain]  Cd Length: 260  Bit Score: 343.63  E-value: 9.24e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQ 369
Cdd:cd08597    2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 370 YAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVdSMPSPEQLRGKILVKGKKLRTIEvdkeeeee 449
Cdd:cd08597   82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGES-YLPSPHDLKGKIIIKGKKLKRRK-------- 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 450 eeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqfllls 529
Cdd:cd08597      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 530 sttiMCPDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFNP 609
Cdd:cd08597  153 ----LCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNP 228
                        330       340       350
                 ....*....|....*....|....*....|..
gi 568905969 610 QEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08597  229 QDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
289-641 1.14e-110

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.


Pssm-ID: 176566 [Multi-domain]  Cd Length: 258  Bit Score: 338.16  E-value: 1.14e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08629    1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLvDSMPSPEQLRGKILVKGKKLRtievdkeeee 448
Cdd:cd08629   81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVT-TSLPSPEQLKGKILLKGKKLK---------- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesilLSKQflll 528
Cdd:cd08629  150 ------------------------------------------------------------------------LVPE---- 153
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttimcpdLSALVVYLRTVPFCSFTHSKENYH-IYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNF 607
Cdd:cd08629  154 ---------LSDMIIYCKSVHFGGFSSPGTSGQaFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNY 224
                        330       340       350
                 ....*....|....*....|....*....|....
gi 568905969 608 NPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08629  225 SPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
289-641 4.35e-108

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 331.13  E-value: 4.35e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08595    1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKlrtievdkeeee 448
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKK------------ 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipeSILLSkqflll 528
Cdd:cd08595  149 ---------------------------------------------------------------------KIAKA------ 153
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttimcpdLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08595  154 ---------LSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYN 224
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08595  225 PQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
289-641 6.60e-99

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 307.34  E-value: 6.60e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDG--PDGEPVVYHGHTLTSRILFKDVLAT 366
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 367 LAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVD---SMPSPEQLRGKILVKGKKlrtievd 443
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEpgvPLPSPNDLKRKILIKNKK------- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 444 keeeeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillsk 523
Cdd:cd08591      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 524 qflllssttimcpdLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTD 603
Cdd:cd08591  154 --------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVD 219
                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 568905969 604 SSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08591  220 SSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
289-641 2.20e-95

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 297.24  E-value: 2.20e-95
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08598    1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGlLVDSMPSPEQLRGKILVKGKKLrtievdkeeee 448
Cdd:cd08598   81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDG-LEDELPSPEELRGKILIKVKKE----------- 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08598      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttimcpdlsalvvylrtvpfcsfthSKENYHIYdisSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08598  149 ---------------------------SKTPNHIF---SLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFN 198
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08598  199 PLPFWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
290-641 2.14e-92

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 289.33  E-value: 2.14e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQ 369
Cdd:cd08592    2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 370 YAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEgLLVDSMPSPEQLRGKILVKGKKLrtievdkeeeee 449
Cdd:cd08592   82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVD-RNADQLPSPNQLKRKIIIKHKKL------------ 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 450 eeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqfllls 529
Cdd:cd08592      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 530 sttimcpdlsalvvylrtvpfcsfthskenyhIYDISSFSESKA-KNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08592  149 --------------------------------FYEMSSFPETKAeKYLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYD 196
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08592  197 PVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
289-641 1.48e-90

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 176536 [Multi-domain]  Cd Length: 227  Bit Score: 284.39  E-value: 1.48e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08594    1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLlrNTLEGLLVDS--MPSPEQLRGKILVKGKKlrtievdkee 446
Cdd:cd08594   81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKL--DLSSVISGDSkqLPSPQSLKGKILIKGKK---------- 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 447 eeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqfl 526
Cdd:cd08594      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 527 llssttimcpdlsalvvylrtvpfcsfthskenyhiYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSN 606
Cdd:cd08594  149 ------------------------------------WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSN 192
                        330       340       350
                 ....*....|....*....|....*....|....*
gi 568905969 607 FNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08594  193 FNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
290-641 3.79e-88

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 279.23  E-value: 3.79e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQ 369
Cdd:cd08633    2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 370 YAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKLrtievdkeeeee 449
Cdd:cd08633   82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGKKL------------ 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 450 eeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmAQApssipesillskqfllls 529
Cdd:cd08633  150 -----------------------------------------------------------SRA------------------ 152
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 530 sttimcpdLSALVVYLRTVPfcsfTHSKEN--YHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNF 607
Cdd:cd08633  153 --------LSDLVKYTKSVR----VHDIETeaTSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNY 220
                        330       340       350
                 ....*....|....*....|....*....|....
gi 568905969 608 NPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08633  221 NPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
289-641 1.36e-86

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.


Pssm-ID: 176569 [Multi-domain]  Cd Length: 253  Bit Score: 274.98  E-value: 1.36e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08632    1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDSMPSPEQLRGKILVKGKKLrtievdkeeee 448
Cdd:cd08632   81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGKKL----------- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqflll 528
Cdd:cd08632      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttimCPDLSALVVYlrtvpfcsfTHSKENYHIYD------ISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRT 602
Cdd:cd08632  150 ------CRDLSDLVVY---------TNSVAAQDIVDdgstgnVLSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRI 214
                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 568905969 603 DSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08632  215 DSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
292-434 2.42e-84

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 264.75  E-value: 2.42e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  292 MTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQYA 371
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568905969  372 FQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVDsMPSPEQLRGKILVKG 434
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTE-LPSPEDLKGKILIKG 142
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
289-641 1.03e-79

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176563 [Multi-domain]  Cd Length: 257  Bit Score: 257.00  E-value: 1.03e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGP--DGEPVVYHGHTLTSRILFKDVLAT 366
Cdd:cd08626    1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 367 LAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLVD---SMPSPEQLRGKILVKGKKlrtievd 443
Cdd:cd08626   81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLEpgvPLPSPNKLKRKILIKNKR------- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 444 keeeeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillsk 523
Cdd:cd08626      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 524 qflllssttimcpdLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTD 603
Cdd:cd08626  154 --------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVD 219
                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 568905969 604 SSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08626  220 SSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
290-641 7.01e-79

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 254.59  E-value: 7.01e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQ 369
Cdd:cd08628    2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 370 YAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGlLVDSMPSPEQLRGKILVKGKKLRTIevdkeeeee 449
Cdd:cd08628   82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEA-SADQLPSPTQLKEKIIIKHKKLIAI--------- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 450 eeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqfllls 529
Cdd:cd08628      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 530 sttimcpDLSALVVYLRtvPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFNP 609
Cdd:cd08628  152 -------ELSDLVVYCK--PTSKTKDNLENPDFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDP 222
                        330       340       350
                 ....*....|....*....|....*....|..
gi 568905969 610 QEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08628  223 FRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
290-641 3.14e-78

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176538 [Multi-domain]  Cd Length: 254  Bit Score: 252.85  E-value: 3.14e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQ 369
Cdd:cd08596    2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 370 YAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTL-EGLLVD--SMPSPEQLRGKILVKGKKlrtievdkee 446
Cdd:cd08596   82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLfESDFSDdpSLPSPLQLKNKILLKNKK---------- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 447 eeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqfl 526
Cdd:cd08596      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 527 llssttimCPDLSALVVYLRTVPFCSFTHSKenyhIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSN 606
Cdd:cd08596  152 --------APELSDLVIYCQAVKFPGLSTPK----CYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSN 219
                        330       340       350
                 ....*....|....*....|....*....|....*
gi 568905969 607 FNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08596  220 PNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
PLN02228 PLN02228
Phosphoinositide phospholipase C
207-784 1.04e-77

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 261.89  E-value: 1.04e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 207 EIEEIFEDFSSDkQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEpsENGRLLH--VLSKDGFLKYLCSKdgniFNSD 284
Cdd:PLN02228  25 SIKRLFEAYSRN-GKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVK--HHNVFHHhgLVHLNAFYRYLFSD----TNSP 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 285 cLP----IYQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDG-EPVVYHGHTLTSRIL 359
Cdd:PLN02228  98 -LPmsgqVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHED 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 360 FKDVLATLAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGllVDSMPSPEQLRGKILVKGKklrt 439
Cdd:PLN02228 177 LQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSES--TKHFPSPEELKNKILISTK---- 250
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 440 ievdkeeeeeeeeeelekdegpdldPASPELDTQPQPETQgqaagnkkerkkkvmkCPMsclliCGHVMAQAPSSIPESI 519
Cdd:PLN02228 251 -------------------------PPKEYLESKTVQTTR----------------TPT-----VKETSWKRVADAENKI 284
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 520 LLSKQflLLSSTTIMCPDLSALVVYLRTVPFCSFTHSKENYHIYdiSSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSG 599
Cdd:PLN02228 285 LEEYK--DEESEAVGYRDLIAIHAANCKDPLKDCLSDDPEKPIR--VSMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKG 360
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 600 LRTDSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEFLRDTQSSFNPERPISLykAQILVVQVI 679
Cdd:PLN02228 361 TRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPI--KTTLKVKIY 438
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 680 SGQ----QLPKvDKTKETTVVDPLVKVELYGVPEDTKEQETsHVENNGINPYWG-ETFYFRLQVPELAMLRFVVKDYSRK 754
Cdd:PLN02228 439 TGEgwdlDFHL-THFDQYSPPDFFVKIGIAGVPRDTVSYRT-ETAVDQWFPIWGnDEFLFQLRVPELALLWFKVQDYDND 516
                        570       580       590
                 ....*....|....*....|....*....|
gi 568905969 755 SRNNFIGQYTLPWTCMKQGYRHVSLLSRDG 784
Cdd:PLN02228 517 TQNDFAGQTCLPLPELKSGVRAVRLHDRAG 546
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
289-641 2.12e-76

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176561 [Multi-domain]  Cd Length: 261  Bit Score: 248.43  E-value: 2.12e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDG--PDGEPVVYHGHTLTSRILFKDVLAT 366
Cdd:cd08624    1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 367 LAQYAFQSSDYPLILSLENHC-TWEQQRTMAHHLTEILGEQLLRNTLEGLLVD---SMPSPEQLRGKILVKGKKLRtiev 442
Cdd:cd08624   81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKpgvPLPSPEDLRGKILIKNKKYE---- 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 443 dkeeeeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesills 522
Cdd:cd08624      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 523 kqflllssttimcpDLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRT 602
Cdd:cd08624  157 --------------EMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRM 222
                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 568905969 603 DSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08624  223 DSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
290-641 5.36e-74

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 240.70  E-value: 5.36e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQ 369
Cdd:cd08627    2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 370 YAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEgLLVDSMPSPEQLRGKILVKGKKLrtievdkeeeee 449
Cdd:cd08627   82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVD-INADGLPSPNQLKRKILIKHKKL------------ 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 450 eeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskqfllls 529
Cdd:cd08627      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 530 sttimcpdlsalvvylrtvpfcsfthskenyhIYDISSFSESKAKNLIKEA-GNEFVQHNARQLCRVYPSGLRTDSSNFN 608
Cdd:cd08627  149 --------------------------------YRDMSSFPETKAEKYVNRSkGKKFLQYNRRQLSRIYPKGQRLDSSNYD 196
                        330       340       350
                 ....*....|....*....|....*....|...
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08627  197 PLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229
PLN02952 PLN02952
phosphoinositide phospholipase C
187-794 1.59e-72

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 248.76  E-value: 1.59e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 187 SDDLGSEEFVQF--YKALTKRTEIE------EIFEDFSSDKQKLTLLEFVDFLRKEQKEKD----HAPDLALELID-RYE 253
Cdd:PLN02952  11 NNDSGSYNYKMFnlFNRKFKITEAEppddvkDVFCKFSVGGGHMGADQLRRFLVLHQDELDctlaEAQRIVEEVINrRHH 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 254 PSENGRllHVLSKDGFLKYLCSKDgniFNSDCLP-IYQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCR 332
Cdd:PLN02952  91 VTRYTR--HGLNLDDFFHFLLYDD---LNGPITPqVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVR 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 333 CVEVDTWDGPDGEPV-VYHGHTLTSRILFKDVLATLAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNT 411
Cdd:PLN02952 166 VIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYPE 245
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 412 LEGLLvdSMPSPEQLRGKILVKGKKLRTIEVDKEEEEEEEEEELE---KDEGPDLDPASPELDTQPQPETQGQAAGNKKE 488
Cdd:PLN02952 246 SDSLV--QFPSPESLKHRIIISTKPPKEYLESSGPIVIKKKNNVSpsgRNSSEETEEAQTLESMLFEQEADSRSDSDQDD 323
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 489 RKKKVMKCPMSCLLICGHvmaqapSSIPESILLSKqflllssttimcpdLSALVVYLRTVpfcsfthskenyhiydisSF 568
Cdd:PLN02952 324 NKSGELQKPAYKRLITIH------AGKPKGTLKDA--------------MKVAVDKVRRL------------------SL 365
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 569 SESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYVL 648
Cdd:PLN02952 366 SEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLK 445
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 649 KPEFLRDT---QSSFNPERPISLYKAQILVVQVISGQQLpKVDKTKETTVVDP--LVKVELYGVPEDTKEQETSHVENNG 723
Cdd:PLN02952 446 KPDFLMKKgfhDEVFDPKKKLPVKKTLKVKVYLGDGWRL-DFSHTHFDSYSPPdfYTKMYIVGVPADNAKKKTKIIEDNW 524
                        570       580       590       600       610       620       630
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568905969 724 iNPYWGETFYFRLQVPELAMLRFVVKDYSRKSRNNFIGQYTLPWTCMKQGYRHVSLLSRDGTSLNPASIFV 794
Cdd:PLN02952 525 -YPAWNEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLM 594
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
291-641 1.92e-72

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176562 [Multi-domain]  Cd Length: 258  Bit Score: 237.65  E-value: 1.92e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 291 DMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDG--PDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08625    3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHC-TWEQQRTMAHHLTEILGEQLLRNTLEGLLVD---SMPSPEQLRGKILVKGKKlrtievdk 444
Cdd:cd08625   83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVpgvQLPSPQELMGKILVKNKK-------- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 445 eeeeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillskq 524
Cdd:cd08625      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 525 flllssttimcpdLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDS 604
Cdd:cd08625  155 -------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDS 221
                        330       340       350
                 ....*....|....*....|....*....|....*..
gi 568905969 605 SNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08625  222 SNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258
PLN02222 PLN02222
phosphoinositide phospholipase C 2
207-794 2.50e-67

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 234.15  E-value: 2.50e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 207 EIEEIFEDFSsDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDryepsENGRLLHV--LSKDGFLKYLCSKDGNIFNSD 284
Cdd:PLN02222  26 EIKTIFEKYS-ENGVMTVDHLHRFLIDVQKQDKATREDAQSIIN-----SASSLLHRngLHLDAFFKYLFGDNNPPLALH 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 285 clPIYQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPV-VYHGHTLTSRILFKDV 363
Cdd:PLN02222 100 --EVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKC 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 364 LATLAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLeGLLVDSMPSPEQLRGKILVKGKKLRtievd 443
Cdd:PLN02222 178 LKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPV-GESLKEFPSPNSLKKRIIISTKPPK----- 251
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 444 keeEEEEEEEELEKDEGPDLDPAS------PELDTQPQPETQGQAAGNKKERKKKVMKcpmscllicgHVMAQAPssiPE 517
Cdd:PLN02222 252 ---EYKEGKDDEVVQKGKDLGDEEvwgrevPSFIQRNKSVDKNDSNGDDDDDDDDGED----------KSKKNAP---PQ 315
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 518 SillsKQFLLLSSTTIMCPDLSALVVYLRTVPFCSFTHSKenyhiydISSFSESKAKNLIKeagneFVQHNarqLCRVYP 597
Cdd:PLN02222 316 Y----KHLIAIHAGKPKGGITECLKVDPDKVRRLSLSEEQ-------LEKAAEKYAKQIVR-----FTQHN---LLRIYP 376
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 598 SGLRTDSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEFLRDTQSS---FNPErpISLYKAQIL 674
Cdd:PLN02222 377 KGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDsdiFDPK--ATLPVKTTL 454
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 675 VVQVISGQ----QLPKVdKTKETTVVDPLVKVELYGVPEDTKEQETSHVENNGInPYWGETFYFRLQVPELAMLRFVVKD 750
Cdd:PLN02222 455 RVTIYMGEgwyfDFRHT-HFDQYSPPDFYTRVGIAGVPGDTVMKKTKTLEDNWI-PAWDEVFEFPLTVPELALLRLEVHE 532
                        570       580       590       600
                 ....*....|....*....|....*....|....*....|....
gi 568905969 751 YSRKSRNNFIGQYTLPWTCMKQGYRHVSLLSRDGTSLNPASIFV 794
Cdd:PLN02222 533 YDMSEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLV 576
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
139-277 6.06e-67

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4.


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 218.17  E-value: 6.06e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD 218
Cdd:cd16219    2 IRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSAD 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568905969 219 KQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16219   82 GQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
292-435 4.43e-65

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 213.30  E-value: 4.43e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   292 MTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQYA 371
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568905969   372 FQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLvDSMPSPEQLRGKILVKGK 435
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSL-EVLPSPEQLRGKILLKVR 143
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
539-653 5.59e-63

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 206.71  E-value: 5.59e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   539 SALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFNPQEHWNVGCQ 618
Cdd:smart00149   1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 568905969   619 MVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEFL 653
Cdd:smart00149  81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
290-641 9.22e-63

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 211.48  E-value: 9.22e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 290 QDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDG--PDGEPVVYHGHTLTSRILFKDVLATL 367
Cdd:cd08623    2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 368 AQYAFQSSDYPLILSLENHC-TWEQQRTMAHHLTEILGEQLLRNTLEGLLVDS---MPSPEQLRGKILVKGKKlrtievd 443
Cdd:cd08623   82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESgvpLPSPMDLMYKILVKNKK------- 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 444 keeeeeeeeeelekdegpdldpaspeldtqpqpetqgqaagnkkerkkkvmkcpmscllicghvmaqapssipesillsk 523
Cdd:cd08623      --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 524 qflllssttimcpdLSALVVYLRTVPFCSFTHSKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTD 603
Cdd:cd08623  155 --------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVD 220
                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 568905969 604 SSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08623  221 SSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258
PLN02230 PLN02230
phosphoinositide phospholipase C 4
189-794 2.27e-60

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 215.34  E-value: 2.27e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 189 DLGSEEFVQFYKALTKRTE------IEEIFEDFSSDKQKLTLLEFVDFLrkeQKEKDHAPDLALELIDRYEPSENGRLLH 262
Cdd:PLN02230   6 EMGSYKFCLIFTRKFRMTEsgpvadVRDLFEKYADGDAHMSPEQLQKLM---AEEGGGEGETSLEEAERIVDEVLRRKHH 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 263 V-------LSKDGFLKYLCSKDGNIFNSDclPIYQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVE 335
Cdd:PLN02230  83 IakftrrnLTLDDFNYYLFSTDLNPPIAD--QVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 336 VDTWDGPDGEPVVYHGHTLTSRILFKDVLATLAQYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGl 415
Cdd:PLN02230 161 LDLWPRGTDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHDSEG- 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 416 lVDSMPSPEQLRGKILVKGKKLRtievdKEEEEEEEEEELEKDEGPDLDP----ASPE--LDTQPQPETQGQAAGNKKER 489
Cdd:PLN02230 240 -CQEFPSPEELKEKILISTKPPK-----EYLEANDAKEKDNGEKGKDSDEdvwgKEPEdlISTQSDLDKVTSSVNDLNQD 313
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 490 KKKVMKCP--MSCLLicghvmaQAPSSipesillsKQFLLLSSTTimcPDlSALVVYLRTVPfcsfthskenyHIYDISS 567
Cdd:PLN02230 314 DEERGSCEsdTSCQL-------QAPEY--------KRLIAIHAGK---PK-GGLRMALKVDP-----------NKIRRLS 363
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 568 FSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFNPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYV 647
Cdd:PLN02230 364 LSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYV 443
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 648 LKPEFLRDTQSS---FNPERpiSLYKAQILVVQVISGQQ-LPKVDKTKETTVVDP--LVKVELYGVPEDtKEQETSHVEN 721
Cdd:PLN02230 444 KKPDFLMDAGPNgqdFYPKD--NSCPKKTLKVKVCMGDGwLLDFKKTHFDSYSPPdfFVRVGIAGAPVD-EVMEKTKIEY 520
                        570       580       590       600       610       620       630
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568905969 722 NGINPYWGETFYFRLQVPELAMLRFVVKDYSRKSRNNFIGQYTLPWTCMKQGYRHVSLLSRDGTSLNPASIFV 794
Cdd:PLN02230 521 DTWTPIWNKEFIFPLAVPELALLRVEVHEHDINEKDDFGGQTCLPVSEIRQGIHAVPLFNRKGVKYSSTRLLM 593
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
538-652 9.60e-60

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 459794  Cd Length: 114  Bit Score: 197.68  E-value: 9.60e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  538 LSALVVYLRTVPFCSFTHsKENYHIYDISSFSESKAKNLIKEAGNEFVQHNARQLCRVYPSGLRTDSSNFNPQEHWNVGC 617
Cdd:pfam00387   1 LSDLVVYTQSVKFKSFST-PESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568905969  618 QMVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEF 652
Cdd:pfam00387  80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
289-641 5.25e-59

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 200.29  E-value: 5.25e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTSRILFKDVLATLA 368
Cdd:cd08599    1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 369 QYAFQSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLvDSMPSPEQLRGKILVKgkklrtievdkeeee 448
Cdd:cd08599   81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLP-EEFPSPEELKGKILIS--------------- 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 449 eeeeeelekdegpdldpaspeldTQPqpetqgqaagnkkerkkkvmkcPMscllicghvmaqapssipesillskqflll 528
Cdd:cd08599  145 -----------------------DKP----------------------PV------------------------------ 149
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 529 ssttIMCpdlsalvvylrtvpfcsfthskenyhiydisSFSESKAKNLI-KEAGNEFVQHNARQLCRVYPSGLRTDSSNF 607
Cdd:cd08599  150 ----IRN-------------------------------SLSETQLKKVIeGEHPTDLIEFTQKNLLRVYPAGLRITSSNY 194
                        330       340       350
                 ....*....|....*....|....*....|....
gi 568905969 608 NPQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd08599  195 DPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
289-641 3.29e-58

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176497 [Multi-domain]  Cd Length: 274  Bit Score: 199.80  E-value: 3.29e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 289 YQDMTQPLSHYYINSSHNTYLVGDQL-----CGQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLTsRILFKDV 363
Cdd:cd00137    1 HHPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 364 LATLAQYAFQSSDYPLILSLENHC--TWEQQRTMAHHLTEILGEQLLrnTLEGLLVDSMPSPEQLRGKILVKGKKLRTie 441
Cdd:cd00137   80 IEAIAQFLKKNPPETIIMSLKNEVdsMDSFQAKMAEYCRTIFGDMLL--TPPLKPTVPLPSLEDLRGKILLLNKKNGF-- 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 442 vdkeeeeeeeeeelekdegpdLDPASPELDTQP---QPETQGQAAgnkkerkkkvmkcpmscllicghvmaqapssipes 518
Cdd:cd00137  156 ---------------------SGPTGSSNDTGFvsfEFSTQKNRS----------------------------------- 179
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 519 illskqflllssttimcpdlsalvvylrtvpfcsfthskenyhiYDISSFSESKA----KNLIKEAGNEFVQHNARQLCR 594
Cdd:cd00137  180 --------------------------------------------YNISSQDEYKAyddeKVKLIKATVQFVDYNKNQLSR 215
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568905969 595 VYPSGLR---------TDSSNFNPQEHWN---VGCQMVAMNMQTAGSAMDICDGLFRQN 641
Cdd:cd00137  216 NYPSGTSggtawyyyaMDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
139-277 1.67e-54

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 184.35  E-value: 1.67e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD 218
Cdd:cd16202    2 LKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTKRPEIEELFKKYSGD 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568905969 219 KQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16202   82 DEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
18-133 3.41e-52

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) consists of three family members, delta 1, 2, and 3. PLC-delta1 is the most well studied. PLC-delta is activated by high calcium levels generated by other PLC family members, and functions as a calcium amplifier within the cell. PLC-delta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. The PH domain binds PIP2 and promotes activation of the catalytic core as well as tethering the enzyme to the plasma membrane. The C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. The PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Its leucine-rich nuclear export signal (NES) in its EF hand motif, as well as a Nuclear localization signal within its linker region allow PLC-delta 1 to actively translocate into and out of the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270169  Cd Length: 117  Bit Score: 177.13  E-value: 3.41e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  18 MQEGTMMRKVRTKSWKKLRYFRLQNDGMTVWHGSQPESMP-KPTFSISDVERIRKGQDSELLRYLVEEFPLEQGFTVVFH 96
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKKTRSNsKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 568905969  97 GRRPNLDLVANSVEEAQIWMRGLQLLVDLVASMDHQE 133
Cdd:cd13363   81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
671-796 3.94e-48

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 166.56  E-value: 3.94e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 671 AQILVVQVISGQQLPKvDKTKETTVVDPLVKVELYGVPE-DTKEQETSHVENNGINPYWGETFYFRLQVPELAMLRFVVK 749
Cdd:cd00275    1 PLTLTIKIISGQQLPK-PKGDKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVY 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 568905969 750 DYSrKSRNNFIGQYTLPWTCMKQGYRHVSLLSRDGTSLNPASIFVYT 796
Cdd:cd00275   80 DED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHI 125
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
198-282 7.49e-46

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme.


Pssm-ID: 401279 [Multi-domain]  Cd Length: 85  Bit Score: 158.56  E-value: 7.49e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  198 FYKALTKRTEIEEIFEDFSSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80

                  ....*
gi 568905969  278 GNIFN 282
Cdd:pfam09279  81 GSIFN 85
PLN02223 PLN02223
phosphoinositide phospholipase C
218-786 2.64e-40

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 156.34  E-value: 2.64e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 218 DKQKLTLLEFVDFLRKEQKEK----DHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKDGNIFNSDCLPiYQDMT 293
Cdd:PLN02223  31 DDMPELLPRFIELLDTEKDEDgaglNAAEKIAAELKRRKCDILAFRNLRCLELDHLNEFLFSTELNPPIGDQVR-HHDMH 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 294 QPLSHYYINSSHNTYLVGDQLCGQS-SVEGYIRALKRGCRCVEVDTWdgPDGEP--VVYHGHTLTSRILFKDVLATLAQY 370
Cdd:PLN02223 110 APLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL--PDGKDgiCVRPKWNFEKPLELQECLDAIKEH 187
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 371 AF-QSSDYPLILSLENHCTWEQQRTMAHHLTEILGEQLLRNTLEGLLvDSMPSPEQLRGKILVKGKKLRTIEVDKEEEEE 449
Cdd:PLN02223 188 AFtKCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSL-EEFPSPAELQNKILISRRPPKELLYAKADDGG 266
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 450 EEeeelekdegpdldpASPELDTQpqpetQGQAAGNKKErkkkvmkcpmsclLICGHVMAqapssiPESILlsKQFLLLS 529
Cdd:PLN02223 267 VG--------------VRNELEIQ-----EGPADKNYQS-------------LVGFHAVE------PRGML--QKALTGK 306
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 530 STTIMCPdlsalvvylrtvpfcsfthskeNYHIYDISSFSEskaknlikeagNEFVQHN-ARQLCRVYPSglrtdssnFN 608
Cdd:PLN02223 307 ADDIQQP----------------------GWYERDIISFTQ-----------KKFLRTRpKKKNLLINAP--------YK 345
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 609 PQEHWNVGCQMVAMNMQTAGSAMDICDGLFRQNGGSGYVLKPEFLRDTQSS--FNP-ERPISLykaQILVVQVISGQQLp 685
Cdd:PLN02223 346 PQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNAGPSgvFYPtENPVVV---KILKVKIYMGDGW- 421
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 686 KVDKTKET---TVVDPLVKVELYGVPEDTKEQETShVENNGINPYWGETFYFRLQVPELAMLRFVVKDYSRKSRNNFIGQ 762
Cdd:PLN02223 422 IVDFKKRIgrlSKPDLYVRISIAGVPHDEKIMKTT-VKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADAFCGQ 500
                        570       580
                 ....*....|....*....|....
gi 568905969 763 YTLPWTCMKQGYRHVSLLSRDGTS 786
Cdd:PLN02223 501 TCLPVSELIEGIRAVPLYDERGKA 524
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
143-277 3.19e-36

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (PLCD1), or phospholipase C-III (PLC-III), or phospholipase C-delta-1 (PLC-delta-1), is present in high abundancy in the brain, heart, lung, skeletal muscle and testis. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. PI-PLC-delta1 is required for maintenance of homeostasis in skin and metabolic tissues. Moreover, it is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta1 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta1 can be positively or negatively regulated by several binding partners, including p122/Rho GTPase activating protein (RhoGAP), Gha/Transglutaminase II, RalA, and calmodulin. It is involved in Alzheimer's disease and hypertension. Furthermore, PI-PLC-delta1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity and p27 levels. It can be activated by alpha1-adrenoreceptors (AR) in a calcium-dependent manner and may be important for G protein-coupled receptors (GPCR) responses in vascular smooth muscle (VSM). PI-PLC-delta1 may also be involved in noradrenaline (NA)-induced phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and modulate sustained contraction of mesenteric small arteries. In addition, it inhibits thermogenesis and induces lipid accumulation, and therefore contributes to the development of obesity. PI-PLC-delta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. In addition, PI-PLC-delta1 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, as well as a nuclear localization signal within its linker region, both of which may be responsible for translocating PI-PLC-delta1 into and out of the cell nucleus.


Pssm-ID: 320047 [Multi-domain]  Cd Length: 139  Bit Score: 133.33  E-value: 3.19e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 143 FQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSDKQKL 222
Cdd:cd16217    6 LRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAKSDGTM 85
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 568905969 223 TLLEFVDFLRKEQKEKDhAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16217   86 SRNNLLNFLQEEQREEV-APAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
138-277 1.03e-32

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 123.16  E-value: 1.03e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 138 MLNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSS 217
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEPIFKKYAG 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568905969 218 DKQK-LTLLEFVDFLRKEQKEkDHAPDLALELIDRYEPSENGRLlhvLSKDGFLKYLCSKD 277
Cdd:cd15898   81 TNRDyMTLEEFIRFLREEQGE-NVSEEECEELIEKYEPERENRQ---LSFEGFTNFLLSPE 137
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
139-277 1.77e-27

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLCD3), phospholipase C-delta-3 (PLC-delta-3), is expressed abundantly in brain, skeletal muscle and heart. PI-PLC-delta3 gene expression is down-regulation by cAMP and calcium. PI-PLC-delta3 acts as anchoring of myosin VI on plasma membrane, and further modulates Myosin IV expression and microvilli formation in enterocytes. It negatively regulates RhoA expression, inhibits RhoA/Rho kinase signaling, and plays an essential role in normal neuronal migration by promoting neuronal outgrowth in the developing brain. Moreover, PI-PLC-delta3 is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta3 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. In addition, PI-PLC-delta3 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, which may be responsible transporting PI-PLC-delta3 from the cell nucleus.


Pssm-ID: 320048 [Multi-domain]  Cd Length: 138  Bit Score: 108.29  E-value: 1.77e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD 218
Cdd:cd16218    2 IHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSGE 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568905969 219 KQKLTLLEFVDFLrKEQKEkDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16218   82 DCVLSAEELREFL-KDQGE-DASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
143-277 3.90e-25

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 101.69  E-value: 3.90e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 143 FQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDD-LGSEEFVQFYKALTKRTEIEEIFEDFSSDKQK 221
Cdd:cd16205    6 FEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGtLDFEEFCAFYKMMSTRRELYLLLLSYSNKKDY 85
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568905969 222 LTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16205   86 LTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
673-779 6.13e-24

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 96.79  E-value: 6.13e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   673 ILVVQVISGQQLPKVDKTketTVVDPLVKVELYGVPEdtKEQETSHVENNGiNPYWGETFYFRLQVPELAMLRFVVKDYS 752
Cdd:smart00239   1 TLTVKIISARNLPPKDKG---GKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKD 74
                           90       100
                   ....*....|....*....|....*..
gi 568905969   753 RKSRNNFIGQYTLPWTCMKQGYRHVSL 779
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
302-436 1.76e-23

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.


Pssm-ID: 176498 [Multi-domain]  Cd Length: 179  Bit Score: 98.28  E-value: 1.76e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 302 NSSHNTYLVGDQlcgQSSVEGYIRALKRGCRCVEVDTWDGPDGEPVVYHGHTLT------SRILFKDVLATLAQYAFqSS 375
Cdd:cd08555    1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NP 76
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568905969 376 DYPLILSLENHCTWEQqrtmahhlteilGEQLLRNTLEGLLVDsmpSPEQLRGKILVKGKK 436
Cdd:cd08555   77 DYTIILSLEIKQDSPE------------YDEFLAKVLKELRVY---FDYDLRGKVVLSSFN 122
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
18-123 3.19e-21

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269952  Cd Length: 108  Bit Score: 89.30  E-value: 3.19e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  18 MQEGTMMRKVRTKSWKKLRYFRLQNDGMTVWHGSQPESMPKPTFSISDVERIRKGQDSELLR--YLVEEFPLEQGFTVVF 95
Cdd:cd01248    1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKKSEKKSIDISDIKEIRPGKDTDGFKrkKKSNKPKEERCFSIIY 80
                         90       100
                 ....*....|....*....|....*...
gi 568905969  96 HGRRPNLDLVANSVEEAQIWMRGLQLLV 123
Cdd:cd01248   81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
138-277 3.52e-21

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1, or phospholipase C-zeta-1 (PLC-zeta-1), or testis-development protein NYD-SP27, is only found in the testis. The sperm-specific PI-PLC plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. PI-PLC-zeta1 contains an N-terminal four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike other PI-PLCs, PI-PLC-zeta is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. There is only one PLC-zeta isozyme. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 320034 [Multi-domain]  Cd Length: 142  Bit Score: 90.25  E-value: 3.52e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 138 MLNEWFQQA--DRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDF 215
Cdd:cd16204    1 MENRWFLSIiqDRFRKGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTY 80
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568905969 216 SSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16204   81 SENRKILSAPNLVGFLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
150-277 2.11e-20

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 88.07  E-value: 2.11e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 150 QDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDF-SSDKQKLTLLEFV 228
Cdd:cd16207   15 GDERLDFEDVEKLCRRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLKRRKDIKAIFKQLtKPGSDGLTLEEFL 94
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568905969 229 DFLRKEQKEkDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16207   95 KFLRDVQKE-DVDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
139-275 9.82e-20

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320050 [Multi-domain]  Cd Length: 141  Bit Score: 86.23  E-value: 9.82e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSD-DLGSEEFVQFYKALTKRTEIEEIFEDFSS 217
Cdd:cd16220    2 VKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQgTLTFEEFCVFYKMMSLRRDLYLLLLSYSD 81
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 568905969 218 DKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCS 275
Cdd:cd16220   82 KKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRS 139
C2 pfam00168
C2 domain;
672-776 2.86e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 83.52  E-value: 2.86e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  672 QILVVQVISGQQLPKVDKTKEttvVDPLVKVELYGvpeDTKEQETsHVENNGINPYWGETFYFRLQVPELAMLRFVVKDY 751
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGT---SDPYVKVYLLD---GKQKKKT-KVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDY 73
                          90       100
                  ....*....|....*....|....*
gi 568905969  752 SRKSRNNFIGQYTLPWTCMKQGYRH 776
Cdd:pfam00168  74 DRFGRDDFIGEVRIPLSELDSGEGL 98
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
139-277 3.29e-19

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); This family represents a class of metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(also known as p130 or PLC-L1), which is predominantly expressed in the brain, and PRIP-2 (also known as PLC-L2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 320036 [Multi-domain]  Cd Length: 143  Bit Score: 84.57  E-value: 3.29e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEadVTQSDD-----LGSEEFVQFYKALTKRTEIEEIFE 213
Cdd:cd16206    2 LESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKE--LQKKKDgargrVSSDEFVELFKELATRPEIYFLLV 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568905969 214 DFSSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16206   80 RYASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
183-277 1.64e-17

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family includes invertebrate homologs of phosphoinositide phospholipase C beta (PI-PLC-beta) named PLC21 from cephalopod retina. It also includes PLC21 encoded by plc-21 gene, which is expressed in the central nervous system of Drosophila. Like beta-class of vertebrate PI-PLCs, PLC21 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320043  Cd Length: 154  Bit Score: 80.42  E-value: 1.64e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 183 DVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSDKQK-LTLLEFVDFLRKEQKEKD--------HAPDLALELIDRYE 253
Cdd:cd16213   51 DAIDPKKFTFEDFFNFYRRLTGRQEVEKIFDELGAKKKPyLTTEQFVDFLNKTQRDPRlneilypyANPKRARDLINQYE 130
                         90       100
                 ....*....|....*....|....
gi 568905969 254 PSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16213  131 PNKSFAKKGHLSVEGFLRYLMSED 154
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
139-275 2.63e-16

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 76.51  E-value: 2.63e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADvtqSDD----LGSEEFVQFYKALTKRTEIEEIFED 214
Cdd:cd16221    2 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEAD---TDDnqgtLGFEEFCAFYKMMSTRRDLYLLMLT 78
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568905969 215 FSSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCS 275
Cdd:cd16221   79 YSNHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRS 139
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
674-766 3.14e-15

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 72.10  E-value: 3.14e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKettVVDPLVKVELygvpEDTKEQETSHVENNgINPYWGETFYFRLQVPELAMLRFVVKDYSR 753
Cdd:cd00030    1 LRVTVIEARNLPAKDLNG---KSDPYVKVSL----GGKQKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWDKDR 72
                         90
                 ....*....|...
gi 568905969 754 KSRNNFIGQYTLP 766
Cdd:cd00030   73 FSKDDFLGEVEIP 85
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
183-277 3.50e-15

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta isozymes; PI-PLC-beta isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors (EC 3.1.4.11). They have been implicated in numerous processes relevant to central nervous system (CNS), including chemotaxis, cardiovascular function, neuronal signaling, and opioid sensitivity. Like other PI-PLC isozymes, PI-PLC-beta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, they have a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PI-PLC-beta isozymes (1-4). PI-PLC-beta1 and PI-PLC-beta3 are expressed in a wide range of tissues and cell types, whereas PI-PLC-beta2 and PI-PLC-beta4 have been found only in hematopoietic and neuronal tissues, respectively. All PI-PLC-beta isozymes are activated by the heterotrimeric G protein alpha subunits of the Gq class through their C2 domain and long C-terminal extension. They are GTPase-activating proteins (GAPs) for these G alpha(q) proteins. PI-PLC-beta2 and PI-PLC-beta3 can also be activated by beta-gamma subunits of the G alpha(i/o) family of heterotrimeric G proteins and the small GTPases such as Rac and Cdc42. This family also includes two invertebrate homologs of PI-PLC-beta, PLC21 from cephalopod retina and No receptor potential A protein (NorpA) from Drosophila melanogaster.


Pssm-ID: 320030 [Multi-domain]  Cd Length: 153  Bit Score: 73.43  E-value: 3.50e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 183 DVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD-KQKLTLLEFVDFLRKEQKekD----------HAPDLALELIDR 251
Cdd:cd16200   50 DEIDPEDFTFEKFFKLYNKLCPRPDIDEIFKELGGKrKPYLTLEQLVDFLNEEQR--DprlneilfpfHTKEQAKKLIDK 127
                         90       100
                 ....*....|....*....|....*.
gi 568905969 252 YEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16200  128 YEPNEKNKKKGQLTLEGFLRYLMSDE 153
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
18-124 5.10e-15

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 270170  Cd Length: 109  Bit Score: 71.54  E-value: 5.10e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  18 MQEGTMMRKVRTKSWKKLRYFRLQNDGMTV-WHGSQPESmPKPTFSISDVERIRKGQDSELLRYLV--EEFPLEQGFTVV 94
Cdd:cd13364    1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIrWKPSKKKS-EKAKIPISSIREVREGKTTDIFRSCDisGDFPEECCFSII 79
                         90       100       110
                 ....*....|....*....|....*....|
gi 568905969  95 FHGRRPNLDLVANSVEEAQIWMRGLQLLVD 124
Cdd:cd13364   80 YGEEYETLDLVASSPDEANIWITGLRYLMS 109
EF-hand_10 pfam14788
EF hand;
153-202 1.33e-14

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 68.60  E-value: 1.33e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568905969  153 RMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKAL 202
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
139-277 6.99e-13

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); PRIP-2, also termed phospholipase C-L2, or phospholipase C-epsilon-2 (PLC-epsilon-2), or inactive phospholipase C-like protein 2 (PLC-L2), is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that exhibits a relatively ubiquitous expression. It functions as a novel negative regulator of B-cell receptor (BCR) signaling and immune responses. PRIP-2 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-2 does not have PLC enzymatic activity.


Pssm-ID: 320053 [Multi-domain]  Cd Length: 144  Bit Score: 66.85  E-value: 6.99e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDE---EYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDF 215
Cdd:cd16223    2 LSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTskiELKFKELHKSKEKGGTEVTKEEFIEVFHELCTRPEIYFLLVQF 81
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568905969 216 SSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16223   82 SSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPE 143
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
143-238 4.78e-12

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 64.13  E-value: 4.78e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 143 FQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALT-KRTEIEEIFEDF--SSDK 219
Cdd:cd16201    6 FYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTRRRGELGFDDFAQLYHKLMfDQKIIEDFFKKYsySSDG 85
                         90
                 ....*....|....*....
gi 568905969 220 QKLTLLEFVDFLRKEQKEK 238
Cdd:cd16201   86 QTVTLEDFQRFLLEEQKEP 104
EFh_NorpA_like cd16212
EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...
183-277 1.44e-11

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and similar proteins; NorpA, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, is an eye-specific phosphoinositide phospholipase C (PI-PLC) encoded by norpA gene in Drosophila. It is expressed predominantly in photoreceptors and plays an essential role in the phototransduction pathway of Drosophila. A mutation within the norpA gene can render the fly blind without affecting any of the obvious structures of the eye. Like beta-class of vertebrate PI-PLCs, NorpA contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320042 [Multi-domain]  Cd Length: 153  Bit Score: 63.34  E-value: 1.44e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 183 DVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSDKQK-LTLLEFVDFLRKEQKEkdhaPDL------------ALELI 249
Cdd:cd16212   50 DSIEKEDFTFEKFYALYHKICPRNDIEELFTSITKGKGEhISLAQLINFMNDKQRD----PRLneilyplydekrCTEII 125
                         90       100
                 ....*....|....*....|....*...
gi 568905969 250 DRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16212  126 KAYEQNEENIKNKRMSKDGFIRYLMSDE 153
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
671-776 2.66e-10

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 58.75  E-value: 2.66e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 671 AQILVVQVISGQQLPKVDKTKETtvvDPLVKVELYGVPEDTKEQETSHVENNgINPYWGETFYFrlQVPELAM----LRF 746
Cdd:cd00276   13 AERLTVVVLKARNLPPSDGKGLS---DPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSF--DVPAEQLeevsLVI 86
                         90       100       110
                 ....*....|....*....|....*....|
gi 568905969 747 VVKDYSRKSRNNFIGQYTLPWTCMKQGYRH 776
Cdd:cd00276   87 TVVDKDSVGRNEVIGQVVLGPDSGGEELEH 116
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
139-277 3.26e-10

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); PRIP-1, also termed phospholipase C-deleted in lung carcinoma, or inactive phospholipase C-like protein 1 (PLC-L1), or p130, is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that is predominantly expressed in the brain. It is involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. It interacts with the catalytic subunits of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), and functions as a scaffold to regulate the activities and subcellular localizations of both PP1 and PP2A in phospho-dependent cellular signaling. It also promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of hormone-sensitive lipase (HSL) and perilipin A, thus reducing protein kinase A (PKA)-mediated lipolysis. Moreover, PRIP-1 plays an important role in insulin granule exocytosis through the association with GABAA-receptor-associated protein (GABARAP) to form a complex to regulate KIF5B-mediated insulin secretion. It also inhibits regulated exocytosis through direct interactions with syntaxin 1 and synaptosomal-associated protein 25 (SNAP-25) via its C2 domain. Furthermore, PRIP-1 has been implicated in the negative regulation of bone formation. PRIP-1 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-1 does not have PLC enzymatic activity.


Pssm-ID: 320052 [Multi-domain]  Cd Length: 143  Bit Score: 59.11  E-value: 3.26e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDE---EYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDF 215
Cdd:cd16222    2 LSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEakiRLKFKEIQKSKEKLTTRVTEEEFCEAYSELCTRPEVYFLLVQI 81
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568905969 216 SSDKQKLTLLEFVDFLRKEQKEKDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16222   82 SKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
130-233 1.10e-09

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 57.11  E-value: 1.10e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 130 DHQEQMDQMLNEWFQQADRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKAL-TKRTEI 208
Cdd:COG5126   26 DFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALgVSEEEA 105
                         90       100
                 ....*....|....*....|....*.
gi 568905969 209 EEIFEDFSSDKQ-KLTLLEFVDFLRK 233
Cdd:COG5126  106 DELFARLDTDGDgKISFEEFVAAVRD 131
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
674-770 1.32e-09

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 56.50  E-value: 1.32e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETTvvDPLVKVELygVPEDTKEQETShVENNGINPYWGETFYFRLQVPEL--AMLRFVVKDY 751
Cdd:cd08390   16 LTVSLIKARNLPPRTKDVAHC--DPFVKVCL--LPDERRSLQSK-VKRKTQNPNFDETFVFQVSFKELqrRTLRLSVYDV 90
                         90
                 ....*....|....*....
gi 568905969 752 SRKSRNNFIGQYTLPWTCM 770
Cdd:cd08390   91 DRFSRHCIIGHVLFPLKDL 109
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
17-124 1.94e-09

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 55.63  E-value: 1.94e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969    17 LMQEGTMMRKVRT--KSWKKlRYFRLQNDGMTVW--HGSQPESMPKPTFSISDVErIRKGQDSEllrylveEFPLEQGFT 92
Cdd:smart00233   1 VIKEGWLYKKSGGgkKSWKK-RYFVLFNSTLLYYksKKDKKSYKPKGSIDLSGCT-VREAPDPD-------SSKKPHCFE 71
                           90       100       110
                   ....*....|....*....|....*....|..
gi 568905969    93 VVfHGRRPNLDLVANSVEEAQIWMRGLQLLVD 124
Cdd:smart00233  72 IK-TSDRKTLLLQAESEEEREKWVEALRKAIA 102
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
669-766 7.47e-09

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 54.64  E-value: 7.47e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 669 YKAQILVVQVISGQQLPKVDKTKETtvvDPLVKVELygVPeDTKEQETSHVENNGINPYWGETFYFRLQVPELAMLRFV- 747
Cdd:cd08386   13 FQESTLTLKILKAVELPAKDFSGTS---DPFVKIYL--LP-DKKHKLETKVKRKNLNPHWNETFLFEGFPYEKLQQRVLy 86
                         90       100
                 ....*....|....*....|.
gi 568905969 748 --VKDYSRKSRNNFIGQYTLP 766
Cdd:cd08386   87 lqVLDYDRFSRNDPIGEVSLP 107
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
674-761 2.32e-08

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 53.42  E-value: 2.32e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKettVVDPLVKVELYGVPEDTKEQETSHVENNgINPYWGETFYFRLQVP-ELAMLRFVVKDYS 752
Cdd:cd04026   15 LTVEVREAKNLIPMDPNG---LSDPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPAdKDRRLSIEVWDWD 90

                 ....*....
gi 568905969 753 RKSRNNFIG 761
Cdd:cd04026   91 RTTRNDFMG 99
PH pfam00169
PH domain; PH stands for pleckstrin homology.
17-123 2.81e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 52.18  E-value: 2.81e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   17 LMQEGTMMRKV--RTKSWKKlRYFRLQNDGMTVW--HGSQPESMPKPTFSISDVERIRKGQDsellrylvEEFPLEQGFT 92
Cdd:pfam00169   1 VVKEGWLLKKGggKKKSWKK-RYFVLFDGSLLYYkdDKSGKSKEPKGSISLSGCEVVEVVAS--------DSPKRKFCFE 71
                          90       100       110
                  ....*....|....*....|....*....|...
gi 568905969   93 VVFHGRRPN--LDLVANSVEEAQIWMRGLQLLV 123
Cdd:pfam00169  72 LRTGERTGKrtYLLQAESEEERKDWIKAIQSAI 104
EFh_PI-PLCbeta3 cd16210
EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...
149-273 2.94e-08

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, or phospholipase C-beta-3 (PLC-beta3), is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta3 associates with CXC chemokine receptor 2 (CXCR2) and Na+/H+ exchanger regulatory factor-1 (NHERF1) to form macromolecular complexes at the plasma membrane of pancreatic cancer cells, which functionally couple chemokine signaling to PI-PLC-beta3-mediated signaling cascade. Moreover, PI-PLC-beta3 directly interacts with the M3 muscarinic receptor (M3R), a prototypical G alpha-q-coupled receptor that promotes PI-PLC-beta3 localization to the plasma membrane. This binding can alter G alpha-q-dependent PLC activation. Furthermore, PI-PLC-beta3 inhibits the proliferation of hematopoietic stem cells (HSCs) and myeloid cells through the interaction of SH2-domain-containing protein phosphatase 1 (SHP-1) and signal transducer and activator of transcription 5 (Stat5), and the augment of the dephosphorylating activity of SHP-1 toward Stat5, leading to the inactivation of Stat5. It is also involved in atopic dermatitis (AD) pathogenesis via regulating the expression of periostin in fibroblasts and thymic stromal lymphopoietin (TSLP) in keratinocytes. In addition, PI-PLC-beta3 mediates the thrombin-induced Ca2+ response in glial cells. PI-PLC-beta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320040  Cd Length: 151  Bit Score: 53.38  E-value: 2.94e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 149 NQDGRMSFREAQRLLLL--MNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD-KQKLTLL 225
Cdd:cd16210   12 NQDGRIPVKNILKMFSAdkKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEIGAKgKPYLTLE 91
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568905969 226 EFVDFLRKEQKEK--------DHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYL 273
Cdd:cd16210   92 QLMDFINQKQRDPrlnevlypPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYL 147
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
34-124 3.95e-08

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the second class of PLC discovered. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). This cd contains PLC members from fungi and plants. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270171  Cd Length: 115  Bit Score: 52.29  E-value: 3.95e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  34 KLRYFRLQNDGMTV-WhgSQPESMPKPTFSISDVERIRKGQDSE-LLRYLVEEFPlEQGFTVVFHGRRPNLDLVANSVEE 111
Cdd:cd13365   26 HFRYFWLSPDELTLyW--SSPKKGSEKRVRLSSVSRIIPGQRTVvFKRPPPPGLE-EHSFSIIYADGERSLDLTCKDRQE 102
                         90
                 ....*....|...
gi 568905969 112 AQIWMRGLQLLVD 124
Cdd:cd13365  103 FDTWFTGLRYLLS 115
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
674-777 5.15e-08

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 52.43  E-value: 5.15e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETtvvDPLVKVELYGVPEDTKEQETsHVENNGINPYWGETFYFRLQVPEL--AMLRFVVKDY 751
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLA---DPYVKVNLYYGKKRISKKKT-HVKKCTLNPVFNESFVFDIPSEELedISVEFLVLDS 92
                         90       100
                 ....*....|....*....|....*.
gi 568905969 752 SRKSRNNFIGQYTLPWTCMKQGYRHV 777
Cdd:cd08404   93 DRVTKNEVIGRLVLGPKASGSGGHHW 118
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
674-762 6.85e-08

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 52.20  E-value: 6.85e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETtvvDPLVKVELYGVPEDTKEQETSHVENNgINPYWGETFYFRLQVPEL--AMLRFVVKDY 751
Cdd:cd08410   16 LNVDIIRAKQLLQTDMSQGS---DPFVKIQLVHGLKLIKTKKTSCMRGT-IDPFYNESFSFKVPQEELenVSLVFTVYGH 91
                         90
                 ....*....|.
gi 568905969 752 SRKSRNNFIGQ 762
Cdd:cd08410   92 NVKSSNDFIGR 102
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
697-766 1.52e-07

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 50.71  E-value: 1.52e-07
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568905969 697 DPLVKVELYGVPedtkeQETSHVENNGiNPYWGETFYFRLQ-VPEL-AMLRFVVKDYSRKSRNNFIGQYTLP 766
Cdd:cd08373   16 DRIAKVTFRGVK-----KKTRVLENEL-NPVWNETFEWPLAgSPDPdESLEIVVKDYEKVGRNRLIGSATVS 81
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
673-766 3.70e-07

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 50.04  E-value: 3.70e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 673 ILVVQVISGQQLPKVDKTKettVVDPLVKVELYgVPEDTKEQETSHVE--NNGINPYWGETFYFRLqVPELAMLRFVVKD 750
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFG---ASDPYVKISLY-DPDGNGEIDSVQTKtiKKTLNPKWNEEFFFRV-NPREHRLLFEVFD 75
                         90
                 ....*....|....*.
gi 568905969 751 YSRKSRNNFIGQYTLP 766
Cdd:cd04033   76 ENRLTRDDFLGQVEVP 91
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
193-277 4.25e-07

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, or phospholipase C-beta-4 (PLC-beta4), is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It may play a critical role in linking anxiety behaviors and theta rhythm heterogeneity. PI-PLC-beta4 is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta4 functions as a downstream signaling molecule of type 1 metabotropic glutamate receptors (mGluR1s). The thalamic mGluR1-PI-PLC-beta4 cascade is essential for formalin-induced inflammatory pain by regulating the response of ventral posterolateral thalamic nucleus (VPL) neurons. Moreover, PI-PLC-beta4 is essential for long-term depression (LTD) in the rostral cerebellum, which may be required for the acquisition of the conditioned eyeblink response. Besides, PI-PLC-beta4 may play an important role in maintenance of the status epilepticus. The mutations of PI-PLC-beta4 has been identified as the major cause of autosomal dominant auriculocondylar syndrome (ACS). PI-PLC-beta4 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320041  Cd Length: 153  Bit Score: 50.11  E-value: 4.25e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 193 EEFVQFYKALTKRTEIEEIFEDFSSDKQK-LTLLEFVDFLRKEQKEkdhaPDL------------ALELIDRYEPSENGR 259
Cdd:cd16211   60 EKFYELYHKICPRTDIEELFKKINGDKKDyLTVDQLISFLNEHQRD----PRLneilfpfydrkrVMQIIETYEVDEEFK 135
                         90
                 ....*....|....*...
gi 568905969 260 LLHVLSKDGFLKYLCSKD 277
Cdd:cd16211  136 KKEQLSSDGFCRYLMSDE 153
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
671-767 5.93e-07

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 49.34  E-value: 5.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 671 AQILVVQVISGQQLPKVDKTKETtvvDPLVKVEL-YGvpeDTK-EQETSHVENNGINPYWGETFYFRLQVPEL--AMLRF 746
Cdd:cd08405   14 ANRITVNIIKARNLKAMDINGTS---DPYVKVWLmYK---DKRvEKKKTVIKKRTLNPVFNESFIFNIPLERLreTTLII 87
                         90       100
                 ....*....|....*....|.
gi 568905969 747 VVKDYSRKSRNNFIGQYTLPW 767
Cdd:cd08405   88 TVMDKDRLSRNDLIGKIYLGW 108
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
671-761 7.15e-07

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 49.16  E-value: 7.15e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 671 AQILVVQVISGQQLPKVDktkETTVVDPLVKVELygVPE----DTKEQETShVENNGINPYWGETFYFRLQVPEL----A 742
Cdd:cd04009   15 EQSLRVEILNARNLLPLD---SNGSSDPFVKVEL--LPRhlfpDVPTPKTQ-VKKKTLFPLFDESFEFNVPPEQCsvegA 88
                         90
                 ....*....|....*....
gi 568905969 743 MLRFVVKDYSRKSRNNFIG 761
Cdd:cd04009   89 LLLFTVKDYDLLGSNDFEG 107
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
139-273 2.06e-06

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 47.86  E-value: 2.06e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 139 LNEWFQQADRNQDGRMSFREAQRLLLLMNVEmdeeyafsLFQEADVTQSDDLGSEEFVQFYKALTKRT---EIEEIFEDF 215
Cdd:COG5126    7 LDRRFDLLDADGDGVLERDDFEALFRRLWAT--------LFSEADTDGDGRISREEFVAGMESLFEATvepFARAAFDLL 78
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 568905969 216 SSDK-QKLTLLEFVDFLRkeqkEKDHAPDLALELIDRYEPSENGRllhvLSKDGFLKYL 273
Cdd:COG5126   79 DTDGdGKISADEFRRLLT----ALGVSEEEADELFARLDTDGDGK----ISFEEFVAAV 129
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
669-766 2.92e-06

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 46.86  E-value: 2.92e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 669 YKAQILVVQVISGQQLPKVDKTKETTvvDPLVKVelYGVPEDTKE--QETShVENNGINPYWGETFYFRLQVPEL--AML 744
Cdd:cd08521   11 YKTGSLEVHIKECRNLAYADEKKKRS--NPYVKV--YLLPDKSKQskRKTS-VKKNTTNPVFNETLKYHISKSQLetRTL 85
                         90       100
                 ....*....|....*....|..
gi 568905969 745 RFVVKDYSRKSRNNFIGQYTLP 766
Cdd:cd08521   86 QLSVWHHDRFGRNTFLGEVEIP 107
PH_12 pfam16457
Pleckstrin homology domain;
13-124 3.81e-06

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 46.87  E-value: 3.81e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969   13 QDLLLMQEGTMMRKVR-TKSWKKLRYFRLQNDGMTVWHGSQPESMP-KPTF-------SISDVERIRKGQDSELLRylVE 83
Cdd:pfam16457   4 QRLNCLLEGAWFPKVRgRRRKKKYRFCRLSPNRKVLHYGDFEEKPTvDPSLeslpekiDLSDIKEVVTGKECPHVR--ES 81
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568905969   84 EFPLEQ-----GFTVVFHGR-RPNLDLVANSVEEAQIWMRGLQLLVD 124
Cdd:pfam16457  82 GKKSKKtsstlAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLLG 128
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
674-776 6.69e-06

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 46.19  E-value: 6.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETtvvDPLVKVELygVPEDTKE-QETSHVENNGINPYWGETFYFRLQVPELA--MLRFVVKD 750
Cdd:cd08384   15 LIVGIIRCVNLAAMDANGYS---DPFVKLYL--KPDAGKKsKHKTQVKKKTLNPEFNEEFFYDIKHSDLAkkTLEITVWD 89
                         90       100
                 ....*....|....*....|....*.
gi 568905969 751 YSRKSRNNFIGQYTLPWTCMKQGYRH 776
Cdd:cd08384   90 KDIGKSNDYIGGLQLGINAKGERLRH 115
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
669-766 1.06e-05

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 45.51  E-value: 1.06e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 669 YKAQILVVQVISGQQLPKVDKTKETTvvDPLVKVelYGVPEDTKE-QETSHVENNGINPYWGETFYFRLQVPELAM--LR 745
Cdd:cd04029   12 YKTQSLNVHVKECRNLAYGDEAKKRS--NPYVKT--YLLPDKSRQsKRKTSIKRNTTNPVYNETLKYSISHSQLETrtLQ 87
                         90       100
                 ....*....|....*....|.
gi 568905969 746 FVVKDYSRKSRNNFIGQYTLP 766
Cdd:cd04029   88 LSVWHYDRFGRNTFLGEVEIP 108
EFh_PI-PLCbeta2 cd16209
EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...
183-274 1.24e-05

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, or phospholipase C-beta-2 (PLC-beta2), is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits (G alpha(q)) through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta2 has two cellular binding partners, alpha- and gamma-synuclein. The binding of either alpha- and gamma-synuclein inhibits PI-PLC-beta2 activity through preventing the binding of its activator G alpha(q). However, the binding of gamma-synuclein to PI-PLC-beta2 does not affect its binding to G beta(gamma) subunits or small G proteins, but enhances these signals. Meanwhile, gamma-synuclein may protect PI-PLC-beta2 from protease degradation and contribute to its over-expression in breast cancer. In leukocytes, the G beta(gamma)-mediated activation of PI-PLC-beta2 can be promoted by a scaffolding protein WDR26, which is also required for the translocation of PI-PLC-beta2 from the cytosol to the membrane in polarized leukocytes. PI-PLC-beta2 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320039  Cd Length: 151  Bit Score: 46.02  E-value: 1.24e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 183 DVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDFSSD-KQKLTLLEFVDFLRKEQKEK--------DHAPDLALELIDRYE 253
Cdd:cd16209   48 DAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSYHAKaKPYMTKEHLTKFINKKQRDSrlneelfpPARPDQVQGLIEKYE 127
                         90       100
                 ....*....|....*....|.
gi 568905969 254 PSENGRLLHVLSKDGFLKYLC 274
Cdd:cd16209  128 PSGINAQRGQLSPEGMVWFLC 148
PH_PLC_fungal cd13360
Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...
18-129 2.20e-05

Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been characterized in the yeast Saccharomyces cerevisiae via deletion studies which resulted in a pleiotropic phenotype, with defects in growth, carbon source utilization, and sensitivity to osmotic stress and high temperature. Unlike Saccharomyces several other fungi including Neurospora crassa, Cryphonectria parasitica , and Magnaporthe oryzae (Mo) have several PLC proteins, some of which lack a PH domain, with varied functions. MoPLC1-mediated regulation of Ca2+ level is important for conidiogenesis and appressorium formation while both MoPLC2 and MoPLC3 are required for asexual reproduction, cell wall integrity, appressorium development, and pathogenicity. The fungal PLCs in this hierarchy contain an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241514  Cd Length: 118  Bit Score: 44.48  E-value: 2.20e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  18 MQEGTMMRKVRTKSwKKLRYFRLQND-GMTVWHGSQPESMpkptFSISDVERIRKGQDSellRYLVEEFPLEQGF----- 91
Cdd:cd13360    1 LRQGTPLLKVTKKK-KKRILFKLDPEsGKITWDSKKPSKS----LYIDDIKEIRTGEDA---RNYREEFGISEEFedrwi 72
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 568905969  92 TVVFHGRRPN----LDLVANSVEEAQIWMRGLQLLV----DLVASM 129
Cdd:cd13360   73 TIIYFVPKKNklktLHLIADTEEDFKLWTTTLEGLVklrrELMESL 118
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
674-765 2.55e-05

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 44.70  E-value: 2.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETtvvDPLVKVELYGVPEDTKEQETShVENNGINPYWGETFYFrlQVP----ELAMLRFVVK 749
Cdd:cd08402   17 LTVVILEAKNLKKMDVGGLS---DPYVKIHLMQNGKRLKKKKTT-IKKRTLNPYYNESFSF--EVPfeqiQKVHLIVTVL 90
                         90
                 ....*....|....*.
gi 568905969 750 DYSRKSRNNFIGQYTL 765
Cdd:cd08402   91 DYDRIGKNDPIGKVVL 106
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
673-766 2.56e-05

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 43.71  E-value: 2.56e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 673 ILVVQVISGQQLPKVDKTKETtvvDPLVKVELYGVPEDTKEQETShvenngINPYWGETFYFRLQVPELAMLRFVVKDys 752
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEP---SPYVELTVGKTTQKSKVKERT------NNPVWEEGFTFLVRNPENQELEIEVKD-- 69
                         90
                 ....*....|....
gi 568905969 753 rKSRNNFIGQYTLP 766
Cdd:cd04050   70 -DKTGKSLGSLTLP 82
EF-hand_7 pfam13499
EF-hand domain pair;
143-200 2.59e-05

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 42.63  E-value: 2.59e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  143 FQQADRNQDGRMSFREAQRLL--LLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYK 200
Cdd:pfam13499   8 FKLLDSDGDGYLDVEELKKLLrkLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
676-763 3.33e-05

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 43.72  E-value: 3.33e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 676 VQVISGQQLPkvdktkeTTVVDPLVKVELYGVPEDTKEQETshveNNgiNPYWGETFYFRLQVPELAM----LRFVVKDY 751
Cdd:cd04011    8 VRVIEARQLV-------GGNIDPVVKVEVGGQKKYTSVKKG----TN--CPFYNEYFFFNFHESPDELfdkiIKISVYDS 74
                         90
                 ....*....|..
gi 568905969 752 SRKSRNNFIGQY 763
Cdd:cd04011   75 RSLRSDTLIGSF 86
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
674-766 6.15e-05

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 43.24  E-value: 6.15e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETtvvDPLVKVELYGvpedtKEQETSHVENNGInPYWGETFYFRLQVPELAMLRFVVKDYSR 753
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTS---DPFVRVFYNG-----QTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDL 72
                         90
                 ....*....|...
gi 568905969 754 KSRNNFIGQYTLP 766
Cdd:cd04025   73 VSKNDFLGKVVFS 85
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
222-277 6.64e-05

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases.


Pssm-ID: 320033  Cd Length: 174  Bit Score: 44.24  E-value: 6.64e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 568905969 222 LTLLEFVDFLRKEQKEkDHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16203  120 LTISQLKDFLENHQME-HITEEEAIKIIQRHEPDPILRSKNCLSFEGFARYLMDKD 174
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
670-762 1.47e-04

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 42.23  E-value: 1.47e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 670 KAQILVVQVISGQQLPKVDktkETTVVDPLVKVELYGVPEDTKEQETSHVENNgINPYWGETF-YFRLQVPEL--AMLRF 746
Cdd:cd04031   14 VTSQLIVTVLQARDLPPRD---DGSLRNPYVKVYLLPDRSEKSKRRTKTVKKT-LNPEWNQTFeYSNVRRETLkeRTLEV 89
                         90
                 ....*....|....*.
gi 568905969 747 VVKDYSRKSRNNFIGQ 762
Cdd:cd04031   90 TVWDYDRDGENDFLGE 105
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
674-737 1.47e-04

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 41.86  E-value: 1.47e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568905969 674 LVVQVISGQQLPKVDktkETTVVDPLVKVELYGVPEDTKEqeTSHVENNgINPYWGETFYFRLQ 737
Cdd:cd04036    2 LTVRVLRATNITKGD---LLSTPDCYVELWLPTASDEKKR--TKTIKNS-INPVWNETFEFRIQ 59
EFh_PI-PLCbeta1 cd16208
EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...
149-277 1.88e-04

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, or PLC-154, or phospholipase C-I (PLC-I), or phospholipase C-beta-1 (PLC-beta1), is expressed at highest levels in specific regions of the brain, as well as in the cardiovascular system. It has two splice variants, PI-PLC-beta1a and PI-PLC-beta1b, both of which are present within the nucleus. Nuclear PI-PLC-beta1 is a key molecule for nuclear inositide signaling, where it plays a role in cell cycle progression, proliferation and differentiation. It also contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta1 acts as an effector and a GTPase activating protein (GAP) specifically activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It regulates neuronal activity in the cerebral cortex and hippocampus, and has been implicated for participations in diverse critical functions related to forebrain diseases such as schizophrenia. It may play an important role in maintenance of the status epilepticus, and in osteosarcoma-related signal transduction pathways. PI-PLC-beta1 also functions as a regulator of erythropoiesis in kinamycin F, a potent inducer of gamma-globin production in K562 cells. The G protein activation and the degradation of PI-PLC-beta1 can be regulated by the interaction of alpha-synuclein. As a result, it may reduce cell damage under oxidative stress. Moreover, PI-PLC-beta1 works as a new intermediate in the HIV-1 gp120-triggered phosphatidylcholine-specific phospholipase C (PC-PLC)-driven signal transduction pathway leading to cytoplasmic CCL2 secretion in macrophages. PI-PLC-beta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.


Pssm-ID: 320038  Cd Length: 151  Bit Score: 42.56  E-value: 1.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 149 NQDGRMSFREAQRLLLL--MNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYKALTKRTEIEEIFEDF-SSDKQKLTLL 225
Cdd:cd16208   12 NPEGRIPVKNIYRLFSAdrKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEFgAKSKPYLSVD 91
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 226 EFVDFLRKEQKEK--------DHAPDLALELIDRYEPSENGRLLHVLSKDGFLKYLCSKD 277
Cdd:cd16208   92 QMTEFINSKQRDPrlneilypPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
674-782 2.09e-04

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 41.95  E-value: 2.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETTvvDPLVKVELygVPEdTKEQETSHVENNGINPYWGETFYF----RLQVPELAmLRFVVK 749
Cdd:cd08388   18 LLVNIIECRDLPAMDEQSGTS--DPYVKLQL--LPE-KEHKVKTRVLRKTRNPVYDETFTFygipYNQLQDLS-LHFAVL 91
                         90       100       110
                 ....*....|....*....|....*....|...
gi 568905969 750 DYSRKSRNNFIGQYTLPWTCMKQGYRHVSLLSR 782
Cdd:cd08388   92 SFDRYSRDDVIGEVVCPLAGADLLNEGELLVSR 124
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
665-784 3.97e-04

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 43.98  E-value: 3.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  665 PISLYK-AQILVVQVISGQQLPKVDKTKETtvvDPLVKVELYGvpedtKEQETSHVENNGINPYWGETFYFRLQVPELAM 743
Cdd:COG5038  1032 PVEMVEnSGYLTIMLRSGENLPSSDENGYS---DPFVKLFLNE-----KSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDV 1103
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568905969  744 LRFVVKDYSRKSRNNFIGQYTLPWTCMKQGYRHVSLLSRDG 784
Cdd:COG5038  1104 LTINVNDWDSGEKNDLLGTAEIDLSKLEPGGTTNSNIPLDG 1144
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
295-432 4.92e-04

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar proteins; This subfamily corresponds to the catalytic domain present in bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) and their sequence homologs found in eukaryota. Bacterial PI-PLCs participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. Bacterial PI-PLCs contain a single TIM-barrel type catalytic domain. Its catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. Eukaryotic homologs in this family are named as phosphatidylinositol-specific phospholipase C X domain containing proteins (PI-PLCXD). They are distinct from the typical eukaryotic phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11), which have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, eukaryotic PI-PLCXDs contain a single TIM-barrel type catalytic domain, X domain, which is closely related to that of bacterial PI-PLCs. Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may be distinct from that of typical eukaryotic PI-PLCs. This family also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host's immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 42.85  E-value: 4.92e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 295 PLSHYYINSSHN--TYLVGDQLCGQSSV----EGYIR-ALKRGCRCVEVDTW-DGPDGEPVVYHGHTLTSRILFKDVLAT 366
Cdd:cd08557    8 PLSQLSIPGTHNsyAYTIDGNSPIVSKWsktqDLSITdQLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDVLNE 87
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568905969 367 LAQYafqSSDYP---LILSLENHCTWEQQRTMA---HHLTEILGEQLLRNTLEGllvDSMPSPEQLR-GKILV 432
Cdd:cd08557   88 VKDF---LDAHPsevVILDLEHEYGGDNGEDHDeldALLRDVLGDPLYRPPVRA---GGWPTLGELRaGKRVL 154
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
666-763 5.69e-04

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 41.08  E-value: 5.69e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 666 ISLYKAQILVvQVISGQ-QLPKVDKTKETTV-VDPLVKVELYGvpedtKEQETSHVENNgINPYWGETFYFRLQVPELA- 742
Cdd:cd04018    4 FKIYRAEDLP-QMDSGImANVKKAFLGEKKElVDPYVEVSFAG-----QKVKTSVKKNS-YNPEWNEQIVFPEMFPPLCe 76
                         90       100
                 ....*....|....*....|.
gi 568905969 743 MLRFVVKDYSRKSRNNFIGQY 763
Cdd:cd04018   77 RIKIQIRDWDRVGNDDVIGTH 97
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
20-119 7.71e-04

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 39.45  E-value: 7.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  20 EGTMMRK--VRTKSWKKlRYFRLQNDGMTVW-HGSQPESMPKPTFSISDVERIRKGQDSELlrylveefplEQGFTVVFH 96
Cdd:cd00821    2 EGYLLKRggGGLKSWKK-RWFVLFEGVLLYYkSKKDSSYKPKGSIPLSGILEVEEVSPKER----------PHCFELVTP 70
                         90       100
                 ....*....|....*....|...
gi 568905969  97 GRRpNLDLVANSVEEAQIWMRGL 119
Cdd:cd00821   71 DGR-TYYLQADSEEERQEWLKAL 92
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
674-766 1.01e-03

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 40.05  E-value: 1.01e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKvdktKETTVVDPLVKVEL-YGVPEDTKEqetSHVENNGINPYWGETFYFRLQVP------------- 739
Cdd:cd08675    1 LSVRVLECRDLAL----KSNGTCDPFARVTLnYSSKTDTKR---TKVKKKTNNPRFDEAFYFELTIGfsyekksfkveee 73
                         90       100
                 ....*....|....*....|....*....
gi 568905969 740 --ELAMLRFVVKDYSRKSRNNFIGQYTLP 766
Cdd:cd08675   74 dlEKSELRVELWHASMVSGDDFLGEVRIP 102
C2B_Tac2-N cd08692
C2 domain second repeat found in Tac2-N (Tandem C2 protein in Nucleus); Tac2-N contains two C2 ...
676-762 1.07e-03

C2 domain second repeat found in Tac2-N (Tandem C2 protein in Nucleus); Tac2-N contains two C2 domains and a short C-terminus including a WHXL motif, which are key in stabilizing transport vesicles to the plasma membrane by binding to a plasma membrane. However unlike the usual carboxyl-terminal-type (C-type) tandem C2 proteins, it lacks a transmembrane domain, a Slp-homology domain, and a Munc13-1-interacting domain. Homology search analysis indicate that no known protein motifs are located in its N-terminus, making Tac2-N a novel class of Ca2+-independent, C-type tandem C2 proteins. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176074  Cd Length: 135  Bit Score: 39.91  E-value: 1.07e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 676 VQVISGQQLPKvdkTKETTVVDPLVKVELYGVPEDTKEQETSHVENNGINPYWGETFYFRLQVPELAmLRFVVKDYSRKS 755
Cdd:cd08692   18 LQILEAQNLPS---SSTPLTLSFFVKVGMFSTGGLLYKKKTRLVKSSNGQVKWGETMIFPVTQQEHG-IQFLIKLYSRSS 93

                 ....*....
gi 568905969 756 --RNNFIGQ 762
Cdd:cd08692   94 vrRKHFLGQ 102
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
21-124 1.75e-03

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270168  Cd Length: 121  Bit Score: 39.18  E-value: 1.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  21 GTMMRKVRTKSWKKLRYFRLQNDGMTVWHGSQPESMPKPTFSISDVERIRKGQDS-ELLRYLVEEFPLEQG--FtVVFHG 97
Cdd:cd13362    4 GTVMTKFYQKKRPERRTFQVKLETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSkDFERWPDEAKKLDPSccF-VILYG 82
                         90       100       110
                 ....*....|....*....|....*....|
gi 568905969  98 ---RRPNLDLVANSVEEAQIWMRGLQLLVD 124
Cdd:cd13362   83 tefRLKTLSVAATSEEECDMWIKGLRYLVE 112
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
147-200 1.99e-03

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 37.14  E-value: 1.99e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568905969 147 DRNQDGRMSFREAQRLLLLMNVEMDEEYAFSLFQEADVTQSDDLGSEEFVQFYK 200
Cdd:cd00051   10 DKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
674-762 2.73e-03

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 38.06  E-value: 2.73e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLPKVDKTKETTvvDPLVKVELygvpeDTKEQETShVENNGINPYWgETFYFRLQVPELAM----LRFVVK 749
Cdd:cd08688    1 LKVRVVAARDLPVMDRSSDLT--DAFVEVKF-----GSTTYKTD-VVKKSLNPVW-NSEWFRFEVDDEELqdepLQIRVM 71
                         90
                 ....*....|...
gi 568905969 750 DYSRKSRNNFIGQ 762
Cdd:cd08688   72 DHDTYSANDAIGK 84
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
672-762 3.05e-03

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 38.41  E-value: 3.05e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 672 QILVVQVISGQQLPKVDKTKettVVDPLVKVELYgvPEDTKE--QETSHVENNgINPYWGETFYFRLQVPELA--MLRFV 747
Cdd:cd04030   16 QKLIVTVHKCRNLPPCDSSD---IPDPYVRLYLL--PDKSKStrRKTSVKKDN-LNPVFDETFEFPVSLEELKrrTLDVA 89
                         90
                 ....*....|....*..
gi 568905969 748 VK-DYSRKSR-NNFIGQ 762
Cdd:cd04030   90 VKnSKSFLSReKKLLGQ 106
EF-hand_7 pfam13499
EF-hand domain pair;
172-232 3.45e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 36.85  E-value: 3.45e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568905969  172 EEYAFSLFQEADVTQSDDLGSEEFVQFYKAL-----TKRTEIEEIFEDFSSDKQ-KLTLLEFVDFLR 232
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeegepLSDEEVEELFKEFDLDKDgRISFEEFLELYS 67
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
674-766 4.00e-03

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 38.12  E-value: 4.00e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969 674 LVVQVISGQQLpkvdkTKETTVVDPLVKVELygvpEDTKEQETSHVENNGINPYWGETFYFRLQvPELAMLRFVVKDYSR 753
Cdd:cd08678    1 LLVKNIKANGL-----SEAAGSSNPYCVLEM----DEPPQKYQSSTQKNTSNPFWDEHFLFELS-PNSKELLFEVYDNGK 70
                         90
                 ....*....|...
gi 568905969 754 KSRNNFIGQYTLP 766
Cdd:cd08678   71 KSDSKFLGLAIVP 83
PH_Bud4 cd13278
Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the ...
17-132 6.81e-03

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241432  Cd Length: 139  Bit Score: 37.57  E-value: 6.81e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  17 LMQEGTmmrkvRTKSWKKlRYFRLQNDGMTVWHgsqpESMPKPTFSI----------SDVERIRKGQDSELL--RYLVEE 84
Cdd:cd13278   25 LLQEGG-----DCEYWRR-RFFKLQGTKLVAYH----EVTRKPRATInllkvvdvvdDDDARERTSSFKRNFtdLVLFEE 94
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568905969  85 fpleqGFTVVF-HGRRpnLDLVANSVEEAQIWMRGLQLLVDLVASmdHQ 132
Cdd:cd13278   95 -----CFRLVFaNGEV--IDFYADSKEEKADWYSKLKEVVELNRF--HQ 134
PH_ELMO1_CED-12 cd13359
Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of ...
13-124 8.48e-03

Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of cytokinesis 2), a hematopoietic cell-specific, atypical GEF, controls lymphocyte migration through Rac activation. A DOCK2-ELMO1 complex s necessary for DOCK2-mediated Rac signaling. DOCK2 contains a SH3 domain at its N-terminus, followed by a lipid binding DHR1 domain, and a Rac-binding DHR2 domain at its C-terminus. ELMO1, a mammalian homolog of C. elegans CED-12, contains the N-terminal RhoG-binding region, the ELMO domain, the PH domain, and the C-terminal sequence with three PxxP motifs. The C-terminal region of ELMO1, including the Pro-rich sequence, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle along with the PH domain of ELMO1. Autoinhibition of ELMO1 and DOCK2 is accomplished by the interactions of the EID and EAD domains and SH3 and DHR2 domains, respectively. The interaction of DOCK2 and ELMO1 mutually relieve their autoinhibition and results in the activation of Rac1. The PH domain of ELMO1 does not bind phosphoinositides due to the absence of key binding residues. It more closely resembles the FERM domain rather than other PH domains. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270166 [Multi-domain]  Cd Length: 126  Bit Score: 37.29  E-value: 8.48e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905969  13 QDLLLMQEGTMMRKVRTKSWK-KLRYFRLQNDGMTVWHGSQPESmPKPT--------FSISDVERIRKGQDSELLRYL-V 82
Cdd:cd13359    6 QRLNFLVEGTLFPKYNARGRKdKFWYCRLSPNHKVLHYGDCEES-AQPApleelpekLPVADIKALVTGKDCPHMKELkK 84
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 568905969  83 EEFPLEQGFTVVFHGRRPnLDLVANSVEEAQIWMRGLQLLVD 124
Cdd:cd13359   85 NKSVASLAFSILYDSDES-LDFVAPNETVFDIWTDGLNALLG 125
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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