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Conserved domains on  [gi|1034568425|ref|XP_016871801|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 isoform X9 [Homo sapiens]

Protein Classification

EFh_PI-PLCepsilon and PI-PLCc_epsilon domain-containing protein( domain architecture ID 13059350)

protein containing domains EFh_PI-PLCepsilon, PI-PLCc_epsilon, RA1_PLC-epsilon, and RA2_PLC-epsilon

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 1067-1509 1.49e-152

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: 470.10  E-value: 1.49e-152
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1067 IKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAID 1146
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1147 RSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPDQLrkkvllknkklkahqtpvd 1226
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQL------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1227 ilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikka 1306
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1307 dnsacnKGKVydmelgeefyLDQNKKesrqiAPELSDLVIYCQAVKFPGLStlnasgssrgkerksrksifgnnpgrmsp 1386
Cdd:cd08596    142 ------KNKI----------LLKNKK-----APELSDLVIYCQAVKFPGLS----------------------------- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1387 getasfnktsgksscegirqtweesssplnpttslsaiirTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPA 1466
Cdd:cd08596    172 ----------------------------------------TPKCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPA 211

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|...
gi 1034568425 1467 ATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08596    212 ATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 874-1054 5.60e-91

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: 292.69  E-value: 5.60e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  874 GGMKGFQSFMVSDSNMSFVEFVELFKSFSVRSRKDLKDLFDVYAVPCNRSGSESAPLYTNLTIDENTSDLQPDLDLLTRN 953
Cdd:cd16203      1 GGLKGFSIGEVQDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAPLKRSLSISESYSGLFPDLDLLTRN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  954 VSDLGLFIKSKQqlsdnQRQISDAIAAASIVTNGTGIEstSLGIFGVGILQLNDFLVNCQGEHCTYDEILSIIQKFEPSI 1033
Cdd:cd16203     81 TSLDGLFISKKQ-----QKKIYDAIAAASIVTNGAGVD--SSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEPDP 153

                          170       180
                   ....*....|....*....|.
gi 1034568425 1034 SMCHQGLMSFEGFARFLMDKE 1054
Cdd:cd16203    154 ILRSKNCLSFEGFARYLMDKD 174
RA1_PLC-epsilon cd17229
Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1683-1790 9.24e-68

Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the first RA domain of PLC-epsilon.


:

Pssm-ID: 340749  Cd Length: 108  Bit Score: 223.56  E-value: 9.24e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1683 ERKCLQTHRVTVHGVPGPEPFTVFTINGGTKAKQLLQQILTNEQDIKPVTTDYFLMEEKYFISKEKNECRKQPFQRAIGP 1762
Cdd:cd17229      1 ERKALQTHKVTVHGVPGPEPFTVFTISEGTTAKQLLQQILATEQGIEPDTTDYFLMEEKYFISKEKNECRKPPFQRVIGP 80

                           90       100
                   ....*....|....*....|....*...
gi 1034568425 1763 EEEIMQILSSWFPEEGYMGRIVLKTQQE 1790
Cdd:cd17229     81 EEEILQILNSWFPEEGYVGRIILKTREE 108
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1810-1912 4.41e-48

Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon.


:

Pssm-ID: 340478  Cd Length: 102  Bit Score: 166.73  E-value: 4.41e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1810 EESFFVQVHDVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSYSIlsnpnPSDYVLLEEVVKDTTNKKTTTPKSS----Q 1885
Cdd:cd01780      1 EDTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDI-----PSDFVLVEELEKEPTSDKSSSKSSSskteQ 75

                           90       100
                   ....*....|....*....|....*..
gi 1034568425 1886 RVLLDQECVFQAQSKWKGAGKFILKLK 1912
Cdd:cd01780     76 RVLGDQENVYQAQSRWKGAGKFILKLR 102
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 1548-1660 1.94e-37

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: 137.67  E-value: 1.94e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1548 SLTIVSGQNVCPSNSMG----SPCIEVDVLGMPLDSCH-FRTKPIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVENNSS 1622
Cdd:cd00275      5 TIKIISGQQLPKPKGDKgsivDPYVEVEIHGLPADDSAkFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSG 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1034568425 1623 AVT--AQRIIPLKALKRGYRHLQLRNLHNEVLEISSLFIN 1660
Cdd:cd00275     85 DDDflGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVH 124
RasGEF super family cl02485
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 223-516 1.49e-21

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


The actual alignment was detected with superfamily member smart00147:

Pssm-ID: 470590  Cd Length: 242  Bit Score: 95.77  E-value: 1.49e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   223 FPEEVASILMEQEQTIYRRVLPvdylcfltrdlgtPECQSSLPCLKASISASILTtqngehnaLEDLVMRFNEVSSWVTW 302
Cdd:smart00147    5 DPKELAEQLTLLDFELFRKIDP-------------SELLGSVWGKRSKKSPSPLN--------LEAFIRRFNEVSNWVAT 63

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   303 LILTAGSMEEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVL---KMWQFMDQSDIETMRSLKDAMAQHESSCEY 379
Cdd:smart00147   64 EILKQTTPKDRAELLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISrlkKTWEKLPSKYKKLFEELEELLSPERNYKNY 143

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   380 RKVVtRALHIPGCkvVPFCGVFLKELcevldgasglmklcprynsqeetlefVADYSGQDNFLqrvgQNGLKNSEKESTV 459
Cdd:smart00147  144 REAL-SSCNLPPC--IPFLGVLLKDL--------------------------TFIDEGNPDFL----ENGLVNFEKRRQI 190

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034568425   460 NSIFQVIRSCNRSLEtDEEDSPSEGNSsrksslkdksrWQFIIGDLLDSDNDIFEQS 516
Cdd:smart00147  191 AEILREIRQLQSQPY-NLRPNRSDIQS-----------LLQQLLDHLDEEEELYQLS 235
 
Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 1067-1509 1.49e-152

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: 470.10  E-value: 1.49e-152
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1067 IKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAID 1146
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1147 RSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPDQLrkkvllknkklkahqtpvd 1226
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQL------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1227 ilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikka 1306
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1307 dnsacnKGKVydmelgeefyLDQNKKesrqiAPELSDLVIYCQAVKFPGLStlnasgssrgkerksrksifgnnpgrmsp 1386
Cdd:cd08596    142 ------KNKI----------LLKNKK-----APELSDLVIYCQAVKFPGLS----------------------------- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1387 getasfnktsgksscegirqtweesssplnpttslsaiirTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPA 1466
Cdd:cd08596    172 ----------------------------------------TPKCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPA 211

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|...
gi 1034568425 1467 ATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08596    212 ATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 874-1054 5.60e-91

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: 292.69  E-value: 5.60e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  874 GGMKGFQSFMVSDSNMSFVEFVELFKSFSVRSRKDLKDLFDVYAVPCNRSGSESAPLYTNLTIDENTSDLQPDLDLLTRN 953
Cdd:cd16203      1 GGLKGFSIGEVQDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAPLKRSLSISESYSGLFPDLDLLTRN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  954 VSDLGLFIKSKQqlsdnQRQISDAIAAASIVTNGTGIEstSLGIFGVGILQLNDFLVNCQGEHCTYDEILSIIQKFEPSI 1033
Cdd:cd16203     81 TSLDGLFISKKQ-----QKKIYDAIAAASIVTNGAGVD--SSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEPDP 153

                          170       180
                   ....*....|....*....|.
gi 1034568425 1034 SMCHQGLMSFEGFARFLMDKE 1054
Cdd:cd16203    154 ILRSKNCLSFEGFARYLMDKD 174
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 1070-1206 1.33e-69

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: 230.08  E-value: 1.33e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1070 LQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSA 1149
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034568425 1150 FINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKflfeTDFSDDPMLPSPDQ 1206
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTP----PLDDDLTELPSPED 133
RA1_PLC-epsilon cd17229
Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1683-1790 9.24e-68

Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the first RA domain of PLC-epsilon.


Pssm-ID: 340749  Cd Length: 108  Bit Score: 223.56  E-value: 9.24e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1683 ERKCLQTHRVTVHGVPGPEPFTVFTINGGTKAKQLLQQILTNEQDIKPVTTDYFLMEEKYFISKEKNECRKQPFQRAIGP 1762
Cdd:cd17229      1 ERKALQTHKVTVHGVPGPEPFTVFTISEGTTAKQLLQQILATEQGIEPDTTDYFLMEEKYFISKEKNECRKPPFQRVIGP 80

                           90       100
                   ....*....|....*....|....*...
gi 1034568425 1763 EEEIMQILSSWFPEEGYMGRIVLKTQQE 1790
Cdd:cd17229     81 EEEILQILNSWFPEEGYVGRIILKTREE 108
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 1073-1206 1.34e-61

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: 207.13  E-value: 1.34e-61
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1073 PLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFIN 1152
Cdd:smart00148    4 PLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFAFVT 83

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1034568425  1153 SDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSddpmLPSPDQ 1206
Cdd:smart00148   84 SPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQ 133
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1810-1912 4.41e-48

Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon.


Pssm-ID: 340478  Cd Length: 102  Bit Score: 166.73  E-value: 4.41e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1810 EESFFVQVHDVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSYSIlsnpnPSDYVLLEEVVKDTTNKKTTTPKSS----Q 1885
Cdd:cd01780      1 EDTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDI-----PSDFVLVEELEKEPTSDKSSSKSSSskteQ 75

                           90       100
                   ....*....|....*....|....*..
gi 1034568425 1886 RVLLDQECVFQAQSKWKGAGKFILKLK 1912
Cdd:cd01780     76 RVLGDQENVYQAQSRWKGAGKFILKLR 102
PLN02228 PLN02228
Phosphoinositide phospholipase C
 1008-1659 7.54e-43

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 166.75  E-value: 7.54e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1008 FLVNCQGE-HCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFLMdkENFASKNDESQENIKELQLPLSYYYIESSHNTY 1086
Cdd:PLN02228    47 FVSEVQGErHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLF--SDTNSPLPMSGQVHHDMKAPLSHYFVYTGHNSY 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1087 LTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPI-IYHGHTLTTKIPFKEVVEAIDRSAFINSDLPIIISIENHC 1165
Cdd:PLN02228   125 LTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAeVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL 204

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1166 SLPQQRKMAEIFKTVFGeklvtKFLFETDFSDDPMLPSPDQlrkkvllknkklkahqtpvdiLKQKAhqLASMQvqayng 1245
Cdd:PLN02228   205 PPNLQAQVAKMLTKTFR-----GMLFRCTSESTKHFPSPEE---------------------LKNKI--LISTK------ 250

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1246 gnaNPRpanneeeedeedeydydyeslsddNILEDRPENKSCNDKLQfeynEEIPKRIKKADNsacnkgkvydmelgeef 1325
Cdd:PLN02228   251 ---PPK------------------------EYLESKTVQTTRTPTVK----ETSWKRVADAEN----------------- 282

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1326 yldqnkkesrQIAPELSDLviYCQAVKFPGLSTLNAsgssrGKERKSRKSIFGNNPGRmspgetasfnktsgksscegir 1405
Cdd:PLN02228   283 ----------KILEEYKDE--ESEAVGYRDLIAIHA-----ANCKDPLKDCLSDDPEK---------------------- 323

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1406 qtweesssplnpttslsaIIRTpkcyhisSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNPLMFWLHGI 1485
Cdd:PLN02228   324 ------------------PIRV-------SMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGA 378

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1486 QLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPVLWDKncpmYQKFSPLER--DLDSMDPAVYSltiVSGQNV-CPSNS 1562
Cdd:PLN02228   379 QMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDE----HTLFDPCKRlpIKTTLKVKIYT---GEGWDLdFHLTH 451

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1563 MG--SP---CIEVDVLGMPLDSCHFRTKpIHRNTLNPMW-NEQFLFHVHFEDLVFLRFAVVE---NNSSAVTAQRIIPLK 1633
Cdd:PLN02228   452 FDqySPpdfFVKIGIAGVPRDTVSYRTE-TAVDQWFPIWgNDEFLFQLRVPELALLWFKVQDydnDTQNDFAGQTCLPLP 530

                          650       660
                   ....*....|....*....|....*.
gi 1034568425 1634 ALKRGYRHLQLRNLHNEVLEISSLFI 1659
Cdd:PLN02228   531 ELKSGVRAVRLHDRAGKAYKNTRLLV 556
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 1548-1660 1.94e-37

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: 137.67  E-value: 1.94e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1548 SLTIVSGQNVCPSNSMG----SPCIEVDVLGMPLDSCH-FRTKPIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVENNSS 1622
Cdd:cd00275      5 TIKIISGQQLPKPKGDKgsivDPYVEVEIHGLPADDSAkFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSG 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1034568425 1623 AVT--AQRIIPLKALKRGYRHLQLRNLHNEVLEISSLFIN 1660
Cdd:cd00275     85 DDDflGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVH 124
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
223-516 1.49e-21

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 95.77  E-value: 1.49e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   223 FPEEVASILMEQEQTIYRRVLPvdylcfltrdlgtPECQSSLPCLKASISASILTtqngehnaLEDLVMRFNEVSSWVTW 302
Cdd:smart00147    5 DPKELAEQLTLLDFELFRKIDP-------------SELLGSVWGKRSKKSPSPLN--------LEAFIRRFNEVSNWVAT 63

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   303 LILTAGSMEEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVL---KMWQFMDQSDIETMRSLKDAMAQHESSCEY 379
Cdd:smart00147   64 EILKQTTPKDRAELLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISrlkKTWEKLPSKYKKLFEELEELLSPERNYKNY 143

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   380 RKVVtRALHIPGCkvVPFCGVFLKELcevldgasglmklcprynsqeetlefVADYSGQDNFLqrvgQNGLKNSEKESTV 459
Cdd:smart00147  144 REAL-SSCNLPPC--IPFLGVLLKDL--------------------------TFIDEGNPDFL----ENGLVNFEKRRQI 190

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034568425   460 NSIFQVIRSCNRSLEtDEEDSPSEGNSsrksslkdksrWQFIIGDLLDSDNDIFEQS 516
Cdd:smart00147  191 AEILREIRQLQSQPY-NLRPNRSDIQS-----------LLQQLLDHLDEEEELYQLS 235
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 231-405 6.95e-21

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 91.88  E-value: 6.95e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  231 LMEQEqtIYRRVLPVDylcFLTRDLGTPECQSSLPCLKASISasilttqngehnaledlvmRFNEVSSWVTWLILTAGSM 310
Cdd:pfam00617    8 LIEFE--LFRKIKPRE---LLGSAWSKKDKKENSPNIEAMIA-------------------RFNKLSNWVASEILSEEDL 63

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  311 EEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKV--LKM-WQFMDQSDIETMRSLKDAMAQHESSCEYRKVVTRAl 387
Cdd:pfam00617   64 KKRAKVIKKFIKIAEHCRELNNFNSLMAILSGLNSSPIsrLKKtWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSA- 142

                          170
                   ....*....|....*...
gi 1034568425  388 hIPGCkvVPFCGVFLKEL 405
Cdd:pfam00617  143 -SPPC--IPFLGLYLTDL 157
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 224-405 1.91e-15

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 77.68  E-value: 1.91e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  224 PEEVASILMEQEQTIYRRVLPVDYLCFLTRDLGTPEcqSSLPCLKASISasilttqngehnaledlvmRFNEVSSWVTWL 303
Cdd:cd00155      6 PKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNI--HLSPNLERFIE-------------------RFNNLSNWVASE 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  304 ILTAGSMEEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVL---KMWQFMDQSDIETMRSLKDAMAQHESSCEYR 380
Cdd:cd00155     65 ILLCTNPKKRARLLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISrlkKTWEVLSSKLKKLFEELEELVDPSRNFKNYR 144

                          170       180
                   ....*....|....*....|....*
gi 1034568425  381 KVVTRALHIPGCkvVPFCGVFLKEL 405
Cdd:cd00155    145 KLLKSVGPNPPC--VPFLGVYLKDL 167
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1549-1644 4.92e-13

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: 66.74  E-value: 4.92e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1549 LTIVSGQNVCPSNSMGS--PCIEVDVLGMPLDSchFRTKpIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVE---NNSSA 1623
Cdd:smart00239    4 VKIISARNLPPKDKGGKsdPYVKVSLDGDPKEK--KKTK-VVKNTLNPVWNETFEFEVPPPELAELEIEVYDkdrFGRDD 80

                            90       100
                    ....*....|....*....|.
gi 1034568425  1624 VTAQRIIPLKALKRGYRHLQL 1644
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEKL 101
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 1812-1914 4.16e-12

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 63.89  E-value: 4.16e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1812 SFFVQVH--DVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSYSilsnpnPSDYVLLEEVVkdttnkktttPKSSQRVLL 1889
Cdd:pfam00788    2 DGVLKVYteDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDD------PRDYVLVEVLE----------RGGGERRLP 65

                           90       100
                   ....*....|....*....|....*...
gi 1034568425 1890 DQECVFQAQSKWKG---AGKFILKLKEQ 1914
Cdd:pfam00788   66 DDECPLQIQLQWPRdasDSRFLLRKRDD 93
C2 pfam00168
C2 domain;
1548-1647 3.61e-09

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 55.79  E-value: 3.61e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1548 SLTIVSGQNVCPSNSMGS--PCIEVDVLGmplDSCHFRTKpIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVENNSSA-- 1623
Cdd:pfam00168    4 TVTVIEAKNLPPKDGNGTsdPYVKVYLLD---GKQKKKTK-VVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGrd 79

                           90       100
                   ....*....|....*....|....*
gi 1034568425 1624 -VTAQRIIPLKALKRGYRHLQLRNL 1647
Cdd:pfam00168   80 dFIGEVRIPLSELDSGEGLDGWYPL 104
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 1812-1901 5.11e-05

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 43.83  E-value: 5.11e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1812 SFFVQVHDVSPE-QPRTVIKAPRVSTAQDVIQQTLCKAKYsysilsNPNPSDYVLLEEVVKDTtnkktttpkssQRVLLD 1890
Cdd:smart00314    2 TFVLRVYVDDLPgGTYKTLRVSSRTTARDVIQQLLEKFHL------TDDPEEYVLVEVLPDGK-----------ERVLPD 64

                            90
                    ....*....|.
gi 1034568425  1891 QECVFQAQSKW 1901
Cdd:smart00314   65 DENPLQLQKLW 75
 
Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 1067-1509 1.49e-152

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: 470.10  E-value: 1.49e-152
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1067 IKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAID 1146
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1147 RSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPDQLrkkvllknkklkahqtpvd 1226
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQL------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1227 ilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikka 1306
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1307 dnsacnKGKVydmelgeefyLDQNKKesrqiAPELSDLVIYCQAVKFPGLStlnasgssrgkerksrksifgnnpgrmsp 1386
Cdd:cd08596    142 ------KNKI----------LLKNKK-----APELSDLVIYCQAVKFPGLS----------------------------- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1387 getasfnktsgksscegirqtweesssplnpttslsaiirTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPA 1466
Cdd:cd08596    172 ----------------------------------------TPKCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPA 211

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|...
gi 1034568425 1467 ATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08596    212 ATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 1072-1509 2.30e-96

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: 310.15  E-value: 2.30e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1072 LPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFI 1151
Cdd:cd08558      6 QPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIKEYAFV 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1152 NSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFEtdfsDDPMLPSPDQlrkkvllknkklkahqtpvdiLKQK 1231
Cdd:cd08558     86 TSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDE----NPVQLPSPEQ---------------------LKGK 140

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1232 ahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddnILedrpenkscndklqfeyneeIpkrikkadnsac 1311
Cdd:cd08558    141 ---------------------------------------------IL--------------------I------------ 143

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1312 nKGKVYDMelgeefyldqnkkesrqiapelsdlviycqavkfpglstlnasgssrgkerksrksifgnnpgrmspgetAS 1391
Cdd:cd08558    144 -KGKKYHM----------------------------------------------------------------------SS 152

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1392 FNktsgksscegirqtweesssplnpttslsaiirtpkcyhisslnENAAKRLCRRYSQKLTQHTACQLLRTYPAATRID 1471
Cdd:cd08558    153 FS--------------------------------------------ETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVD 188

                          410       420       430
                   ....*....|....*....|....*....|....*...
gi 1034568425 1472 SSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08558    189 SSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 874-1054 5.60e-91

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: 292.69  E-value: 5.60e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  874 GGMKGFQSFMVSDSNMSFVEFVELFKSFSVRSRKDLKDLFDVYAVPCNRSGSESAPLYTNLTIDENTSDLQPDLDLLTRN 953
Cdd:cd16203      1 GGLKGFSIGEVQDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAPLKRSLSISESYSGLFPDLDLLTRN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  954 VSDLGLFIKSKQqlsdnQRQISDAIAAASIVTNGTGIEstSLGIFGVGILQLNDFLVNCQGEHCTYDEILSIIQKFEPSI 1033
Cdd:cd16203     81 TSLDGLFISKKQ-----QKKIYDAIAAASIVTNGAGVD--SSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEPDP 153

                          170       180
                   ....*....|....*....|.
gi 1034568425 1034 SMCHQGLMSFEGFARFLMDKE 1054
Cdd:cd16203    154 ILRSKNCLSFEGFARYLMDKD 174
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 1073-1509 5.46e-80

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: 264.58  E-value: 5.46e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1073 PLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFIN 1152
Cdd:cd08593      7 PLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIREYAFKV 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1153 SDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetdfsDDPM--LPSPDQLrkkvllknkklkahqtpvdilkq 1230
Cdd:cd08593     87 SPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPL------DGVLtaLPSPEEL----------------------- 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1231 kahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikkadnsa 1310
Cdd:cd08593        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1311 cnKGKVydmelgeefyLDQNKKesRQIAPELSDLVIYCQAVKFPGLstlnasgssrgkerksrksifgnnpgrmspgeta 1390
Cdd:cd08593    138 --KGKI----------LVKGKK--LKLAKELSDLVIYCKSVHFKSF---------------------------------- 169

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1391 sfnktsgksscegirqtwEESSSPlnpttslsaiirtPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRI 1470
Cdd:cd08593    170 ------------------EHSKEN-------------YHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRT 218

                          410       420       430
                   ....*....|....*....|....*....|....*....
gi 1034568425 1471 DSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08593    219 DSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 1068-1509 2.91e-75

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: 251.10  E-value: 2.91e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDG--DDGMPIIYHGHTLTTKIPFKEVVEAI 1145
Cdd:cd08591      2 QDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1146 DRSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetdfSDDPM-----LPSPDQlrkkvllknkklka 1220
Cdd:cd08591     82 AETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPL-----EKYPLepgvpLPSPND-------------- 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1221 hqtpvdiLKQKahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddnILedrpenkscndklqfeyneeip 1300
Cdd:cd08591    143 -------LKRK---------------------------------------------IL---------------------- 148

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1301 krIKkadnsacnkgkvydmelgeefyldqNKKesrqiapeLSDLVIYCQAVKFPGLstlnasgssrgKERKSRKsifgnn 1380
Cdd:cd08591    149 --IK-------------------------NKK--------LSSLVNYIQPVKFQGF-----------EVAEKRN------ 176

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1381 pgrmspgetasfnktsgksscegirqtweesssplnpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQL 1460
Cdd:cd08591    177 ------------------------------------------------KHYEMSSFNESKGLGYLKKSPIEFVNYNKRQL 208

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*....
gi 1034568425 1461 LRTYPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08591    209 SRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 1070-1206 1.33e-69

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: 230.08  E-value: 1.33e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1070 LQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSA 1149
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034568425 1150 FINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKflfeTDFSDDPMLPSPDQ 1206
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTP----PLDDDLTELPSPED 133
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 1070-1509 2.01e-69

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: 233.29  E-value: 2.01e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1070 LQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSA 1149
Cdd:cd08598      4 LSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKKYA 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1150 FINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTkflfETDFSDDPMLPSPDQlrkkvllknkklkahqtpvdiLK 1229
Cdd:cd08598     84 FVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVT----EPLDGLEDELPSPEE---------------------LR 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1230 QKahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddnILedrpenkscndklqfeyneeipkrIKkadns 1309
Cdd:cd08598    139 GK---------------------------------------------IL------------------------IK----- 144

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1310 acnkgkvydmelgeefyldqnkkesrqiapelsdlviycqaVKfpglstlnasgssrgKERKSRKSIFgnnpgrmspget 1389
Cdd:cd08598    145 -----------------------------------------VK---------------KESKTPNHIF------------ 156

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1390 asfnktsgksscegirqtweesssplnpttSLSaiirtpkcyhisslnENAAKRLCRRYSQKLTQHTACQLLRTYPAATR 1469
Cdd:cd08598    157 ------------------------------SLS---------------ERSLLKLLKDKRAALDKHNRRHLMRVYPSGTR 191

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|
gi 1034568425 1470 IDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08598    192 ISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231
RA1_PLC-epsilon cd17229
Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1683-1790 9.24e-68

Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the first RA domain of PLC-epsilon.


Pssm-ID: 340749  Cd Length: 108  Bit Score: 223.56  E-value: 9.24e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1683 ERKCLQTHRVTVHGVPGPEPFTVFTINGGTKAKQLLQQILTNEQDIKPVTTDYFLMEEKYFISKEKNECRKQPFQRAIGP 1762
Cdd:cd17229      1 ERKALQTHKVTVHGVPGPEPFTVFTISEGTTAKQLLQQILATEQGIEPDTTDYFLMEEKYFISKEKNECRKPPFQRVIGP 80

                           90       100
                   ....*....|....*....|....*...
gi 1034568425 1763 EEEIMQILSSWFPEEGYMGRIVLKTQQE 1790
Cdd:cd17229     81 EEEILQILNSWFPEEGYVGRIILKTREE 108
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 1073-1509 4.55e-66

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: 224.99  E-value: 4.55e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1073 PLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFIN 1152
Cdd:cd08597      7 PLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINEYAFVA 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1153 SDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFEtdfsDDPMLPSPDQlrkkvllknkklkahqtpvdiLKQKa 1232
Cdd:cd08597     87 SEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNE----GESYLPSPHD---------------------LKGK- 140

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1233 hqlasmqvqaynggnanprpanneeeedeedeydydyeslsddnILedrpenkscndklqfeyneeipkrikkadnsacN 1312
Cdd:cd08597    141 --------------------------------------------II---------------------------------I 143

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1313 KGKvydmelgeefyldqnKKESRQIAPELSDLVIYCQAVKFPGLSTlnasgssrgkERKSRksifgnnpgrmspgetasf 1392
Cdd:cd08597    144 KGK---------------KLKRRKLCKELSDLVSLCKSVRFQDFPT----------SAQNQ------------------- 179

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1393 nktsgksscegirqtweesssplnpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDS 1472
Cdd:cd08597    180 ------------------------------------KYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDS 223

                          410       420       430
                   ....*....|....*....|....*....|....*..
gi 1034568425 1473 SNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08597    224 SNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 1069-1509 7.50e-66

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: 223.07  E-value: 7.50e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1069 ELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRS 1148
Cdd:cd08592      3 DMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKEH 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1149 AFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetDFSDDpMLPSPDQlrkkvllknkklkahqtpvdiL 1228
Cdd:cd08592     83 AFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPV---DRNAD-QLPSPNQ---------------------L 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1229 KQKahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddnILedrpenkscndklqfeyneeipkrIKkadn 1308
Cdd:cd08592    138 KRK---------------------------------------------II------------------------IK---- 144

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1309 sacNKGKVYDMElgeefyldqnkkesrqiapelsdlviycqavKFPglstlnasgssrgkERKSRKSIFgnnpgrmspge 1388
Cdd:cd08592    145 ---HKKLFYEMS-------------------------------SFP--------------ETKAEKYLN----------- 165

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1389 tasfnktsgksscegirqtweesssplnpttslsaiirtpkcyhisslnenaakrlcRRYSQKLTQHTACQLLRTYPAAT 1468
Cdd:cd08592    166 ---------------------------------------------------------RQKGKIFLKYNRRQLSRVYPKGQ 188

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|.
gi 1034568425 1469 RIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08592    189 RVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 1073-1206 1.34e-61

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: 207.13  E-value: 1.34e-61
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1073 PLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFIN 1152
Cdd:smart00148    4 PLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFAFVT 83

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1034568425  1153 SDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSddpmLPSPDQ 1206
Cdd:smart00148   84 SPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQ 133
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 1068-1509 3.65e-61

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: 210.65  E-value: 3.65e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08630      2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetdfsDDP---MLPSPDQLrkkvllknkklkahqtp 1224
Cdd:cd08630     82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPL------DSLnpeELPSPEEL----------------- 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1225 vdilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrik 1304
Cdd:cd08630        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1305 kadnsacnKGKVydmelgeefyLDQNKKesRQIAPELSDLVIYCQAVKFPGLSTLNasgssrgkerksrksifgNNPgrm 1384
Cdd:cd08630    139 --------KGRV----------LVKGKK--LQISPELSALAVYCQATRLRTLEPAP------------------VQP--- 177

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1385 spgetasfnktsgksscegirqtweesssplnpttslsaiirtPKCyHISSLNENAAKRLCRRYSQKLTQHTACQLLRTY 1464
Cdd:cd08630    178 -------------------------------------------QPC-QVSSLSERKAKKLIREAGNSFVRHNARQLTRVY 213

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*
gi 1034568425 1465 PAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08630    214 PLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 1068-1509 4.42e-58

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: 201.92  E-value: 4.42e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDG--DDGMPIIYHGHTLTTKIPFKEVVEAI 1145
Cdd:cd08626      2 QDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGkgEDQEPIITHGKAMCTDILFKDVIQAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1146 DRSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPDQlrkkvllknkklkahqtpv 1225
Cdd:cd08626     82 KDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNK------------------- 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1226 diLKQKahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddnILedrpenkscndklqfeyneeipkrIKk 1305
Cdd:cd08626    143 --LKRK---------------------------------------------IL------------------------IK- 150

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1306 adnsacnkgkvydmelgeefyldqNKKesrqiapeLSDLVIYCQAVKFPGLstlnasgsSRGKERKsrksifgnnpgrms 1385
Cdd:cd08626    151 ------------------------NKR--------LSSLVNYAQPVKFQGF--------DVAEERN-------------- 176

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1386 pgetasfnktsgksscegirqtweesssplnpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYP 1465
Cdd:cd08626    177 -------------------------------------------IHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYP 213

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....
gi 1034568425 1466 AATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08626    214 KGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 1068-1206 5.94e-56

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: 194.48  E-value: 5.94e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKflfETDFSDDPmLPSPDQ 1206
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTK---PVDINADG-LPSPNQ 136
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 1068-1509 9.28e-56

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: 194.87  E-value: 9.28e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08633      2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVtkfLFETDFSDDPMLPSPDQLrkkvllknkklkahqtpvdi 1227
Cdd:cd08633     82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLD---LSSVISNDCTRLPSPEIL-------------------- 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1228 lkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikkad 1307
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1308 nsacnKGKVydmelgeefyLDQNKKESRQiapeLSDLVIYCQAVKFPGLSTlnasgssrgkerksrksifgnnpgrmspg 1387
Cdd:cd08633    139 -----KGKI----------LVKGKKLSRA----LSDLVKYTKSVRVHDIET----------------------------- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1388 etasfnktsgksscegirqtwEESSSplnpttslsaiirtpkcYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAA 1467
Cdd:cd08633    171 ---------------------EATSS-----------------WQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSS 212

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|..
gi 1034568425 1468 TRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08633    213 YRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 1067-1509 2.21e-55

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: 194.12  E-value: 2.21e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1067 IKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAID 1146
Cdd:cd08628      1 PQDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1147 RSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKflfetdfsddPMLPSPDQLrkkvllknkklkahqtpvd 1226
Cdd:cd08628     81 DHAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMK----------PLEASADQL------------------- 131

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1227 ilkqkahqlasmqvqaynggnanPRPAnneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikka 1306
Cdd:cd08628    132 -----------------------PSPT----------------------------------------------------- 135

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1307 dnsacnkgkvydmELGEEFYLdqnkKESRQIAPELSDLVIYCQavkfpglstlnasgssrgkerksrksifgnnpgrmsp 1386
Cdd:cd08628    136 -------------QLKEKIII----KHKKLIAIELSDLVVYCK------------------------------------- 161

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1387 getasfnktsgksscegirqtweesssplnPTTSLSAIIRTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPA 1466
Cdd:cd08628    162 ------------------------------PTSKTKDNLENPDFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPK 211

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|...
gi 1034568425 1467 ATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08628    212 GQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 1068-1509 5.66e-55

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: 192.85  E-value: 5.66e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetDFSDDPMLPSPDQLrkkvllknkklkahqtpvdi 1227
Cdd:cd08631     82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTL---DGVLPTQLPSPEEL-------------------- 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1228 lkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikkad 1307
Cdd:cd08631        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1308 nsacnKGKVydmelgeefyLDQNKKesRQIAPELSDLVIYCQAVKFpglstlnasgssrgkerksrksifgnnpgrmspg 1387
Cdd:cd08631    139 -----RGKI----------LLKGKK--IRLSPELSDCVIYCKSVSF---------------------------------- 167

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1388 etASFNKTSGKSscegirqtweesssplnpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAA 1467
Cdd:cd08631    168 --RSFTHSREHY-----------------------------HFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSG 216

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|..
gi 1034568425 1468 TRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08631    217 LRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 1073-1252 1.88e-54

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: 190.01  E-value: 1.88e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1073 PLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFIN 1152
Cdd:cd08594      7 PLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINKYAFIK 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1153 SDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLFETDFSDdpmLPSPDQ------------LRKKVLLKNKKLKA 1220
Cdd:cd08594     87 NEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQ---LPSPQSlkgkilikgkkwQVSSFSETRAHQIV 163

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1034568425 1221 HQTPVDILKQKAHQLASMQVQAY--NGGNANPRP 1252
Cdd:cd08594    164 QQKAAQFLRFNQRQLSRIYPSAYriDSSNFNPQP 197
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 1068-1509 3.40e-54

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: 190.63  E-value: 3.40e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08632      2 QDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVtkfLFETDFSDDPMLPSPDQLrkkvllknkklkahqtpvdi 1227
Cdd:cd08632     82 YAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLD---LSSVLTGDPKQLPSPQLL-------------------- 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1228 lkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikkad 1307
Cdd:cd08632        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1308 nsacnKGKVydmelgeefyLDQNKKESRqiapELSDLVIYCQAVkfpglstlnasgssrgkerkSRKSIFGNNpgrmSPG 1387
Cdd:cd08632    139 -----KGKI----------LVKGKKLCR----DLSDLVVYTNSV--------------------AAQDIVDDG----STG 175

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1388 ETASFNKTSgksscegirqtweesssplnpttslsaiirtpkcyhisslnenaAKRLCRRYSQKLTQHTACQLLRTYPAA 1467
Cdd:cd08632    176 NVLSFSETR--------------------------------------------AHQLVQQKAEQFMTYNQKQLTRIYPSA 211

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|..
gi 1034568425 1468 TRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08632    212 YRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 1068-1509 1.15e-53

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: 189.09  E-value: 1.15e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetdfsDDPM--LPSPDQLrkkvllknkklkahqtpv 1225
Cdd:cd08629     82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPL------DGVTtsLPSPEQL------------------ 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1226 dilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrikk 1305
Cdd:cd08629        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1306 adnsacnKGKvydmelgeefYLDQNKKesRQIAPELSDLVIYCQAVKFPGLStlnasgSSRGKERksrksifgnnpgrms 1385
Cdd:cd08629    138 -------KGK----------ILLKGKK--LKLVPELSDMIIYCKSVHFGGFS------SPGTSGQ--------------- 177

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1386 pgetaSFnktsgksscegirqtweesssplnpttslsaiirtpkcYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYP 1465
Cdd:cd08629    178 -----AF--------------------------------------YEMASFSESRALRLLQESGNGFVRHNVSCLSRIYP 214

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....
gi 1034568425 1466 AATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08629    215 AGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 1068-1509 1.85e-52

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: 185.53  E-value: 1.85e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:cd08595      2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLVTKFLfetdfsDDP---MLPSPDQlrkkvllknkklkahqtp 1224
Cdd:cd08595     82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPI------DDPatgELPSPEA------------------ 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1225 vdiLKQKahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrik 1304
Cdd:cd08595    138 ---LKFK------------------------------------------------------------------------- 141

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1305 kadnsacnkgkvydmelgeefYLDQNKKesrQIAPELSDLVIYCQAVKFpglstlnasgssrgkerksrksifgnnpgrm 1384
Cdd:cd08595    142 ---------------------ILVKNKK---KIAKALSDLVIYTKSEKF------------------------------- 166

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1385 spgetASFNKTSGKSscegirqtweesssplnpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTY 1464
Cdd:cd08595    167 -----CSFTHSRDNQ-----------------------------HSYENNSIGENKARKLLKSSGADFVGHTQRFITRIY 212

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*
gi 1034568425 1465 PAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08595    213 PKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 1068-1509 1.61e-51

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: 182.95  E-value: 1.61e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGD--DGMPIIYHGHTLTTKIPFKEVVEAI 1145
Cdd:cd08624      2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMTTEILFKDAIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1146 DRSAFINSDLPIIISIENHCSLP-QQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPDQLrkkvllknkklkahqtp 1224
Cdd:cd08624     82 AESAFKTSPYPVILSFENHVDSPkQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDL----------------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1225 vdilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrik 1304
Cdd:cd08624        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1305 kadnsacnKGKVydmelgeefyLDQNKKESrqiapELSDLVIYCQAVKFpglstlnasgssrgkerksrksifgnnpgrm 1384
Cdd:cd08624    145 --------RGKI----------LIKNKKYE-----EMSSLVNYIQPTKF------------------------------- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1385 spgetASFNKTSGKSscegirqtweesssplnpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTY 1464
Cdd:cd08624    171 -----VSFEFSAQKN-----------------------------RSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIY 216

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*
gi 1034568425 1465 PAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08624    217 PKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 1067-1509 9.63e-49

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: 174.86  E-value: 9.63e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1067 IKELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDG--DDGMPIIYHGHTLTTKIPFKEVVEA 1144
Cdd:cd08625      1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1145 IDRSAFINSDLPIIISIENHC-SLPQQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSPdqlrkkvllknkklkahqt 1223
Cdd:cd08625     81 IAESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSP------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1224 pvdilkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeynEEIPKRI 1303
Cdd:cd08625    142 -------------------------------------------------------------------------QELMGKI 148

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1304 kkadnsacnkgkvydmelgeefyLDQNKKesrqiapeLSDLVIYCQAVKFpglstlnasgssrgkerksrksifgnnpgr 1383
Cdd:cd08625    149 -----------------------LVKNKK--------MSTLVNYIEPVKF------------------------------ 167

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1384 mspgetasfnktsgksscegirqtweesssplnptTSLSAIIRTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRT 1463
Cdd:cd08625    168 -----------------------------------KSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRI 212

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*.
gi 1034568425 1464 YPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08625    213 YPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1810-1912 4.41e-48

Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon.


Pssm-ID: 340478  Cd Length: 102  Bit Score: 166.73  E-value: 4.41e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1810 EESFFVQVHDVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSYSIlsnpnPSDYVLLEEVVKDTTNKKTTTPKSS----Q 1885
Cdd:cd01780      1 EDTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDI-----PSDFVLVEELEKEPTSDKSSSKSSSskteQ 75

                           90       100
                   ....*....|....*....|....*..
gi 1034568425 1886 RVLLDQECVFQAQSKWKGAGKFILKLK 1912
Cdd:cd01780     76 RVLGDQENVYQAQSRWKGAGKFILKLR 102
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 1341-1519 3.20e-46

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 161.86  E-value: 3.20e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1341 LSDLVIYCQAVKFPGLSTLNASgssrgkerksrksifgnnpgrmspgetasfnktsgksscegirqtweesssplnptts 1420
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTPESK---------------------------------------------------------- 22

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1421 lsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLH 1500
Cdd:pfam00387   23 --------TPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQMVALNWQTPDEGMQ 94

                          170
                   ....*....|....*....
gi 1034568425 1501 LNAAMFEANGGCGYVLKPP 1519
Cdd:pfam00387   95 LNEGMFADNGGCGYVLKPE 113
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 1430-1521 8.74e-44

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: 155.09  E-value: 8.74e-44
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1430 CYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:smart00149   24 FYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQMVALNFQTPDKPMQLNQGMFRAN 103

                            90
                    ....*....|..
gi 1034568425  1510 GGCGYVLKPPVL 1521
Cdd:smart00149  104 GGCGYVLKPDFL 115
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 1068-1509 3.29e-43

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: 159.09  E-value: 3.29e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1068 KELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDG--DDGMPIIYHGHTLTTKIPFKEVVEAI 1145
Cdd:cd08623      2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1146 DRSAFINSDLPIIISIENHCSLP-QQRKMAEIFKTVFGEKLVTKFLFETDFSDDPMLPSpdqlrkkvllknkklkahqtP 1224
Cdd:cd08623     82 AECAFKTSPFPILLSFENHVDSPkQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPS--------------------P 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1225 VDILkqkahqlasmqvqaynggnanprpanneeeedeedeydydyeslsddniledrpenkscndklqfeyneeipkrik 1304
Cdd:cd08623    142 MDLM---------------------------------------------------------------------------- 145

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1305 kadnsacnkGKVydmelgeefyLDQNKKesrqiapeLSDLVIYCQAVKFpglstlnasgssrgkerksrksifgnnpgrm 1384
Cdd:cd08623    146 ---------YKI----------LVKNKK--------MSNLVNYIQPVKF------------------------------- 167

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1385 spgetASFnktsgksscegirqtweESSSPLNpttslsaiirtpKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTY 1464
Cdd:cd08623    168 -----ESF-----------------EASKKRN------------KSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIY 213

                          410       420       430       440
                   ....*....|....*....|....*....|....*....|....*
gi 1034568425 1465 PAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEAN 1509
Cdd:cd08623    214 PKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258
PLN02228 PLN02228
Phosphoinositide phospholipase C
 1008-1659 7.54e-43

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 166.75  E-value: 7.54e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1008 FLVNCQGE-HCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFLMdkENFASKNDESQENIKELQLPLSYYYIESSHNTY 1086
Cdd:PLN02228    47 FVSEVQGErHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLF--SDTNSPLPMSGQVHHDMKAPLSHYFVYTGHNSY 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1087 LTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPI-IYHGHTLTTKIPFKEVVEAIDRSAFINSDLPIIISIENHC 1165
Cdd:PLN02228   125 LTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAeVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL 204

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1166 SLPQQRKMAEIFKTVFGeklvtKFLFETDFSDDPMLPSPDQlrkkvllknkklkahqtpvdiLKQKAhqLASMQvqayng 1245
Cdd:PLN02228   205 PPNLQAQVAKMLTKTFR-----GMLFRCTSESTKHFPSPEE---------------------LKNKI--LISTK------ 250

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1246 gnaNPRpanneeeedeedeydydyeslsddNILEDRPENKSCNDKLQfeynEEIPKRIKKADNsacnkgkvydmelgeef 1325
Cdd:PLN02228   251 ---PPK------------------------EYLESKTVQTTRTPTVK----ETSWKRVADAEN----------------- 282

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1326 yldqnkkesrQIAPELSDLviYCQAVKFPGLSTLNAsgssrGKERKSRKSIFGNNPGRmspgetasfnktsgksscegir 1405
Cdd:PLN02228   283 ----------KILEEYKDE--ESEAVGYRDLIAIHA-----ANCKDPLKDCLSDDPEK---------------------- 323

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1406 qtweesssplnpttslsaIIRTpkcyhisSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNPLMFWLHGI 1485
Cdd:PLN02228   324 ------------------PIRV-------SMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGA 378

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1486 QLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPVLWDKncpmYQKFSPLER--DLDSMDPAVYSltiVSGQNV-CPSNS 1562
Cdd:PLN02228   379 QMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDE----HTLFDPCKRlpIKTTLKVKIYT---GEGWDLdFHLTH 451

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1563 MG--SP---CIEVDVLGMPLDSCHFRTKpIHRNTLNPMW-NEQFLFHVHFEDLVFLRFAVVE---NNSSAVTAQRIIPLK 1633
Cdd:PLN02228   452 FDqySPpdfFVKIGIAGVPRDTVSYRTE-TAVDQWFPIWgNDEFLFQLRVPELALLWFKVQDydnDTQNDFAGQTCLPLP 530

                          650       660
                   ....*....|....*....|....*.
gi 1034568425 1634 ALKRGYRHLQLRNLHNEVLEISSLFI 1659
Cdd:PLN02228   531 ELKSGVRAVRLHDRAGKAYKNTRLLV 556
PLN02952 PLN02952
phosphoinositide phospholipase C
 994-1659 7.29e-42

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 164.40  E-value: 7.29e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  994 SLGIFGVGILQLNDFLVNCQGE-HCTYDEILSIIqkfEPSISMCHQgLMSFEGFARFLMDKENFASKNDESQENI----K 1068
Cdd:PLN02952    48 SVGGGHMGADQLRRFLVLHQDElDCTLAEAQRIV---EEVINRRHH-VTRYTRHGLNLDDFFHFLLYDDLNGPITpqvhH 123

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1069 ELQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPI-IYHGHTLTTKIPFKEVVEAIDR 1147
Cdd:PLN02952   124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRD 203

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1148 SAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEKLvtkFLFETDfsDDPMLPSPDQLRkkvllknkklkaHQTPVDI 1227
Cdd:PLN02952   204 YAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESD--SLVQFPSPESLK------------HRIIIST 266

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1228 LKQKAHQLASMQVQAYNGGNANPRPANNEeeedeedeydydyeslsddniledrpenkscndklqfEYNEEIpkrikkad 1307
Cdd:PLN02952   267 KPPKEYLESSGPIVIKKKNNVSPSGRNSS-------------------------------------EETEEA-------- 301

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1308 nsACNKGKVYDMELGEEFYLDQNKKESRQI-APELSDLViycqavkfpglsTLNAsgssrGKERKSRKSIFgnnpgrmsp 1386
Cdd:PLN02952   302 --QTLESMLFEQEADSRSDSDQDDNKSGELqKPAYKRLI------------TIHA-----GKPKGTLKDAM--------- 353

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1387 getasfnktsgKSSCEGIRQTweesssplnpttslsaiirtpkcyhisSLNENAAKRLCRRYSQKLTQHTACQLLRTYPA 1466
Cdd:PLN02952   354 -----------KVAVDKVRRL---------------------------SLSEQELEKAATTNGQDVVRFTQRNILRIYPK 395

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1467 ATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPVLWDKNcPMYQKFSPlERDLDSMDPAV 1546
Cdd:PLN02952   396 GTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKG-FHDEVFDP-KKKLPVKKTLK 473

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1547 YSLTIVSGQNVCPS----NSMGSP--CIEVDVLGMPLDSCHFRTKPIHRNtLNPMWNEQFLFHVHFEDLVFLRFAVVENN 1620
Cdd:PLN02952   474 VKVYLGDGWRLDFShthfDSYSPPdfYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYD 552

                          650       660       670       680
                   ....*....|....*....|....*....|....*....|..
gi 1034568425 1621 SSA---VTAQRIIPLKALKRGYRHLQLRNLHNEVLEISSLFI 1659
Cdd:PLN02952   553 MSEkddFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLM 594
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 1005-1646 4.60e-40

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 158.65  E-value: 4.60e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1005 LNDFLVNCQGE-HCTYDEILSIIQKfepSISMCHQGLMSFEGFARFLmdkenFASKND--ESQENIKELQLPLSYYYIES 1081
Cdd:PLN02222    45 LHRFLIDVQKQdKATREDAQSIINS---ASSLLHRNGLHLDAFFKYL-----FGDNNPplALHEVHHDMDAPISHYFIFT 116

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1082 SHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPI-IYHGHTLTTKIPFKEVVEAIDRSAFINSDLPIIIS 1160
Cdd:PLN02222   117 GHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVT 196

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1161 IENHCSLPQQRKMAEIFKTVFGEKLVTKFLFET--DFsddpmlPSPdqlrkkvllknkklkahqtpvDILKQKAhQLASM 1238
Cdd:PLN02222   197 LEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESlkEF------PSP---------------------NSLKKRI-IISTK 248

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1239 QVQAYNGGnanprpanneeeedeedeydydyeslSDDNILedrpenKSCNDKLQFE-YNEEIPKRIKKADNSACNkgkvy 1317
Cdd:PLN02222   249 PPKEYKEG--------------------------KDDEVV------QKGKDLGDEEvWGREVPSFIQRNKSVDKN----- 291

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1318 DMELGEEFYLDQNKKESRQIAPELSDLVIYCQAVKFPGlstlnasgssrgkerksrksifgnnpgrmspgetasfnktsG 1397
Cdd:PLN02222   292 DSNGDDDDDDDDGEDKSKKNAPPQYKHLIAIHAGKPKG-----------------------------------------G 330

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1398 KSSCEGIrqtweesssplnpttslsaiirTPKCYHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNP 1477
Cdd:PLN02222   331 ITECLKV----------------------DPDKVRRLSLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNP 388

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1478 LMFWLHGIQLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPVLWDKNCpmyqkfsplerDLDSMDPAVySLTIVSGQNV 1557
Cdd:PLN02222   389 LVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGS-----------DSDIFDPKA-TLPVKTTLRV 456

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1558 CPSNSMG-------------SP---CIEVDVLGMPLDSCHFRTKPIHRNTLnPMWNEQFLFHVHFEDLVFLRFAVVENNS 1621
Cdd:PLN02222   457 TIYMGEGwyfdfrhthfdqySPpdfYTRVGIAGVPGDTVMKKTKTLEDNWI-PAWDEVFEFPLTVPELALLRLEVHEYDM 535

                          650       660
                   ....*....|....*....|....*...
gi 1034568425 1622 SA---VTAQRIIPLKALKRGYRHLQLRN 1646
Cdd:PLN02222   536 SEkddFGGQTCLPVWELSQGIRAFPLHS 563
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 1073-1206 1.74e-39

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: 147.13  E-value: 1.74e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1073 PLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLTTKIPFKEVVEAIDRSAFIN 1152
Cdd:cd08599      7 PLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKENAFTA 86

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034568425 1153 SDLPIIISIENHCSLPQQRKMAEIFKTVFGEKlvtkfLFETDfSDDPM--LPSPDQ 1206
Cdd:cd08599     87 SEYPVIITLENHLSPELQAKAAQILRETLGDK-----LFYPD-SEDLPeeFPSPEE 136
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1687-1788 7.64e-38

Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction.


Pssm-ID: 340634  Cd Length: 97  Bit Score: 137.47  E-value: 7.64e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1687 LQTHRVTVHGVPGPEPFTVFTINGGTKAKQLLQQILTNEQDIKPVTTDYFLMEEKYFISKEKnECRKQPFQRAIGPEEEI 1766
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRK-ETEKPGSQRILDMDEKI 79

                           90       100
                   ....*....|....*....|..
gi 1034568425 1767 MQILSSWFPEegymGRIVLKTQ 1788
Cdd:cd17114     80 LQAQSKWKGS----GRFILKKL 97
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 1548-1660 1.94e-37

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: 137.67  E-value: 1.94e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1548 SLTIVSGQNVCPSNSMG----SPCIEVDVLGMPLDSCH-FRTKPIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVENNSS 1622
Cdd:cd00275      5 TIKIISGQQLPKPKGDKgsivDPYVEVEIHGLPADDSAkFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSG 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1034568425 1623 AVT--AQRIIPLKALKRGYRHLQLRNLHNEVLEISSLFIN 1660
Cdd:cd00275     85 DDDflGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVH 124
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 1041-1646 9.26e-34

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 139.84  E-value: 9.26e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1041 MSFEGFARFLMDKENFASKNDESQENikeLQLPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLQGCRSVELDCWDGD 1120
Cdd:PLN02230    91 LTLDDFNYYLFSTDLNPPIADQVHQN---MDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRG 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1121 DGMPIIYHGHTLTTKIPFKEVVEAIDRSAFINSDLPIIISIENHCSLPQQRKMAEIFKTVFGEklvtkFLFETDFSDDPM 1200
Cdd:PLN02230   168 TDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGD-----MLYYHDSEGCQE 242

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1201 LPSPDQlrkkvllknkklkahqtpvdiLKQKAHQLASMQVQAYNGGNANPRPANNEEEEdeedeydydyeslSDDNILED 1280
Cdd:PLN02230   243 FPSPEE---------------------LKEKILISTKPPKEYLEANDAKEKDNGEKGKD-------------SDEDVWGK 288

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1281 RPEnkscnDKLQFEYNEEipkRIKKADNSacnkgkvydmelgeefyLDQNKKESRQIApelSDLVIYCQAVKFPGLSTLN 1360
Cdd:PLN02230   289 EPE-----DLISTQSDLD---KVTSSVND-----------------LNQDDEERGSCE---SDTSCQLQAPEYKRLIAIH 340

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1361 AsGSSRGKERKSRKSifgnNPGRmspgetasfnktsgksscegIRQTweesssplnpttslsaiirtpkcyhisSLNENA 1440
Cdd:PLN02230   341 A-GKPKGGLRMALKV----DPNK--------------------IRRL---------------------------SLSEQL 368

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1441 AKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPV 1520
Cdd:PLN02230   369 LEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDF 448

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1521 LWDKNCPMyQKFSPLErdlDSMDPAVYSLTIVSGQNVCPS------NSMGSP--CIEVDVLGMPLDSCHFRTKpIHRNTL 1592
Cdd:PLN02230   449 LMDAGPNG-QDFYPKD---NSCPKKTLKVKVCMGDGWLLDfkkthfDSYSPPdfFVRVGIAGAPVDEVMEKTK-IEYDTW 523

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034568425 1593 NPMWNEQFLFHVHFEDLVFLRFAVVE---NNSSAVTAQRIIPLKALKRGYRHLQLRN 1646
Cdd:PLN02230   524 TPIWNKEFIFPLAVPELALLRVEVHEhdiNEKDDFGGQTCLPVSEIRQGIHAVPLFN 580
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 1810-1912 1.67e-33

Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction.


Pssm-ID: 340634  Cd Length: 97  Bit Score: 125.15  E-value: 1.67e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1810 EESFFVQVHDVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYsysilSNPNPSDYVLLEEVVkDTTNKKTTTPKSSQRVLL 1889
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGK-----SLERVTDYVLVEEVQ-KGWDRKETEKPGSQRILD 74

                           90       100
                   ....*....|....*....|...
gi 1034568425 1890 DQECVFQAQSKWKGAGKFILKLK 1912
Cdd:cd17114     75 MDEKILQAQSKWKGSGRFILKKL 97
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 1073-1206 3.55e-32

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: 127.77  E-value: 3.55e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1073 PLSYYYIESSHNTYLTGHQL-----KGESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLtTKIPFKEVVEAIDR 1147
Cdd:cd00137      7 PLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTF-LDIFLKEVIEAIAQ 85

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034568425 1148 SAFINSDLPIIISIENHCSLP--QQRKMAEIFKTVFGEklvtkflFETDFSDDPM--LPSPDQ 1206
Cdd:cd00137     86 FLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGD-------MLLTPPLKPTvpLPSLED 141
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
223-516 1.49e-21

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 95.77  E-value: 1.49e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   223 FPEEVASILMEQEQTIYRRVLPvdylcfltrdlgtPECQSSLPCLKASISASILTtqngehnaLEDLVMRFNEVSSWVTW 302
Cdd:smart00147    5 DPKELAEQLTLLDFELFRKIDP-------------SELLGSVWGKRSKKSPSPLN--------LEAFIRRFNEVSNWVAT 63

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   303 LILTAGSMEEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVL---KMWQFMDQSDIETMRSLKDAMAQHESSCEY 379
Cdd:smart00147   64 EILKQTTPKDRAELLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISrlkKTWEKLPSKYKKLFEELEELLSPERNYKNY 143

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425   380 RKVVtRALHIPGCkvVPFCGVFLKELcevldgasglmklcprynsqeetlefVADYSGQDNFLqrvgQNGLKNSEKESTV 459
Cdd:smart00147  144 REAL-SSCNLPPC--IPFLGVLLKDL--------------------------TFIDEGNPDFL----ENGLVNFEKRRQI 190

                           250       260       270       280       290
                    ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034568425   460 NSIFQVIRSCNRSLEtDEEDSPSEGNSsrksslkdksrWQFIIGDLLDSDNDIFEQS 516
Cdd:smart00147  191 AEILREIRQLQSQPY-NLRPNRSDIQS-----------LLQQLLDHLDEEEELYQLS 235
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 231-405 6.95e-21

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 91.88  E-value: 6.95e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  231 LMEQEqtIYRRVLPVDylcFLTRDLGTPECQSSLPCLKASISasilttqngehnaledlvmRFNEVSSWVTWLILTAGSM 310
Cdd:pfam00617    8 LIEFE--LFRKIKPRE---LLGSAWSKKDKKENSPNIEAMIA-------------------RFNKLSNWVASEILSEEDL 63

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  311 EEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKV--LKM-WQFMDQSDIETMRSLKDAMAQHESSCEYRKVVTRAl 387
Cdd:pfam00617   64 KKRAKVIKKFIKIAEHCRELNNFNSLMAILSGLNSSPIsrLKKtWELVSKKYKKTLEELEKLMSPSRNFKNYREALSSA- 142

                          170
                   ....*....|....*...
gi 1034568425  388 hIPGCkvVPFCGVFLKEL 405
Cdd:pfam00617  143 -SPPC--IPFLGLYLTDL 157
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 1081-1191 6.21e-19

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: 86.34  E-value: 6.21e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1081 SSHNTYLTGHQlkgESSVELYSQVLLQGCRSVELDCWDGDDGMPIIYHGHTLT------TKIPFKEVVEAIDRSAFiNSD 1154
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1034568425 1155 LPIIISIENHCS----LPQQRKMAEIFKTVFGEKLVTKFLF 1191
Cdd:cd08555     78 YTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGKVVL 118
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 1424-1509 5.41e-18

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: 85.24  E-value: 5.41e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1424 IIRTPKCyHISSLNENAAKRLCRRYSQKLTQHTACQLLRTYPAATRIDSSNPNPLMFWLHGIQLVALNYQTDDLPLHLNA 1503
Cdd:cd08594    143 LIKGKKW-QVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNR 221


                   ....*.
gi 1034568425 1504 AMFEAN 1509
Cdd:cd08594    222 AKFRAN 227
PLN02223 PLN02223
phosphoinositide phospholipase C
 1448-1644 1.74e-15

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 81.99  E-value: 1.74e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1448 YSQKLTQHTACQLLRTYPAATRIDSSNP-NPLMFWLHGIQLVALNYQTDDLPLHLNAAMFEANGGCGYVLKPPVLWdkNC 1526
Cdd:PLN02223   316 YERDIISFTQKKFLRTRPKKKNLLINAPyKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLL--NA 393

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1527 PMYQKFSPLErdldsmDPAVYSLT----------IVSGQNVCPSNSMGSPCIEVDVLGMPLDSCHFRTKpIHRNTLNPMW 1596
Cdd:PLN02223   394 GPSGVFYPTE------NPVVVKILkvkiymgdgwIVDFKKRIGRLSKPDLYVRISIAGVPHDEKIMKTT-VKNNEWKPTW 466

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034568425 1597 NEQFLFHVHFEDLVFLRFAVVE---NNSSAVTAQRIIPLKALKRGYRHLQL 1644
Cdd:PLN02223   467 GEEFTFPLTYPDLALISFEVYDyevSTADAFCGQTCLPVSELIEGIRAVPL 517
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 224-405 1.91e-15

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 77.68  E-value: 1.91e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  224 PEEVASILMEQEQTIYRRVLPVDYLCFLTRDLGTPEcqSSLPCLKASISasilttqngehnaledlvmRFNEVSSWVTWL 303
Cdd:cd00155      6 PKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNI--HLSPNLERFIE-------------------RFNNLSNWVASE 64

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  304 ILTAGSMEEKREVFSYLVHVAKCCWNMGNYNAVMEFLAGLRSRKVL---KMWQFMDQSDIETMRSLKDAMAQHESSCEYR 380
Cdd:cd00155     65 ILLCTNPKKRARLLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISrlkKTWEVLSSKLKKLFEELEELVDPSRNFKNYR 144

                          170       180
                   ....*....|....*....|....*
gi 1034568425  381 KVVTRALHIPGCkvVPFCGVFLKEL 405
Cdd:cd00155    145 KLLKSVGPNPPC--VPFLGVYLKDL 167
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1549-1644 4.92e-13

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: 66.74  E-value: 4.92e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1549 LTIVSGQNVCPSNSMGS--PCIEVDVLGMPLDSchFRTKpIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVE---NNSSA 1623
Cdd:smart00239    4 VKIISARNLPPKDKGGKsdPYVKVSLDGDPKEK--KKTK-VVKNTLNPVWNETFEFEVPPPELAELEIEVYDkdrFGRDD 80

                            90       100
                    ....*....|....*....|.
gi 1034568425  1624 VTAQRIIPLKALKRGYRHLQL 1644
Cdd:smart00239   81 FIGQVTIPLSDLLLGGRHEKL 101
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 886-1054 1.27e-12

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: 66.92  E-value: 1.27e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  886 DSNMSFVEFVELFKSFSVR-SRKDLKDLFDVYAVpcNRSGSesaplytnLTIDEntsdlqpdldlltrnvsdLGLFIKSK 964
Cdd:cd15898     14 DGKLSLKEIKKLLKRLNIRvSEKELKKLFKEVDT--NGDGT--------LTFDE------------------FEELYKSL 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  965 QQLSDnqrqisdaiaAASIVTNGTGIestslgifGVGILQLND---FLVNCQGEHCTYDEILSIIQKFEPsisMCHQGLM 1041
Cdd:cd15898     66 TERPE----------LEPIFKKYAGT--------NRDYMTLEEfirFLREEQGENVSEEECEELIEKYEP---ERENRQL 124

                          170
                   ....*....|...
gi 1034568425 1042 SFEGFARFLMDKE 1054
Cdd:cd15898    125 SFEGFTNFLLSPE 137
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 1812-1914 4.16e-12

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.


Pssm-ID: 425871  Cd Length: 93  Bit Score: 63.89  E-value: 4.16e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1812 SFFVQVH--DVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSYSilsnpnPSDYVLLEEVVkdttnkktttPKSSQRVLL 1889
Cdd:pfam00788    2 DGVLKVYteDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDD------PRDYVLVEVLE----------RGGGERRLP 65

                           90       100
                   ....*....|....*....|....*...
gi 1034568425 1890 DQECVFQAQSKWKG---AGKFILKLKEQ 1914
Cdd:pfam00788   66 DDECPLQIQLQWPRdasDSRFLLRKRDD 93
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
 1814-1910 1.64e-10

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub); Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.


Pssm-ID: 340563  Cd Length: 87  Bit Score: 59.25  E-value: 1.64e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1814 FVQVH--DVSPEQPRTVIKAPRVSTAQDVIQQTLCKAKYSysilsnPNPSDYVLLEEVVkdttnkktttPKSSQRVLLDQ 1891
Cdd:cd17043      1 VLKVYddDLAPGSAYKSILVSSTTTAREVVQLLLEKYGLE------EDPEDYSLYEVSE----------KQETERVLHDD 64

                           90       100
                   ....*....|....*....|..
gi 1034568425 1892 ECVFQAQSKWK---GAGKFILK 1910
Cdd:cd17043     65 ECPLLIQLEWGpqgTEFRFVLK 86
C2 pfam00168
C2 domain;
1548-1647 3.61e-09

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 55.79  E-value: 3.61e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1548 SLTIVSGQNVCPSNSMGS--PCIEVDVLGmplDSCHFRTKpIHRNTLNPMWNEQFLFHVHFEDLVFLRFAVVENNSSA-- 1623
Cdd:pfam00168    4 TVTVIEAKNLPPKDGNGTsdPYVKVYLLD---GKQKKKTK-VVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGrd 79

                           90       100
                   ....*....|....*....|....*
gi 1034568425 1624 -VTAQRIIPLKALKRGYRHLQLRNL 1647
Cdd:pfam00168   80 dFIGEVRIPLSELDSGEGLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1548-1616 4.26e-07

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: 50.14  E-value: 4.26e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034568425 1548 SLTIVSGQNVCPSNSMGS--PCIEVDVLGmpldSCHFRTKpIHRNTLNPMWNEQFLFHVHFEDLVFLRFAV 1616
Cdd:cd00030      2 RVTVIEARNLPAKDLNGKsdPYVKVSLGG----KQKFKTK-VVKNTLNPVWNETFEFPVLDPESDTLTVEV 67
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 1004-1054 2.46e-05

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: 46.47  E-value: 2.46e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1004 QLNDFLVNCQGE---------HCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFLMDKE 1054
Cdd:cd16200     94 QLVDFLNEEQRDprlneilfpFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 1812-1901 5.11e-05

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)


Pssm-ID: 214612  Cd Length: 90  Bit Score: 43.83  E-value: 5.11e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425  1812 SFFVQVHDVSPE-QPRTVIKAPRVSTAQDVIQQTLCKAKYsysilsNPNPSDYVLLEEVVKDTtnkktttpkssQRVLLD 1890
Cdd:smart00314    2 TFVLRVYVDDLPgGTYKTLRVSSRTTARDVIQQLLEKFHL------TDDPEEYVLVEVLPDGK-----------ERVLPD 64

                            90
                    ....*....|.
gi 1034568425  1891 QECVFQAQSKW 1901
Cdd:smart00314   65 DENPLQLQKLW 75
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 1005-1054 2.63e-04

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: 42.98  E-value: 2.63e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034568425 1005 LNDFLVNCQGEHCTYDE-ILSIIQKFEPSISMCHQGLMSFEGFARFLMDKE 1054
Cdd:cd16202     90 LRRFLQEEQKVKDVTLEwAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 1002-1054 3.14e-04

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: 43.06  E-value: 3.14e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034568425 1002 ILQLNDFLVNCQgEHCTYDEIL----------SIIQKFEPSISMCHQGLMSFEGFARFLMDKE 1054
Cdd:cd16213     93 TEQFVDFLNKTQ-RDPRLNEILypyanpkrarDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1551-1618 3.36e-04

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 42.32  E-value: 3.36e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1551 IVSGQNVCPSNSMGS--PCIEVDVLGMpldscHFRTKPIHRNtLNPMWNEQFLFHVHfeDLVFLRFAVVE 1618
Cdd:cd04022      6 VVDAQDLMPKDGQGSssAYVELDFDGQ-----KKRTRTKPKD-LNPVWNEKLVFNVS--DPSRLSNLVLE 67
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 1007-1051 4.54e-04

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: 42.24  E-value: 4.54e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1034568425 1007 DFLVNCQGEHCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFLM 1051
Cdd:cd16207     95 KFLRDVQKEDVDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLL 139
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 1582-1617 5.79e-04

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 41.09  E-value: 5.79e-04
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1034568425 1582 FRTKPIhRNTLNPMWNEQFLFHVHFEDLVF-LRFAVV 1617
Cdd:cd04039     39 FRTSWR-RHTLNPVFNERLAFEVYPHEKNFdIQFKVL 74
RA_Myosin-IX cd01779
Ras-associating (RA) domain found in Myosin-IX; Myosins IX (Myo9) is a class of unique motor ...
 1815-1901 8.81e-04

Ras-associating (RA) domain found in Myosin-IX; Myosins IX (Myo9) is a class of unique motor proteins with a common structure of an N-terminal extension preceding a myosin head homologous to the Ras-association (RA) domain, a head (motor) domain, a neck with IQ motifs that bind light chains and a C-terminal tail containing a Rho-GTPase activating protein (RhoGAP) domain. The RA domain is located at its head domain and has the beta-grasp ubiquitin-like fold with unknown function. There are two genes for myosins IX in humans, IXa and IXb, that are different in their expression and localization. IXa is expressed abundantly in brain and testis and IXb is expressed abundantly in tissues of the immune system.


Pssm-ID: 340477  Cd Length: 97  Bit Score: 40.38  E-value: 8.81e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034568425 1815 VQVH--DVSPEQPRTVIKAPRVSTAQDVIQQTLCKakysysiLSNPNPSDYVLLEEVVKDTTNKKtttpkssQRVLLDQE 1892
Cdd:cd01779      2 VRVYpgALSPETEFLSVEATKQTTASEVIECLVAK-------LRLDKAECYELAEVCGSGGQGCK-------ERRLGPSE 67


                   ....*....
gi 1034568425 1893 CVFQAQSKW 1901
Cdd:cd01779     68 NPVQVQLLW 76
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1582-1616 1.54e-03

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; 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 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 as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. 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: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 40.33  E-value: 1.54e-03
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1034568425 1582 FRTKpIHRNTLNPMWNEQFLFHVHFEDLV--FLRFAV 1616
Cdd:cd08385     53 FETK-VHRKTLNPVFNETFTFKVPYSELGnkTLVFSV 88
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1582-1637 3.25e-03

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 39.96  E-value: 3.25e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034568425 1582 FRTKPIHRNTLNPMWNEQFLFHVH--FEDLVFLRFAVVENNSSAVTAQRI-IPLKALKR 1637
Cdd:cd04019     34 LRTRPSQTRNGNPSWNEELMFVAAepFEDHLILSVEDRVGPNKDEPLGRAvIPLNDIER 92
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 1005-1050 3.45e-03

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: 39.67  E-value: 3.45e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1034568425 1005 LNDFLVNCQG-EHCTYDEILSIIQKFEPSISMCHQGLMSFEGFARFL 1050
Cdd:cd16205     91 LARFLEVEQKmTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYM 137
 
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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