NCBI Conserved Domain Search

Conserved domains on [gi|300539701|emb|CBU87812|]

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unnamed protein product [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

316-694

7.87e-177

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: 521.13 E-value: 7.87e-177

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 395
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  396 IAEAAFKTSPYPVILSFENHVDSaKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpst 475
Cdd:cd08591    81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnateeMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPM 635
Cdd:cd08591   154 -----------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPI 198

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08591   199 EFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

154-304

1.63e-98

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

Pssm-ID: 320040 Cd Length: 151 Bit Score: 309.93 E-value: 1.63e-98

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILLEI 233
Cdd:cd16210     1 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300539701  234 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16210    81 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PLC-beta_C

pfam08703

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...

1029-1202

2.93e-65

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of phospholipase C beta.

Pssm-ID: 462571 [Multi-domain] Cd Length: 176 Bit Score: 218.40 E-value: 2.93e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1029 KQYREFQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDRKRNNSISE 1108
Cdd:pfam08703    1 KQVRELKERLEQELLELREEQYEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1109 AKTREKHK-KEVELT-EINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKLLAQLTQECQEQRERLPQE 1186
Cdd:pfam08703   81 AKKRTSDKaAQERLKkEINNSHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAE 160

                          170
                   ....*....|....*.
gi 300539701  1187 IRRCLLGETAEGLGDG 1202
Cdd:pfam08703  161 VRESVKSCLKEGFPDE 176

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

22-149

2.78e-60

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is regulated by heterotrimeric G protein-coupled receptors through their C2 domain and long C-terminal extension which forms an autoinhibitory helix. There are four isoforms: PLC-beta1-4. The PH domain of PLC-beta2 and PLC-beta3 plays a dual role, much like PLC-delta1, by binding to the plasma membrane, as well as the interaction site for the catalytic activator. However, PLC-beta binds to the lipid surface independent of PIP2. PLC-beta1 seems to play unspecified roles in cellular proliferation and differentiation. PLC-beta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, a C2 domain and a C-terminal PDZ. Members of the Rho GTPase family (e.g., Rac1, Rac2, Rac3, and cdc42) have been implicated in their activation by binding to an alternate site on the N-terminal PH domain. A basic amino acid region within the enzyme's long C-terminal tail appears to function as a Nuclear Localization Signal for import into the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

Pssm-ID: 270167 Cd Length: 127 Bit Score: 202.03 E-value: 2.78e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   22 LRRGSKFIKWDEEASSRNLVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVlGFGGPDTRLEE 101
Cdd:cd13361     1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 300539701  102 KLMTVVAGPDPVNTTFLNFMAVQDDTVKVWSEELFKLAMNILAQNASR 149
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PLN02952 super family

cl31960

phosphoinositide phospholipase C

318-834

9.28e-60

phosphoinositide phospholipase C

The actual alignment was detected with superfamily member PLN02952:

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 216.79 E-value: 9.28e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:PLN02952  124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS-TKDEILVLHGRTLTTPVPLIKCLKSIR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLidpldkYPLSAG-IPLPSPQDLMGRILVknkkrhrpSTG 476
Cdd:PLN02952  203 DYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFPSPESLKHRIII--------STK 267

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 VPdssvrKRPLEQSNSALSESSAATEPSSpqlgspssdscpglsngeevglEKTSLEPQKSLGEESLSREPNVPMPDRDR 556
Cdd:PLN02952  268 PP-----KEYLESSGPIVIKKKNNVSPSG----------------------RNSSEETEEAQTLESMLFEQEADSRSDSD 320

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 EDEEEDEEEEETTDPKKPTTDEGTASSEVNatEEMSTLVNYVEPVkfksfeaarkrnkcfemsSFVETKAMEQLTKSPME 636
Cdd:PLN02952  321 QDDNKSGELQKPAYKRLITIHAGKPKGTLK--DAMKVAVDKVRRL------------------SLSEQELEKAATTNGQD 380

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFMRRP---DKSF 713
Cdd:PLN02952  381 VVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVF 460

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  714 DPFTEVivdgIVANALRVKVISG----------QFLSDKKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDEEpFD 783
Cdd:PLN02952  461 DPKKKL----PVKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK-KTKIIEDN-WYPAWNEE-FS 533

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 300539701  784 FPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEANQPL 834
Cdd:PLN02952  534 FPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

316-694

7.87e-177

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 521.13 E-value: 7.87e-177

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 395
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  396 IAEAAFKTSPYPVILSFENHVDSaKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpst 475
Cdd:cd08591    81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnateeMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPM 635
Cdd:cd08591   154 -----------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPI 198

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08591   199 EFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

154-304

1.63e-98

Pssm-ID: 320040 Cd Length: 151 Bit Score: 309.93 E-value: 1.63e-98

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILLEI 233
Cdd:cd16210     1 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300539701  234 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16210    81 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

319-467

2.60e-74

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: 242.41 E-value: 2.60e-74

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   319 MTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIAE 398
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGYTLTSKIPFRDVLEAIKD 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701   399 AAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKN 467
Cdd:pfam00388   79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLD----DDLTELPSPEDLKGKILIKG 142

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

592-706

2.46e-65

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: 215.95 E-value: 2.46e-65

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    592 STLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQ 671
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 300539701    672 LVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFM 706
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PLC-beta_C

pfam08703

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...

1029-1202

2.93e-65

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of phospholipase C beta.

Pssm-ID: 462571 [Multi-domain] Cd Length: 176 Bit Score: 218.40 E-value: 2.93e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1029 KQYREFQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDRKRNNSISE 1108
Cdd:pfam08703    1 KQVRELKERLEQELLELREEQYEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1109 AKTREKHK-KEVELT-EINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKLLAQLTQECQEQRERLPQE 1186
Cdd:pfam08703   81 AKKRTSDKaAQERLKkEINNSHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAE 160

                          170
                   ....*....|....*.
gi 300539701  1187 IRRCLLGETAEGLGDG 1202
Cdd:pfam08703  161 VRESVKSCLKEGFPDE 176

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

22-149

2.78e-60

Pssm-ID: 270167 Cd Length: 127 Bit Score: 202.03 E-value: 2.78e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   22 LRRGSKFIKWDEEASSRNLVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVlGFGGPDTRLEE 101
Cdd:cd13361     1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 300539701  102 KLMTVVAGPDPVNTTFLNFMAVQDDTVKVWSEELFKLAMNILAQNASR 149
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PLN02952

phosphoinositide phospholipase C

318-834

9.28e-60

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 216.79 E-value: 9.28e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:PLN02952  124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS-TKDEILVLHGRTLTTPVPLIKCLKSIR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLidpldkYPLSAG-IPLPSPQDLMGRILVknkkrhrpSTG 476
Cdd:PLN02952  203 DYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFPSPESLKHRIII--------STK 267

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 VPdssvrKRPLEQSNSALSESSAATEPSSpqlgspssdscpglsngeevglEKTSLEPQKSLGEESLSREPNVPMPDRDR 556
Cdd:PLN02952  268 PP-----KEYLESSGPIVIKKKNNVSPSG----------------------RNSSEETEEAQTLESMLFEQEADSRSDSD 320

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 EDEEEDEEEEETTDPKKPTTDEGTASSEVNatEEMSTLVNYVEPVkfksfeaarkrnkcfemsSFVETKAMEQLTKSPME 636
Cdd:PLN02952  321 QDDNKSGELQKPAYKRLITIHAGKPKGTLK--DAMKVAVDKVRRL------------------SLSEQELEKAATTNGQD 380

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFMRRP---DKSF 713
Cdd:PLN02952  381 VVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVF 460

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  714 DPFTEVivdgIVANALRVKVISG----------QFLSDKKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDEEpFD 783
Cdd:PLN02952  461 DPKKKL----PVKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK-KTKIIEDN-WYPAWNEE-FS 533

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 300539701  784 FPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEANQPL 834
Cdd:PLN02952  534 FPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

PLN02228

Phosphoinositide phospholipase C

285-832

2.83e-53

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 196.80 E-value: 2.83e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  285 FLERDQMSMEGFSRYLGGEENGILPLEAlDLSMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELD 364
Cdd:PLN02228   75 FHHHGLVHLNAFYRYLFSDTNSPLPMSG-QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELD 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  365 VWKGrPPEEEPFITHGFTMTTEVPLRDVLEAIAEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALL--IDPL 442
Cdd:PLN02228  154 LWPN-PSGNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL-PPNLQAQVAKMLTKTFRGMLFrcTSES 231

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  443 DKYplsagipLPSPQDLMGRILVknkkrhrpSTGVPDSSVRKRPLEQSNSALSESSAATEpsspqlgspssdscpgLSNG 522
Cdd:PLN02228  232 TKH-------FPSPEELKNKILI--------STKPPKEYLESKTVQTTRTPTVKETSWKR----------------VADA 280

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  523 EEVGLEKTSLEPQKSLGEESLsrepnvpmpdrdredeeedeeeeettdpkkpttdegTASSEVNATEEMSTLVNYvEPVK 602
Cdd:PLN02228  281 ENKILEEYKDEESEAVGYRDL------------------------------------IAIHAANCKDPLKDCLSD-DPEK 323

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  603 FKSFEAARKrnkcfemssFVETKAMeqlTKSPmEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDL 682
Cdd:PLN02228  324 PIRVSMDEQ---------WLETMVR---TRGT-DLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGK 390

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  683 PMQLNAGVFEYNGRSGYLLKPEFMRRPDKSFDPFTEVIVDgivaNALRVKVISGQ----------FLSDKKVGIYVEVDM 752
Cdd:PLN02228  391 QLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPIK----TTLKVKIYTGEgwdldfhlthFDQYSPPDFFVKIGI 466

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  753 FGLPVDTrRKYRTRTSQGNSFnPVWDEEPFDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRN 828
Cdd:PLN02228  467 AGVPRDT-VSYRTETAVDQWF-PIWGNDEFLFQLRV-PELALLWFKVQDydndTQNDFAGQTCLPLPELKSGVRAVRLHD 543


                  ....
gi 300539701  829 EANQ 832
Cdd:PLN02228  544 RAGK 547

PH_14

pfam17787

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...

17-146

2.23e-46

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C enzymes.

Pssm-ID: 465506 Cd Length: 131 Bit Score: 162.55 E-value: 2.23e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    17 TVVETLRRGSKFIKWDEEASSRN-LVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVLGFGGP 95
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEpNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 300539701    96 DTRLEEKLMTVVAGPDPVNTTFLNFMAVQDDTVKVWSEELFKLAMNILAQN 146
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

729-844

8.30e-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: 134.98 E-value: 8.30e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  729 LRVKVISGQFLSD------KKVGIYVEVDMFGLPVDTRRKYRTRTSQGNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEE 802
Cdd:cd00275     4 LTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVYDE 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 300539701  803 GG---KFVGHRILPVSAIRSGYHYVCLRNEANQPLCLPALLIYTE 844
Cdd:cd00275    82 DSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHID 126

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

729-826

1.32e-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: 67.90 E-value: 1.32e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    729 LRVKVISGQFLSDKKVG----IYVEVDMFGlpvDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:smart00239    2 LTVKIISARNLPPKDKGgksdPYVKVSLDG---DPKEKKKTKVVK-NTLNPVWNET-FEFE-VPPPELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 300539701    805 ----KFVGHRILPVSAIRSGYHYVCL 826
Cdd:smart00239   76 fgrdDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

729-823

5.34e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 51.94 E-value: 5.34e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   729 LRVKVISGQFLSDKKVGI----YVEVDMfglpVDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:pfam00168    3 LTVTVIEAKNLPPKDGNGtsdpYVKVYL----LDGKQKKKTKVVK-NTLNPVWNET-FTFS-VPDPENAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|...
gi 300539701   805 ----KFVGHRILPVSAIRSGYHY 823
Cdd:pfam00168   76 fgrdDFIGEVRIPLSELDSGEGL 98

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

216-308

2.35e-07

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

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 49.55 E-value: 2.35e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   216 FLNKLCLRPDIDKILLEIGAKGKpYLTLEQLMDFINQKQRDPRlnevlypplRSSQ-ARLLIEKYETNKQFLERDQMSME 294
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQ-KLSLDELVDFLREEQREED---------ASPAlALSLIERYEPSETAKKQHAMTKD 70

                           90
                   ....*....|....
gi 300539701   295 GFSRYLGGEENGIL 308
Cdd:pfam09279   71 GFLMYLCSPDGSIF 84

PTZ00121

MAEBL; Provisional

956-1150

3.94e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 48.21 E-value: 3.94e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRshKAMVKLRSRQDRDLRELHKKHQRKAVALTRRLLD--GLAQARAEgkcrpspsalgKATNSEDVKEEEEAKQYRE 1033
Cdd:PTZ00121 1537 DEAK--KAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEdkNMALRKAE-----------EAKKAEEARIEEVMKLYEE 1603

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1034 FQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDT--HTTQFKRLKELNEREKKELQKILDRKRNNSiSEAKT 1111
Cdd:PTZ00121 1604 EKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEkkKAEELKKAEEENKIKAAEEAKKAEEDKKKA-EEAKK 1682

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 300539701 1112 REKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:PTZ00121 1683 AEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEEL 1721

YhaN

COG4717

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

967-1150

2.95e-04

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 45.14 E-value: 2.95e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  967 LRSRQDRDLRELHKKHQRKavalTRRLLDGLAQARAEGKcrpspsalgkatnsedvKEEEEAKQYREFQNRQVQSLLELR 1046
Cdd:COG4717    47 LLERLEKEADELFKPQGRK----PELNLKELKELEEELK-----------------EAEEKEEEYAELQEELEELEEELE 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1047 EAQADVETKR----KLEHLRQAHQRLKEVV-LDTHTTQF-KRLKELNEREK--KELQKILDRKRNNsISEAKTREKHKKE 1118
Cdd:COG4717   106 ELEAELEELReeleKLEKLLQLLPLYQELEaLEAELAELpERLEELEERLEelRELEEELEELEAE-LAELQEELEELLE 184

                         170       180       190
                  ....*....|....*....|....*....|..
gi 300539701 1119 vELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:COG4717   185 -QLSLATEEELQDLAEELEELQQRLAELEEEL 215

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

1020-1187

2.15e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 42.36 E-value: 2.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1020 EDVKEEEEA--KQYREFQNRQVQSLLELREAQADVETKRK-LEHLRQAHQRLKEvvldthttqfkRLKELNEREKKELQK 1096
Cdd:TIGR02169  684 EGLKRELSSlqSELRRIENRLDELSQELSDASRKIGEIEKeIEQLEQEEEKLKE-----------RLEELEEDLSSLEQE 752

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1097 ILDRKR----NNSISEAKTREKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKL---- 1168
Cdd:TIGR02169  753 IENVKSelkeLEARIEELEEDLHKLEEALNDLEARLSHSRIPEIQAELSKLEEEVSRIEARLREIEQKLNRLTLEKeyle 832

                          170       180
                   ....*....|....*....|....
gi 300539701  1169 -----LAQLTQECQEQRERLPQEI 1187
Cdd:TIGR02169  833 keiqeLQEQRIDLKEQIKSIEKEI 856

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

316-694

7.87e-177

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 521.13 E-value: 7.87e-177

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 395
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  396 IAEAAFKTSPYPVILSFENHVDSaKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpst 475
Cdd:cd08591    81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnateeMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPM 635
Cdd:cd08591   154 -----------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPI 198

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08591   199 EFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

316-694

2.33e-175

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: 517.30 E-value: 2.33e-175

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 395
Cdd:cd08625     1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEEEPFITHGFTMTTEIPFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  396 IAEAAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpst 475
Cdd:cd08625    81 IAESAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08625       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnateeMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPM 635
Cdd:cd08625   155 -----------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPM 199

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08625   200 EFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

PI-PLCc_beta2

cd08624

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...

316-694

3.23e-146

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: 441.42 E-value: 3.23e-146

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 395
Cdd:cd08624     1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  396 IAEAAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpst 475
Cdd:cd08624    81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08624       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnaTEEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPM 635
Cdd:cd08624   155 --------------------------------YEEMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASV 202

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08624   203 QFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261

PI-PLCc_beta1

cd08623

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...

316-694

8.64e-136

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: 414.10 E-value: 8.64e-136

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEA 395
Cdd:cd08623     1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  396 IAEAAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpst 475
Cdd:cd08623    81 IAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08623       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnateeMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPM 635
Cdd:cd08623   155 -----------------------------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPV 199

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08623   200 EFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258

PI-PLCc_eukaryota

cd08558

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...

317-694

2.77e-127

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: 389.89 E-value: 2.77e-127

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  317 MDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAI 396
Cdd:cd08558     2 QDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGHTLTSKILFKDVIEAI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  397 AEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPlsagIPLPSPQDLMGRILVKNKKRHrpstg 476
Cdd:cd08558    80 KEYAFVTSPYPVILSLENHC-SLEQQKKMAQILKEIFGDKLLTPPLDENP----VQLPSPEQLKGKILIKGKKYH----- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 vpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdr 556
Cdd:cd08558       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 edeeedeeeeettdpkkpttdegtassevnateemstlvnyvepvkfksfeaarkrnkcfeMSSFVETKAMEQLTKSPME 636
Cdd:cd08558   150 -------------------------------------------------------------MSSFSETKALKLLKESPEE 168

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08558   169 FVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_beta4

cd08626

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...

317-694

1.23e-117

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: 365.63 E-value: 1.23e-117

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  317 MDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRPPEEEPFITHGFTMTTEVPLRDVLEAI 396
Cdd:cd08626     2 QDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  397 AEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpstg 476
Cdd:cd08626    82 KDTAFVTSDYPVILSFENHC-SKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKR------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 vpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdr 556
Cdd:cd08626       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 edeeedeeeeettdpkkpttdegtassevnateeMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08626   154 ----------------------------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIE 199

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08626   200 FVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

317-694

6.44e-109

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: 342.40 E-value: 6.44e-109

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  317 MDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAI 396
Cdd:cd08593     2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDG--PDGEPIIYHGHTLTSKILFKDVIQAI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  397 AEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKNKKRHrpstg 476
Cdd:cd08593    80 REYAFKVSPYPVILSLENHC-SVEQQKVMAQHLKSILGDKLLTQPLD----GVLTALPSPEELKGKILVKGKKLK----- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 vpdssvrkrpleqsnsaLSessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdr 556
Cdd:cd08593   150 -----------------LA------------------------------------------------------------- 151

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 edeeedeeeeettdpkkpttdegtassevnatEEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08593   152 --------------------------------KELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQESGNE 199

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08593   200 FVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

154-304

1.63e-98

Pssm-ID: 320040 Cd Length: 151 Bit Score: 309.93 E-value: 1.63e-98

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILLEI 233
Cdd:cd16210     1 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300539701  234 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16210    81 GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PI-PLCc_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

318-694

1.91e-88

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: 286.62 E-value: 1.91e-88

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08597     3 DMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDG--PNGEPVIYHGHTLTSKISFRSVIEAIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKyplsAGIPLPSPQDLMGRILVKNKKrhrpstgv 477
Cdd:cd08597    81 EYAFVASEYPLILCIENHC-SEKQQLVMAQYLKEIFGDKLYTEPPNE----GESYLPSPHDLKGKIIIKGKK-------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssVRKRPLeqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08597   148 ----LKRRKL---------------------------------------------------------------------- 153

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnaTEEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08597   154 ------------------------------CKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDF 203

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08597   204 VNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLCc_gamma

cd08592

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...

317-694

2.14e-79

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: 260.44 E-value: 2.14e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  317 MDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAI 396
Cdd:cd08592     2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPIIYHGHTLTSKIKFMDVLKTI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  397 AEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKyplSAGIpLPSPQDLMGRILVKNKKRHRpstg 476
Cdd:cd08592    80 KEHAFVTSEYPVILSIENHC-SLPQQRNMAQAFKEVFGDMLLTQPVDR---NADQ-LPSPNQLKRKIIIKHKKLFY---- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 vpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdr 556
Cdd:cd08592       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 edeeedeeeeettdpkkpttdegtassevnateemstlvnyvepvkfksfeaarkrnkcfEMSSFVETKAMEQLTKS-PM 635
Cdd:cd08592   151 ------------------------------------------------------------EMSSFPETKAEKYLNRQkGK 170

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08592   171 IFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLCc_zeta

cd08595

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...

318-694

3.75e-79

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: 261.02 E-value: 3.75e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08595     3 DMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDG--ADNEPVVYHGYTLTSKILFKEVITTVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAgipLPSPQDLMGRILVKNKKRhrpstgv 477
Cdd:cd08595    81 KYAFEKSDYPVVLSLENHC-STEQQEIMAHYLVSILGEKLLRAPIDDPATGE---LPSPEALKFKILVKNKKK------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08595       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnATEEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08595   150 -----------------------------IAKALSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSSGADF 200

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08595   201 VGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLC1c_yeast

cd08598

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...

318-691

6.40e-79

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: 259.10 E-value: 6.40e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08598     3 DLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDG--DDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVDSAkQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKNKKrhrpstgv 477
Cdd:cd08598    81 KYAFVTSPYPLILSLEVHCDAE-QQERMVEIMKETFGDLLVTEPLD----GLEDELPSPEELRGKILIKVKK-------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatEPSSPqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08598   148 ------------------------ESKTP--------------------------------------------------- 152

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnateemstlvnyvepvkfksfeaarkrNKCFemsSFVETKAMEQLTKSPMEF 637
Cdd:cd08598   153 -------------------------------------------------------NHIF---SLSERSLLKLLKDKRAAL 174

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVF 691
Cdd:cd08598   175 DKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228

PI-PLCc_delta1

cd08629

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...

318-694

3.31e-77

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: 255.34 E-value: 3.31e-77

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08629     3 DMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVLRAIR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKNKKrhrpstgv 477
Cdd:cd08629    81 DYAFKASPYPVILSLENHC-SLEQQRVMARHLRAILGPILLDQPLD----GVTTSLPSPEQLKGKILLKGKK-------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08629       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtasseVNATEEMSTLVNYVEPVKFKSFEAARKRNKCF-EMSSFVETKAMEQLTKSPME 636
Cdd:cd08629   148 ---------------------------LKLVPELSDMIIYCKSVHFGGFSSPGTSGQAFyEMASFSESRALRLLQESGNG 200

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08629   201 FVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLCc_delta4

cd08631

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...

318-694

3.04e-75

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: 249.86 E-value: 3.04e-75

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08631     3 DMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDG--PNGEPIVYHGHTFTSKILFKDVVAAVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLD-KYPLSagipLPSPQDLMGRILVKNKKrhrpstg 476
Cdd:cd08631    81 QYAFQVSDYPVILSLENHC-GVEQQQTMAQHLTEILGEKLLSTTLDgVLPTQ----LPSPEELRGKILLKGKK------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 vpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdr 556
Cdd:cd08631       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 edeeedeeeeettdpkkpttdegtasseVNATEEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPME 636
Cdd:cd08631   149 ----------------------------IRLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNE 200

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08631   201 FVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_epsilon

cd08596

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...

318-694

1.21e-74

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: 248.23 E-value: 1.21e-74

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRppEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08596     3 DLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGD--DGMPIIYHGHTLTTKIPFKDVVEAIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpstgv 477
Cdd:cd08596    81 RSAFITSDYPVILSIENHC-SLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK-------- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08596       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnaTEEMSTLVNYVEPVKFKSFEAArkrnKCFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08596   152 ------------------------------APELSDLVIYCQAVKFPGLSTP----KCYHISSLNENAAKRLCRRYPQKL 197

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08596   198 VQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

319-467

2.60e-74

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: 242.41 E-value: 2.60e-74

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   319 MTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIAE 398
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGYTLTSKIPFRDVLEAIKD 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701   399 AAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKN 467
Cdd:pfam00388   79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLD----DDLTELPSPEDLKGKILIKG 142

PI-PLCc_delta3

cd08630

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...

318-694

2.68e-74

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: 247.24 E-value: 2.68e-74

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08630     3 DMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG--PGGEPVIYHGHTLTSKILFRDVIQAVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLSAgipLPSPQDLMGRILVKNKkrhrpstgv 477
Cdd:cd08630    81 QHAFTASPYPVILSLENHC-GLEQQAAMARHLQTILGDMLVTQPLDSLNPEE---LPSPEELKGRVLVKGK--------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevgleKTSLEPqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08630   148 ---------------------------------------------------KLQISP----------------------- 153

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnateEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08630   154 --------------------------------ELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREAGNSF 201

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08630   202 VRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

154-304

1.03e-68

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: 227.13 E-value: 1.03e-68

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILL 231
Cdd:cd16200     1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKkrKRVLKALKALGLPDGKNDEIDPEDFTFEKFFKLYNKLCPRPDIDEIFK 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300539701  232 EIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16200    81 ELGGKRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

PI-PLCc_eta

cd08594

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...

318-694

7.97e-67

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: 225.07 E-value: 7.97e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08594     3 DMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKILFRDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLidpLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpstgv 477
Cdd:cd08594    81 KYAFIKNEYPVILSIENHC-SVQQQKKMAQYLKEILGDKLD---LSSVISGDSKQLPSPQSLKGKILIKGKK-------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08594       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnateemstlvnyvepvkfksfeaarkrnkcFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08594   149 ----------------------------------------------------------WQVSSFSETRAHQIVQQKAAQF 170

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08594   171 LRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

PI-PLCc

cd00137

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...

318-694

1.74e-66

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: 225.99 E-value: 1.74e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLA-----GPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTtEVPLRDV 392
Cdd:cd00137     3 PDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDG--KPEEPIIYHGPTFL-DIFLKEV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  393 LEAIAEAAFKTSPYPVILSFENHVDSA-KQQAKMAEYCRSIFGDALLIDPLDKyplsaGIPLPSPQDLMGRILVKNKKrh 471
Cdd:cd00137    80 IEAIAQFLKKNPPETIIMSLKNEVDSMdSFQAKMAEYCRTIFGDMLLTPPLKP-----TVPLPSLEDLRGKILLLNKK-- 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  472 rpSTGVPdssvrkrpleqsnsalsessaatepsspqLGSPSSDSCPGlsngeevglektslepqkslgeeslsrepnvpm 551
Cdd:cd00137   153 --NGFSG-----------------------------PTGSSNDTGFV--------------------------------- 168

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  552 pdrdredeeedeeeeettdpkkpttdegtassevnateemstlvnyvepvkFKSFEAARKRNkcFEMSSFVETKAME--- 628
Cdd:cd00137   169 ---------------------------------------------------SFEFSTQKNRS--YNISSQDEYKAYDdek 195

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  629 -QLTKSPMEFVEYNKQQLSRIYPKGTRV---------DSSNYMPQLFWN---VGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd00137   196 vKLIKATVQFVDYNKNQLSRNYPSGTSGgtawyyyamDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274

EFh_PI-PLCbeta1

cd16208

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...

155-304

4.23e-66

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

Pssm-ID: 320038 Cd Length: 151 Bit Score: 219.75 E-value: 4.23e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  155 KAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILLEIG 234
Cdd:cd16208     2 KAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEFG 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  235 AKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16208    82 AKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

PI-PLCc_eta2

cd08633

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...

318-694

1.69e-65

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: 222.22 E-value: 1.69e-65

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08633     3 DMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALlidPLDKYPLSAGIPLPSPQDLMGRILVKNKKrhrpstgv 477
Cdd:cd08633    81 KYAFIKNEYPVILSIENHC-SVPQQKKMAQYLTEILGDKL---DLSSVISNDCTRLPSPEILKGKILVKGKK-------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeesLSRepnvpmpdrdre 557
Cdd:cd08633   149 -----------------------------------------------------------------LSR------------ 151

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnateEMSTLVNYVEPVKFKSFEAarKRNKCFEMSSFVETKAMEQLTKSPMEF 637
Cdd:cd08633   152 --------------------------------ALSDLVKYTKSVRVHDIET--EATSSWQVSSFSETKAHQILQQKPAQY 197

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  638 VEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08633   198 LRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

592-706

2.46e-65

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 215.95 E-value: 2.46e-65

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    592 STLVNYVEPVKFKSFEAARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQ 671
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 300539701    672 LVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFM 706
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_gamma2

cd08628

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...

317-694

2.47e-65

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: 221.85 E-value: 2.47e-65

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  317 MDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAI 396
Cdd:cd08628     2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDG--PDGKPIIYHGWTRTTKIKFDDVVQAI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  397 AEAAFKTSPYPVILSFENHVDsAKQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKNKKRhrpstg 476
Cdd:cd08628    80 KDHAFVTSEYPVILSIEEHCS-VEQQRHMAKVFKEVFGDKLLMKPLE----ASADQLPSPTQLKEKIIIKHKKL------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 vpdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdr 556
Cdd:cd08628       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 edeeedeeeeettdpkkpttdegtassevnATEEMSTLVNYVEPvkfKSFEAARKRNKCF-EMSSFVETKAMEQLTKSPM 635
Cdd:cd08628   149 ------------------------------IAIELSDLVVYCKP---TSKTKDNLENPDFkEIRSFVETKAPSIIRQKPV 195

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08628   196 QLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254

PLC-beta_C

pfam08703

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...

1029-1202

2.93e-65

PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of phospholipase C beta.

Pssm-ID: 462571 [Multi-domain] Cd Length: 176 Bit Score: 218.40 E-value: 2.93e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1029 KQYREFQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDRKRNNSISE 1108
Cdd:pfam08703    1 KQVRELKERLEQELLELREEQYEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1109 AKTREKHK-KEVELT-EINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKLLAQLTQECQEQRERLPQE 1186
Cdd:pfam08703   81 AKKRTSDKaAQERLKkEINNSHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAE 160

                          170
                   ....*....|....*.
gi 300539701  1187 IRRCLLGETAEGLGDG 1202
Cdd:pfam08703  161 VRESVKSCLKEGFPDE 176

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

22-149

2.78e-60

Pssm-ID: 270167 Cd Length: 127 Bit Score: 202.03 E-value: 2.78e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   22 LRRGSKFIKWDEEASSRNLVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVlGFGGPDTRLEE 101
Cdd:cd13361     1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 300539701  102 KLMTVVAGPDPVNTTFLNFMAVQDDTVKVWSEELFKLAMNILAQNASR 149
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PI-PLC-Y

pfam00387

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...

591-705

3.77e-60

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 201.15 E-value: 3.77e-60

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   591 MSTLVNYVEPVKFKSFEAArKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGC 670
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTP-ESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 300539701   671 QLVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEF 705
Cdd:pfam00387   80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PI-PLCc_eta1

cd08632

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...

318-694

4.88e-60

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: 206.42 E-value: 4.88e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08632     3 DMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKITFRDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKyplsaGIP--LPSPQDLMGRILVKNKKRHRpst 475
Cdd:cd08632    81 KYAFVKNEFPVILSIENHC-SIQQQKKIAQYLKEIFGDKLDLSSVLT-----GDPkqLPSPQLLKGKILVKGKKLCR--- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsALSESSAATEpsspqlgSPSSDSCpglsngeevglektslepqkslgeeslsrepnvpmpdrd 555
Cdd:cd08632   152 -----------------DLSDLVVYTN-------SVAAQDI--------------------------------------- 168

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkptTDEGTASSEVnateemstlvnyvepvkfksfeaarkrnkcfemsSFVETKAMEQLTKSPM 635
Cdd:cd08632   169 --------------------VDDGSTGNVL----------------------------------SFSETRAHQLVQQKAE 194

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08632   195 QFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

319-468

5.00e-60

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: 202.13 E-value: 5.00e-60

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    319 MTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIAE 398
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDG--PDGEPVIYHGHTFTLPIKLSEVLEAIKD 78

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    399 AAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplSAGIPLPSPQDLMGRILVKNK 468
Cdd:smart00148   79 FAFVTSPYPVILSLENHC-SPDQQAKMAQMFKEIFGDMLYTPPLT----SSLEVLPSPEQLRGKILLKVR 143

PLN02952

phosphoinositide phospholipase C

318-834

9.28e-60

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 216.79 E-value: 9.28e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:PLN02952  124 DMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS-TKDEILVLHGRTLTTPVPLIKCLKSIR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLidpldkYPLSAG-IPLPSPQDLMGRILVknkkrhrpSTG 476
Cdd:PLN02952  203 DYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFPSPESLKHRIII--------STK 267

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  477 VPdssvrKRPLEQSNSALSESSAATEPSSpqlgspssdscpglsngeevglEKTSLEPQKSLGEESLSREPNVPMPDRDR 556
Cdd:PLN02952  268 PP-----KEYLESSGPIVIKKKNNVSPSG----------------------RNSSEETEEAQTLESMLFEQEADSRSDSD 320

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  557 EDEEEDEEEEETTDPKKPTTDEGTASSEVNatEEMSTLVNYVEPVkfksfeaarkrnkcfemsSFVETKAMEQLTKSPME 636
Cdd:PLN02952  321 QDDNKSGELQKPAYKRLITIHAGKPKGTLK--DAMKVAVDKVRRL------------------SLSEQELEKAATTNGQD 380

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFMRRP---DKSF 713
Cdd:PLN02952  381 VVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVF 460

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  714 DPFTEVivdgIVANALRVKVISG----------QFLSDKKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDEEpFD 783
Cdd:PLN02952  461 DPKKKL----PVKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK-KTKIIEDN-WYPAWNEE-FS 533

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 300539701  784 FPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRNEANQPL 834
Cdd:PLN02952  534 FPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

PI-PLCc_gamma1

cd08627

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...

318-694

3.46e-59

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: 203.34 E-value: 3.46e-59

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08627     3 EMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkypLSAGiPLPSPQDLMGRILVKNKKRHRpstgv 477
Cdd:cd08627    81 EHAFVTSEYPIILSIEDHC-SIVQQRNMAQHFKKVFGDMLLTKPVD---INAD-GLPSPNQLKRKILIKHKKLYR----- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  478 pdssvrkrpleqsnsalsessaatepsspqlgspssdscpglsngeevglektslepqkslgeeslsrepnvpmpdrdre 557
Cdd:cd08627       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  558 deeedeeeeettdpkkpttdegtassevnateemstlvnyvepvkfksfeaarkrnkcfEMSSFVETKAMEQLTKSP-ME 636
Cdd:cd08627   151 -----------------------------------------------------------DMSSFPETKAEKYVNRSKgKK 171

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701  637 FVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08627   172 FLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

EFh_PI-PLC21

cd16213

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...

154-304

2.26e-58

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: 197.91 E-value: 2.26e-58

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSA---DKKRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKIL 230
Cdd:cd16213     1 EKAYTKLTLQTDKEGKIPVKNIVKMFAQhkdDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300539701  231 LEIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16213    81 DELGAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

PLN02222

phosphoinositide phospholipase C 2

285-829

1.81e-54

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 200.64 E-value: 1.81e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  285 FLERDQMSMEGFSRYLGGEENGilPLEALDLSMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELD 364
Cdd:PLN02222   73 LLHRNGLHLDAFFKYLFGDNNP--PLALHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELD 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  365 VWKGRpPEEEPFITHGFTMTTEVPLRDVLEAIAEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDK 444
Cdd:PLN02222  151 IWPNS-DKDDIDVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHL-TPDLQSKVAEMVTEIFGEILFTPPVGE 228

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  445 yplsAGIPLPSPQDLMGRILVKNKKRHRPSTGVPDSSVRKrpleqsnsalsessaatepsspqlgspssdsCPGLSNGEE 524
Cdd:PLN02222  229 ----SLKEFPSPNSLKKRIIISTKPPKEYKEGKDDEVVQK-------------------------------GKDLGDEEV 273

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  525 VGLEKTS-LEPQKSLGEESLSREPNvpmpdrdredeeedeeeeettdpkkPTTDEGTASSEVNATEEMSTLVnyvepvkf 603
Cdd:PLN02222  274 WGREVPSfIQRNKSVDKNDSNGDDD-------------------------DDDDDGEDKSKKNAPPQYKHLI-------- 320

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  604 kSFEAARKR---NKCFEMS-------SFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLV 673
Cdd:PLN02222  321 -AIHAGKPKggiTECLKVDpdkvrrlSLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMV 399

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  674 ALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFMRRPDKS---FDPFTEVIVDgivaNALRVKVISGQ----------FLS 740
Cdd:PLN02222  400 AFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDsdiFDPKATLPVK----TTLRVTIYMGEgwyfdfrhthFDQ 475

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  741 DKKVGIYVEVDMFGLPVDTRRKyRTRTSQGNsFNPVWDeEPFDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSA 816
Cdd:PLN02222  476 YSPPDFYTRVGIAGVPGDTVMK-KTKTLEDN-WIPAWD-EVFEFPLTV-PELALLRLEVHEydmsEKDDFGGQTCLPVWE 551

                         570
                  ....*....|...
gi 300539701  817 IRSGYHYVCLRNE 829
Cdd:PLN02222  552 LSQGIRAFPLHSR 564

PI-PLCc_plant

cd08599

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...

318-694

2.63e-53

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: 186.42 E-value: 2.63e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVWKGRppEEEPFITHGFTMTTEVPLRDVLEAIA 397
Cdd:cd08599     3 DMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGG--RGDICVLHGGTLTKPVKFEDCIKAIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  398 EAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLidpldkYPLSAGIP--LPSPQDLMGRILVknkkrhrpst 475
Cdd:cd08599    81 ENAFTASEYPVIITLENHL-SPELQAKAAQILRETLGDKLF------YPDSEDLPeeFPSPEELKGKILI---------- 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  476 gvpdssvrkrpleqsnsalsessaatepsspqlgspsSDSCPGLSNgeevglektslepqkSLGEeslsrepnvpmpdrd 555
Cdd:cd08599   144 -------------------------------------SDKPPVIRN---------------SLSE--------------- 156

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  556 redeeedeeeeettdpkkpttdegtassevnateemSTLVNYVEpvkfksfeaarkrnkcfemssfvetkameqlTKSPM 635
Cdd:cd08599   157 ------------------------------------TQLKKVIE-------------------------------GEHPT 169

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 300539701  636 EFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYN 694
Cdd:cd08599   170 DLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

PLN02228

Phosphoinositide phospholipase C

285-832

2.83e-53

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 196.80 E-value: 2.83e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  285 FLERDQMSMEGFSRYLGGEENGILPLEAlDLSMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELD 364
Cdd:PLN02228   75 FHHHGLVHLNAFYRYLFSDTNSPLPMSG-QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELD 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  365 VWKGrPPEEEPFITHGFTMTTEVPLRDVLEAIAEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALL--IDPL 442
Cdd:PLN02228  154 LWPN-PSGNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL-PPNLQAQVAKMLTKTFRGMLFrcTSES 231

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  443 DKYplsagipLPSPQDLMGRILVknkkrhrpSTGVPDSSVRKRPLEQSNSALSESSAATEpsspqlgspssdscpgLSNG 522
Cdd:PLN02228  232 TKH-------FPSPEELKNKILI--------STKPPKEYLESKTVQTTRTPTVKETSWKR----------------VADA 280

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  523 EEVGLEKTSLEPQKSLGEESLsrepnvpmpdrdredeeedeeeeettdpkkpttdegTASSEVNATEEMSTLVNYvEPVK 602
Cdd:PLN02228  281 ENKILEEYKDEESEAVGYRDL------------------------------------IAIHAANCKDPLKDCLSD-DPEK 323

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  603 FKSFEAARKrnkcfemssFVETKAMeqlTKSPmEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDL 682
Cdd:PLN02228  324 PIRVSMDEQ---------WLETMVR---TRGT-DLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGK 390

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  683 PMQLNAGVFEYNGRSGYLLKPEFMRRPDKSFDPFTEVIVDgivaNALRVKVISGQ----------FLSDKKVGIYVEVDM 752
Cdd:PLN02228  391 QLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPIK----TTLKVKIYTGEgwdldfhlthFDQYSPPDFFVKIGI 466

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  753 FGLPVDTrRKYRTRTSQGNSFnPVWDEEPFDFPKVVlPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLRN 828
Cdd:PLN02228  467 AGVPRDT-VSYRTETAVDQWF-PIWGNDEFLFQLRV-PELALLWFKVQDydndTQNDFAGQTCLPLPELKSGVRAVRLHD 543


                  ....
gi 300539701  829 EANQ 832
Cdd:PLN02228  544 RAGK 547

EFh_PI-PLCbeta2

cd16209

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...

155-304

7.00e-50

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

Pssm-ID: 320039 Cd Length: 151 Bit Score: 173.53 E-value: 7.00e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  155 KAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILLEIG 234
Cdd:cd16209     2 KIYVKLKMQLNSEGKIPVKNFFQMFPADRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSYH 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  235 AKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16209    82 AKAKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151

PH_14

pfam17787

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...

17-146

2.23e-46

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C enzymes.

Pssm-ID: 465506 Cd Length: 131 Bit Score: 162.55 E-value: 2.23e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    17 TVVETLRRGSKFIKWDEEASSRN-LVTLRVDPNGFFLYWTGPNMEVDTLDISSIRDTRTGRYARLPKDPKIREVLGFGGP 95
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEpNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 300539701    96 DTRLEEKLMTVVAGPDPVNTTFLNFMAVQDDTVKVWSEELFKLAMNILAQN 146
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

PLN02230

phosphoinositide phospholipase C 4

288-828

4.17e-43

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 167.19 E-value: 4.17e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  288 RDQMSMEGFSRYLGGEEngILPLEALDLSMDMTQPLSAYFINSSHNTYLTAGQLAGPSSVEMYRQALLWGCRCVELDVW- 366
Cdd:PLN02230   88 RRNLTLDDFNYYLFSTD--LNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWp 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  367 KGrppEEEPFITHGFTMTTEVPLRDVLEAIAEAAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIdpldkYP 446
Cdd:PLN02230  166 RG---TDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHL-TPKLQFKVAKMITQTFGDMLYY-----HD 236

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  447 LSAGIPLPSPQDLMGRILVknkkrhrpSTGVPdssvrKRPLEQSNSAlsessaatepsspqlgspssdscpglsngeevg 526
Cdd:PLN02230  237 SEGCQEFPSPEELKEKILI--------STKPP-----KEYLEANDAK--------------------------------- 270

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  527 lEKTSLEPQKSLGEESLSREPNVPMPDRDREDEEEDEEEEETTDPKKPTTDEGTASSEVNATEEMSTLVNYVEPVKFKSF 606
Cdd:PLN02230  271 -EKDNGEKGKDSDEDVWGKEPEDLISTQSDLDKVTSSVNDLNQDDEERGSCESDTSCQLQAPEYKRLIAIHAGKPKGGLR 349

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  607 EAARKRNKCFEMSSFVETKAMEQLTKSPMEFVEYNKQQLSRIYPKGTRVDSSNYMPQLFWNVGCQLVALNFQTLDLPMQL 686
Cdd:PLN02230  350 MALKVDPNKIRRLSLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWL 429

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  687 NAGVFEYNGRSGYLLKPEFMRRPDKSFDPFTEVIvDGIVANALRVKVISG----------QFLSDKKVGIYVEVDMFGLP 756
Cdd:PLN02230  430 MEGMFRANGGCGYVKKPDFLMDAGPNGQDFYPKD-NSCPKKTLKVKVCMGdgwlldfkktHFDSYSPPDFFVRVGIAGAP 508

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  757 VD-----TRRKYRTRTsqgnsfnPVWDEEpFDFPkVVLPTLASLRIAAFE----EGGKFVGHRILPVSAIRSGYHYVCLR 827
Cdd:PLN02230  509 VDevmekTKIEYDTWT-------PIWNKE-FIFP-LAVPELALLRVEVHEhdinEKDDFGGQTCLPVSEIRQGIHAVPLF 579


                  .
gi 300539701  828 N 828
Cdd:PLN02230  580 N 580

EFh_PI-PLCbeta4

cd16211

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...

154-304

1.56e-39

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

Pssm-ID: 320041 Cd Length: 153 Bit Score: 143.72 E-value: 1.56e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILL 231
Cdd:cd16211     1 KKHWMRLCFLVNPNGKIPVRSITRTFASGKteKIVFQSLKELGLPSGKNDEIEPEAFTFEKFYELYHKICPRTDIEELFK 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300539701  232 EIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16211    81 KINGDKKDYLTVDQLISFLNEHQRDPRLNEILFPFYDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

729-844

8.30e-37

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 134.98 E-value: 8.30e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  729 LRVKVISGQFLSD------KKVGIYVEVDMFGLPVDTRRKYRTRTSQGNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEE 802
Cdd:cd00275     4 LTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVYDE 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 300539701  803 GG---KFVGHRILPVSAIRSGYHYVCLRNEANQPLCLPALLIYTE 844
Cdd:cd00275    82 DSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHID 126

EFh_NorpA_like

cd16212

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...

154-304

4.59e-32

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

Pssm-ID: 320042 [Multi-domain] Cd Length: 153 Bit Score: 122.66 E-value: 4.59e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLNFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILL 231
Cdd:cd16212     1 KKHWMRLGFMVDSGGKIPVKHIARTFASGKteKLVYQCLAEMGLPSGKGDSIEKEDFTFEKFYALYHKICPRNDIEELFT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300539701  232 EIGAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRSSQARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16212    81 SITKGKGEHISLAQLINFMNDKQRDPRLNEILYPLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153

PLN02223

phosphoinositide phospholipase C

318-829

4.59e-24

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 108.19 E-value: 4.59e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  318 DMTQPLSAYFINSSHNTYLTAGQLAGPS-SVEMYRQALLWGCRCVELDVWkgrpPEEEPFITHGFTMTTEVPLR--DVLE 394
Cdd:PLN02223  107 DMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL----PDGKDGICVRPKWNFEKPLElqECLD 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  395 AIAEAAF-KTSPYPVILSFEnhvDSAKQ--QAKMAEYCRSIFGDALLidplDKYPLSAGIPLPSPQDLMGRILVKNKkrh 471
Cdd:PLN02223  183 AIKEHAFtKCRSYPLIITFK---DGLKPdlQSKATQMIDQTFGDMVY----HEDPQHSLEEFPSPAELQNKILISRR--- 252

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  472 rpstgvpdssvrkrpleqsnsalsessaatePSSPQLGSPSSDSCPGLSNGEEVglektslepqkslgeeslsrepnvpm 551
Cdd:PLN02223  253 -------------------------------PPKELLYAKADDGGVGVRNELEI-------------------------- 275

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  552 pdrdredeeedeeeeettdpkkpttdegtassevnatEEMSTLVNYVEPVKFKSFEAARKRNKCFEMSSfvetKAMEQLT 631
Cdd:PLN02223  276 -------------------------------------QEGPADKNYQSLVGFHAVEPRGMLQKALTGKA----DDIQQPG 314

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  632 KSPMEFVEYNKQQLSRIYPKGTRVDS-SNYMPQLFWNVGCQLVALNFQTLDLPMQLNAGVFEYNGRSGYLLKPEFMRR-- 708
Cdd:PLN02223  315 WYERDIISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNag 394

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  709 PDKSFDPftevIVDGIVANALRVKVISGQ-FLSD--KKVG------IYVEVDMFGLPVDtrRKYRTRTSQGNSFNPVWDE 779
Cdd:PLN02223  395 PSGVFYP----TENPVVVKILKVKIYMGDgWIVDfkKRIGrlskpdLYVRISIAGVPHD--EKIMKTTVKNNEWKPTWGE 468

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....
gi 300539701  780 EpFDFPkVVLPTLA--SLRIAAFE--EGGKFVGHRILPVSAIRSGYHYVCLRNE 829
Cdd:PLN02223  469 E-FTFP-LTYPDLAliSFEVYDYEvsTADAFCGQTCLPVSELIEGIRAVPLYDE 520

PI-PLCc_GDPD_SF

cd08555

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...

329-438

1.74e-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: 87.49 E-value: 1.74e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  329 NSSHNTYLTAGQlagPSSVEMYRQALLWGCRCVELDVWKGrpPEEEPFITHGFTMTTEVP------LRDVLEAIAEAAFk 402
Cdd:cd08555     1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLT--KDGELVVYHGPTLDRTTAgilpptLEEVLELIADYLK- 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 300539701  403 TSPYPVILSFENHVDSA---KQQAKMAEYCRSIFGDALL 438
Cdd:cd08555    75 NPDYTIILSLEIKQDSPeydEFLAKVLKELRVYFDYDLR 113

EFh_PI-PLC

cd15898

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...

154-304

8.55e-19

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: 83.87 E-value: 8.55e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  154 RKAYTKLKLQVNQDGRIPVKNILKMFSADKKRV---ETALESCGLNFNRVESIRPDEFpleifERFLNKLCLRPDIDKIL 230
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVsekELKKLFKEVDTNGDGTLTFDEF-----EELYKSLTERPELEPIF 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300539701  231 LEIGAKGKPYLTLEQLMDFINQKQrdprlnevlYPPLRSSQARLLIEKYETNKqflERDQMSMEGFSRYLGGEE 304
Cdd:cd15898    76 KKYAGTNRDYMTLEEFIRFLREEQ---------GENVSEEECEELIEKYEPER---ENRQLSFEGFTNFLLSPE 137

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

729-826

1.32e-13

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 67.90 E-value: 1.32e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701    729 LRVKVISGQFLSDKKVG----IYVEVDMFGlpvDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:smart00239    2 LTVKIISARNLPPKDKGgksdPYVKVSLDG---DPKEKKKTKVVK-NTLNPVWNET-FEFE-VPPPELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 300539701    805 ----KFVGHRILPVSAIRSGYHYVCL 826
Cdd:smart00239   76 fgrdDFIGQVTIPLSDLLLGGRHEKL 101

PH_PLC_ELMO1

cd01248

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...

22-138

4.58e-12

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

Pssm-ID: 269952 Cd Length: 108 Bit Score: 63.88 E-value: 4.58e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   22 LRRGSKFIKWdEEASSRNLVTLRVDPNGFFLYWTGP--NMEVDTLDISSIRDTRTGRYARLPKDpkirevlgFGGPDTRL 99
Cdd:cd01248     1 LQQGTLLLKY-REGSKPKERTFYLDPDGTRITWESSkkKSEKKSIDISDIKEIRPGKDTDGFKR--------KKKSNKPK 71

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 300539701  100 EEKLMTVVAGPdpvNTTFLNFMAVQDDTVKVWSEELFKL 138
Cdd:cd01248    72 EERCFSIIYGS---NNKTLDLVAPSEDEANLWVEGLRAL 107

EFh_PI-PLCdelta

cd16202

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...

164-300

9.01e-12

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: 63.78 E-value: 9.01e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  164 VNQDGRI---PVKNILKM--FSADKKRVETALESCglNFNRVESIRPDEFpleifERFLNKLCLRPDIDKILLEIgAKGK 238
Cdd:cd16202    11 KNGDGKLsfkECKKLLKKlnVKVDKDYAKKLFQEA--DTSGEDVLDEEEF-----VQFYNRLTKRPEIEELFKKY-SGDD 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 300539701  239 PYLTLEQLMDFINQKQRDPRLNEvlypplrsSQARLLIEKYETNKQFLERDQMSMEGFSRYL 300
Cdd:cd16202    83 EALTVEELRRFLQEEQKVKDVTL--------EWAEQLIETYEPSEDLKAQGLMSLDGFTLFL 136

pfam00168

C2 domain;

729-823

5.34e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 51.94 E-value: 5.34e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   729 LRVKVISGQFLSDKKVGI----YVEVDMfglpVDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRIAAFEEGG 804
Cdd:pfam00168    3 LTVTVIEAKNLPPKDGNGtsdpYVKVYL----LDGKQKKKTKVVK-NTLNPVWNET-FTFS-VPDPENAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|...
gi 300539701   805 ----KFVGHRILPVSAIRSGYHY 823
Cdd:pfam00168   76 fgrdDFIGEVRIPLSELDSGEGL 98

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

216-308

2.35e-07

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 49.55 E-value: 2.35e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   216 FLNKLCLRPDIDKILLEIGAKGKpYLTLEQLMDFINQKQRDPRlnevlypplRSSQ-ARLLIEKYETNKQFLERDQMSME 294
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQ-KLSLDELVDFLREEQREED---------ASPAlALSLIERYEPSETAKKQHAMTKD 70

                           90
                   ....*....|....
gi 300539701   295 GFSRYLGGEENGIL 308
Cdd:pfam09279   71 GFLMYLCSPDGSIF 84

EFh_PI-PLCdelta4

cd16219

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...

165-304

5.99e-07

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

Pssm-ID: 320049 [Multi-domain] Cd Length: 140 Bit Score: 50.23 E-value: 5.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  165 NQDGRI---PVKNILKMFSADKKRvETALEScglnFNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILLEIGAKGKPyL 241
Cdd:cd16219    12 NKDGRMnfkEVRDLLKMMNVDMNE-EHALRL----FQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSADGQK-L 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300539701  242 TLEQLMDFINQKQRDPRLNEVLypplrssqARLLIEKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16219    86 TLLEFVDFLQQEQLERENTEEL--------AMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

EFh_ScPlc1p_like

cd16207

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...

213-300

1.68e-06

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: 48.78 E-value: 1.68e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  213 FERFLNKLCLRPDIDKILLEIGAKGKPYLTLEQLMDFINQKQRDprlnevlypPLRSSQARLLIEKYETNKQFLERDQMS 292
Cdd:cd16207    60 FQEFVKLLKRRKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVQKE---------DVDRETWEKIFEKFARRIDDSDSLTMT 130


                  ....*...
gi 300539701  293 MEGFSRYL 300
Cdd:cd16207   131 LEGFTSFL 138

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

729-797

3.29e-06

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: 47.06 E-value: 3.29e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300539701  729 LRVKVISGQFLSDKKVGI----YVEVDmfglpVDTRRKYRTRTSQgNSFNPVWDEEpFDFPkVVLPTLASLRI 797
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGksdpYVKVS-----LGGKQKFKTKVVK-NTLNPVWNET-FEFP-VLDPESDTLTV 65

PTZ00121

MAEBL; Provisional

956-1150

3.94e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 48.21 E-value: 3.94e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRshKAMVKLRSRQDRDLRELHKKHQRKAVALTRRLLD--GLAQARAEgkcrpspsalgKATNSEDVKEEEEAKQYRE 1033
Cdd:PTZ00121 1537 DEAK--KAEEKKKADELKKAEELKKAEEKKKAEEAKKAEEdkNMALRKAE-----------EAKKAEEARIEEVMKLYEE 1603

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1034 FQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDT--HTTQFKRLKELNEREKKELQKILDRKRNNSiSEAKT 1111
Cdd:PTZ00121 1604 EKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEkkKAEELKKAEEENKIKAAEEAKKAEEDKKKA-EEAKK 1682

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 300539701 1112 REKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:PTZ00121 1683 AEEDEKKAAEALKKEAEEAKKAEELKKKEAEEKKKAEEL 1721

DUF5401

pfam17380

Family of unknown function (DUF5401); This is a family of unknown function found in ...

938-1184

6.36e-05

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

Pssm-ID: 375164 [Multi-domain] Cd Length: 722 Bit Score: 47.43 E-value: 6.36e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   938 QRDDLIASILSEVTPTPLEELRSHKAMVKLRsrQDRDLRELHKKHQRKAvALTRRLLDGLAQARAEGKCRPSPSALGKAT 1017
Cdd:pfam17380  345 ERERELERIRQEERKRELERIRQEEIAMEIS--RMRELERLQMERQQKN-ERVRQELEAARKVKILEEERQRKIQQQKVE 421

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1018 NSEDVKEEEEAKQyrefqnRQVQSLLELREA------QADVETKRKLEHLRQ--AHQRLKEVVLDTHTTQFKRLKELN-- 1087
Cdd:pfam17380  422 MEQIRAEQEEARQ------REVRRLEEERARemervrLEEQERQQQVERLRQqeEERKRKKLELEKEKRDRKRAEEQRrk 495

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1088 --EREKKE-LQKILDRKRNNSISEAKTREKHKKEVEltEINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEE 1164
Cdd:pfam17380  496 ilEKELEErKQAMIEEERKRKLLEKEMEERQKAIYE--EERRREAEEERRKQQEMEERRRIQEQMRKATEERSRLEAMER 573

                          250       260
                   ....*....|....*....|
gi 300539701  1165 EPKLLAQLTqECQEQRERLP 1184
Cdd:pfam17380  574 EREMMRQIV-ESEKARAEYE 592

PTZ00121

MAEBL; Provisional

956-1186

7.47e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 47.44 E-value: 7.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRS----HKAMVKLRSRQDRDLR----ELHKKHQRKAVALTRRLLDGLAQARAEgKCRPSPSALGKAtnsEDVKEEEE 1027
Cdd:PTZ00121 1555 EELKKaeekKKAEEAKKAEEDKNMAlrkaEEAKKAEEARIEEVMKLYEEEKKMKAE-EAKKAEEAKIKA---EELKKAEE 1630

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1028 AK----QYREFQNRQVQSLLELR------------EAQADVETKRKLEHLRQAHQ--RLKEVVLDTHTTQFKRLKELNER 1089
Cdd:PTZ00121 1631 EKkkveQLKKKEAEEKKKAEELKkaeeenkikaaeEAKKAEEDKKKAEEAKKAEEdeKKAAEALKKEAEEAKKAEELKKK 1710

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1090 EKKELQKILDRKRNNSISEAKTREKHKKEVElteinrrhitesvnSIRRLEEAQKQRHERlvagqqqvlqqleeeepKLL 1169
Cdd:PTZ00121 1711 EAEEKKKAEELKKAEEENKIKAEEAKKEAEE--------------DKKKAEEAKKDEEEK-----------------KKI 1759

                         250
                  ....*....|....*..
gi 300539701 1170 AQLTQECQEQRERLPQE 1186
Cdd:PTZ00121 1760 AHLKKEEEKKAEEIRKE 1776

EFh_PRIP

cd16206

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...

206-304

8.19e-05

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

Pssm-ID: 320036 [Multi-domain] Cd Length: 143 Bit Score: 44.12 E-value: 8.19e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  206 DEFpLEIFErflnKLCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrsSQARLLIEKYETNKQF 285
Cdd:cd16206    59 DEF-VELFK----ELATRPEIYFLLVRY-ASNKDYLTVDDLMLFLEAEQGMTGVTK--------EKCLEIINKYEPSEEG 124

                          90
                  ....*....|....*....
gi 300539701  286 LERDQMSMEGFSRYLGGEE 304
Cdd:cd16206   125 REKGQLGIDGFTRYLLSEE 143

EFh_PRIP2

cd16223

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...

203-300

9.61e-05

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

Pssm-ID: 320053 [Multi-domain] Cd Length: 144 Bit Score: 43.74 E-value: 9.61e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  203 IRPDEFpLEIFerflNKLCLRPDIDKILLEIGAKgKPYLTLEQLMDFINQKQRDPRLNEvlypplrssQARL-LIEKYET 281
Cdd:cd16223    56 VTKEEF-IEVF----HELCTRPEIYFLLVQFSSN-KEFLDTKDLMMFLEAEQGMAHVTE---------EISLdIIHKYEP 120

                          90
                  ....*....|....*....
gi 300539701  282 NKQFLERDQMSMEGFSRYL 300
Cdd:cd16223   121 SKEGQEKGWLSLDGFTNYL 139

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

211-304

9.66e-05

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

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 43.57 E-value: 9.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  211 EIfERFLNKLCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRdprlnEVLYPPLrssqARLLIEKYETNKQFLERDQ 290
Cdd:cd16217    57 EI-EEFYKLLTKREEIDVIFGEY-AKSDGTMSRNNLLNFLQEEQR-----EEVAPAY----ALSLIEKYEPDETAKAQRQ 125

                          90
                  ....*....|....
gi 300539701  291 MSMEGFSRYLGGEE 304
Cdd:cd16217   126 MTKDGFLMYLLSPE 139

PTZ00121

MAEBL; Provisional

956-1189

1.60e-04

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 46.29 E-value: 1.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRSHKAMVKLRSRQDRDLRELHKKHQ--RKAVALTRRLLDGL----AQARAEGKcRPSPSALGKATNS----EDVKEE 1025
Cdd:PTZ00121 1401 EEDKKKADELKKAAAAKKKADEAKKKAEekKKADEAKKKAEEAKkadeAKKKAEEA-KKAEEAKKKAEEAkkadEAKKKA 1479

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1026 EEAKQYREFQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKevvldthTTQFKRLKElnEREKKELQKILDRKRNNS 1105
Cdd:PTZ00121 1480 EEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKK-------ADEAKKAEE--AKKADEAKKAEEKKKADE 1550

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1106 ISEAKTREKhKKEVELTEINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKLLAQLTQECQEQRERLPQ 1185
Cdd:PTZ00121 1551 LKKAEELKK-AEEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAE 1629


                  ....
gi 300539701 1186 EIRR 1189
Cdd:PTZ00121 1630 EEKK 1633

EFh_PI-PLCdelta3

cd16218

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...

165-300

1.60e-04

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

Pssm-ID: 320048 [Multi-domain] Cd Length: 138 Bit Score: 43.20 E-value: 1.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  165 NQDGRIP---VKNILKMFSADKKRVETAL--ESCglnfNRVESIRPDEfpLEIfERFLNKLCLRPDIDKILLEIGAKGKp 239
Cdd:cd16218    12 NKDGKMSfeeIKDLLQMINIDLNEQYAYQlfKEC----DRSNDDRLEE--HEI-EEFCRRLMQRPELEEIFHQYSGEDC- 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300539701  240 YLTLEQLMDFINQKQRDPRLnevlypplrsSQARLLIEKYETNKQFLERDQMSMEGFSRYL 300
Cdd:cd16218    84 VLSAEELREFLKDQGEDASL----------VHAKELIQTYELNEKAKQHQLMTLDGFTMYM 134

EFh_PI-PLCeta

cd16205

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...

161-300

2.05e-04

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: 42.75 E-value: 2.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  161 KLQVNqdgrIPVKNILKMFsadkKRVETALESCGLNFnrvesirpdefplEIFERFLNKLCLRPDIDKILLEIGAKgKPY 240
Cdd:cd16205    28 KLNVN----LPRRKVRQMF----KEADTDDNQGTLDF-------------EEFCAFYKMMSTRRELYLLLLSYSNK-KDY 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  241 LTLEQLMDFINQKQRdprLNEVlypPLRSSQArlLIEKYETNKQFLERDQMSMEGFSRYL 300
Cdd:cd16205    86 LTLEDLARFLEVEQK---MTNV---TLEYCLD--IIEKFEPSEENKKNGLLGIDGFTNYM 137

YhaN

COG4717

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

967-1150

2.95e-04

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 45.14 E-value: 2.95e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  967 LRSRQDRDLRELHKKHQRKavalTRRLLDGLAQARAEGKcrpspsalgkatnsedvKEEEEAKQYREFQNRQVQSLLELR 1046
Cdd:COG4717    47 LLERLEKEADELFKPQGRK----PELNLKELKELEEELK-----------------EAEEKEEEYAELQEELEELEEELE 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1047 EAQADVETKR----KLEHLRQAHQRLKEVV-LDTHTTQF-KRLKELNEREK--KELQKILDRKRNNsISEAKTREKHKKE 1118
Cdd:COG4717   106 ELEAELEELReeleKLEKLLQLLPLYQELEaLEAELAELpERLEELEERLEelRELEEELEELEAE-LAELQEELEELLE 184

                         170       180       190
                  ....*....|....*....|....*....|..
gi 300539701 1119 vELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:COG4717   185 -QLSLATEEELQDLAEELEELQQRLAELEEEL 215

Smc

COG1196

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...

1026-1150

3.49e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 44.93 E-value: 3.49e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1026 EEAKQYREFQN----RQVQ-SLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDR 1100
Cdd:COG1196   210 EKAERYRELKEelkeLEAElLLLKLRELEAELEELEAELEELEAELEELEAELAELEAELEELRLELEELELELEEAQAE 289

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 300539701 1101 KRNNSISEAKTREKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:COG1196   290 EYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEEL 339

PI-PLCc_bacteria_like

cd08557

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...

316-441

3.74e-04

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

Pssm-ID: 176500 [Multi-domain] Cd Length: 271 Bit Score: 44.01 E-value: 3.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  316 SMDMTQPLSAYFINSSHN--TYLTAGQLAGPSSVEMY-----RQALLWGCRCVELDVWKgRPPEEEPFITHGFTMTTEVP 388
Cdd:cd08557     2 ALLDDLPLSQLSIPGTHNsyAYTIDGNSPIVSKWSKTqdlsiTDQLDAGVRYLDLRVAY-DPDDGDLYVCHGLFLLNGQT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701  389 LRDVLEAIaeAAF-KTSPY-PVILSFENHV--DSAKQQAKMAEYCRSIFGDALLIDP 441
Cdd:cd08557    81 LEDVLNEV--KDFlDAHPSeVVILDLEHEYggDNGEDHDELDALLRDVLGDPLYRPP 135

Smc

COG1196

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...

956-1145

7.23e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 44.16 E-value: 7.23e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRSHKAMVKLRSRQDRDLRELHKKHQRKAVALTRRLLDGLAQARAEgkcrpspSALGKATNSEDVKEEEEAKQYREFQ 1035
Cdd:COG1196   317 RLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAE-------EALLEAEAELAEAEEELEELAEELL 389

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1036 NRQvQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDRKRNNSISEAKTREKH 1115
Cdd:COG1196   390 EAL-RAAAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAELEEEEEALLELLAEL 468

                         170       180       190
                  ....*....|....*....|....*....|
gi 300539701 1116 KKEVELTEINRRHITESVNSIRRLEEAQKQ 1145
Cdd:COG1196   469 LEEAALLEAALAELLEELAEAAARLLLLLE 498

EFh_PI-PLCzeta

cd16204

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...

197-304

1.74e-03

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

Pssm-ID: 320034 [Multi-domain] Cd Length: 142 Bit Score: 40.18 E-value: 1.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  197 FNRVESIRPDEFPLEIFERFLNKLCLRPDIDKILlEIGAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrsSQARLLI 276
Cdd:cd16204    44 FKKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIF-NTYSENRKILSAPNLVGFLKKEQFQDEADE--------TIASELI 114

                          90       100
                  ....*....|....*....|....*...
gi 300539701  277 EKYETNKQFLERDQMSMEGFSRYLGGEE 304
Cdd:cd16204   115 AKYEPIEEVRKRKQMSFEGFIRYMTSED 142

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

1020-1187

2.15e-03

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 42.36 E-value: 2.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1020 EDVKEEEEA--KQYREFQNRQVQSLLELREAQADVETKRK-LEHLRQAHQRLKEvvldthttqfkRLKELNEREKKELQK 1096
Cdd:TIGR02169  684 EGLKRELSSlqSELRRIENRLDELSQELSDASRKIGEIEKeIEQLEQEEEKLKE-----------RLEELEEDLSSLEQE 752

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1097 ILDRKR----NNSISEAKTREKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKL---- 1168
Cdd:TIGR02169  753 IENVKSelkeLEARIEELEEDLHKLEEALNDLEARLSHSRIPEIQAELSKLEEEVSRIEARLREIEQKLNRLTLEKeyle 832

                          170       180
                   ....*....|....*....|....
gi 300539701  1169 -----LAQLTQECQEQRERLPQEI 1187
Cdd:TIGR02169  833 keiqeLQEQRIDLKEQIKSIEKEI 856

PTZ00121

MAEBL; Provisional

956-1150

2.69e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 42.44 E-value: 2.69e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRSHKAMVKLRSRQDRDLRELHKKHQRKAVAltrrllDGLAQARAEGKCRpspsalgKATNSEDVKEEEEAKQYREFQ 1035
Cdd:PTZ00121 1480 EEAKKADEAKKKAEEAKKKADEAKKAAEAKKKA------DEAKKAEEAKKAD-------EAKKAEEAKKADEAKKAEEKK 1546

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1036 N-RQVQSLLELREAQA--DVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDRKRNNSI--SEAK 1110
Cdd:PTZ00121 1547 KaDELKKAEELKKAEEkkKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIkaEELK 1626

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 300539701 1111 TREKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:PTZ00121 1627 KAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKIKAAEE 1666

SMC_prok_A

TIGR02169

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...

956-1150

3.23e-03

Pssm-ID: 274009 [Multi-domain] Cd Length: 1164 Bit Score: 41.98 E-value: 3.23e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701   956 EELRSHKAMVKLRSRQDRDLRELHK---KHQRKAVALTRRL---LDGLAQARAEGKCRPSPSALGKATNSEDVKEE-EEA 1028
Cdd:TIGR02169  227 ELLKEKEALERQKEAIERQLASLEEeleKLTEEISELEKRLeeiEQLLEELNKKIKDLGEEEQLRVKEKIGELEAEiASL 306

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1029 KQYREFQNRQVQSLlELREAQADVETKRKLEHLRQahqrlkevvLDTHTTQFKRLKELNEREKKELQKILDRKRNNSISE 1108
Cdd:TIGR02169  307 ERSIAEKERELEDA-EERLAKLEAEIDKLLAEIEE---------LEREIEEERKRRDKLTEEYAELKEELEDLRAELEEV 376

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 300539701  1109 AK----TREKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHERL 1150
Cdd:TIGR02169  377 DKefaeTRDELKDYREKLEKLKREINELKRELDRLQEELQRLSEEL 422

PRK00409

recombination and DNA strand exchange inhibitor protein; Reviewed

1026-1151

3.49e-03

recombination and DNA strand exchange inhibitor protein; Reviewed

Pssm-ID: 234750 [Multi-domain] Cd Length: 782 Bit Score: 41.74 E-value: 3.49e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1026 EEAK-QYREFQ---NRQVQSLLELREAQadvETKRK-LEHLRQAHQRLKEVVLdthttqfKRLKELNEREKKELQKiLDR 1100
Cdd:PRK00409  505 EEAKkLIGEDKeklNELIASLEELEREL---EQKAEeAEALLKEAEKLKEELE-------EKKEKLQEEEDKLLEE-AEK 573

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 300539701 1101 KRNNSISEAK------TREKHKKEVELTEINRRHITESvnSIRRLEEAQKQRHERLV 1151
Cdd:PRK00409  574 EAQQAIKEAKkeadeiIKELRQLQKGGYASVKAHELIE--ARKRLNKANEKKEKKKK 628

Smc

COG1196

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...

968-1189

3.74e-03

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

Pssm-ID: 440809 [Multi-domain] Cd Length: 983 Bit Score: 41.46 E-value: 3.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  968 RSRQDRDLRELHKkhQRKAVALTRRLLDGLAQARAEGKcRPSPSALGKATNSEDVKEEEEAKQYREFQNRQVQSLLELRE 1047
Cdd:COG1196   555 DDEVAAAAIEYLK--AAKAGRATFLPLDKIRARAALAA-ALARGAIGAAVDLVASDLREADARYYVLGDTLLGRTLVAAR 631

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1048 AQADVETKRKLEHLRQAHQRLKEVVLDT------HTTQFKRLKELNEREKKELQKILDRKRNNSISEAKTREKHKKEVEL 1121
Cdd:COG1196   632 LEAALRRAVTLAGRLREVTLEGEGGSAGgsltggSRRELLAALLEAEAELEELAERLAEEELELEEALLAEEEEERELAE 711

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 300539701 1122 TEINRRHITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKLLAQLtQECQEQRERLPQEIRR 1189
Cdd:COG1196   712 AEEERLEEELEEEALEEQLEAEREELLEELLEEEELLEEEALEELPEPPDL-EELERELERLEREIEA 778

YhaN

COG4717

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

1024-1189

3.90e-03

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

Pssm-ID: 443752 [Multi-domain] Cd Length: 641 Bit Score: 41.29 E-value: 3.90e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1024 EEEEAKQYREFQNRQVQSLLELREAQADV-ETKRKLEHLRQAHQRLKEVVldthttqfKRLKELnEREKKELQKILDRKR 1102
Cdd:COG4717    52 EKEADELFKPQGRKPELNLKELKELEEELkEAEEKEEEYAELQEELEELE--------EELEEL-EAELEELREELEKLE 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1103 NNSISEAKTREKHKKEVELTEINRR--HITESVNSIRRLEEAQKQRHERLVAGQQQVLQQLEEEEPKLLAQLtQECQEQR 1180
Cdd:COG4717   123 KLLQLLPLYQELEALEAELAELPERleELEERLEELRELEEELEELEAELAELQEELEELLEQLSLATEEEL-QDLAEEL 201


                  ....*....
gi 300539701 1181 ERLPQEIRR 1189
Cdd:COG4717   202 EELQQRLAE 210

COG4913

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

959-1189

4.03e-03

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

Pssm-ID: 443941 [Multi-domain] Cd Length: 1089 Bit Score: 41.44 E-value: 4.03e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  959 RSHKAMVKLRSRQD--RDLRELHKKHQRKAVALT--RRLLDGLAQARAEgkcrpspsalgkatnsedvkeeeeaKQYREF 1034
Cdd:COG4913   239 RAHEALEDAREQIEllEPIRELAERYAAARERLAelEYLRAALRLWFAQ-------------------------RRLELL 293

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1035 QNRQVQSLLELREAQADVET-KRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKIlDRKRNN--------S 1105
Cdd:COG4913   294 EAELEELRAELARLEAELERlEARLDALREELDELEAQIRGNGGDRLEQLEREIERLERELEER-ERRRARleallaalG 372

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1106 ISEAKTREkhkkevELTEiNRRHITESVNSIRRLEEAQKQRHERLVAGQqqvlqqleeeepkllaqltQECQEQRERLPQ 1185
Cdd:COG4913   373 LPLPASAE------EFAA-LRAEAAALLEALEEELEALEEALAEAEAAL-------------------RDLRRELRELEA 426


                  ....
gi 300539701 1186 EIRR 1189
Cdd:COG4913   427 EIAS 430

PTZ00121

MAEBL; Provisional

956-1152

4.73e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 41.28 E-value: 4.73e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  956 EELRSHKAMVKLRSRQDRDLRELHKK---HQRKAVALTRRLLDGLAQARAEGKCRPSPSALGKATNSEDVKEEEEAKQYR 1032
Cdd:PTZ00121 1374 EEAKKKADAAKKKAEEKKKADEAKKKaeeDKKKADELKKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKA 1453

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1033 EFQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKKELQKILDRKRNNsisEAKTR 1112
Cdd:PTZ00121 1454 EEAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKAD---EAKKA 1530

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 300539701 1113 EKHKKEVELT---------EINRRHITESVNSIRRLEEAQKQRHERLVA 1152
Cdd:PTZ00121 1531 EEAKKADEAKkaeekkkadELKKAEELKKAEEKKKAEEAKKAEEDKNMA 1579

MAT1

pfam06391

CDK-activating kinase assembly factor MAT1; MAT1 is an assembly/targeting factor for ...

1017-1135

5.98e-03

CDK-activating kinase assembly factor MAT1; MAT1 is an assembly/targeting factor for cyclin-dependent kinase-activating kinase (CAK), which interacts with the transcription factor TFIIH. The domain found to the N-terminal side of this domain is a C3HC4 RING finger.

Pssm-ID: 461894 [Multi-domain] Cd Length: 202 Bit Score: 39.53 E-value: 5.98e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1017 TNSEDVKE-EEEAKQYREfQNRQVQSLLELREAQADVEtkrkLEHLRQAHQRLKEvvldthttqfKRLKELN-----ERE 1090
Cdd:pfam06391   58 TNGIDVEEtEKKIEQYEK-ENKDLILKNKMKLSQEEEE----LEELLELEKREKE----------ERRKEEKqeeeeEKE 122

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 300539701  1091 KKELQK--ILDRKRNNSISEAKTREKHKKEVELTEINRRHITESVNS 1135
Cdd:pfam06391  123 KKEKAKqeLIDELMTSNKDAEEIIAQHKKTAKKRKSERRRKLEELNR 169

PTZ00121

MAEBL; Provisional

949-1149

7.58e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 40.89 E-value: 7.58e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  949 EVTPTPLEELRSHKAMVKLRSRQDRDLRELHKKHQRKAV-ALTRRLLDGLAQARAEGKCRPSPSALGKATNSEDVKEEEE 1027
Cdd:PTZ00121 1234 EAKKDAEEAKKAEEERNNEEIRKFEEARMAHFARRQAAIkAEEARKADELKKAEEKKKADEAKKAEEKKKADEAKKKAEE 1313

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1028 AKQYREFQNRQVQSLLELREAQADVETKRKLEHLRQAHQRLKEVVLDTHTTQFKRLKELNEREKK---ELQKILDRKRNN 1104
Cdd:PTZ00121 1314 AKKADEAKKKAEEAKKKADAAKKKAEEAKKAAEAAKAEAEAAADEAEAAEEKAEAAEKKKEEAKKkadAAKKKAEEKKKA 1393

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 300539701 1105 SISEAKTREKHKK--EVELTEINRRHITES---VNSIRRLEEAQKQRHER 1149
Cdd:PTZ00121 1394 DEAKKKAEEDKKKadELKKAAAAKKKADEAkkkAEEKKKADEAKKKAEEA 1443

C2C_MCTP_PRT_plant

cd04019

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

729-817

8.04e-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: 38.42 E-value: 8.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  729 LRVKVISGQ--FLSDKKV--GIYVEVDMfGLPVdtrrkYRTRTSQGNSFNPVWDE-------EPFDFPKVVlptlaSL-- 795
Cdd:cd04019     2 LRVTVIEAQdlVPSDKNRvpEVFVKAQL-GNQV-----LRTRPSQTRNGNPSWNEelmfvaaEPFEDHLIL-----SVed 70

                          90       100
                  ....*....|....*....|..
gi 300539701  796 RIAAFEEGgkFVGHRILPVSAI 817
Cdd:cd04019    71 RVGPNKDE--PLGRAVIPLNDI 90

EFh_PRIP1

cd16222

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...

211-304

8.92e-03

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

Pssm-ID: 320052 [Multi-domain] Cd Length: 143 Bit Score: 37.92 E-value: 8.92e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  211 EIFERFLNKLCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrsSQARLLIEKYETNKQFLERDQ 290
Cdd:cd16222    59 EEFCEAYSELCTRPEVYFLLVQI-SKNKEYLDAKDLMLFLEAEQGMTHITE--------EMCLDIIRRYEPSQEGRLKGF 129

                          90
                  ....*....|....
gi 300539701  291 MSMEGFSRYLGGEE 304
Cdd:cd16222   130 LGIDGFTQYLLSSE 143

Caldesmon

pfam02029

Caldesmon;

1014-1144

9.28e-03

Caldesmon;

Pssm-ID: 460421 [Multi-domain] Cd Length: 495 Bit Score: 40.24 E-value: 9.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  1014 GKATNSEDVKEEEEAKQYREFQNRQVQSLLELrEAQADVETKRKLEHLRQAHQrlkevvlDTHTTQFKRLKELN---ERE 1090
Cdd:pfam02029  207 VKSQNGEEEVTKLKVTTKRRQGGLSQSQEREE-EAEVFLEAEQKLEELRRRRQ-------EKESEEFEKLRQKQqeaELE 278

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 300539701  1091 KKELQKILDRKRNNSISEAKTREKHKKEVEL-TEINRRHITESVnSIRRLEEAQK 1144
Cdd:pfam02029  279 LEELKKKREERRKLLEEEEQRRKQEEAERKLrEEEEKRRMKEEI-ERRRAEAAEK 332

PRK03918

DNA double-strand break repair ATPase Rad50;

1015-1146

9.74e-03

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 40.43 E-value: 9.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701 1015 KATNSEDVKEEEEAKQYREfQNRQVQSLLELREAQADVETKRK-LEHLRQA-----HQRLKEVVLD---THTTQFKRLKE 1085
Cdd:PRK03918  606 ELKDAEKELEREEKELKKL-EEELDKAFEELAETEKRLEELRKeLEELEKKyseeeYEELREEYLElsrELAGLRAELEE 684

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300539701 1086 LNEReKKELQKILDRKRNnsisEAKTREKHKKEVELTEINRRHITESVNSIRRLEEAQKQR 1146
Cdd:PRK03918  685 LEKR-REEIKKTLEKLKE----ELEEREKAKKELEKLEKALERVEELREKVKKYKALLKER 740

PTZ00121

MAEBL; Provisional

998-1148

9.76e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 40.51 E-value: 9.76e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300539701  998 AQARAEGKCRPSPSALGKATNSEDVKEEEEAKQYREfqnrqVQSLLELREAQAD--VETKRKLEHLRQAHQRLKevvldt 1075
Cdd:PTZ00121 1103 AKKTETGKAEEARKAEEAKKKAEDARKAEEARKAED-----ARKAEEARKAEDAkrVEIARKAEDARKAEEARK------ 1171

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300539701 1076 hTTQFKRLKElnEREKKELQKILDRKRNNSISEAKTREKHKKEVELTEINRRHITESVNSIRRLEEAQKQRHE 1148
Cdd:PTZ00121 1172 -AEDAKKAEA--ARKAEEVRKAEELRKAEDARKAEAARKAEEERKAEEARKAEDAKKAEAVKKAEEAKKDAEE 1241

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