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Conserved domains on  [gi|2782110376|ref|XP_066907870|]
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uncharacterized protein [Halyomorpha halys]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 2616-3034 5.11e-139

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: 434.66  E-value: 5.11e-139
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDEPCLPSPAQLKYRILIKNKKlmadippay 2775
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK--------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2776 plqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasq 2855
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2856 qplemdwvmeddgiapkkkqiARELSDLVIYIQAIKFRQLNTIspnssvrckrasavpsvatsamlkkgsggslvgptgs 2935
Cdd:cd08596    152 ---------------------APELSDLVIYCQAVKFPGLSTP------------------------------------- 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2936 psssdshsypkqrvntyhPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVAL 3015
Cdd:cd08596    174 ------------------KCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVAL 235

                          410
                   ....*....|....*....
gi 2782110376 3016 NYQTEDSALHINTAMFEQN 3034
Cdd:cd08596    236 NYQTDDLPMHLNAAMFEAN 254
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 2431-2603 2.51e-74

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


:

Pssm-ID: 320033  Cd Length: 174  Bit Score: 245.70  E-value: 2.51e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2431 HFRHGSItHETQLDFIDFVALFRSFSLRARKDLKDLFDQFAMSCRSMSDSSLNDGSLKSSPEHSSRA-PKIGLLTRNSSA 2509
Cdd:cd16203      5 GFSIGEV-QDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAPLKRSLSISESYSGLfPDLDLLTRNTSL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2510 DLMDYRNTpamQKKKIFDAIATSSIVTNCAGVDTSKSQVITLSNFAKFLETKQLEQHTEEEVKELIQRHEPDPTLRSHNC 2589
Cdd:cd16203     84 DGLFISKK---QQKKIYDAIAAASIVTNGAGVDSSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEPDPILRSKNC 160

                          170
                   ....*....|....
gi 2782110376 2590 LSFEGFARFLMDKE 2603
Cdd:cd16203    161 LSFEGFARYLMDKD 174
PLN02952 super family cl31960
phosphoinositide phospholipase C
 2549-3184 3.14e-51

phosphoinositide phospholipase C


The actual alignment was detected with superfamily member PLN02952:

Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 193.29  E-value: 3.14e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2549 ITLSNFAKFLETKQLEQHT-----EEEVKELIQRHEpDPTLRSHNCLSFEGFARFLMDKENFAFVCEKVSPDekeMEYPL 2623
Cdd:PLN02952    54 MGADQLRRFLVLHQDELDCtlaeaQRIVEEVINRRH-HVTRYTRHGLNLDDFFHFLLYDDLNGPITPQVHHD---MTAPL 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2624 SHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSP-QIYHGHTFTTKIQFKSVVEAINRSAFVTS 2702
Cdd:PLN02952   130 SHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFSSS 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2703 PYPVILSIENHCSLQQQTRMAHIFQSVFGDKLvtkFLFEADFSDEpcLPSPAQLKYRILIKNKklmadiPPAYPLQrgkt 2782
Cdd:PLN02952   210 PYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESDSLVQ--FPSPESLKHRIIISTK------PPKEYLE---- 274

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2783 rshqaprassiisnTSGGSVNDDFSDEDDDDDDDDDENIEATvtdcprtdSLSSHDSALKTPSRStgkspasqqplemDW 2862
Cdd:PLN02952   275 --------------SSGPIVIKKKNNVSPSGRNSSEETEEAQ--------TLESMLFEQEADSRS-------------DS 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2863 VMEDDgiapKKKQIARELSDLVIYIQAIKfrqlntisPNSSVRCKRASAVPSVatsamlkkgsggslvgptgspsssdsh 2942
Cdd:PLN02952   320 DQDDN----KSGELQKPAYKRLITIHAGK--------PKGTLKDAMKVAVDKV--------------------------- 360

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2943 sypkQRVntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQTEDS 3022
Cdd:PLN02952   361 ----RRL----------SLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGK 426

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3023 ALHINTAMFEQNGRCGYVLKPavmrdrTHMMYRRFNpwDKEFDGLHSSQIILNVISGQYV--------CQNNLTA----N 3090
Cdd:PLN02952   427 SLWLMHGMFRANGGCGYLKKP------DFLMKKGFH--DEVFDPKKKLPVKKTLKVKVYLgdgwrldfSHTHFDSysppD 498

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3091 VIVEIEMIGIPVDCNKQKTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMPLKCLRPGYRHV 3167
Cdd:PLN02952   499 FYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREydmSEKDDFGGQTCLPVSELRPGIRSV 577

                          650
                   ....*....|....*..
gi 2782110376 3168 RMRTPQNQPLQLSTLFV 3184
Cdd:PLN02952   578 PLHDKKGEKLKNVRLLM 594
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3219-3315 6.48e-47

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


:

Pssm-ID: 340634  Cd Length: 97  Bit Score: 164.05  E-value: 6.48e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3219 RRMFFLMVYGVVPDETSTILKITQESTTHEVVLQALQKAGQSADKVNDYVLVEEVSRGWDRKDREAPASQRVLDPQECPL 3298
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRKETEKPGSQRILDMDEKIL 80

                           90
                   ....*....|....*..
gi 2782110376 3299 QAQAQWQGEGKFLLKRL 3315
Cdd:cd17114     81 QAQSKWKGSGRFILKKL 97
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
 3343-3431 2.20e-41

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


The actual alignment was detected with superfamily member cd01780:

Pssm-ID: 475130  Cd Length: 102  Bit Score: 148.63  E-value: 2.20e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3343 DNFLVCVYNVSPEIPYAILKMPQSACAQDVLAQALVKARRMED-PTRFILLEELEWSANAK-----------VQRILADD 3410
Cdd:cd01780      2 DTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDiPSDFVLVEELEKEPTSDkssskssssktEQRVLGDQ 81

                           90       100
                   ....*....|....*....|.
gi 2782110376 3411 ENIYRTQSQWQTIGRFILRER 3431
Cdd:cd01780     82 ENVYQAQSRWKGAGKFILKLR 102
RasGEF super family cl02485
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1818-1988 1.12e-21

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


The actual alignment was detected with superfamily member smart00147:

Pssm-ID: 470590  Cd Length: 242  Bit Score: 96.93  E-value: 1.12e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1818 LLHFPEEVALSLAQEEDALFYQVPPIDYLRQVTLDLGGapppqppqpHDHHRASVRSLIKRFNEVSSWVTHLIISQPTHE 1897
Cdd:smart00147    2 LLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSK---------KSPSPLNLEAFIRRFNEVSNWVATEILKQTTPK 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1898 DRKSVLSCILRVALFSWNIGNFNGAMEIVAGLKSTKLKPFWLSITEKEPVPTLDF------LSAALLSVEYERALNRALA 1971
Cdd:smart00147   73 DRAELLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFeeleelLSPERNYKNYREALSSCNL 152

                           170
                    ....*....|....*..
gi 2782110376  1972 MPeccVVPFFGSFLRDL 1988
Cdd:smart00147  153 PP---CIPFLGVLLKDL 166
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
463-534 1.05e-11

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 68.83  E-value: 1.05e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARETIPwesVVEM-IERGAQVSLPNRRGVRASDLA 534
Cdd:COG0666    157 LHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLE---IVKLlLEAGADVNAKDNDGKTALDLA 226
B41 super family cl33382
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1504-1686 5.25e-05

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


The actual alignment was detected with superfamily member smart00295:

Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 46.90  E-value: 5.25e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1504 DDHEETDKEYCRLLHM-------VVTGELPCSKEEAAALAGIQLRIEEtwgrphgpisPDDNTLKPISEDKESfllpvpt 1576
Cdd:smart00295   83 PDPNQLKEDPTRLNLLylqvrndILEGRLPCPEEEALLLAALALQAEF----------GDYDEELHDLRGELS------- 145

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1577 fgatrpvsplveeaegaedseggtgaqpprahsllrkcypsrstqvpfmpaghLEDCLPPCYHGTKAmAKLIKEQKRKLF 1656
Cdd:smart00295  146 -----------------------------------------------------LKRFLPKQLLDSRK-LKEWRERIVELH 171

                           170       180       190
                    ....*....|....*....|....*....|
gi 2782110376  1657 HTSIYDSEIQLKKLYIQTCRRLPSHGCKVY 1686
Cdd:smart00295  172 KELIGLSPEEAKLKYLELARKLPTYGVELF 201
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
 185-210 2.23e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


:

Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 37.95  E-value: 2.23e-03
                            10        20
                    ....*....|....*....|....*.
gi 2782110376   185 NALHLAVEYGAVDVLRLLLKYGLEPN 210
Cdd:smart00248    4 TPLHLAAENGNLEVVKLLLDKGADIN 29
 
Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 2616-3034 5.11e-139

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: 434.66  E-value: 5.11e-139
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDEPCLPSPAQLKYRILIKNKKlmadippay 2775
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK--------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2776 plqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasq 2855
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2856 qplemdwvmeddgiapkkkqiARELSDLVIYIQAIKFRQLNTIspnssvrckrasavpsvatsamlkkgsggslvgptgs 2935
Cdd:cd08596    152 ---------------------APELSDLVIYCQAVKFPGLSTP------------------------------------- 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2936 psssdshsypkqrvntyhPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVAL 3015
Cdd:cd08596    174 ------------------KCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVAL 235

                          410
                   ....*....|....*....
gi 2782110376 3016 NYQTEDSALHINTAMFEQN 3034
Cdd:cd08596    236 NYQTDDLPMHLNAAMFEAN 254
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 2619-2764 1.73e-78

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: 256.28  E-value: 1.73e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2619 MEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRSA 2698
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2782110376 2699 FVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEadfsDEPCLPSPAQLKYRILIKN 2764
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPEDLKGKILIKG 142
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 2431-2603 2.51e-74

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


Pssm-ID: 320033  Cd Length: 174  Bit Score: 245.70  E-value: 2.51e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2431 HFRHGSItHETQLDFIDFVALFRSFSLRARKDLKDLFDQFAMSCRSMSDSSLNDGSLKSSPEHSSRA-PKIGLLTRNSSA 2509
Cdd:cd16203      5 GFSIGEV-QDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAPLKRSLSISESYSGLfPDLDLLTRNTSL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2510 DLMDYRNTpamQKKKIFDAIATSSIVTNCAGVDTSKSQVITLSNFAKFLETKQLEQHTEEEVKELIQRHEPDPTLRSHNC 2589
Cdd:cd16203     84 DGLFISKK---QQKKIYDAIAAASIVTNGAGVDSSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEPDPILRSKNC 160

                          170
                   ....*....|....
gi 2782110376 2590 LSFEGFARFLMDKE 2603
Cdd:cd16203    161 LSFEGFARYLMDKD 174
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 2619-2765 1.94e-67

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: 224.85  E-value: 1.94e-67
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  2619 MEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRSA 2698
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2782110376  2699 FVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEADFSdepcLPSPAQLKYRILIKNK 2765
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQLRGKILLKVR 143
PLN02228 PLN02228
Phosphoinositide phospholipase C
 2542-3169 1.18e-51

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 194.10  E-value: 1.18e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2542 DTSKSQVITLSNFAKFLETKQLEQHTE-EEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKENFAF-VCEKVSPDekeM 2619
Cdd:PLN02228    32 AYSRNGKMSFDELLRFVSEVQGERHAGlDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLpMSGQVHHD---M 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2620 EYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDG-SPQIYHGHTFTTKIQFKSVVEAINRSA 2698
Cdd:PLN02228   109 KAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLNAIKDNA 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2699 FVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKlvtkfLFEADFSDEPCLPSPAQLKYRILIKNKklmadiPPAYPLQ 2778
Cdd:PLN02228   189 FQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGM-----LFRCTSESTKHFPSPEELKNKILISTK------PPKEYLE 257

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2779 rgktrshqaprassiiSNTSGGSvnddfsdedddddddddenieatvtdcpRTDSLSShdsalktpsrstgkSPASQqpl 2858
Cdd:PLN02228   258 ----------------SKTVQTT----------------------------RTPTVKE--------------TSWKR--- 276

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2859 emdwvmeddgIAPKKKQIARELSDLviYIQAIKFRQLNTIspnSSVRCKRAsavpsvatsamLKKGSGGSLVGPtgspss 2938
Cdd:PLN02228   277 ----------VADAENKILEEYKDE--ESEAVGYRDLIAI---HAANCKDP-----------LKDCLSDDPEKP------ 324

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2939 sdshsypkQRVntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQ 3018
Cdd:PLN02228   325 --------IRV----------SMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQ 386

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3019 TEDSALHINTAMFEQNGRCGYVLKPAVMRDRTHMmyrrFNP-------------------WDKEFDGLHSSQIIlnvisg 3079
Cdd:PLN02228   387 GHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTL----FDPckrlpikttlkvkiytgegWDLDFHLTHFDQYS------ 456

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3080 qyvcqnnlTANVIVEIEMIGIPVDCNKQKTKvVQRNALNPIW-NESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVM 3155
Cdd:PLN02228   457 --------PPDFFVKIGIAGVPRDTVSYRTE-TAVDQWFPIWgNDEFLFQLRVPELALLWFKVQDydnDTQNDFAGQTCL 527

                          650
                   ....*....|....
gi 2782110376 3156 PLKCLRPGYRHVRM 3169
Cdd:PLN02228   528 PLPELKSGVRAVRL 541
PLN02952 PLN02952
phosphoinositide phospholipase C
 2549-3184 3.14e-51

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 193.29  E-value: 3.14e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2549 ITLSNFAKFLETKQLEQHT-----EEEVKELIQRHEpDPTLRSHNCLSFEGFARFLMDKENFAFVCEKVSPDekeMEYPL 2623
Cdd:PLN02952    54 MGADQLRRFLVLHQDELDCtlaeaQRIVEEVINRRH-HVTRYTRHGLNLDDFFHFLLYDDLNGPITPQVHHD---MTAPL 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2624 SHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSP-QIYHGHTFTTKIQFKSVVEAINRSAFVTS 2702
Cdd:PLN02952   130 SHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFSSS 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2703 PYPVILSIENHCSLQQQTRMAHIFQSVFGDKLvtkFLFEADFSDEpcLPSPAQLKYRILIKNKklmadiPPAYPLQrgkt 2782
Cdd:PLN02952   210 PYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESDSLVQ--FPSPESLKHRIIISTK------PPKEYLE---- 274

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2783 rshqaprassiisnTSGGSVNDDFSDEDDDDDDDDDENIEATvtdcprtdSLSSHDSALKTPSRStgkspasqqplemDW 2862
Cdd:PLN02952   275 --------------SSGPIVIKKKNNVSPSGRNSSEETEEAQ--------TLESMLFEQEADSRS-------------DS 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2863 VMEDDgiapKKKQIARELSDLVIYIQAIKfrqlntisPNSSVRCKRASAVPSVatsamlkkgsggslvgptgspsssdsh 2942
Cdd:PLN02952   320 DQDDN----KSGELQKPAYKRLITIHAGK--------PKGTLKDAMKVAVDKV--------------------------- 360

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2943 sypkQRVntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQTEDS 3022
Cdd:PLN02952   361 ----RRL----------SLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGK 426

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3023 ALHINTAMFEQNGRCGYVLKPavmrdrTHMMYRRFNpwDKEFDGLHSSQIILNVISGQYV--------CQNNLTA----N 3090
Cdd:PLN02952   427 SLWLMHGMFRANGGCGYLKKP------DFLMKKGFH--DEVFDPKKKLPVKKTLKVKVYLgdgwrldfSHTHFDSysppD 498

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3091 VIVEIEMIGIPVDCNKQKTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMPLKCLRPGYRHV 3167
Cdd:PLN02952   499 FYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREydmSEKDDFGGQTCLPVSELRPGIRSV 577

                          650
                   ....*....|....*..
gi 2782110376 3168 RMRTPQNQPLQLSTLFV 3184
Cdd:PLN02952   578 PLHDKKGEKLKNVRLLM 594
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3219-3315 6.48e-47

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


Pssm-ID: 340634  Cd Length: 97  Bit Score: 164.05  E-value: 6.48e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3219 RRMFFLMVYGVVPDETSTILKITQESTTHEVVLQALQKAGQSADKVNDYVLVEEVSRGWDRKDREAPASQRVLDPQECPL 3298
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRKETEKPGSQRILDMDEKIL 80

                           90
                   ....*....|....*..
gi 2782110376 3299 QAQAQWQGEGKFLLKRL 3315
Cdd:cd17114     81 QAQSKWKGSGRFILKKL 97
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3343-3431 2.20e-41

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


Pssm-ID: 340478  Cd Length: 102  Bit Score: 148.63  E-value: 2.20e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3343 DNFLVCVYNVSPEIPYAILKMPQSACAQDVLAQALVKARRMED-PTRFILLEELEWSANAK-----------VQRILADD 3410
Cdd:cd01780      2 DTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDiPSDFVLVEELEKEPTSDkssskssssktEQRVLGDQ 81

                           90       100
                   ....*....|....*....|.
gi 2782110376 3411 ENIYRTQSQWQTIGRFILRER 3431
Cdd:cd01780     82 ENVYQAQSRWKGAGKFILKLR 102
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 3074-3185 2.86e-41

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: 149.23  E-value: 2.86e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3074 LNVISGQYVCQNNLTANVI----VEIEMIGIPV-DCNKQKTKVVQRNALNPIWNESFYFQVMFRDLAFLRFSVLDAST-- 3146
Cdd:cd00275      6 IKIISGQQLPKPKGDKGSIvdpyVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSgd 85

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2782110376 3147 NHMICQRVMPLKCLRPGYRHVRMRTPQNQPLQLSTLFVY 3185
Cdd:cd00275     86 DDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVH 124
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1818-1988 1.12e-21

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 96.93  E-value: 1.12e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1818 LLHFPEEVALSLAQEEDALFYQVPPIDYLRQVTLDLGGapppqppqpHDHHRASVRSLIKRFNEVSSWVTHLIISQPTHE 1897
Cdd:smart00147    2 LLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSK---------KSPSPLNLEAFIRRFNEVSNWVATEILKQTTPK 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1898 DRKSVLSCILRVALFSWNIGNFNGAMEIVAGLKSTKLKPFWLSITEKEPVPTLDF------LSAALLSVEYERALNRALA 1971
Cdd:smart00147   73 DRAELLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFeeleelLSPERNYKNYREALSSCNL 152

                           170
                    ....*....|....*..
gi 2782110376  1972 MPeccVVPFFGSFLRDL 1988
Cdd:smart00147  153 PP---CIPFLGVLLKDL 166
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1836-1988 7.35e-20

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


Pssm-ID: 459872  Cd Length: 179  Bit Score: 89.57  E-value: 7.35e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1836 LFYQVPPIDYLRQVtldlggapppQPPQPHDHHRASVRSLIKRFNEVSSWVTHLIISQPTHEDRKSVLSCILRVALFSWN 1915
Cdd:pfam00617   13 LFRKIKPRELLGSA----------WSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHCRE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1916 IGNFNGAMEIVAGLKST---KLKPFWLSITEKEpVPTLDFLSaALLSVE-----YERALNRalAMPECcvVPFFGSFLRD 1987
Cdd:pfam00617   83 LNNFNSLMAILSGLNSSpisRLKKTWELVSKKY-KKTLEELE-KLMSPSrnfknYREALSS--ASPPC--IPFLGLYLTD 156


                   .
gi 2782110376 1988 L 1988
Cdd:pfam00617  157 L 157
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1818-2096 9.96e-16

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


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 79.60  E-value: 9.96e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1818 LLHF-PEEVALSLAQEEDALFYQVPPIDYLRQVTldlggapppQPPQPHDHHRASVRSLIKRFNEVSSWVTHLIISQPTH 1896
Cdd:cd00155      1 FLSLdPKELAEQLTLLDFELFRKIEPFELLGSLW---------SKKDKNIHLSPNLERFIERFNNLSNWVASEILLCTNP 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1897 EDRKSVLSCILRVALFSWNIGNFNGAMEIVAGLKS---TKLKPFWLSITEKepvpTLDFLSAALLSVE-------YERAL 1966
Cdd:cd00155     72 KKRARLLSKFIQVAKHCRELNNFNSLMAIVSALSSspiSRLKKTWEVLSSK----LKKLFEELEELVDpsrnfknYRKLL 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1967 NRALAMPECcvVPFFGSFLRDlrdilsstpslvvlapagdrthLEFIsdYNGEDHYFtrigPGGLINLDKIYKTQAVMDK 2046
Cdd:cd00155    148 KSVGPNPPC--VPFLGVYLKD----------------------LTFL--HEGNPDFL----EGNLVNFEKRRKIAEILRE 197

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2782110376 2047 IASF-HQHYHKRVRDVetLREQFSTIHtesverpymsednEDAENEMDSYR 2096
Cdd:cd00155    198 IRQLqSNSYELNRDED--ILAFLWKLL-------------ELILNEDELYE 233
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 3071-3168 2.31e-14

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: 71.36  E-value: 2.31e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  3071 QIILNVISGQYV--CQNNLTANVIVEIEMIGipVDCNKQKTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLDA---S 3145
Cdd:smart00239    1 TLTVKIISARNLppKDKGGKSDPYVKVSLDG--DPKEKKKTKVVKNT-LNPVWNETFEFEVPPPELAELEIEVYDKdrfG 77

                            90       100
                    ....*....|....*....|...
gi 2782110376  3146 TNHMICQRVMPLKCLRPGYRHVR 3168
Cdd:smart00239   78 RDDFIGQVTIPLSDLLLGGRHEK 100
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3222-3314 1.93e-12

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


Pssm-ID: 425871  Cd Length: 93  Bit Score: 65.43  E-value: 1.93e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3222 FFLMVYG--VVPDETSTILKITQESTTHEVVLQALQKAGQSADKvNDYVLVEEVSRGwdrkdreapASQRVLDPQECPLQ 3299
Cdd:pfam00788    3 GVLKVYTedGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVLERG---------GGERRLPDDECPLQ 72

                           90
                   ....*....|....*...
gi 2782110376 3300 AQAQWQGEG---KFLLKR 3314
Cdd:pfam00788   73 IQLQWPRDAsdsRFLLRK 90
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3222-3314 2.61e-12

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


Pssm-ID: 214612  Cd Length: 90  Bit Score: 65.01  E-value: 2.61e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  3222 FFLMVY-GVVPDETSTILKITQESTTHEVVLQALQKAGQSADkVNDYVLVEEVSRGwdrkdreapaSQRVLDPQECPLQA 3300
Cdd:smart00314    3 FVLRVYvDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDD-PEEYVLVEVLPDG----------KERVLPDDENPLQL 71

                            90
                    ....*....|....*..
gi 2782110376  3301 QAQWQGEGK---FLLKR 3314
Cdd:smart00314   72 QKLWPRRGPnlrFVLRK 88
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
463-534 1.05e-11

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 68.83  E-value: 1.05e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARETIPwesVVEM-IERGAQVSLPNRRGVRASDLA 534
Cdd:COG0666    157 LHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLE---IVKLlLEAGADVNAKDNDGKTALDLA 226
C2 pfam00168
C2 domain;
3071-3166 2.25e-09

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 57.33  E-value: 2.25e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3071 QIILNVISGQYVCQNNL--TANVIVEIEMIGipvDCNKQKTKVVqRNALNPIWNESFYFQVMFRDLAFLRFSVLDAST-- 3146
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGngTSDPYVKVYLLD---GKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRfg 77

                           90       100
                   ....*....|....*....|.
gi 2782110376 3147 -NHMICQRVMPLKCLRPGYRH 3166
Cdd:pfam00168   78 rDDFIGEVRIPLSELDSGEGL 98
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3343-3432 5.94e-09

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


Pssm-ID: 425871  Cd Length: 93  Bit Score: 55.80  E-value: 5.94e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3343 DNFLVCVY--NVSPEIPYAILKMPQSACAQDVLAQALVKARRMEDPTRFILLEELEwsaNAKVQRILADDENIYRTQSQW 3420
Cdd:pfam00788    1 DDGVLKVYteDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVLE---RGGGERRLPDDECPLQIQLQW 77

                           90
                   ....*....|....*
gi 2782110376 3421 QT---IGRFILRERE 3432
Cdd:pfam00788   78 PRdasDSRFLLRKRD 92
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3343-3432 4.90e-08

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


Pssm-ID: 214612  Cd Length: 90  Bit Score: 53.07  E-value: 4.90e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  3343 DNFLVCVYNVSPE-IPYAILKMPQSACAQDVLAQALVKARRMEDPTRFILLEELEwsanAKVQRILADDENIYRTQSQWQ 3421
Cdd:smart00314    1 DTFVLRVYVDDLPgGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVLP----DGKERVLPDDENPLQLQKLWP 76

                            90
                    ....*....|....
gi 2782110376  3422 TIG---RFILRERE 3432
Cdd:smart00314   77 RRGpnlRFVLRKRD 90
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 2543-2607 1.38e-06

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: 48.78  E-value: 1.38e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2782110376 2543 TSKSQVITLSNFAKFLETKQLE-QHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKENFAF 2607
Cdd:pfam09279   19 SGDGQKLSLDELVDFLREEQREeDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPDGSIF 84
Ank_2 pfam12796
Ankyrin repeats (3 copies);
463-502 9.90e-06

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 46.65  E-value: 9.90e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVAR 502
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKN 40
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1504-1686 5.25e-05

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 46.90  E-value: 5.25e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1504 DDHEETDKEYCRLLHM-------VVTGELPCSKEEAAALAGIQLRIEEtwgrphgpisPDDNTLKPISEDKESfllpvpt 1576
Cdd:smart00295   83 PDPNQLKEDPTRLNLLylqvrndILEGRLPCPEEEALLLAALALQAEF----------GDYDEELHDLRGELS------- 145

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1577 fgatrpvsplveeaegaedseggtgaqpprahsllrkcypsrstqvpfmpaghLEDCLPPCYHGTKAmAKLIKEQKRKLF 1656
Cdd:smart00295  146 -----------------------------------------------------LKRFLPKQLLDSRK-LKEWRERIVELH 171

                           170       180       190
                    ....*....|....*....|....*....|
gi 2782110376  1657 HTSIYDSEIQLKKLYIQTCRRLPSHGCKVY 1686
Cdd:smart00295  172 KELIGLSPEEAKLKYLELARKLPTYGVELF 201
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
3108-3163 1.48e-03

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 44.75  E-value: 1.48e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2782110376 3108 KTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMPLKCLRPG 3163
Cdd:COG5038   1076 KTKVVKKT-LNPVWNEEFTIEVLNRVKDVLTINVNDwdsGEKNDLLGTAEIDLSKLEPG 1133
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
 185-210 2.23e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 37.95  E-value: 2.23e-03
                            10        20
                    ....*....|....*....|....*.
gi 2782110376   185 NALHLAVEYGAVDVLRLLLKYGLEPN 210
Cdd:smart00248    4 TPLHLAAENGNLEVVKLLLDKGADIN 29
PHA02878 PHA02878
ankyrin repeat protein; Provisional
 463-521 5.98e-03

ankyrin repeat protein; Provisional


Pssm-ID: 222939 [Multi-domain]  Cd Length: 477  Bit Score: 42.17  E-value: 5.98e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVAReTIPWESVVEMIERGAQVS 521
Cdd:PHA02878   205 LHHAVKHYNKPIVHILLENGASTDARDKCGNTPLHISVGY-CKDYDILKLLLEHGVDVN 262
Ank_2 pfam12796
Ankyrin repeats (3 copies);
185-211 7.97e-03

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 38.17  E-value: 7.97e-03
                           10        20
                   ....*....|....*....|....*..
gi 2782110376  185 NALHLAVEYGAVDVLRLLLKYGLEPNQ 211
Cdd:pfam12796   63 TALHYAARSGHLEIVKLLLEKGADINV 89
 
Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 2616-3034 5.11e-139

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: 434.66  E-value: 5.11e-139
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDEPCLPSPAQLKYRILIKNKKlmadippay 2775
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK--------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2776 plqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasq 2855
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2856 qplemdwvmeddgiapkkkqiARELSDLVIYIQAIKFRQLNTIspnssvrckrasavpsvatsamlkkgsggslvgptgs 2935
Cdd:cd08596    152 ---------------------APELSDLVIYCQAVKFPGLSTP------------------------------------- 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2936 psssdshsypkqrvntyhPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVAL 3015
Cdd:cd08596    174 ------------------KCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVAL 235

                          410
                   ....*....|....*....
gi 2782110376 3016 NYQTEDSALHINTAMFEQN 3034
Cdd:cd08596    236 NYQTDDLPMHLNAAMFEAN 254
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 2616-3034 1.61e-111

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: 354.45  E-value: 1.61e-111
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08558      1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEadfsDEPCLPSPAQLKYRILIKNKKlmadippay 2775
Cdd:cd08558     81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDE----NPVQLPSPEQLKGKILIKGKK--------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2776 plqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasq 2855
Cdd:cd08558        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2856 qplemdwvmeddgiapkkkqiarelsdlviyiqaikfrqlntispnssvrckrasavpsvatsamlkkgsggslvgptgs 2935
Cdd:cd08558        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2936 psssdshsypkqrvntyhpcYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVAL 3015
Cdd:cd08558    148 --------------------YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVAL 207

                          410
                   ....*....|....*....
gi 2782110376 3016 NYQTEDSALHINTAMFEQN 3034
Cdd:cd08558    208 NYQTPDLPMQLNQGKFEQN 226
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 2618-3034 2.91e-94

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: 306.57  E-value: 2.91e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2618 EMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRS 2697
Cdd:cd08593      3 DMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIREY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2698 AFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfeadFSDEPCLPSPAQLKYRILIKNKKLmadippaypl 2777
Cdd:cd08593     83 AFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPL----DGVLTALPSPEELKGKILVKGKKL---------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2778 qrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqqp 2857
Cdd:cd08593        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2858 lemdwvmeddgiapkkkQIARELSDLVIYIQAIKFRQLntispnssvrckrasavpsvaTSAMLKkgsggslvgptgsps 2937
Cdd:cd08593    149 -----------------KLAKELSDLVIYCKSVHFKSF---------------------EHSKEN--------------- 175

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2938 ssdshsypkqrvntyHPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNY 3017
Cdd:cd08593    176 ---------------YHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNF 240

                          410
                   ....*....|....*..
gi 2782110376 3018 QTEDSALHINTAMFEQN 3034
Cdd:cd08593    241 QTPGEEMDLNDGLFRQN 257
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 2616-3034 9.57e-88

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: 287.70  E-value: 9.57e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDG--DDGSPQIYHGHTFTTKIQFKSVVEA 2693
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2694 INRSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfeADFSDEPC--LPSPAQLKYRILIKNKKlmadi 2771
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPL--EKYPLEPGvpLPSPNDLKRKILIKNKK----- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2772 ppayplqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgks 2851
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2852 pasqqplemdwvmeddgiapkkkqiareLSDLVIYIQAIKFRQLNtispNSSVRCKrasavpsvatsamlkkgsggslvg 2931
Cdd:cd08591    154 ----------------------------LSSLVNYIQPVKFQGFE----VAEKRNK------------------------ 177

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2932 ptgspsssdshsypkqrvntyhpCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQ 3011
Cdd:cd08591    178 -----------------------HYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQ 234

                          410       420
                   ....*....|....*....|...
gi 2782110376 3012 MVALNYQTEDSALHINTAMFEQN 3034
Cdd:cd08591    235 MVALNFQTPDLPMQLNQGKFEYN 257
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 2616-3034 6.14e-87

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: 284.14  E-value: 6.14e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTkflfEADFSDEPCLPSPAQLKYRILIKNKKLmadippay 2775
Cdd:cd08598     81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVT----EPLDGLEDELPSPEELRGKILIKVKKE-------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2776 plqrGKTRSHqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasq 2855
Cdd:cd08598    149 ----SKTPNH---------------------------------------------------------------------- 154

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2856 qplemdwvmeddgiapkkkqiarelsdlviyiqaikfrqlntispnssvrckrasavpsvatsamlkkgsggslvgptgs 2935
Cdd:cd08598        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2936 psssdshsypkqrvntyhpcyqCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVAL 3015
Cdd:cd08598    155 ----------------------IFSLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVAL 212

                          410
                   ....*....|....*....
gi 2782110376 3016 NYQTEDSALHINTAMFEQN 3034
Cdd:cd08598    213 NWQTYDLGMQLNEAMFAGS 231
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 2617-3034 1.16e-83

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: 276.22  E-value: 1.16e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08597      2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEadfsDEPCLPSPAQLKYRILIKNKKLmadippayp 2776
Cdd:cd08597     82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNE----GESYLPSPHDLKGKIIIKGKKL--------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08597        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapKKKQIARELSDLVIYIQAIKFRQLNTISPNssvrckrasavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08597    149 ---------------KRRKLCKELSDLVSLCKSVRFQDFPTSAQN----------------------------------- 178

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkqrvntyHPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08597    179 ----------------QKYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMN 242

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08597    243 YQTPGLMMDLNTGKFLEN 260
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 2619-2764 1.73e-78

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: 256.28  E-value: 1.73e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2619 MEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRSA 2698
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2782110376 2699 FVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEadfsDEPCLPSPAQLKYRILIKN 2764
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPEDLKGKILIKG 142
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 2618-3034 8.30e-77

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: 255.04  E-value: 8.30e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2618 EMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRS 2697
Cdd:cd08592      3 DMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKEH 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2698 AFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfEAdfsDEPCLPSPAQLKYRILIKNKKLmadippaypl 2777
Cdd:cd08592     83 AFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPV-DR---NADQLPSPNQLKRKIIIKHKKL---------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2778 qrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqqp 2857
Cdd:cd08592        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2858 lemdwvmeddgiapkkkqiarelsdlviyiqaikfrqlntispnssvrckrasavpsvatsamlkkgsggslvgptgsps 2937
Cdd:cd08592        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2938 ssdshsypkqrvntyhpCYQCTSLNENSAKK-LCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08592    149 -----------------FYEMSSFPETKAEKyLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALN 211

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08592    212 FQTPDKPMQLNQALFMLN 229
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 2431-2603 2.51e-74

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


Pssm-ID: 320033  Cd Length: 174  Bit Score: 245.70  E-value: 2.51e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2431 HFRHGSItHETQLDFIDFVALFRSFSLRARKDLKDLFDQFAMSCRSMSDSSLNDGSLKSSPEHSSRA-PKIGLLTRNSSA 2509
Cdd:cd16203      5 GFSIGEV-QDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAPLKRSLSISESYSGLfPDLDLLTRNTSL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2510 DLMDYRNTpamQKKKIFDAIATSSIVTNCAGVDTSKSQVITLSNFAKFLETKQLEQHTEEEVKELIQRHEPDPTLRSHNC 2589
Cdd:cd16203     84 DGLFISKK---QQKKIYDAIAAASIVTNGAGVDSSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEPDPILRSKNC 160

                          170
                   ....*....|....
gi 2782110376 2590 LSFEGFARFLMDKE 2603
Cdd:cd16203    161 LSFEGFARYLMDKD 174
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 2617-3034 6.21e-72

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: 242.23  E-value: 6.21e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08630      2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfeadfSDEPC--LPSPAQLKYRILIKNKKLmadippa 2774
Cdd:cd08630     82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPL-----DSLNPeeLPSPEELKGRVLVKGKKL------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2775 yplqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspas 2854
Cdd:cd08630        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2855 qqplemdwvmeddgiapkkkQIARELSDLVIYIQAIKFRQLNTIspnssvrckrasavpsvatsamlkkgsggslvgptg 2934
Cdd:cd08630    150 --------------------QISPELSALAVYCQATRLRTLEPA------------------------------------ 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2935 spsssdshsyPKQRvntyHPCyQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVA 3014
Cdd:cd08630    174 ----------PVQP----QPC-QVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 238

                          410       420
                   ....*....|....*....|
gi 2782110376 3015 LNYQTEDSALHINTAMFEQN 3034
Cdd:cd08630    239 LNFQTPGYEMDLNAGRFLVN 258
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 2617-3034 3.40e-71

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: 240.05  E-value: 3.40e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDG--DDGSPQIYHGHTFTTKIQFKSVVEAI 2694
Cdd:cd08626      2 QDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGkgEDQEPIITHGKAMCTDILFKDVIQAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2695 NRSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfeADFSDEPC--LPSPAQLKYRILIKNKKlmadip 2772
Cdd:cd08626     82 KDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPL--ESHPLEPGvpLPSPNKLKRKILIKNKR------ 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2773 payplqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgksp 2852
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2853 asqqplemdwvmeddgiapkkkqiareLSDLVIYIQAIKFRQLNtispnssvrckrasavpsvatsamlkkgsggslvgp 2932
Cdd:cd08626    154 ---------------------------LSSLVNYAQPVKFQGFD------------------------------------ 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2933 tgspsssdshsYPKQRVNTYHpcyqCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQM 3012
Cdd:cd08626    171 -----------VAEERNIHFN----MSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQM 235

                          410       420
                   ....*....|....*....|..
gi 2782110376 3013 VALNYQTEDSALHINTAMFEQN 3034
Cdd:cd08626    236 VSLNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 2617-3034 9.88e-71

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: 239.07  E-value: 9.88e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08595      2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfeaDFSDEPCLPSPAQLKYRILIKNkklmadippayp 2776
Cdd:cd08595     82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPI---DDPATGELPSPEALKFKILVKN------------ 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08595        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkKKQIARELSDLVIYIQAIKFRQLntispnssvrckrasavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08595    147 ----------------KKKIAKALSDLVIYTKSEKFCSF----------------------------------------- 169

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkQRVNTYHPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08595    170 ----------THSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALN 239

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08595    240 FQTLGAPMDLQNGKFLDN 257
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 2617-3034 4.12e-69

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: 234.18  E-value: 4.12e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfEADfSDEpcLPSPAQLKYRILIKNKKLmadippayp 2776
Cdd:cd08628     82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPL-EAS-ADQ--LPSPTQLKEKIIIKHKKL--------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08628        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkkkqIARELSDLVIYiqaikfrqlntispnssvrCKRASavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08628    149 -------------------IAIELSDLVVY-------------------CKPTS-------------------------- 164

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypKQRVNTYHPCY-QCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVAL 3015
Cdd:cd08628    165 ---------KTKDNLENPDFkEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVAL 235

                          410
                   ....*....|....*....
gi 2782110376 3016 NYQTEDSALHINTAMFEQN 3034
Cdd:cd08628    236 NFQTADKYMQLNHALFSLN 254
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 2617-3034 4.32e-69

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: 234.16  E-value: 4.32e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08633      2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVtkfLFEADFSDEPCLPSPAQLKYRILIKNKKLmadippayp 2776
Cdd:cd08633     82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLD---LSSVISNDCTRLPSPEILKGKILVKGKKL--------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkkkqiARELSDLVIYIQAIKFRQLNTISPNSsvrckrasavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08633    150 --------------------SRALSDLVKYTKSVRVHDIETEATSS---------------------------------- 175

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkqrvntyhpcYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08633    176 -------------------WQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALN 236

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08633    237 YQSEGRMLQLNRAKFSAN 254
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 2617-3034 4.81e-69

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: 234.16  E-value: 4.81e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEAdfsdEPCLPSPAQLKYRILIKNKKLmadippayp 2776
Cdd:cd08629     82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGV----TTSLPSPEQLKGKILLKGKKL--------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08629        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkkkQIARELSDLVIYIQAIKFRQLNTISPNSsvrckrasavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08629    149 ------------------KLVPELSDMIIYCKSVHFGGFSSPGTSG---------------------------------- 176

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkqrvntyHPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08629    177 ----------------QAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALN 240

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08629    241 FQTPGPEMDVYLGCFQDN 258
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 2617-3034 6.32e-69

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: 233.77  E-value: 6.32e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08632      2 QDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVtkfLFEADFSDEPCLPSPAQLKYRILIKNKKLmadippayp 2776
Cdd:cd08632     82 YAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLD---LSSVLTGDPKQLPSPQLLKGKILVKGKKL--------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08632        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkkkqiARELSDLVIYIQaikfrqlntispnssvrckrasavpSVATSAMLKKGSGGSLVgptgsp 2936
Cdd:cd08632    150 --------------------CRDLSDLVVYTN-------------------------SVAAQDIVDDGSTGNVL------ 178

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkqrvntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08632    179 -----------------------SFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALN 235

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08632    236 YQSEGRMMQLNRAKFMVN 253
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 2617-3034 4.26e-68

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: 230.07  E-value: 4.26e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08594      2 QDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDepcLPSPAQLKYRILIKNKKlmadippayp 2776
Cdd:cd08594     82 YAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQ---LPSPQSLKGKILIKGKK---------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08594        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkkkqiarelsdlviyiqaikfrqlntispnssvrckrasavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08594        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkqrvntyhpcYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08594    149 -------------------WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALN 209

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08594    210 YQTEGRMLQLNRAKFRAN 227
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 2619-2765 1.94e-67

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: 224.85  E-value: 1.94e-67
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  2619 MEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRSA 2698
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2782110376  2699 FVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEADFSdepcLPSPAQLKYRILIKNK 2765
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQLRGKILLKVR 143
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 2617-3034 2.11e-66

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: 226.37  E-value: 2.11e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLfeaDFSDEPCLPSPAQLKYRILIKNKKLmadippayp 2776
Cdd:cd08631     82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTL---DGVLPTQLPSPEELRGKILLKGKKI--------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2777 lqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspasqq 2856
Cdd:cd08631        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2857 plemdwvmeddgiapkkkQIARELSDLVIYIQAIKFRQLntispnssvrckrasavpsvatsamlkkgsggslvgptgsp 2936
Cdd:cd08631    150 ------------------RLSPELSDCVIYCKSVSFRSF----------------------------------------- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2937 sssdshsypkQRVNTYHPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALN 3016
Cdd:cd08631    171 ----------THSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALN 240

                          410
                   ....*....|....*...
gi 2782110376 3017 YQTEDSALHINTAMFEQN 3034
Cdd:cd08631    241 FQTAGLEMDLNDGLFRQN 258
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 2617-2771 1.47e-62

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: 214.51  E-value: 1.47e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINR 2696
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2782110376 2697 SAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKflfEADFSDEPcLPSPAQLKYRILIKNKKLMADI 2771
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTK---PVDINADG-LPSPNQLKRKILIKHKKLYRDM 152
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 2617-3034 7.80e-61

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: 210.68  E-value: 7.80e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGD--DGSPQIYHGHTFTTKIQFKSVVEAI 2694
Cdd:cd08624      2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMTTEILFKDAIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2695 NRSAFVTSPYPVILSIENHC-SLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDEPCLPSPAQLKYRILIKNKKLmadipp 2773
Cdd:cd08624     82 AESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKKY------ 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2774 ayplqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspa 2853
Cdd:cd08624        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2854 sqqplemdwvmeddgiapkkkqiaRELSDLVIYIQAIKFrqlntISPNSSVRCKRAsavpsvatsamlkkgsggslvgpt 2933
Cdd:cd08624    156 ------------------------EEMSSLVNYIQPTKF-----VSFEFSAQKNRS------------------------ 182

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2934 gspsssdshsypkqrvntyhpcYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMV 3013
Cdd:cd08624    183 ----------------------YVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMV 240

                          410       420
                   ....*....|....*....|.
gi 2782110376 3014 ALNYQTEDSALHINTAMFEQN 3034
Cdd:cd08624    241 ALNFQTMDLPMQQNMALFEFN 261
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 2618-3034 1.92e-59

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: 206.44  E-value: 1.92e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2618 EMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDG--DDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08625      3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHC-SLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDEPCLPSPAQLKYRILIKNKKlmadippa 2774
Cdd:cd08625     83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK-------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2775 yplqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspas 2854
Cdd:cd08625        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2855 qqplemdwvmeddgiapkkkqiareLSDLVIYIQAIKFRqlntispnssvrckrasavpSVATSAMLKKgsggslvgptg 2934
Cdd:cd08625    155 -------------------------MSTLVNYIEPVKFK--------------------SFEAAAKRNK----------- 178

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2935 spsssdshsypkqrvntyhpCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVA 3014
Cdd:cd08625    179 --------------------FFEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVA 238

                          410       420
                   ....*....|....*....|
gi 2782110376 3015 LNYQTEDSALHINTAMFEQN 3034
Cdd:cd08625    239 LNFQTLDLAMQLNMGVFEYN 258
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 2617-3034 1.22e-56

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: 198.38  E-value: 1.22e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2617 KEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDG--DDGSPQIYHGHTFTTKIQFKSVVEAI 2694
Cdd:cd08623      2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2695 NRSAFVTSPYPVILSIENHC-SLQQQTRMAHIFQSVFGDKLVTKFLFEADFSDEPCLPSPAQLKYRILIKNKKlmadipp 2773
Cdd:cd08623     82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2774 ayplqrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspa 2853
Cdd:cd08623        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2854 sqqplemdwvmeddgiapkkkqiareLSDLVIYIQAIKFRQLNTispnssvrckrasavpsvatsamlkkgsggslvgpt 2933
Cdd:cd08623    155 --------------------------MSNLVNYIQPVKFESFEA------------------------------------ 172

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2934 gspsssdshsypKQRVNTyhpCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMV 3013
Cdd:cd08623    173 ------------SKKRNK---SFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMV 237

                          410       420
                   ....*....|....*....|.
gi 2782110376 3014 ALNYQTEDSALHINTAMFEQN 3034
Cdd:cd08623    238 ALNFQTVDLSMQINMGMYEYN 258
PLN02228 PLN02228
Phosphoinositide phospholipase C
 2542-3169 1.18e-51

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 194.10  E-value: 1.18e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2542 DTSKSQVITLSNFAKFLETKQLEQHTE-EEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKENFAF-VCEKVSPDekeM 2619
Cdd:PLN02228    32 AYSRNGKMSFDELLRFVSEVQGERHAGlDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLpMSGQVHHD---M 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2620 EYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDG-SPQIYHGHTFTTKIQFKSVVEAINRSA 2698
Cdd:PLN02228   109 KAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLNAIKDNA 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2699 FVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKlvtkfLFEADFSDEPCLPSPAQLKYRILIKNKklmadiPPAYPLQ 2778
Cdd:PLN02228   189 FQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGM-----LFRCTSESTKHFPSPEELKNKILISTK------PPKEYLE 257

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2779 rgktrshqaprassiiSNTSGGSvnddfsdedddddddddenieatvtdcpRTDSLSShdsalktpsrstgkSPASQqpl 2858
Cdd:PLN02228   258 ----------------SKTVQTT----------------------------RTPTVKE--------------TSWKR--- 276

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2859 emdwvmeddgIAPKKKQIARELSDLviYIQAIKFRQLNTIspnSSVRCKRAsavpsvatsamLKKGSGGSLVGPtgspss 2938
Cdd:PLN02228   277 ----------VADAENKILEEYKDE--ESEAVGYRDLIAI---HAANCKDP-----------LKDCLSDDPEKP------ 324

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2939 sdshsypkQRVntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQ 3018
Cdd:PLN02228   325 --------IRV----------SMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQ 386

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3019 TEDSALHINTAMFEQNGRCGYVLKPAVMRDRTHMmyrrFNP-------------------WDKEFDGLHSSQIIlnvisg 3079
Cdd:PLN02228   387 GHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTL----FDPckrlpikttlkvkiytgegWDLDFHLTHFDQYS------ 456

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3080 qyvcqnnlTANVIVEIEMIGIPVDCNKQKTKvVQRNALNPIW-NESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVM 3155
Cdd:PLN02228   457 --------PPDFFVKIGIAGVPRDTVSYRTE-TAVDQWFPIWgNDEFLFQLRVPELALLWFKVQDydnDTQNDFAGQTCL 527

                          650
                   ....*....|....
gi 2782110376 3156 PLKCLRPGYRHVRM 3169
Cdd:PLN02228   528 PLPELKSGVRAVRL 541
PLN02952 PLN02952
phosphoinositide phospholipase C
 2549-3184 3.14e-51

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 193.29  E-value: 3.14e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2549 ITLSNFAKFLETKQLEQHT-----EEEVKELIQRHEpDPTLRSHNCLSFEGFARFLMDKENFAFVCEKVSPDekeMEYPL 2623
Cdd:PLN02952    54 MGADQLRRFLVLHQDELDCtlaeaQRIVEEVINRRH-HVTRYTRHGLNLDDFFHFLLYDDLNGPITPQVHHD---MTAPL 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2624 SHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSP-QIYHGHTFTTKIQFKSVVEAINRSAFVTS 2702
Cdd:PLN02952   130 SHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFSSS 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2703 PYPVILSIENHCSLQQQTRMAHIFQSVFGDKLvtkFLFEADFSDEpcLPSPAQLKYRILIKNKklmadiPPAYPLQrgkt 2782
Cdd:PLN02952   210 PYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESDSLVQ--FPSPESLKHRIIISTK------PPKEYLE---- 274

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2783 rshqaprassiisnTSGGSVNDDFSDEDDDDDDDDDENIEATvtdcprtdSLSSHDSALKTPSRStgkspasqqplemDW 2862
Cdd:PLN02952   275 --------------SSGPIVIKKKNNVSPSGRNSSEETEEAQ--------TLESMLFEQEADSRS-------------DS 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2863 VMEDDgiapKKKQIARELSDLVIYIQAIKfrqlntisPNSSVRCKRASAVPSVatsamlkkgsggslvgptgspsssdsh 2942
Cdd:PLN02952   320 DQDDN----KSGELQKPAYKRLITIHAGK--------PKGTLKDAMKVAVDKV--------------------------- 360

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2943 sypkQRVntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQTEDS 3022
Cdd:PLN02952   361 ----RRL----------SLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGK 426

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3023 ALHINTAMFEQNGRCGYVLKPavmrdrTHMMYRRFNpwDKEFDGLHSSQIILNVISGQYV--------CQNNLTA----N 3090
Cdd:PLN02952   427 SLWLMHGMFRANGGCGYLKKP------DFLMKKGFH--DEVFDPKKKLPVKKTLKVKVYLgdgwrldfSHTHFDSysppD 498

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3091 VIVEIEMIGIPVDCNKQKTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMPLKCLRPGYRHV 3167
Cdd:PLN02952   499 FYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREydmSEKDDFGGQTCLPVSELRPGIRSV 577

                          650
                   ....*....|....*..
gi 2782110376 3168 RMRTPQNQPLQLSTLFV 3184
Cdd:PLN02952   578 PLHDKKGEKLKNVRLLM 594
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 2880-3044 3.22e-48

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 168.41  E-value: 3.22e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2880 LSDLVIYIQAIKFRQLNTisPNSsvrckrasavpsvatsamlkkgsggslvgptgspsssdshsypkqrvntyHPCYQCT 2959
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFST--PES--------------------------------------------------KTPNHIF 28

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2960 SLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQTEDSALHINTAMFEQNGRCGY 3039
Cdd:pfam00387   29 SFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQMVALNWQTPDEGMQLNEGMFADNGGCGY 108


                   ....*
gi 2782110376 3040 VLKPA 3044
Cdd:pfam00387  109 VLKPE 113
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3219-3315 6.48e-47

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


Pssm-ID: 340634  Cd Length: 97  Bit Score: 164.05  E-value: 6.48e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3219 RRMFFLMVYGVVPDETSTILKITQESTTHEVVLQALQKAGQSADKVNDYVLVEEVSRGWDRKDREAPASQRVLDPQECPL 3298
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRKETEKPGSQRILDMDEKIL 80

                           90
                   ....*....|....*..
gi 2782110376 3299 QAQAQWQGEGKFLLKRL 3315
Cdd:cd17114     81 QAQSKWKGSGRFILKKL 97
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 2616-3034 3.14e-45

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: 164.47  E-value: 3.14e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2616 EKEMEYPLSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAIN 2695
Cdd:cd08599      1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2696 RSAFVTSPYPVILSIENHCSLQQQTRMAHIFQSVFGDKlvtkfLFEADFSDEP-CLPSPAQLKYRILIKNKklmadiPPA 2774
Cdd:cd08599     81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDK-----LFYPDSEDLPeEFPSPEELKGKILISDK------PPV 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2775 yplqrgktrshqaprassiISNTsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspAS 2854
Cdd:cd08599    150 -------------------IRNS-------------------------------------------------------LS 155

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2855 QQPLemdwvmeddgiapkKKQIARELSDLViyiqaIKFrqlntispnssvrckrasavpsvatsamlkkgsggslvgptg 2934
Cdd:cd08599    156 ETQL--------------KKVIEGEHPTDL-----IEF------------------------------------------ 174

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2935 spsssdshsypkqrvntyhpcyqctslnensakklcrkqtlpliahTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVA 3014
Cdd:cd08599    175 ----------------------------------------------TQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVA 208

                          410       420
                   ....*....|....*....|
gi 2782110376 3015 LNYQTEDSALHINTAMFEQN 3034
Cdd:cd08599    209 LNMQGYDRPLWLNRGKFRAN 228
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 2544-3171 1.01e-43

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 170.60  E-value: 1.01e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2544 SKSQVITLSNFAKFL-ETKQLEQHTEEEVKELIQRHEpdpTLRSHNCLSFEGFARFLMDKENFAFVCEKVSPDekeMEYP 2622
Cdd:PLN02222    35 SENGVMTVDHLHRFLiDVQKQDKATREDAQSIINSAS---SLLHRNGLHLDAFFKYLFGDNNPPLALHEVHHD---MDAP 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2623 LSHYYIASSHNTYLTGHQLKGESSVDLYSQVLLAGCRCVELDCW-DGDDGSPQIYHGHTFTTKIQFKSVVEAINRSAFVT 2701
Cdd:PLN02222   109 ISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWpNSDKDDIDVLHGMTLTTPVGLIKCLKAIRAHAFDV 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2702 SPYPVILSIENHCSLQQQTRMAHIFQSVFGDKLVTKFLFEadfsdepCL---PSPAQLKYRILIKNKklmadiPPayplq 2778
Cdd:PLN02222   189 SDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGE-------SLkefPSPNSLKKRIIISTK------PP----- 250

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2779 rgktRSHQAPRASSIISNTSggsvnddfsdedddddddddenieatvtDCPRTDSLSSHDSALKTPSRSTGKSPASQQPL 2858
Cdd:PLN02222   251 ----KEYKEGKDDEVVQKGK----------------------------DLGDEEVWGREVPSFIQRNKSVDKNDSNGDDD 298

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2859 EMDwvmeDDGIAPKKKQIARELSDLvIYIQAIKfrqlntispnssvrckrasavPSVATSAMLKkgsggslVGPTGSpss 2938
Cdd:PLN02222   299 DDD----DDGEDKSKKNAPPQYKHL-IAIHAGK---------------------PKGGITECLK-------VDPDKV--- 342

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2939 sdshsypkQRVntyhpcyqctSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQ 3018
Cdd:PLN02222   343 --------RRL----------SLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQ 404

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3019 TEDSALHINTAMFEQNGRCGYVLKPAVMRdRTHMMYRRFNP-------------------WDKEFDGLHSSQIIlnvisg 3079
Cdd:PLN02222   405 GYGRSLWLMQGMFRANGGCGYIKKPDLLL-KSGSDSDIFDPkatlpvkttlrvtiymgegWYFDFRHTHFDQYS------ 477

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3080 qyvcqnnlTANVIVEIEMIGIPVDCNKQKTKVVQRNALnPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMP 3156
Cdd:PLN02222   478 --------PPDFYTRVGIAGVPGDTVMKKTKTLEDNWI-PAWDEVFEFPLTVPELALLRLEVHEydmSEKDDFGGQTCLP 548

                          650
                   ....*....|....*
gi 2782110376 3157 LKCLRPGYRHVRMRT 3171
Cdd:PLN02222   549 VWELSQGIRAFPLHS 563
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3343-3431 2.20e-41

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


Pssm-ID: 340478  Cd Length: 102  Bit Score: 148.63  E-value: 2.20e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3343 DNFLVCVYNVSPEIPYAILKMPQSACAQDVLAQALVKARRMED-PTRFILLEELEWSANAK-----------VQRILADD 3410
Cdd:cd01780      2 DTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDiPSDFVLVEELEKEPTSDkssskssssktEQRVLGDQ 81

                           90       100
                   ....*....|....*....|.
gi 2782110376 3411 ENIYRTQSQWQTIGRFILRER 3431
Cdd:cd01780     82 ENVYQAQSRWKGAGKFILKLR 102
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 3074-3185 2.86e-41

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: 149.23  E-value: 2.86e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3074 LNVISGQYVCQNNLTANVI----VEIEMIGIPV-DCNKQKTKVVQRNALNPIWNESFYFQVMFRDLAFLRFSVLDAST-- 3146
Cdd:cd00275      6 IKIISGQQLPKPKGDKGSIvdpyVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSgd 85

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2782110376 3147 NHMICQRVMPLKCLRPGYRHVRMRTPQNQPLQLSTLFVY 3185
Cdd:cd00275     86 DDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVH 124
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 2953-3046 2.91e-41

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: 148.54  E-value: 2.91e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  2953 HPCYQCTSLNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQTEDSALHINTAMFE 3032
Cdd:smart00149   22 NPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQMVALNFQTPDKPMQLNQGMFR 101

                            90
                    ....*....|....
gi 2782110376  3033 QNGRCGYVLKPAVM 3046
Cdd:smart00149  102 ANGGCGYVLKPDFL 115
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 2565-3167 3.06e-40

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 160.26  E-value: 3.06e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2565 QHTEEEVKELIQRHEPDPTLRSHNcLSFEGFARFLMDKENFAFVCEKVspdEKEMEYPLSHYYIASSHNTYLTGHQLKGE 2644
Cdd:PLN02230    67 EEAERIVDEVLRRKHHIAKFTRRN-LTLDDFNYYLFSTDLNPPIADQV---HQNMDAPLSHYFIFTGHNSYLTGNQLSSN 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2645 SSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRSAFVTSPYPVILSIENHCSLQQQTRMAH 2724
Cdd:PLN02230   143 CSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAK 222

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2725 IFQSVFGDKLvtkFLFEADFSDEpcLPSPAQLKYRILIKNKklmadiPPAYPLQRGKTRSHQAPRASSIISNTSGGSvnd 2804
Cdd:PLN02230   223 MITQTFGDML---YYHDSEGCQE--FPSPEELKEKILISTK------PPKEYLEANDAKEKDNGEKGKDSDEDVWGK--- 288

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2805 dfsdedddddddDDENIEATVTDCPRTDSlSSHDSALKTPSRSTGKSPASQQpLEmdwvmeddgiAPKKKQIarelsdlv 2884
Cdd:PLN02230   289 ------------EPEDLISTQSDLDKVTS-SVNDLNQDDEERGSCESDTSCQ-LQ----------APEYKRL-------- 336

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2885 IYIQAIK----FRQLNTISPNSSVRckrasavpsvatsamlkkgsggslvgptgspsssdshsypkqrvntyhpcyqcTS 2960
Cdd:PLN02230   337 IAIHAGKpkggLRMALKVDPNKIRR-----------------------------------------------------LS 363

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2961 LNENSAKKLCRKQTLPLIAHTETQLMRTYPAGMRIDSSNFNPVIFWAFGIQMVALNYQTEDSALHINTAMFEQNGRCGYV 3040
Cdd:PLN02230   364 LSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYV 443

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3041 LKPAVMRD---RTHMMYRRFNPWDK---EFDGLHSSQIILNVISGQYvcQNNLTANVIVEIEMIGIPVDCNKQKTKvVQR 3114
Cdd:PLN02230   444 KKPDFLMDagpNGQDFYPKDNSCPKktlKVKVCMGDGWLLDFKKTHF--DSYSPPDFFVRVGIAGAPVDEVMEKTK-IEY 520

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2782110376 3115 NALNPIWNESFYFQVMFRDLAFLRFSVLDASTNH---MICQRVMPLKCLRPGYRHV 3167
Cdd:PLN02230   521 DTWTPIWNKEFIFPLAVPELALLRVEVHEHDINEkddFGGQTCLPVSEIRQGIHAV 576
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 2619-2775 2.96e-39

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: 148.95  E-value: 2.96e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2619 MEYPLSHYYIASSHNTYLTGHQL-----KGESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFtTKIQFKSVVEA 2693
Cdd:cd00137      4 DTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTF-LDIFLKEVIEA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2694 INRSAFVTSPYPVILSIENHCSL--QQQTRMAHIFQSVFGDklvtkflFEADFSDEPC--LPSPAQLKYRILIKNKKLMA 2769
Cdd:cd00137     83 IAQFLKKNPPETIIMSLKNEVDSmdSFQAKMAEYCRTIFGD-------MLLTPPLKPTvpLPSLEDLRGKILLLNKKNGF 155


                   ....*.
gi 2782110376 2770 DIPPAY 2775
Cdd:cd00137    156 SGPTGS 161
PLN02223 PLN02223
phosphoinositide phospholipase C
 2550-3167 1.38e-23

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 108.57  E-value: 1.38e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2550 TLSNFAKFLETKQLE-----QHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKENFAFVCEKVSpdEKEMEYPLS 2624
Cdd:PLN02223    36 LLPRFIELLDTEKDEdgaglNAAEKIAAELKRRKCDILAFRNLRCLELDHLNEFLFSTELNPPIGDQVR--HHDMHAPLS 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2625 HYYIASSHNTYLTGHQLKGES-SVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFTTKIQFKSVVEAINRSAFV-TS 2702
Cdd:PLN02223   114 HYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLPDGKDGICVRPKWNFEKPLELQECLDAIKEHAFTkCR 193

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2703 PYPVILSIENHCSLQQQTRMAHIFQSVFGDKLvtkflfeadFSDEPC-----LPSPAQLKYRILIknkklmadippaypl 2777
Cdd:PLN02223   194 SYPLIITFKDGLKPDLQSKATQMIDQTFGDMV---------YHEDPQhsleeFPSPAELQNKILI--------------- 249

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2778 qrgktrshqaprassiisntsggsvnddfsdedddddddddenieatvtdcprtdslsshdsalktpsrstgkspaSQQP 2857
Cdd:PLN02223   250 ----------------------------------------------------------------------------SRRP 253

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2858 lemdwvmeddgiaPKKKQIARELSDLVIYIQAIKFRQLNTiSPNSsvrcKRASAVPSVATSAMLKKgsggSLVGPTGSPs 2937
Cdd:PLN02223   254 -------------PKELLYAKADDGGVGVRNELEIQEGPA-DKNY----QSLVGFHAVEPRGMLQK----ALTGKADDI- 310

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2938 ssdshsypkQRVNTYHPcyqctslnensakklcrkqtlPLIAHTETQLMRTYPAGMRIDS-SNFNPVIFWAFGIQMVALN 3016
Cdd:PLN02223   311 ---------QQPGWYER---------------------DIISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALS 360

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3017 YQTEDSALHINTAMFEQNGRCGYVLKPAVMRD--RTHMMYRRFNPwdkefdglhssqIILNVISGQYVCQNNLTA----- 3089
Cdd:PLN02223   361 RKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagPSGVFYPTENP------------VVVKILKVKIYMGDGWIVdfkkr 428

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3090 -------NVIVEIEMIGIPVDCNKQKTkVVQRNALNPIWNESFYFQVMFRDLAFLRFSVLD--ASTNHMIC-QRVMPLKC 3159
Cdd:PLN02223   429 igrlskpDLYVRISIAGVPHDEKIMKT-TVKNNEWKPTWGEEFTFPLTYPDLALISFEVYDyeVSTADAFCgQTCLPVSE 507


                   ....*...
gi 2782110376 3160 LRPGYRHV 3167
Cdd:PLN02223   508 LIEGIRAV 515
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1818-1988 1.12e-21

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 96.93  E-value: 1.12e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1818 LLHFPEEVALSLAQEEDALFYQVPPIDYLRQVTLDLGGapppqppqpHDHHRASVRSLIKRFNEVSSWVTHLIISQPTHE 1897
Cdd:smart00147    2 LLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSK---------KSPSPLNLEAFIRRFNEVSNWVATEILKQTTPK 72

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1898 DRKSVLSCILRVALFSWNIGNFNGAMEIVAGLKSTKLKPFWLSITEKEPVPTLDF------LSAALLSVEYERALNRALA 1971
Cdd:smart00147   73 DRAELLSKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFeeleelLSPERNYKNYREALSSCNL 152

                           170
                    ....*....|....*..
gi 2782110376  1972 MPeccVVPFFGSFLRDL 1988
Cdd:smart00147  153 PP---CIPFLGVLLKDL 166
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3221-3313 1.44e-21

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


Pssm-ID: 340478  Cd Length: 102  Bit Score: 92.01  E-value: 1.44e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3221 MFFLMVYGVVPDETSTILKITQESTTHEVVLQALQKAGQSADKVNDYVLVEEVSRGWDRKDREAPAS-----QRVLDPQE 3295
Cdd:cd01780      3 TFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDIPSDFVLVEELEKEPTSDKSSSKSSsskteQRVLGDQE 82

                           90
                   ....*....|....*...
gi 2782110376 3296 CPLQAQAQWQGEGKFLLK 3313
Cdd:cd01780     83 NVYQAQSRWKGAGKFILK 100
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1836-1988 7.35e-20

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


Pssm-ID: 459872  Cd Length: 179  Bit Score: 89.57  E-value: 7.35e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1836 LFYQVPPIDYLRQVtldlggapppQPPQPHDHHRASVRSLIKRFNEVSSWVTHLIISQPTHEDRKSVLSCILRVALFSWN 1915
Cdd:pfam00617   13 LFRKIKPRELLGSA----------WSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHCRE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1916 IGNFNGAMEIVAGLKST---KLKPFWLSITEKEpVPTLDFLSaALLSVE-----YERALNRalAMPECcvVPFFGSFLRD 1987
Cdd:pfam00617   83 LNNFNSLMAILSGLNSSpisRLKKTWELVSKKY-KKTLEELE-KLMSPSrnfknYREALSS--ASPPC--IPFLGLYLTD 156


                   .
gi 2782110376 1988 L 1988
Cdd:pfam00617  157 L 157
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3345-3429 8.53e-17

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


Pssm-ID: 340634  Cd Length: 97  Bit Score: 78.15  E-value: 8.53e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3345 FLVCVYNVSPEIPYAILKMPQSACAQDVLAQALVKARR-MEDPTRFILLEELE--WSANAK----VQRILADDENIYRTQ 3417
Cdd:cd17114      4 FFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKsLERVTDYVLVEEVQkgWDRKETekpgSQRILDMDEKILQAQ 83

                           90
                   ....*....|..
gi 2782110376 3418 SQWQTIGRFILR 3429
Cdd:cd17114     84 SKWKGSGRFILK 95
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 2630-2740 1.58e-16

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: 80.17  E-value: 1.58e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2630 SSHNTYLTGHQlkgESSVDLYSQVLLAGCRCVELDCWDGDDGSPQIYHGHTFT------TKIQFKSVVEAINRSAFvTSP 2703
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 2782110376 2704 YPVILSIENHCS----LQQQTRMAHIFQSVFGDKLVTKFLF 2740
Cdd:cd08555     78 YTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGKVVL 118
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1818-2096 9.96e-16

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


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 79.60  E-value: 9.96e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1818 LLHF-PEEVALSLAQEEDALFYQVPPIDYLRQVTldlggapppQPPQPHDHHRASVRSLIKRFNEVSSWVTHLIISQPTH 1896
Cdd:cd00155      1 FLSLdPKELAEQLTLLDFELFRKIEPFELLGSLW---------SKKDKNIHLSPNLERFIERFNNLSNWVASEILLCTNP 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1897 EDRKSVLSCILRVALFSWNIGNFNGAMEIVAGLKS---TKLKPFWLSITEKepvpTLDFLSAALLSVE-------YERAL 1966
Cdd:cd00155     72 KKRARLLSKFIQVAKHCRELNNFNSLMAIVSALSSspiSRLKKTWEVLSSK----LKKLFEELEELVDpsrnfknYRKLL 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 1967 NRALAMPECcvVPFFGSFLRDlrdilsstpslvvlapagdrthLEFIsdYNGEDHYFtrigPGGLINLDKIYKTQAVMDK 2046
Cdd:cd00155    148 KSVGPNPPC--VPFLGVYLKD----------------------LTFL--HEGNPDFL----EGNLVNFEKRRKIAEILRE 197

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2782110376 2047 IASF-HQHYHKRVRDVetLREQFSTIHtesverpymsednEDAENEMDSYR 2096
Cdd:cd00155    198 IRQLqSNSYELNRDED--ILAFLWKLL-------------ELILNEDELYE 233
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 3071-3168 2.31e-14

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: 71.36  E-value: 2.31e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  3071 QIILNVISGQYV--CQNNLTANVIVEIEMIGipVDCNKQKTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLDA---S 3145
Cdd:smart00239    1 TLTVKIISARNLppKDKGGKSDPYVKVSLDG--DPKEKKKTKVVKNT-LNPVWNETFEFEVPPPELAELEIEVYDKdrfG 77

                            90       100
                    ....*....|....*....|...
gi 2782110376  3146 TNHMICQRVMPLKCLRPGYRHVR 3168
Cdd:smart00239   78 RDDFIGQVTIPLSDLLLGGRHEK 100
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3222-3314 1.93e-12

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


Pssm-ID: 425871  Cd Length: 93  Bit Score: 65.43  E-value: 1.93e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3222 FFLMVYG--VVPDETSTILKITQESTTHEVVLQALQKAGQSADKvNDYVLVEEVSRGwdrkdreapASQRVLDPQECPLQ 3299
Cdd:pfam00788    3 GVLKVYTedGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVLERG---------GGERRLPDDECPLQ 72

                           90
                   ....*....|....*...
gi 2782110376 3300 AQAQWQGEG---KFLLKR 3314
Cdd:pfam00788   73 IQLQWPRDAsdsRFLLRK 90
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3222-3314 2.61e-12

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


Pssm-ID: 214612  Cd Length: 90  Bit Score: 65.01  E-value: 2.61e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  3222 FFLMVY-GVVPDETSTILKITQESTTHEVVLQALQKAGQSADkVNDYVLVEEVSRGwdrkdreapaSQRVLDPQECPLQA 3300
Cdd:smart00314    3 FVLRVYvDDLPGGTYKTLRVSSRTTARDVIQQLLEKFHLTDD-PEEYVLVEVLPDG----------KERVLPDDENPLQL 71

                            90
                    ....*....|....*..
gi 2782110376  3301 QAQWQGEGK---FLLKR 3314
Cdd:smart00314   72 QKLWPRRGPnlrFVLRK 88
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
463-534 1.05e-11

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 68.83  E-value: 1.05e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARETIPwesVVEM-IERGAQVSLPNRRGVRASDLA 534
Cdd:COG0666    157 LHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLE---IVKLlLEAGADVNAKDNDGKTALDLA 226
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 2442-2603 2.35e-11

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: 63.84  E-value: 2.35e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2442 QLDFIDFVALFRSFSLRA-RKDLKDLFDQFAmscrsmsdsslNDGSlksspehssrapkiGLLTRNSSADLMDYRNT-PA 2519
Cdd:cd15898     16 KLSLKEIKKLLKRLNIRVsEKELKKLFKEVD-----------TNGD--------------GTLTFDEFEELYKSLTErPE 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2520 MQKkkIFDAIATSsivtncagvdtsKSQVITLSNFAKFLETKQLEQHTEEEVKELIQRHEPDPTLRshnCLSFEGFARFL 2599
Cdd:cd15898     71 LEP--IFKKYAGT------------NRDYMTLEEFIRFLREEQGENVSEEECEELIEKYEPERENR---QLSFEGFTNFL 133


                   ....
gi 2782110376 2600 MDKE 2603
Cdd:cd15898    134 LSPE 137
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
 3223-3314 7.46e-11

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


Pssm-ID: 340563  Cd Length: 87  Bit Score: 60.79  E-value: 7.46e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3223 FLMVYG--VVPDETSTILKITQESTTHEVVLQALQKAGqSADKVNDYVLVEEvsrgWDRKDREapasqRVLDPQECPLQA 3300
Cdd:cd17043      1 VLKVYDddLAPGSAYKSILVSSTTTAREVVQLLLEKYG-LEEDPEDYSLYEV----SEKQETE-----RVLHDDECPLLI 70

                           90
                   ....*....|....*..
gi 2782110376 3301 QAQW---QGEGKFLLKR 3314
Cdd:cd17043     71 QLEWgpqGTEFRFVLKR 87
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
463-534 1.02e-09

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 62.66  E-value: 1.02e-09
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARETIPwesVVEM-IERGAQVSLPNRRGVRASDLA 534
Cdd:COG0666    124 LHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLE---IVKLlLEAGADVNARDNDGETPLHLA 193
C2 pfam00168
C2 domain;
3071-3166 2.25e-09

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 57.33  E-value: 2.25e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3071 QIILNVISGQYVCQNNL--TANVIVEIEMIGipvDCNKQKTKVVqRNALNPIWNESFYFQVMFRDLAFLRFSVLDAST-- 3146
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGngTSDPYVKVYLLD---GKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRfg 77

                           90       100
                   ....*....|....*....|.
gi 2782110376 3147 -NHMICQRVMPLKCLRPGYRH 3166
Cdd:pfam00168   78 rDDFIGEVRIPLSELDSGEGL 98
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3343-3432 5.94e-09

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


Pssm-ID: 425871  Cd Length: 93  Bit Score: 55.80  E-value: 5.94e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3343 DNFLVCVY--NVSPEIPYAILKMPQSACAQDVLAQALVKARRMEDPTRFILLEELEwsaNAKVQRILADDENIYRTQSQW 3420
Cdd:pfam00788    1 DDGVLKVYteDGKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVLE---RGGGERRLPDDECPLQIQLQW 77

                           90
                   ....*....|....*
gi 2782110376 3421 QT---IGRFILRERE 3432
Cdd:pfam00788   78 PRdasDSRFLLRKRD 92
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 2546-2603 2.00e-08

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: 55.70  E-value: 2.00e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2782110376 2546 SQVITLSNFAKFLETKQLEQH-TEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16202     82 DEALTVEELRRFLQEEQKVKDvTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
463-527 3.34e-08

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 58.04  E-value: 3.34e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARETIpwESVVEMIERGAQVSLPNRRG 527
Cdd:COG0666     91 LHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNL--EIVKLLLEAGADVNAQDNDG 153
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3343-3432 4.90e-08

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


Pssm-ID: 214612  Cd Length: 90  Bit Score: 53.07  E-value: 4.90e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  3343 DNFLVCVYNVSPE-IPYAILKMPQSACAQDVLAQALVKARRMEDPTRFILLEELEwsanAKVQRILADDENIYRTQSQWQ 3421
Cdd:smart00314    1 DTFVLRVYVDDLPgGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVLP----DGKERVLPDDENPLQLQKLWP 76

                            90
                    ....*....|....
gi 2782110376  3422 TIG---RFILRERE 3432
Cdd:smart00314   77 RRGpnlRFVLRKRD 90
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 3072-3143 1.16e-07

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 52.45  E-value: 1.16e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2782110376 3072 IILNVISGQ--YVCQNNLTANVIVEIEMIGIpvdcNKQKTKVVqRNALNPIWNESFYFQVMFRDLAFLRFSVLD 3143
Cdd:cd00030      1 LRVTVIEARnlPAKDLNGKSDPYVKVSLGGK----QKFKTKVV-KNTLNPVWNETFEFPVLDPESDTLTVEVWD 69
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
463-549 1.96e-07

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 55.73  E-value: 1.96e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARETIpwESVVEMIERGAQVSLPNRRGVRASDLAPTGLLPHL 542
Cdd:COG0666    190 LHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNL--EIVKLLLEAGADLNAKDKDGLTALLLAAAAGAALI 267


                   ....*..
gi 2782110376  543 QAALVNN 549
Cdd:COG0666    268 VKLLLLA 274
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 2545-2603 8.00e-07

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: 51.48  E-value: 8.00e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2782110376 2545 KSQVITLSNFAKFLETKQLEQ---------HTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16200     86 RKPYLTLEQLVDFLNEEQRDPrlneilfpfHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 2543-2607 1.38e-06

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: 48.78  E-value: 1.38e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2782110376 2543 TSKSQVITLSNFAKFLETKQLE-QHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKENFAF 2607
Cdd:pfam09279   19 SGDGQKLSLDELVDFLREEQREeDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPDGSIF 84
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 2547-2603 2.16e-06

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: 49.84  E-value: 2.16e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2782110376 2547 QVITLSNFAKFLETKQLE-QHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16219     83 QKLTLLEFVDFLQQEQLErENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140
Ank_2 pfam12796
Ankyrin repeats (3 copies);
463-502 9.90e-06

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 46.65  E-value: 9.90e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVAR 502
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKN 40
RA cd17043
Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA ...
 3347-3430 1.16e-05

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


Pssm-ID: 340563  Cd Length: 87  Bit Score: 46.16  E-value: 1.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3347 VCVYNVSPEIPYAILKMPQSACAQDVLAQALVKARRMEDPTRFILLEELEWSAnakVQRILADDENIYRTQSQW---QTI 3423
Cdd:cd17043      4 VYDDDLAPGSAYKSILVSSTTTAREVVQLLLEKYGLEEDPEDYSLYEVSEKQE---TERVLHDDECPLLIQLEWgpqGTE 80


                   ....*..
gi 2782110376 3424 GRFILRE 3430
Cdd:cd17043     81 FRFVLKR 87
RA2_DAGK-theta cd01783
Ras-associating (RA) domain 2 found in diacylgylcerol kinase theta (DAGK-theta) and similar ...
 3238-3299 1.77e-05

Ras-associating (RA) domain 2 found in diacylgylcerol kinase theta (DAGK-theta) and similar proteins; DAGK phosphorylates the second messenger diacylglycerol to phosphatidic acid as part of a protein kinase C pathway. DAGK-theta is characterized as a type V DAGK that has three cysteine-rich domains (all other isoforms have two), a proline/glycine-rich domain at its N-terminal, and a proposed Ras-associating (RA) domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. There are ten mammalian isoforms of DAGK have been identified to date, these are organized into five categories based on the domain architecture. DAGK-theta also contains a pleckstrin homology (PH) domain. The subcellular localization and the activity of DAGK-theta are regulated in a complex (stimulation- and cell type-dependent) manner. This family corresponds to the second RA domain of DAGK-theta.


Pssm-ID: 340481  Cd Length: 95  Bit Score: 46.07  E-value: 1.77e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2782110376 3238 LKITQESTTHEVVLQALQKAGQSADKVNDYVLVEEVsrgWDRKdreapASQRVLDPQECPLQ 3299
Cdd:cd01783     19 IPVTKETTVEEVIKEALPKFGLQDEDPEDFRLVEVL---MDKG-----VVERVMLRDECPWL 72
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 3093-3143 3.73e-05

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


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 46.10  E-value: 3.73e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2782110376 3093 VEIEMIGIPVDCNKQKTKVVQRNaLNPIWNESFYFQVMFRDL-AFLRFSVLD 3143
Cdd:cd04026     38 VKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPADKdRRLSIEVWD 88
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 2622-2734 4.84e-05

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: 48.24  E-value: 4.84e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 2622 PLSHYYIASSHNTY---LTGHQLKGESSV-----DLYSQvLLAGCRCVELDCW-DGDDGSPQIYHGHTFTTKIQFKSVVE 2692
Cdd:cd08557      8 PLSQLSIPGTHNSYaytIDGNSPIVSKWSktqdlSITDQ-LDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDVLN 86

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2782110376 2693 AINRsaFVTS-PY-PVILSIENHCSLQQQTRMA---HIFQSVFGDKL 2734
Cdd:cd08557     87 EVKD--FLDAhPSeVVILDLEHEYGGDNGEDHDeldALLRDVLGDPL 131
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1504-1686 5.25e-05

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 46.90  E-value: 5.25e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1504 DDHEETDKEYCRLLHM-------VVTGELPCSKEEAAALAGIQLRIEEtwgrphgpisPDDNTLKPISEDKESfllpvpt 1576
Cdd:smart00295   83 PDPNQLKEDPTRLNLLylqvrndILEGRLPCPEEEALLLAALALQAEF----------GDYDEELHDLRGELS------- 145

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376  1577 fgatrpvsplveeaegaedseggtgaqpprahsllrkcypsrstqvpfmpaghLEDCLPPCYHGTKAmAKLIKEQKRKLF 1656
Cdd:smart00295  146 -----------------------------------------------------LKRFLPKQLLDSRK-LKEWRERIVELH 171

                           170       180       190
                    ....*....|....*....|....*....|
gi 2782110376  1657 HTSIYDSEIQLKKLYIQTCRRLPSHGCKVY 1686
Cdd:smart00295  172 KELIGLSPEEAKLKYLELARKLPTYGVELF 201
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 2557-2603 5.49e-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: 45.66  E-value: 5.49e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2782110376 2557 FLETKQ-LEQHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16206     96 FLEAEQgMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143
RA_RASSF7 cd16135
Ras-associating (RA) domain found in N-terminal Ras-association domain family 7 (RASSF7); ...
 3240-3316 6.08e-05

Ras-associating (RA) domain found in N-terminal Ras-association domain family 7 (RASSF7); RASSF7, also termed HRAS1-related cluster protein 1, is a member of the N-terminus RASSF7-10 protein family. RASSF7-10 has an RA-domain at the N-terminus and lacks a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that is found in members of the RASSF1-6 family. The RA domain of N-terminal RASSF protein family has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. RASSF7 is a potential Ras effector as its function has been linked to some key biological processes including the regulation of cell death and proliferation; for example, RASSF7 is up-regulated in pancreatic cancer.


Pssm-ID: 340552  Cd Length: 83  Bit Score: 44.17  E-value: 6.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3240 ITQESTTHEVVLQALQKAGQSADkvndYVLVEEVsrgwdrKDREapasqRVLDPQECPLQAQA---QWQGEGKFLLKRLG 3316
Cdd:cd16135     17 VSEQTTCQEVVIALAQAIGQTGR----YVLIQKL------RDKE-----RQLLANECPLEALAkcgQYANDVQFILRRTG 81
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 3101-3160 1.52e-04

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


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 44.17  E-value: 1.52e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2782110376 3101 PVDCNKQKTKVvQRNALNPIWNESFYFQVMFRDL--AFLRFSVLDA---STNHMICQRVMPLKCL 3160
Cdd:cd08390     46 PDERRSLQSKV-KRKTQNPNFDETFVFQVSFKELqrRTLRLSVYDVdrfSRHCIIGHVLFPLKDL 109
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 3106-3157 3.28e-04

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 43.02  E-value: 3.28e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2782110376 3106 KQKTKVvQRNALNPIWNESFYFQVMFRDLA--FLRFSVLDA---STNHMICQRVMPL 3157
Cdd:cd08385     52 KFETKV-HRKTLNPVFNETFTFKVPYSELGnkTLVFSVYDFdrfSKHDLIGEVRVPL 107
RA2_Afadin cd01781
Ras-associating (RA) domain 2 found in Afadin; Afadin, also termed ALL1-fused gene from ...
 3236-3314 3.52e-04

Ras-associating (RA) domain 2 found in Afadin; Afadin, also termed ALL1-fused gene from chromosome 6 protein (AF-6), or canoe, is involved in many fundamental signaling cascades in cells. In addition, it is involved in oncogenesis and metastasis. Afadin has multiple domains: from the N-terminus to the C-terminus it has two Ras-associated (RA) domains, a forkhead-associated domain, a dilute domain, a PDZ domain, three proline-rich domains, and an F-actin binding domain. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The RA domain has a beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. Afadin is abundant at cadherin-based adherens junctions in epithelial cells, endothelial cells, and fibroblasts. This family corresponds to the second RA domain of afadin.


Pssm-ID: 340479  Cd Length: 102  Bit Score: 42.26  E-value: 3.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3236 TILkITQESTTHEVVLQALQKAGqsADKVN--DYVLV---------EEVSRGWDRkdreapasQRVLDPQECPLQAQAQW 3304
Cdd:cd01781     19 TLL-LSTNDTADFVVREALEKYG--LEKENpkDYCLVqvvlppggsPRLDGGGGK--------ERILDDDECPLAILMRW 87

                           90
                   ....*....|...
gi 2782110376 3305 Q---GEGKFLLKR 3314
Cdd:cd01781     88 PpskGTLVFQLRR 100
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 3088-3148 7.24e-04

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 42.32  E-value: 7.24e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2782110376 3088 TANVIVEIEMigipvDCNKQKTKVVQRNaLNPIWNESFYFQVmfRDLAFLRFSVLDASTNH 3148
Cdd:cd04022     20 SSSAYVELDF-----DGQKKRTRTKPKD-LNPVWNEKLVFNV--SDPSRLSNLVLEVYVYN 72
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 3106-3150 8.99e-04

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


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 42.02  E-value: 8.99e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2782110376 3106 KQKTkVVQRNALNPIWNESFYFQVMF---RDLAFLrFSVLD---ASTNHMI 3150
Cdd:cd08405     53 KKKT-VIKKRTLNPVFNESFIFNIPLerlRETTLI-ITVMDkdrLSRNDLI 101
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 3108-3162 9.39e-04

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 41.40  E-value: 9.39e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2782110376 3108 KTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMPLKCLRP 3162
Cdd:cd04040     35 KTKTIKKT-LNPVWNESFEVPVPSRVRAVLKVEVYDwdrGGKDDLLGSAYIDLSDLEP 91
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 3106-3166 9.51e-04

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 42.19  E-value: 9.51e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2782110376 3106 KQKTKVVQRNaLNPIWNESFYFQVMFRDL--AFLRFSVLDAS---TNHMICQRVMPLKCLRPGYRH 3166
Cdd:cd00276     52 KKKTSVKKGT-LNPVFNEAFSFDVPAEQLeeVSLVITVVDKDsvgRNEVIGQVVLGPDSGGEELEH 116
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 2547-2603 9.75e-04

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: 42.10  E-value: 9.75e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2782110376 2547 QVITLSNFAKFLETKQLEQHTEEEVK-ELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16204     85 KILSAPNLVGFLKKEQFQDEADETIAsELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142
RA1_PLC-epsilon cd17229
Ras-associating (RA) domain 1 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3226-3313 1.04e-03

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


Pssm-ID: 340749  Cd Length: 108  Bit Score: 41.36  E-value: 1.04e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3226 VYGVVPDETSTILKITQESTTHEVVLQALQKAGQSADKVNDYVLVEE-VSRGWDRKDREAPASQRVLDPQECPLQAQAQW 3304
Cdd:cd17229     12 VHGVPGPEPFTVFTISEGTTAKQLLQQILATEQGIEPDTTDYFLMEEkYFISKEKNECRKPPFQRVIGPEEEILQILNSW 91

                           90
                   ....*....|...
gi 2782110376 3305 QGE----GKFLLK 3313
Cdd:cd17229     92 FPEegyvGRIILK 104
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 3106-3143 1.32e-03

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


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 41.56  E-value: 1.32e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2782110376 3106 KQKTKVVQRNaLNPIWNESFYFQVMFRDLA--FLRFSVLD 3143
Cdd:cd08384     51 KHKTQVKKKT-LNPEFNEEFFYDIKHSDLAkkTLEITVWD 89
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
3108-3163 1.48e-03

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 44.75  E-value: 1.48e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2782110376 3108 KTKVVQRNaLNPIWNESFYFQVMFRDLAFLRFSVLD---ASTNHMICQRVMPLKCLRPG 3163
Cdd:COG5038   1076 KTKVVKKT-LNPVWNEEFTIEVLNRVKDVLTINVNDwdsGEKNDLLGTAEIDLSKLEPG 1133
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 2543-2603 1.56e-03

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: 41.65  E-value: 1.56e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2782110376 2543 TSKSQVITLSNFAKFLEtKQLEQHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16218     79 SGEDCVLSAEELREFLK-DQGEDASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 3068-3157 1.65e-03

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


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 41.08  E-value: 1.65e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3068 HSSQIILNVISGQ--YVCQNNLTANVIVEIEMIGIPVDCNKQKTKVVQRnALNPIWNESFYFQVMFR-DL--AFLRFSVL 3142
Cdd:cd04031     14 VTSQLIVTVLQARdlPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKK-TLNPEWNQTFEYSNVRReTLkeRTLEVTVW 92

                           90
                   ....*....|....*...
gi 2782110376 3143 D---ASTNHMICQRVMPL 3157
Cdd:cd04031     93 DydrDGENDFLGEVVIDL 110
RA_Myosin-IX cd01779
Ras-associating (RA) domain found in Myosin-IX; Myosins IX (Myo9) is a class of unique motor ...
 3229-3304 1.93e-03

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


Pssm-ID: 340477  Cd Length: 97  Bit Score: 40.00  E-value: 1.93e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2782110376 3229 VVPDETSTILKITQESTTHEVVLQALQKAgqSADKVNDYVLVEEV-SRGWDRKdreapasQRVLDPQECPLQAQAQW 3304
Cdd:cd01779      9 LSPETEFLSVEATKQTTASEVIECLVAKL--RLDKAECYELAEVCgSGGQGCK-------ERRLGPSENPVQVQLLW 76
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 2557-2603 2.01e-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: 41.39  E-value: 2.01e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2782110376 2557 FLETKQ-LEQHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16222     96 FLEAEQgMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143
ANK smart00248
ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four ...
 185-210 2.23e-03

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.


Pssm-ID: 197603 [Multi-domain]  Cd Length: 30  Bit Score: 37.95  E-value: 2.23e-03
                            10        20
                    ....*....|....*....|....*.
gi 2782110376   185 NALHLAVEYGAVDVLRLLLKYGLEPN 210
Cdd:smart00248    4 TPLHLAAENGNLEVVKLLLDKGADIN 29
Ank_4 pfam13637
Ankyrin repeats (many copies);
459-503 2.87e-03

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 38.41  E-value: 2.87e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2782110376  459 TLPVLFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVARE 503
Cdd:pfam13637    1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNG 45
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 2544-2603 2.96e-03

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: 40.87  E-value: 2.96e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2782110376 2544 SKSQVITLSNFAKFLETKQLEQHTEE---------EVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16211     85 DKKDYLTVDQLISFLNEHQRDPRLNEilfpfydrkRVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153
RA_RASSF7_like cd16123
Ras-associating (RA) domain found in Ras-association domain family members, RASSF7, RASSF8, ...
 3240-3314 3.49e-03

Ras-associating (RA) domain found in Ras-association domain family members, RASSF7, RASSF8, RASSF9, and RASSF10; The RASSF family of proteins shares a conserved RalGDS/AF6 Ras association (RA) domain either in the C-terminus (RASSF1-6) or N-terminus (RASSF7-10). RASSF7-10 lacks a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that is found in members of the RASSF1-6 family. The structural differences between the C-terminus and N-terminus RASSF subgroups have led to the suggestion that they are two distinct families. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ras proteins are small GTPases that are involved in cellular signal transduction. The N-terminus RASSF proteins are potential Ras effectors that have been linked to key biological processes, including cell death, proliferation, microtubule stability, promoter methylation, vesicle trafficking and response to hypoxia.


Pssm-ID: 340540  Cd Length: 81  Bit Score: 38.77  E-value: 3.49e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2782110376 3240 ITQESTTHEVVLQALQKAGQSADkVNDYVLVEEvsrgWdrKDREapasqRVLDPQECPLQAQAQW---QGEGKFLLKR 3314
Cdd:cd16123     16 VTERTTCQDVIYALAQATGQTND-TGRYVLVER----W--RGIE-----RPLPPRTRILKVWKAWgeeQSNVQFVLRR 81
EFh_NorpA_like cd16212
EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...
 2541-2603 4.19e-03

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: 40.61  E-value: 4.19e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2782110376 2541 VDTSKSQVITLSNFAKFLETKQLE---------QHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16212     82 ITKGKGEHISLAQLINFMNDKQRDprlneilypLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 3108-3150 4.23e-03

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


Pssm-ID: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 39.54  E-value: 4.23e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2782110376 3108 KTKVvQRNALNPIWNESFYFQVMFRDLAF-LRFSVLDA---STNHMI 3150
Cdd:cd04039     40 RTSW-RRHTLNPVFNERLAFEVYPHEKNFdIQFKVLDKdkfSFNDYV 85
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 2523-2600 4.34e-03

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: 40.31  E-value: 4.34e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2782110376 2523 KKIFDAIATSSivtncagvdtskSQVITLSNFAKFLETKQLEQHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLM 2600
Cdd:cd16207     74 KAIFKQLTKPG------------SDGLTLEEFLKFLRDVQKEDVDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLL 139
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 2553-2603 5.85e-03

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: 39.72  E-value: 5.85e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2782110376 2553 NFAKFLETKQLEQHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFLMDKE 2603
Cdd:cd16217     89 NLLNFLQEEQREEVAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139
PHA02878 PHA02878
ankyrin repeat protein; Provisional
 463-521 5.98e-03

ankyrin repeat protein; Provisional


Pssm-ID: 222939 [Multi-domain]  Cd Length: 477  Bit Score: 42.17  E-value: 5.98e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2782110376  463 LFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVAReTIPWESVVEMIERGAQVS 521
Cdd:PHA02878   205 LHHAVKHYNKPIVHILLENGASTDARDKCGNTPLHISVGY-CKDYDILKLLLEHGVDVN 262
PHA02876 PHA02876
ankyrin repeat protein; Provisional
 449-525 6.83e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165207 [Multi-domain]  Cd Length: 682  Bit Score: 42.36  E-value: 6.83e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2782110376  449 AETYTRPYLFTLPVLFlAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLAVArETIPWESVVEMIERGAQVSLPNR 525
Cdd:PHA02876   366 ANVNARDYCDKTPIHY-AAVRNNVVIINTLLDYGADIEALSQKIGTALHFALC-GTNPYMSVKTLIDRGANVNSKNK 440
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 2549-2599 6.89e-03

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


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 39.67  E-value: 6.89e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2782110376 2549 ITLSNFAKFLETKQ-LEQHTEEEVKELIQRHEPDPTLRSHNCLSFEGFARFL 2599
Cdd:cd16205     86 LTLEDLARFLEVEQkMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYM 137
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 3071-3146 7.95e-03

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 38.71  E-value: 7.95e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2782110376 3071 QIILNVISGQYVCQNNLTANVIVEIemigipvdCNKQKTKVVQRNALNPIWNESFYF------QVMFRDLafLRFSVLDA 3144
Cdd:cd04011      5 QVRVRVIEARQLVGGNIDPVVKVEV--------GGQKKYTSVKKGTNCPFYNEYFFFnfhespDELFDKI--IKISVYDS 74


                   ..
gi 2782110376 3145 ST 3146
Cdd:cd04011     75 RS 76
Ank_2 pfam12796
Ankyrin repeats (3 copies);
185-211 7.97e-03

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 38.17  E-value: 7.97e-03
                           10        20
                   ....*....|....*....|....*..
gi 2782110376  185 NALHLAVEYGAVDVLRLLLKYGLEPNQ 211
Cdd:pfam12796   63 TALHYAARSGHLEIVKLLLEKGADINV 89
Ank_5 pfam13857
Ankyrin repeats (many copies);
462-499 9.11e-03

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 36.94  E-value: 9.11e-03
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2782110376  462 VLFLAVVRGNPTLVYLLLKYGAAVNFQDSHGNTALHLA 499
Cdd:pfam13857   19 PLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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