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Conserved domains on  [gi|1734340688|ref|NP_001360635|]
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Phosphoinositide phospholipase C [Caenorhabditis elegans]

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 ...
 2545-3009 2.37e-133

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: 418.48  E-value: 2.37e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEADFSDSPRLPCPLQMknkiliknkkmivdpptpl 2704
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQL------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2705 pmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedspktskraeksarnik 2784
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2785 qqdslcsdhsveqakpstskttsktndrktedevlyaqlaqnaiRNQQPRKNNTgvqiAPELSDIVIYMQATKFKGFPpv 2864
Cdd:cd08596    142 --------------------------------------------KNKILLKNKK----APELSDLVIYCQAVKFPGLS-- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2865 dgiqsprimeegpasaslsfssrartpsnllntpapprrqrsstqlsqelaaeflgsvranaTATCYQVTSLNENAAKKL 2944
Cdd:cd08596    172 --------------------------------------------------------------TPKCYHISSLNENAAKRL 189

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2945 MKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08596    190 CRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 2351-2531 2.95e-79

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: 259.95  E-value: 2.95e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2351 SGLSGPSGKEFQEKPLTLVEFAELFRLFNTRMRKDLRDVFNDVLSTATTPQHCPKRerdrhsprmQSRLASVSNSYNADF 2430
Cdd:cd16203      1 GGLKGFSIGEVQDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAP---------LKRSLSISESYSGLF 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2431 LSNDFLTRNTAVTSHHISEKQN-KIYNALALASVNSMGGLMDTSRSSMLTPQMLRAFVNTHQMEQIDEQTAIKLIQDHEP 2509
Cdd:cd16203     72 PDLDLLTRNTSLDGLFISKKQQkKIYDAIAAASIVTNGAGVDSSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEP 151

                          170       180
                   ....*....|....*....|..
gi 1734340688 2510 DGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16203    152 DPILRSKNCLSFEGFARYLMDK 173
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3371-3474 6.66e-52

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: 178.68  E-value: 6.66e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3371 GDTFLVCVHNVSEDQPYAILRAGIHSTAADIIRQVFVKARRSNVDDSEFVLVEETCDDPKLNQGQMtpKYPNNRTTSRVL 3450
Cdd:cd01780      1 EDTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDIPSDFVLVEELEKEPTSDKSSS--KSSSSKTEQRVL 78

                           90       100
                   ....*....|....*....|....
gi 1734340688 3451 GQNENVWKAQSRWKSMGRFVLENR 3474
Cdd:cd01780     79 GDQENVYQAQSRWKGAGKFILKLR 102
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1698-1969 1.90e-51

Guanine nucleotide exchange factor for Ras-like small GTPases;


:

Pssm-ID: 214539  Cd Length: 242  Bit Score: 182.83  E-value: 1.90e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1698 YILHFPEEVAFQLSSTEYQLFYSIQPMDYVRYVSCDLTSVpvSENPSPVRNLVKRLSEVSSWITHVIVSQPTHDDRKVAL 1777
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKK--SPSPLNLEAFIRRFNEVSNWVATEILKQTTPKDRAELL 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1778 TAILRIVETCWNIGNFNAAVEVLMGLKSEKLRPF---WLSLRQEEKSQFDSLCETLLPANqalPSQAYINAVQralRMPQ 1854
Cdd:smart00147   79 SKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLkktWEKLPSKYKKLFEELEELLSPER---NYKNYREALS---SCNL 152

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1855 SRVIPFFGIFLRDLYAIVNDLPNIVvigqegetqklefmsdPNGEDHFSSRIGVGGLLnaDKINLVAIVLDNLelfhRHS 1934
Cdd:smart00147  153 PPCIPFLGVLLKDLTFIDEGNPDFL----------------ENGLVNFEKRRQIAEIL--REIRQLQSQPYNL----RPN 210

                           250       260       270
                    ....*....|....*....|....*....|....*
gi 1734340688  1935 RTMIKLLEEQAVPPIqipQNEREQKEKEAKTYEPV 1969
Cdd:smart00147  211 RSDIQSLLQQLLDHL---DEEEELYQLSLKIEPRV 242
PLN02952 super family cl31960
phosphoinositide phospholipase C
 2476-3165 5.22e-39

phosphoinositide phospholipase C


The actual alignment was detected with superfamily member PLN02952:

Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 156.70  E-value: 5.22e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2476 SMLTPQMLRAFVNTHQME-QIDEQTAIKLIQD--HEPDGICR-QKNQMSFEGFTRFLC-DPVNFAFVPETiepdEEDLRY 2550
Cdd:PLN02952    52 GHMGADQLRRFLVLHQDElDCTLAEAQRIVEEviNRRHHVTRyTRHGLNLDDFFHFLLyDDLNGPITPQV----HHDMTA 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2551 PLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLP-LIYHGHTLVSKIGFRQVVEIIKKSAFI 2629
Cdd:PLN02952   128 PLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFS 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2630 TSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLvsnFLFEADfsdsprlpcplqmknkiliknkkMIVDPPTPLPMIER 2709
Cdd:PLN02952   208 SSPYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESD-----------------------SLVQFPSPESLKHR 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2710 gavqrgetqLNLHRKQSKNSYESSTVDevedddldeflddeeneeddqeevqvrSEKEDSPKTSKRAEKSARNikQQDSL 2789
Cdd:PLN02952   262 ---------IIISTKPPKEYLESSGPI---------------------------VIKKKNNVSPSGRNSSEET--EEAQT 303

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2790 CSDHSVEQakpstskttsKTNDRKTEDEvlyaqlaqnairnqqpRKNNTGVQIAPELSDIvIYMQATKFKGfppvdgiqs 2869
Cdd:PLN02952   304 LESMLFEQ----------EADSRSDSDQ----------------DDNKSGELQKPAYKRL-ITIHAGKPKG--------- 347

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2870 primeegpasaslsfssrartpsnllntpapprrqrsstQLSQELaaeflgSVRANATatcyQVTSLNENAAKKLMKRHP 2949
Cdd:PLN02952   348 ---------------------------------------TLKDAM------KVAVDKV----RRLSLSEQELEKAATTNG 378

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2950 AKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWDEShlLY 3029
Cdd:PLN02952   379 QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKG--FH 456

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3030 NKFLPLSKDIAGHSALLLNLTIISGQHV-YPNTHYAS-----LYVEIEVIGIHNDCVREKSKVVQRNSvNPIWNHTTQLR 3103
Cdd:PLN02952   457 DEVFDPKKKLPVKKTLKVKVYLGDGWRLdFSHTHFDSysppdFYTKMYIVGVPADNAKKKTKIIEDNW-YPAWNEEFSFP 535

                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340688 3104 IACVDLAFLRIAV--CDSGQNGRVVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRFE 3165
Cdd:PLN02952   536 LTVPELALLRIEVreYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLMRFIFV 599
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
190-338 4.08e-14

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 75.76  E-value: 4.08e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  190 MNTLHMAVAHKQRDIVELLLKNGYDPNTPASchcKGNctatgnipltsiiprthsmtpelcstcsqlrvvsivdqTPLGV 269
Cdd:COG0666    121 ETPLHLAAYNGNLEIVKLLLEAGADVNAQDN---DGN--------------------------------------TPLHL 159

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340688  270 AVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESplSWPCLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:COG0666    160 AAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENG--HLEIVKLLLEAGADVNAKDNDGKTALDLA 226
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
 3205-3299 2.66e-11

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 cd17114:

Pssm-ID: 475130  Cd Length: 97  Bit Score: 62.36  E-value: 2.66e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3205 KQIFVLRITGAFADETAITVHSESGSTVKTVMQQALLNAGKNADQVEEYVLIEESLPAPSGED---PIEQRVLPLNEPIM 3281
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRKEtekPGSQRILDMDEKIL 80

                           90
                   ....*....|....*...
gi 1734340688 3282 DAVACWNGSmRRFVLRKK 3299
Cdd:cd17114     81 QAQSKWKGS-GRFILKKL 97
B41 super family cl33382
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1371-1548 1.28e-10

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: 63.47  E-value: 1.28e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1371 YLEFQDQVISGSLPCPKEEAAYLASIQLSVEEQWPSNKRTQtirrhllkgqfgrirdlaqkimvtpwevdqnlyctpprf 1450
Cdd:smart00295   99 YLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHD--------------------------------------- 139

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1451 pnesanasraqsvveeiqhrsrtptllrcitntdgLMSEEMQAQCLPVDLRgDRRTIKLVKERKRKLFHSQVYESEIGMK 1530
Cdd:smart00295  140 -----------------------------------LRGELSLKRFLPKQLL-DSRKLKEWRERIVELHKELIGLSPEEAK 183

                           170
                    ....*....|....*...
gi 1734340688  1531 KLYIQTAKKLAAFGCKVF 1548
Cdd:smart00295  184 LKYLELARKLPTYGVELF 201
 
Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 2545-3009 2.37e-133

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: 418.48  E-value: 2.37e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEADFSDSPRLPCPLQMknkiliknkkmivdpptpl 2704
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQL------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2705 pmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedspktskraeksarnik 2784
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2785 qqdslcsdhsveqakpstskttsktndrktedevlyaqlaqnaiRNQQPRKNNTgvqiAPELSDIVIYMQATKFKGFPpv 2864
Cdd:cd08596    142 --------------------------------------------KNKILLKNKK----APELSDLVIYCQAVKFPGLS-- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2865 dgiqsprimeegpasaslsfssrartpsnllntpapprrqrsstqlsqelaaeflgsvranaTATCYQVTSLNENAAKKL 2944
Cdd:cd08596    172 --------------------------------------------------------------TPKCYHISSLNENAAKRL 189

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2945 MKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08596    190 CRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 2351-2531 2.95e-79

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: 259.95  E-value: 2.95e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2351 SGLSGPSGKEFQEKPLTLVEFAELFRLFNTRMRKDLRDVFNDVLSTATTPQHCPKRerdrhsprmQSRLASVSNSYNADF 2430
Cdd:cd16203      1 GGLKGFSIGEVQDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAP---------LKRSLSISESYSGLF 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2431 LSNDFLTRNTAVTSHHISEKQN-KIYNALALASVNSMGGLMDTSRSSMLTPQMLRAFVNTHQMEQIDEQTAIKLIQDHEP 2509
Cdd:cd16203     72 PDLDLLTRNTSLDGLFISKKQQkKIYDAIAAASIVTNGAGVDSSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEP 151

                          170       180
                   ....*....|....*....|..
gi 1734340688 2510 DGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16203    152 DPILRSKNCLSFEGFARYLMDK 173
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 2548-2684 1.48e-69

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


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 230.47  E-value: 1.48e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2548 LRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKKSA 2627
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1734340688 2628 FITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEadfsDSPRLPCPLQ 2684
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPED 133
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 2548-2685 1.16e-63

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


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 213.68  E-value: 1.16e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  2548 LRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKKSA 2627
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1734340688  2628 FITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEADFSdsprLPCPLQM 2685
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQL 134
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3371-3474 6.66e-52

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: 178.68  E-value: 6.66e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3371 GDTFLVCVHNVSEDQPYAILRAGIHSTAADIIRQVFVKARRSNVDDSEFVLVEETCDDPKLNQGQMtpKYPNNRTTSRVL 3450
Cdd:cd01780      1 EDTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDIPSDFVLVEELEKEPTSDKSSS--KSSSSKTEQRVL 78

                           90       100
                   ....*....|....*....|....
gi 1734340688 3451 GQNENVWKAQSRWKSMGRFVLENR 3474
Cdd:cd01780     79 GDQENVYQAQSRWKGAGKFILKLR 102
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1698-1969 1.90e-51

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 182.83  E-value: 1.90e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1698 YILHFPEEVAFQLSSTEYQLFYSIQPMDYVRYVSCDLTSVpvSENPSPVRNLVKRLSEVSSWITHVIVSQPTHDDRKVAL 1777
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKK--SPSPLNLEAFIRRFNEVSNWVATEILKQTTPKDRAELL 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1778 TAILRIVETCWNIGNFNAAVEVLMGLKSEKLRPF---WLSLRQEEKSQFDSLCETLLPANqalPSQAYINAVQralRMPQ 1854
Cdd:smart00147   79 SKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLkktWEKLPSKYKKLFEELEELLSPER---NYKNYREALS---SCNL 152

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1855 SRVIPFFGIFLRDLYAIVNDLPNIVvigqegetqklefmsdPNGEDHFSSRIGVGGLLnaDKINLVAIVLDNLelfhRHS 1934
Cdd:smart00147  153 PPCIPFLGVLLKDLTFIDEGNPDFL----------------ENGLVNFEKRRQIAEIL--REIRQLQSQPYNL----RPN 210

                           250       260       270
                    ....*....|....*....|....*....|....*
gi 1734340688  1935 RTMIKLLEEQAVPPIqipQNEREQKEKEAKTYEPV 1969
Cdd:smart00147  211 RSDIQSLLQQLLDHL---DEEEELYQLSLKIEPRV 242
PLN02952 PLN02952
phosphoinositide phospholipase C
 2476-3165 5.22e-39

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 156.70  E-value: 5.22e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2476 SMLTPQMLRAFVNTHQME-QIDEQTAIKLIQD--HEPDGICR-QKNQMSFEGFTRFLC-DPVNFAFVPETiepdEEDLRY 2550
Cdd:PLN02952    52 GHMGADQLRRFLVLHQDElDCTLAEAQRIVEEviNRRHHVTRyTRHGLNLDDFFHFLLyDDLNGPITPQV----HHDMTA 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2551 PLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLP-LIYHGHTLVSKIGFRQVVEIIKKSAFI 2629
Cdd:PLN02952   128 PLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFS 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2630 TSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLvsnFLFEADfsdsprlpcplqmknkiliknkkMIVDPPTPLPMIER 2709
Cdd:PLN02952   208 SSPYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESD-----------------------SLVQFPSPESLKHR 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2710 gavqrgetqLNLHRKQSKNSYESSTVDevedddldeflddeeneeddqeevqvrSEKEDSPKTSKRAEKSARNikQQDSL 2789
Cdd:PLN02952   262 ---------IIISTKPPKEYLESSGPI---------------------------VIKKKNNVSPSGRNSSEET--EEAQT 303

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2790 CSDHSVEQakpstskttsKTNDRKTEDEvlyaqlaqnairnqqpRKNNTGVQIAPELSDIvIYMQATKFKGfppvdgiqs 2869
Cdd:PLN02952   304 LESMLFEQ----------EADSRSDSDQ----------------DDNKSGELQKPAYKRL-ITIHAGKPKG--------- 347

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2870 primeegpasaslsfssrartpsnllntpapprrqrsstQLSQELaaeflgSVRANATatcyQVTSLNENAAKKLMKRHP 2949
Cdd:PLN02952   348 ---------------------------------------TLKDAM------KVAVDKV----RRLSLSEQELEKAATTNG 378

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2950 AKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWDEShlLY 3029
Cdd:PLN02952   379 QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKG--FH 456

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3030 NKFLPLSKDIAGHSALLLNLTIISGQHV-YPNTHYAS-----LYVEIEVIGIHNDCVREKSKVVQRNSvNPIWNHTTQLR 3103
Cdd:PLN02952   457 DEVFDPKKKLPVKKTLKVKVYLGDGWRLdFSHTHFDSysppdFYTKMYIVGVPADNAKKKTKIIEDNW-YPAWNEEFSFP 535

                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340688 3104 IACVDLAFLRIAV--CDSGQNGRVVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRFE 3165
Cdd:PLN02952   536 LTVPELALLRIEVreYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLMRFIFV 599
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 3044-3165 9.10e-35

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: 130.74  E-value: 9.10e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3044 ALLLNLTIISGQHVYPNTHY----ASLYVEIEVIGIHN-DCVREKSKVVQRNSVNPIWNHTTQLRIACVDLAFLRIAVCD 3118
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKGDkgsiVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1734340688 3119 SGQNGR-VVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRFE 3165
Cdd:cd00275     81 EDSGDDdFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1705-1871 1.18e-20

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


Pssm-ID: 459872  Cd Length: 179  Bit Score: 91.88  E-value: 1.18e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1705 EVAFQLSSTEYQLFYSIQPMDYVRYVSCDLTSVPVSENpspVRNLVKRLSEVSSWITHVIVSQPTHDDRKVALTAILRIV 1784
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPN---IEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIA 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1785 ETCWNIGNFNAAVEVLMGLKS---EKLRPFWLSLRQEEKSQFDSLCETLLPANQalpSQAYINAVQRAlrmpQSRVIPFF 1861
Cdd:pfam00617   78 EHCRELNNFNSLMAILSGLNSspiSRLKKTWELVSKKYKKTLEELEKLMSPSRN---FKNYREALSSA----SPPCIPFL 150

                          170
                   ....*....|
gi 1734340688 1862 GIFLRDLYAI 1871
Cdd:pfam00617  151 GLYLTDLTFI 160
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1699-1879 2.05e-15

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


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 78.45  E-value: 2.05e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1699 ILHF-PEEVAFQLSSTEYQLFYSIQPMDYVRYVScDLTSVPVSENPSpVRNLVKRLSEVSSWITHVIVSQPTHDDRKVAL 1777
Cdd:cd00155      1 FLSLdPKELAEQLTLLDFELFRKIEPFELLGSLW-SKKDKNIHLSPN-LERFIERFNNLSNWVASEILLCTNPKKRARLL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1778 TAILRIVETCWNIGNFNAAVEVLMGLKS---EKLRPFWLSLRQEEKSQFDSLCETLLPANQALPSQAYINAVQralrmPQ 1854
Cdd:cd00155     79 SKFIQVAKHCRELNNFNSLMAIVSALSSspiSRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVG-----PN 153

                          170       180
                   ....*....|....*....|....*
gi 1734340688 1855 SRVIPFFGIFLRDLYAIVNDLPNIV 1879
Cdd:cd00155    154 PPCVPFLGVYLKDLTFLHEGNPDFL 178
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
190-338 4.08e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 75.76  E-value: 4.08e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  190 MNTLHMAVAHKQRDIVELLLKNGYDPNTPASchcKGNctatgnipltsiiprthsmtpelcstcsqlrvvsivdqTPLGV 269
Cdd:COG0666    121 ETPLHLAAYNGNLEIVKLLLEAGADVNAQDN---DGN--------------------------------------TPLHL 159

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340688  270 AVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESplSWPCLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:COG0666    160 AAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENG--HLEIVKLLLEAGADVNAKDNDGKTALDLA 226
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 3046-3145 1.05e-11

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: 63.66  E-value: 1.05e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  3046 LLNLTIISGQHVYP--NTHYASLYVEIEVIGIHNdcVREKSKVVqRNSVNPIWNHTTQLRIACVDLAFLRIAVCDSGQNG 3123
Cdd:smart00239    1 TLTVKIISARNLPPkdKGGKSDPYVKVSLDGDPK--EKKKTKVV-KNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFG 77

                            90       100
                    ....*....|....*....|....
gi 1734340688  3124 R--VVAHRVVPVKCIRPGFRHLPL 3145
Cdd:smart00239   78 RddFIGQVTIPLSDLLLGGRHEKL 101
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3205-3299 2.66e-11

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: 62.36  E-value: 2.66e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3205 KQIFVLRITGAFADETAITVHSESGSTVKTVMQQALLNAGKNADQVEEYVLIEESLPAPSGED---PIEQRVLPLNEPIM 3281
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRKEtekPGSQRILDMDEKIL 80

                           90
                   ....*....|....*...
gi 1734340688 3282 DAVACWNGSmRRFVLRKK 3299
Cdd:cd17114     81 QAQSKWKGS-GRFILKKL 97
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3208-3300 3.82e-11

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: 61.93  E-value: 3.82e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  3208 FVLRITGAF-ADETAITVHSESGSTVKTVMQQALLNAGKNaDQVEEYVLIEESlpapsgEDPIEQRVLPLNEPIMDAVAC 3286
Cdd:smart00314    3 FVLRVYVDDlPGGTYKTLRVSSRTTARDVIQQLLEKFHLT-DDPEEYVLVEVL------PDGKERVLPDDENPLQLQKLW 75

                            90
                    ....*....|....*
gi 1734340688  3287 -WNGSMRRFVLRKKG 3300
Cdd:smart00314   76 pRRGPNLRFVLRKRD 90
PLN02223 PLN02223
phosphoinositide phospholipase C
 2480-2663 4.53e-11

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 68.51  E-value: 4.53e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2480 PQMLRAFVNTHQMEQIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDPVN-FAFVPETIEP-----DEEDLRYPLS 2553
Cdd:PLN02223    34 PELLPRFIELLDTEKDEDGAGLNAAEKIAAELKRRKCDILAFRNLRCLELDHLNeFLFSTELNPPigdqvRHHDMHAPLS 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2554 HYYINSSHNTYLTGHQLKGPSSS-EMYRQVLLTGCRCVELDCW-DGDDGLpLIYHGHTLVSKIGFRQVVEIIKKSAFI-T 2630
Cdd:PLN02223   114 HYFIHTSLKSYFTGNNVFGKLYSiEPIIDALEQGVRVVELDLLpDGKDGI-CVRPKWNFEKPLELQECLDAIKEHAFTkC 192

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1734340688 2631 SDLPVILSIENHCSLQQQAKMAQMFKTVLGDLL 2663
Cdd:PLN02223   193 RSYPLIITFKDGLKPDLQSKATQMIDQTFGDMV 225
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1371-1548 1.28e-10

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: 63.47  E-value: 1.28e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1371 YLEFQDQVISGSLPCPKEEAAYLASIQLSVEEQWPSNKRTQtirrhllkgqfgrirdlaqkimvtpwevdqnlyctpprf 1450
Cdd:smart00295   99 YLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHD--------------------------------------- 139

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1451 pnesanasraqsvveeiqhrsrtptllrcitntdgLMSEEMQAQCLPVDLRgDRRTIKLVKERKRKLFHSQVYESEIGMK 1530
Cdd:smart00295  140 -----------------------------------LRGELSLKRFLPKQLL-DSRKLKEWRERIVELHKELIGLSPEEAK 183

                           170
                    ....*....|....*...
gi 1734340688  1531 KLYIQTAKKLAAFGCKVF 1548
Cdd:smart00295  184 LKYLELARKLPTYGVELF 201
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3372-3474 2.25e-10

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: 59.62  E-value: 2.25e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  3372 DTFLVCVHNVS-EDQPYAILRAGIHSTAADIIRQVFVKARRSNvDDSEFVLVEETCDDPKlnqgqmtpkypnnrttsRVL 3450
Cdd:smart00314    1 DTFVLRVYVDDlPGGTYKTLRVSSRTTARDVIQQLLEKFHLTD-DPEEYVLVEVLPDGKE-----------------RVL 62

                            90       100
                    ....*....|....*....|....*..
gi 1734340688  3451 GQNENVWKAQSRWK---SMGRFVLENR 3474
Cdd:smart00314   63 PDDENPLQLQKLWPrrgPNLRFVLRKR 89
Ank_2 pfam12796
Ankyrin repeats (3 copies);
193-328 1.37e-08

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 54.74  E-value: 1.37e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  193 LHMAVAHKQRDIVELLLKNGYDPNtpaschckgnctatgnipltsiiprthsmtpelcstcsqlrVVSIVDQTPLGVAVR 272
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADAN-----------------------------------------LQDKNGRTALHLAAK 39

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688  273 SQSSELIALLIAYgGDVNLGDeDGNTPLMLAVRESPLSwpCLHTLIFFGAQIEQKN 328
Cdd:pfam12796   40 NGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHLE--IVKLLLEKGADINVKD 91
PHA03100 PHA03100
ankyrin repeat protein; Provisional
 189-338 4.98e-07

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 55.44  E-value: 4.98e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  189 MMNTLHMAVAHKQRDIVELLLKNGYDPN-------TPASCHCKGNCTATGNIPLTSII---------PRTHSMTPELCST 252
Cdd:PHA03100    35 PVLPLYLAKEARNIDVVKILLDNGADINsstknnsTPLHYLSNIKYNLTDVKEIVKLLleyganvnaPDNNGITPLLYAI 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  253 CSQLRVVSIVD----------------QTPLGVAVRSQSSEL------------------IALLIAYGGDVNLGDEDGNT 298
Cdd:PHA03100   115 SKKSNSYSIVEylldnganvniknsdgENLLHLYLESNKIDLkilkllidkgvdinaknrVNYLLSYGVPINIKDVYGFT 194

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1734340688  299 PLMLAVRESPLSWpcLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:PHA03100   195 PLHYAVYNNNPEF--VKYLLDLGANPNLVNKYGDTPLHIA 232
C2 pfam00168
C2 domain;
3046-3139 2.12e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.77  E-value: 2.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3046 LLNLTIISGQHVYPNTHYASL--YVEIEvigIHNDCVREKSKVVqRNSVNPIWNHTTQLRIACVDLAFLRIAVCDSGQNG 3123
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSdpYVKVY---LLDGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFG 77

                           90
                   ....*....|....*...
gi 1734340688 3124 R--VVAHRVVPVKCIRPG 3139
Cdd:pfam00168   78 RddFIGEVRIPLSELDSG 95
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 1362-1401 3.77e-04

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 42.64  E-value: 3.77e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1734340688 1362 ENNEQINDE------YLEFQDQVISGSLPCPKEEAAYLASIQLSVE 1401
Cdd:pfam00373    1 DLELLLQDEvtrhllYLQAKDDILEGRLPCSEEEALLLAALQLQAE 46
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3380-3476 1.60e-03

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: 40.39  E-value: 1.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3380 NVSEDQPYAILRAGIHSTAADIIRQVFVKARRSNvDDSEFVLVEETCDdpklnqgqmtpkypnnRTTSRVLGQNENVWKA 3459
Cdd:pfam00788   11 DGKPGTTYKTILVSSSTTAEEVIEALLEKFGLED-DPRDYVLVEVLER----------------GGGERRLPDDECPLQI 73

                           90       100
                   ....*....|....*....|
gi 1734340688 3460 QSRWKS---MGRFVLENRKD 3476
Cdd:pfam00788   74 QLQWPRdasDSRFLLRKRDD 93
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 2478-2531 2.11e-03

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: 39.54  E-value: 2.11e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2478 LTPQMLRAFVNTHQMEQI-DEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDP 2531
Cdd:pfam09279   25 LSLDELVDFLREEQREEDaSPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSP 79
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3223-3299 3.46e-03

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: 39.24  E-value: 3.46e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340688 3223 TVHSESGSTVKTVMQQALLNAGKNADQvEEYVLIEESlpapsgEDPIEQRVLPLNEPIMDAVACW--NGSMRRFVLRKK 3299
Cdd:pfam00788   20 TILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVL------ERGGGERRLPDDECPLQIQLQWprDASDSRFLLRKR 91
 
Name Accession Description Interval E-value
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 2545-3009 2.37e-133

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: 418.48  E-value: 2.37e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08596      1 EEDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEADFSDSPRLPCPLQMknkiliknkkmivdpptpl 2704
Cdd:cd08596     81 RSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQL------------------- 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2705 pmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedspktskraeksarnik 2784
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2785 qqdslcsdhsveqakpstskttsktndrktedevlyaqlaqnaiRNQQPRKNNTgvqiAPELSDIVIYMQATKFKGFPpv 2864
Cdd:cd08596    142 --------------------------------------------KNKILLKNKK----APELSDLVIYCQAVKFPGLS-- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2865 dgiqsprimeegpasaslsfssrartpsnllntpapprrqrsstqlsqelaaeflgsvranaTATCYQVTSLNENAAKKL 2944
Cdd:cd08596    172 --------------------------------------------------------------TPKCYHISSLNENAAKRL 189

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2945 MKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08596    190 CRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 2545-2684 5.89e-82

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: 269.71  E-value: 5.89e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08558      1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEadfsDSPRLPCPLQ 2684
Cdd:cd08558     81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDE----NPVQLPSPEQ 136
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 2351-2531 2.95e-79

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: 259.95  E-value: 2.95e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2351 SGLSGPSGKEFQEKPLTLVEFAELFRLFNTRMRKDLRDVFNDVLSTATTPQHCPKRerdrhsprmQSRLASVSNSYNADF 2430
Cdd:cd16203      1 GGLKGFSIGEVQDTQLTFVEFVELFKSFSLRMRKDLKDLFDQFAVPYSRSGSNAAP---------LKRSLSISESYSGLF 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2431 LSNDFLTRNTAVTSHHISEKQN-KIYNALALASVNSMGGLMDTSRSSMLTPQMLRAFVNTHQMEQIDEQTAIKLIQDHEP 2509
Cdd:cd16203     72 PDLDLLTRNTSLDGLFISKKQQkKIYDAIAAASIVTNGAGVDSSRSSVLTISQLKDFLENHQMEHITEEEAIKIIQRHEP 151

                          170       180
                   ....*....|....*....|..
gi 1734340688 2510 DGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16203    152 DPILRSKNCLSFEGFARYLMDK 173
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 2546-3008 1.68e-78

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: 261.12  E-value: 1.68e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08593      2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIRE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNflfeadfsdsprlpcPLQmknkiliknkkmivDPPTPLP 2705
Cdd:cd08593     82 YAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQ---------------PLD--------------GVLTALP 132

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2706 miergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedSPKtskraeksarnikq 2785
Cdd:cd08593    133 ---------------------------------------------------------------SPE-------------- 135

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2786 qdslcsdhsveqakpstskttsktndrktedevlyaqlaqnAIRNQQPRKNNTGvQIAPELSDIVIYMQATKFKGFPPvd 2865
Cdd:cd08593    136 -----------------------------------------ELKGKILVKGKKL-KLAKELSDLVIYCKSVHFKSFEH-- 171

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2866 giqsprimeegpasaslsfssrartpsnllntpapprrqrsstqlsqelaaeflgsvrANATATCYQVTSLNENAAKKLM 2945
Cdd:cd08593    172 ----------------------------------------------------------SKENYHFYEMSSFSESKALKLA 193

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340688 2946 KRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQ 3008
Cdd:cd08593    194 QESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQ 256
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 2545-3008 1.84e-74

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: 249.56  E-value: 1.84e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDG--DDGLPLIYHGHTLVSKIGFRQVVEI 2622
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2623 IKKSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLfeadfSDSPrlpcplqmknkiliknkkmiVDPPT 2702
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPL-----EKYP--------------------LEPGV 135

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2703 PLPmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedSPKTSKRaeksarn 2782
Cdd:cd08591    136 PLP---------------------------------------------------------------SPNDLKR------- 145

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2783 ikqqdslcsdhsveqakpstskttsktndrktedEVLyaqlaqnaIRNQQprknntgvqiapeLSDIVIYMQATKFKGFp 2862
Cdd:cd08591    146 ----------------------------------KIL--------IKNKK-------------LSSLVNYIQPVKFQGF- 169

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2863 pvdgiqsprimeegpasaslsfssrartpsnllntpapprrqrsstqlsqELAAEflgsvranaTATCYQVTSLNENAAK 2942
Cdd:cd08591    170 --------------------------------------------------EVAEK---------RNKHYEMSSFNESKGL 190

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688 2943 KLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQ 3008
Cdd:cd08591    191 GYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEY 256
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 2548-2684 1.48e-69

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


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 230.47  E-value: 1.48e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2548 LRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKKSA 2627
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1734340688 2628 FITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEadfsDSPRLPCPLQ 2684
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPED 133
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 2545-2684 5.11e-65

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: 221.35  E-value: 5.11e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSnflfEADFSDSPRLPCPLQ 2684
Cdd:cd08598     81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVT----EPLDGLEDELPSPEE 136
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 2548-2685 1.16e-63

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


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 213.68  E-value: 1.16e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  2548 LRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKKSA 2627
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1734340688  2628 FITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEADFSdsprLPCPLQM 2685
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQL 134
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 2546-3009 1.84e-62

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: 215.36  E-value: 1.84e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08597      2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLFEadfsDSPRLPCPlqmknkiliknkkmivdpptplp 2705
Cdd:cd08597     82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNE----GESYLPSP----------------------- 134

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2706 miergavqrgetqlnlHRKQSKNSYESStvdevedddldeflddeeneeddqeevqvrsekedspKTSKRaeksarnikq 2785
Cdd:cd08597    135 ----------------HDLKGKIIIKGK-------------------------------------KLKRR---------- 151

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2786 qdslcsdhsveqakpstskttsktndrktedevlyaqlaqnairnqqprknntgvQIAPELSDIVIYMQATKFKGFPpvd 2865
Cdd:cd08597    152 -------------------------------------------------------KLCKELSDLVSLCKSVRFQDFP--- 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2866 giqsprimeegpasaslsFSSRARtpsnllntpapprrqrsstqlsqelaaeflgsvranataTCYQVTSLNENAAKKLM 2945
Cdd:cd08597    174 ------------------TSAQNQ---------------------------------------KYWEVCSFSENLARRLA 196

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340688 2946 KRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08597    197 NEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 2546-2685 4.27e-62

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: 213.06  E-value: 4.27e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFL-FEADfsdspRLPCPLQM 2685
Cdd:cd08592     82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVdRNAD-----QLPSPNQL 137
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 2546-3006 8.99e-62

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: 213.34  E-value: 8.99e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08630      2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLfeadfsDSPrlpcplqmknkiliknkkmivdPPTPLP 2705
Cdd:cd08630     82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPL------DSL----------------------NPEELP 133

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2706 miergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedSPktskraeksarnikq 2785
Cdd:cd08630    134 ---------------------------------------------------------------SP--------------- 135

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2786 qdslcsdhsvEQAKPSTSKTTSKtndrktedevlyaqlaqnairnqqprknntgVQIAPELSDIVIYMQATKFKGFppvd 2865
Cdd:cd08630    136 ----------EELKGRVLVKGKK-------------------------------LQISPELSALAVYCQATRLRTL---- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2866 giqsprimeegpasaslsfssrartpsnllnTPAPPRRQRSstqlsqelaaeflgsvranatatcyQVTSLNENAAKKLM 2945
Cdd:cd08630    171 -------------------------------EPAPVQPQPC-------------------------QVSSLSERKAKKLI 194

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1734340688 2946 KRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMF 3006
Cdd:cd08630    195 REAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRF 255
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 2546-3009 4.29e-57

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: 199.88  E-value: 4.29e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSnflfeADFSDS-PRLPCPLQMknkiliknkkmivdpptpl 2704
Cdd:cd08629     82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLD-----QPLDGVtTSLPSPEQL------------------- 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2705 pmiergavqRGEtqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeeVQVRSEKedspktskraeksarnik 2784
Cdd:cd08629    138 ---------KGK-------------------------------------------ILLKGKK------------------ 147

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2785 qqdslcsdhsveqakpstskttsktndrktedevlyaqlaqnairnqqprknntgVQIAPELSDIVIYMQATKFKGFppv 2864
Cdd:cd08629    148 -------------------------------------------------------LKLVPELSDMIIYCKSVHFGGF--- 169

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2865 dgiqsprimeEGPASASLSFssrartpsnllntpapprrqrsstqlsqelaaeflgsvranatatcYQVTSLNENAAKKL 2944
Cdd:cd08629    170 ----------SSPGTSGQAF----------------------------------------------YEMASFSESRALRL 193

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2945 MKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08629    194 LQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 2547-3007 7.45e-57

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: 198.84  E-value: 7.45e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2547 DLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDG--DDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08626      3 DMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGkgEDQEPIITHGKAMCTDILFKDVIQAIK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNflfeaDFSDSPrlpcplqmknkiliknkkmiVDPPTPL 2704
Cdd:cd08626     83 DTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTK-----PLESHP--------------------LEPGVPL 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2705 PmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedSPKTSKRaeksarnik 2784
Cdd:cd08626    138 P---------------------------------------------------------------SPNKLKR--------- 145

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2785 qqdslcsdhsveqakpstskttsktndrktedEVLyaqlaqnaIRNQQprknntgvqiapeLSDIVIYMQATKFKGFPpv 2864
Cdd:cd08626    146 --------------------------------KIL--------IKNKR-------------LSSLVNYAQPVKFQGFD-- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2865 dgiqsprimeegpasaslsfssrartpsnllntpapprrqrsstqlsqelaaeflgsvRANATATCYQVTSLNENAAKKL 2944
Cdd:cd08626    171 ----------------------------------------------------------VAEERNIHFNMSSFNESVGLGY 192

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340688 2945 MKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFE 3007
Cdd:cd08626    193 LKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFE 255
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 2546-2682 1.30e-56

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: 197.33  E-value: 1.30e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08594      2 QDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINK 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVsnfLFEADFSDSPRLPCP 2682
Cdd:cd08594     82 YAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLD---LSSVISGDSKQLPSP 135
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 2546-2685 1.12e-53

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: 188.70  E-value: 1.12e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNflfEADFSdSPRLPCPLQM 2685
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTK---PVDIN-ADGLPSPNQL 137
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 2546-3006 2.32e-53

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: 188.73  E-value: 2.32e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLvsnfLFEADFSDSPRLPCPLQMknkilikNKKMIVDpptplp 2705
Cdd:cd08628     82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKL----LMKPLEASADQLPSPTQL-------KEKIIIK------ 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2706 miergavqrgetqlnlHRKqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedspktskraeksarnikq 2785
Cdd:cd08628    145 ----------------HKK------------------------------------------------------------- 147

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2786 qdslcsdhsveqakpstskttsktndrktedevlyaqlaqnairnqqprknntgvQIAPELSDIVIYMQAT-KFKgfppv 2864
Cdd:cd08628    148 -------------------------------------------------------LIAIELSDLVVYCKPTsKTK----- 167

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2865 DGIQSPRIMEegpasaslsfssrartpsnllntpapprrqrsstqlsqelaaeflgsvranatatcyqVTSLNENAAKKL 2944
Cdd:cd08628    168 DNLENPDFKE----------------------------------------------------------IRSFVETKAPSI 189

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1734340688 2945 MKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMF 3006
Cdd:cd08628    190 IRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALF 251
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 2546-2682 5.64e-52

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: 184.86  E-value: 5.64e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08633      2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLL----VSNflfeadfSDSPRLPCP 2682
Cdd:cd08633     82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdlssVIS-------NDCTRLPSP 135
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3371-3474 6.66e-52

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: 178.68  E-value: 6.66e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3371 GDTFLVCVHNVSEDQPYAILRAGIHSTAADIIRQVFVKARRSNVDDSEFVLVEETCDDPKLNQGQMtpKYPNNRTTSRVL 3450
Cdd:cd01780      1 EDTFLVCVHNVSPDQPYTILKAPVSSTAQDIIAQALVKARRSEDIPSDFVLVEELEKEPTSDKSSS--KSSSSKTEQRVL 78

                           90       100
                   ....*....|....*....|....
gi 1734340688 3451 GQNENVWKAQSRWKSMGRFVLENR 3474
Cdd:cd01780     79 GDQENVYQAQSRWKGAGKFILKLR 102
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 2907-3021 8.72e-52

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: 178.59  E-value: 8.72e-52
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  2907 STQLSQELAAEFLGSVRANATATCYQVTSLNENAAKKLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQ 2986
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1734340688  2987 MVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCL 3021
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 2546-2682 1.55e-51

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: 183.69  E-value: 1.55e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08632      2 QDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINK 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVsnfLFEADFSDSPRLPCP 2682
Cdd:cd08632     82 YAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLD---LSSVLTGDPKQLPSP 135
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
1698-1969 1.90e-51

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 182.83  E-value: 1.90e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1698 YILHFPEEVAFQLSSTEYQLFYSIQPMDYVRYVSCDLTSVpvSENPSPVRNLVKRLSEVSSWITHVIVSQPTHDDRKVAL 1777
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKK--SPSPLNLEAFIRRFNEVSNWVATEILKQTTPKDRAELL 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1778 TAILRIVETCWNIGNFNAAVEVLMGLKSEKLRPF---WLSLRQEEKSQFDSLCETLLPANqalPSQAYINAVQralRMPQ 1854
Cdd:smart00147   79 SKFIQVAKHCRELNNFNSLMAIVSALSSSPISRLkktWEKLPSKYKKLFEELEELLSPER---NYKNYREALS---SCNL 152

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1855 SRVIPFFGIFLRDLYAIVNDLPNIVvigqegetqklefmsdPNGEDHFSSRIGVGGLLnaDKINLVAIVLDNLelfhRHS 1934
Cdd:smart00147  153 PPCIPFLGVLLKDLTFIDEGNPDFL----------------ENGLVNFEKRRQIAEIL--REIRQLQSQPYNL----RPN 210

                           250       260       270
                    ....*....|....*....|....*....|....*
gi 1734340688  1935 RTMIKLLEEQAVPPIqipQNEREQKEKEAKTYEPV 1969
Cdd:smart00147  211 RSDIQSLLQQLLDHL---DEEEELYQLSLKIEPRV 242
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 2546-3009 1.98e-51

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: 183.61  E-value: 1.98e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNFLfeaDFSDSPRLPCPLQMknkiliknkkmivdpptplp 2705
Cdd:cd08631     82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTL---DGVLPTQLPSPEEL-------------------- 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2706 miergavqRGEtqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeeVQVRSEKedspktskraeksarnikq 2785
Cdd:cd08631    139 --------RGK-------------------------------------------ILLKGKK------------------- 148

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2786 qdslcsdhsveqakpstskttsktndrktedevlyaqlaqnairnqqprknntgVQIAPELSDIVIYMQATKFKGFppvd 2865
Cdd:cd08631    149 ------------------------------------------------------IRLSPELSDCVIYCKSVSFRSF---- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2866 giqsprimeegpasaslsfsSRARTPSNLlntpapprrqrsstqlsqelaaeflgsvranatatcYQVTSLNENAAKKLM 2945
Cdd:cd08631    171 --------------------THSREHYHF------------------------------------YEISSFTETKARKLI 194

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340688 2946 KRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08631    195 REAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 2546-3006 4.93e-51

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: 182.44  E-value: 4.93e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKK 2625
Cdd:cd08595      2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2626 SAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLVSNflfeadfsdsprlpcplqmknkiliknkkMIVDPPTplp 2705
Cdd:cd08595     82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRA-----------------------------PIDDPAT--- 129

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2706 miergavqrgeTQLnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedspktskraeksarnikq 2785
Cdd:cd08595    130 -----------GEL------------------------------------------------------------------ 132

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2786 qdslcsdhsveqakPSTskttsktndrktedevlyaqlaqNAIRNQQPRKNNTgvQIAPELSDIVIYMQATKFKGFppvd 2865
Cdd:cd08595    133 --------------PSP-----------------------EALKFKILVKNKK--KIAKALSDLVIYTKSEKFCSF---- 169

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2866 giqsprimeegpasaslsfssrartpsnllntpapprrqrSSTQLSQElaaeflgsvranatatCYQVTSLNENAAKKLM 2945
Cdd:cd08595    170 ----------------------------------------THSRDNQH----------------SYENNSIGENKARKLL 193

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1734340688 2946 KRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMF 3006
Cdd:cd08595    194 KSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKF 254
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 2546-3007 2.10e-48

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: 174.86  E-value: 2.10e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGD--DGLPLIYHGHTLVSKIGFRQVVEII 2623
Cdd:cd08624      2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMTTEILFKDAIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2624 KKSAFITSDLPVILSIENHC-SLQQQAKMAQMFKTVLGDLLVSnflfeadfsdSPRLPCPLQmknkiliknkkmivdPPT 2702
Cdd:cd08624     82 AESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLT----------EPLEKYPLK---------------PGV 136

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2703 PLPmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedSPKTskraeksarn 2782
Cdd:cd08624    137 PLP---------------------------------------------------------------SPED---------- 143

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2783 ikqqdslcsdhsveqakpstskttsktndrktedevlyaQLAQNAIRNQQprknntgvqiAPELSDIVIYMQATKFkgfp 2862
Cdd:cd08624    144 ---------------------------------------LRGKILIKNKK----------YEEMSSLVNYIQPTKF---- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2863 pvdgiqsprimeegpasasLSFSSRArtpsnllntpappRRQRSstqlsqelaaeflgsvranatatcYQVTSLNENAAK 2942
Cdd:cd08624    171 -------------------VSFEFSA-------------QKNRS------------------------YVISSFTELKAY 194

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2943 KLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFE 3007
Cdd:cd08624    195 DLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFE 259
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 2546-3007 4.52e-46

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: 167.92  E-value: 4.52e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDG--DDGLPLIYHGHTLVSKIGFRQVVEII 2623
Cdd:cd08625      2 DDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2624 KKSAFITSDLPVILSIENHC-SLQQQAKMAQMFKTVLGDLLVSNflfeadfsdsPRLPCPLQmknkiliknkkmivdPPT 2702
Cdd:cd08625     82 AESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLID----------PLDKYPLV---------------PGV 136

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2703 PLPmiergavqrgetqlnlhrkqsknsyesstvdevedddldeflddeeneeddqeevqvrsekedSPKtskraeksarn 2782
Cdd:cd08625    137 QLP---------------------------------------------------------------SPQ----------- 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2783 ikqqdslcsdhsveqakpstskttsktndrktedEVLYAQLAQNAirnqqprknntgvqiapELSDIVIYMQATKFKGFp 2862
Cdd:cd08625    143 ----------------------------------ELMGKILVKNK-----------------KMSTLVNYIEPVKFKSF- 170

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2863 pvdgiqsprimeegpasaslsfssrartpsnllntPAPPRRQRsstqlsqelaaeflgsvranatatCYQVTSLNENAAK 2942
Cdd:cd08625    171 -----------------------------------EAAAKRNK------------------------FFEMSSFVETKAM 191

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2943 KLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFE 3007
Cdd:cd08625    192 EQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFE 256
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 2546-2685 1.27e-43

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


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 161.02  E-value: 1.27e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2546 EDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDG--DDGLPLIYHGHTLVSKIGFRQVVEII 2623
Cdd:cd08623      2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340688 2624 KKSAFITSDLPVILSIENHC-SLQQQAKMAQMFKTVLGDLLVSNFLFEADFSDSPRLPCPLQM 2685
Cdd:cd08623     82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDL 144
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 2846-3020 3.72e-40

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 145.30  E-value: 3.72e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2846 LSDIVIYMQATKFKGFppvdgiqsprimeegpasaslsfssrartpsnllNTPApprrqrsstqlsqelaaeflgsvran 2925
Cdd:pfam00387    1 LSDLVVYTQSVKFKSF----------------------------------STPE-------------------------- 20

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2926 aTATCYQVTSLNENAAKKLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAM 3005
Cdd:pfam00387   21 -SKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQMVALNWQTPDEGMQLNEGM 99

                          170
                   ....*....|....*
gi 1734340688 3006 FEQSGNCGYQLKPRC 3020
Cdd:pfam00387  100 FADNGGCGYVLKPEF 114
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 2545-2663 1.37e-39

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


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 148.29  E-value: 1.37e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2545 EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIK 2624
Cdd:cd08599      1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1734340688 2625 KSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLL 2663
Cdd:cd08599     81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKL 119
PLN02952 PLN02952
phosphoinositide phospholipase C
 2476-3165 5.22e-39

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 156.70  E-value: 5.22e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2476 SMLTPQMLRAFVNTHQME-QIDEQTAIKLIQD--HEPDGICR-QKNQMSFEGFTRFLC-DPVNFAFVPETiepdEEDLRY 2550
Cdd:PLN02952    52 GHMGADQLRRFLVLHQDElDCTLAEAQRIVEEviNRRHHVTRyTRHGLNLDDFFHFLLyDDLNGPITPQV----HHDMTA 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2551 PLSHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLP-LIYHGHTLVSKIGFRQVVEIIKKSAFI 2629
Cdd:PLN02952   128 PLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFS 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2630 TSDLPVILSIENHCSLQQQAKMAQMFKTVLGDLLvsnFLFEADfsdsprlpcplqmknkiliknkkMIVDPPTPLPMIER 2709
Cdd:PLN02952   208 SSPYPVIITLEDHLTPDLQAKVAEMATQIFGQML---YYPESD-----------------------SLVQFPSPESLKHR 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2710 gavqrgetqLNLHRKQSKNSYESSTVDevedddldeflddeeneeddqeevqvrSEKEDSPKTSKRAEKSARNikQQDSL 2789
Cdd:PLN02952   262 ---------IIISTKPPKEYLESSGPI---------------------------VIKKKNNVSPSGRNSSEET--EEAQT 303

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2790 CSDHSVEQakpstskttsKTNDRKTEDEvlyaqlaqnairnqqpRKNNTGVQIAPELSDIvIYMQATKFKGfppvdgiqs 2869
Cdd:PLN02952   304 LESMLFEQ----------EADSRSDSDQ----------------DDNKSGELQKPAYKRL-ITIHAGKPKG--------- 347

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2870 primeegpasaslsfssrartpsnllntpapprrqrsstQLSQELaaeflgSVRANATatcyQVTSLNENAAKKLMKRHP 2949
Cdd:PLN02952   348 ---------------------------------------TLKDAM------KVAVDKV----RRLSLSEQELEKAATTNG 378

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2950 AKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWDEShlLY 3029
Cdd:PLN02952   379 QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKG--FH 456

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3030 NKFLPLSKDIAGHSALLLNLTIISGQHV-YPNTHYAS-----LYVEIEVIGIHNDCVREKSKVVQRNSvNPIWNHTTQLR 3103
Cdd:PLN02952   457 DEVFDPKKKLPVKKTLKVKVYLGDGWRLdFSHTHFDSysppdFYTKMYIVGVPADNAKKKTKIIEDNW-YPAWNEEFSFP 535

                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340688 3104 IACVDLAFLRIAV--CDSGQNGRVVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRFE 3165
Cdd:PLN02952   536 LTVPELALLRIEVreYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLMRFIFV 599
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 2477-3164 6.99e-38

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 152.88  E-value: 6.99e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2477 MLTPQMLRAFVNTHQMEQIDEQTAIKLIQDHEPdgiCRQKNQMSFEGFTRFLCDPVNfafVPETIEPDEEDLRYPLSHYY 2556
Cdd:PLN02222    40 MTVDHLHRFLIDVQKQDKATREDAQSIINSASS---LLHRNGLHLDAFFKYLFGDNN---PPLALHEVHHDMDAPISHYF 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2557 INSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCW--DGDDGLPLIyHGHTLVSKIGFRQVVEIIKKSAFITSDLP 2634
Cdd:PLN02222   114 IFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWpnSDKDDIDVL-HGMTLTTPVGLIKCLKAIRAHAFDVSDYP 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2635 VILSIENHCSLQQQAKMAQMFKTVLGDLLVSnflfeadfsdsprlpcplqmknkiliknkkmivdPPTplpmiergavqr 2714
Cdd:PLN02222   193 VVVTLEDHLTPDLQSKVAEMVTEIFGEILFT----------------------------------PPV------------ 226

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2715 GETqlnLHRKQSKNSYESSTvdevedddldeflddeeneeddqeEVQVRSEKEDSPKTSKRAEKSARNIKQQDSLCSD-H 2793
Cdd:PLN02222   227 GES---LKEFPSPNSLKKRI------------------------IISTKPPKEYKEGKDDEVVQKGKDLGDEEVWGREvP 279

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2794 SVEQAKPSTSKTTSKTNDRKTEDEvlyaqlaqnaiRNQQPRKNntgvqiAPELSDIVIYMQATKFKGfppvdGIQsprim 2873
Cdd:PLN02222   280 SFIQRNKSVDKNDSNGDDDDDDDD-----------GEDKSKKN------APPQYKHLIAIHAGKPKG-----GIT----- 332

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2874 eegpasaslsfssrartpSNLLNTPAPPRRqrsstqlsqelaaeflgsvranatatcyqvTSLNENAAKKLMKRHPAKCV 2953
Cdd:PLN02222   333 ------------------ECLKVDPDKVRR------------------------------LSLSEEQLEKAAEKYAKQIV 364

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2954 SYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWDESHllynkfl 3033
Cdd:PLN02222   365 RFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGS------- 437

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3034 plSKDIAGHSALL-----LNLTIISGQHVY---PNTHY-----ASLYVEIEVIGIHNDCVREKSKVVQRNSVnPIWNHTT 3100
Cdd:PLN02222   438 --DSDIFDPKATLpvkttLRVTIYMGEGWYfdfRHTHFdqyspPDFYTRVGIAGVPGDTVMKKTKTLEDNWI-PAWDEVF 514

                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688 3101 QLRIACVDLAFLRIAV--CDSGQNGRVVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRF 3164
Cdd:PLN02222   515 EFPLTVPELALLRLEVheYDMSEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKVEF 580
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 3044-3165 9.10e-35

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: 130.74  E-value: 9.10e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3044 ALLLNLTIISGQHVYPNTHY----ASLYVEIEVIGIHN-DCVREKSKVVQRNSVNPIWNHTTQLRIACVDLAFLRIAVCD 3118
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKGDkgsiVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1734340688 3119 SGQNGR-VVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRFE 3165
Cdd:cd00275     81 EDSGDDdFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
PLN02228 PLN02228
Phosphoinositide phospholipase C
 2477-3145 2.73e-34

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 141.71  E-value: 2.73e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2477 MLTPQMLRaFVNTHQMEQideQTAIKLIQD--H--EPDGICRQKNQMSFEGFTRFLCDPVNfAFVPETIEPdEEDLRYPL 2552
Cdd:PLN02228    39 MSFDELLR-FVSEVQGER---HAGLDYVQDifHsvKHHNVFHHHGLVHLNAFYRYLFSDTN-SPLPMSGQV-HHDMKAPL 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2553 SHYYINSSHNTYLTGHQLKGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPL-IYHGHTLVSKIGFRQVVEIIKKSAFITS 2631
Cdd:PLN02228   113 SHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAeVRHGRTLTSHEDLQKCLNAIKDNAFQVS 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2632 DLPVILSIENHCSLQQQAKMAQMFKTVLGDLlvsnfLFEADFSDSPRLPCPLQMknkiliknkkmivdpptplpmierga 2711
Cdd:PLN02228   193 DYPVVITLEDHLPPNLQAQVAKMLTKTFRGM-----LFRCTSESTKHFPSPEEL-------------------------- 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2712 vqrgETQLNLHRKQSKNSYESSTvdevedddldeflddeeneeddqeevqvrsekedspktskraeksarnikqqdslcs 2791
Cdd:PLN02228   242 ----KNKILISTKPPKEYLESKT--------------------------------------------------------- 260

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2792 dhsveqAKPSTSKTTSKTNDRKTEDevlyaqlAQNAIRNQQPRKNNTGVqiapELSDIVIYMQATKfkgfppvdgiqspr 2871
Cdd:PLN02228   261 ------VQTTRTPTVKETSWKRVAD-------AENKILEEYKDEESEAV----GYRDLIAIHAANC-------------- 309

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2872 imeEGPASASLSfssrartpsnllNTPAPPRRqrsstqlsqelaaeflgsvranatatcyqvTSLNENAAKKLMKRHPAK 2951
Cdd:PLN02228   310 ---KDPLKDCLS------------DDPEKPIR------------------------------VSMDEQWLETMVRTRGTD 344

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2952 CVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWDEsHLLYN- 3030
Cdd:PLN02228   345 LVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDE-HTLFDp 423

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3031 -KFLPLSKDiaghsallLNLTIISGQHV---YPNTHY-----ASLYVEIEVIGIHNDCVREKSKvVQRNSVNPIWNHTT- 3100
Cdd:PLN02228   424 cKRLPIKTT--------LKVKIYTGEGWdldFHLTHFdqyspPDFFVKIGIAGVPRDTVSYRTE-TAVDQWFPIWGNDEf 494

                          650       660       670       680
                   ....*....|....*....|....*....|....*....|....*..
gi 1734340688 3101 --QLRIACVDLAFLRIAVCDSGQNGRVVAHRVVPVKCIRPGFRHLPL 3145
Cdd:PLN02228   495 lfQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRL 541
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 2547-2665 3.64e-34

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: 134.31  E-value: 3.64e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2547 DLRYPLSHYYINSSHNTYLTGHQL-----KGPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTLVsKIGFRQVVE 2621
Cdd:cd00137      3 PDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEVIE 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1734340688 2622 IIKKSAFITSDLPVILSIENHCSL--QQQAKMAQMFKTVLGDLLVS 2665
Cdd:cd00137     82 AIAQFLKKNPPETIIMSLKNEVDSmdSFQAKMAEYCRTIFGDMLLT 127
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 2510-3164 1.96e-33

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 139.45  E-value: 1.96e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2510 DGICRQKNQMSfeGFTR--FLCDPVNFAFVPETIEPD-----EEDLRYPLSHYYINSSHNTYLTGHQLKGPSSSEMYRQV 2582
Cdd:PLN02230    74 DEVLRRKHHIA--KFTRrnLTLDDFNYYLFSTDLNPPiadqvHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADA 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2583 LLTGCRCVELDCWDGDDGLPLIYHGHTLVSKIGFRQVVEIIKKSAFITSDLPVILSIENHCSLQQQAKMAQMFKTVLGDL 2662
Cdd:PLN02230   152 LRRGVRVVELDLWPRGTDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDM 231

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2663 lvsnfLFEADFSDSPRLPCPLQMknkiliknkkmivdpptplpmiergavqrgETQLNLHRKQSKNSYESSTvdeveddd 2742
Cdd:PLN02230   232 -----LYYHDSEGCQEFPSPEEL------------------------------KEKILISTKPPKEYLEAND-------- 268

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2743 ldeflddeeneeddqeevqvrSEKEDSPKTSKRAEKSARNIKQQDSLCSDHSVEqakpstsKTTSKTNDRKTEDEvlyaq 2822
Cdd:PLN02230   269 ---------------------AKEKDNGEKGKDSDEDVWGKEPEDLISTQSDLD-------KVTSSVNDLNQDDE----- 315

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2823 laqnairNQQPRKNNTGVQI-APELSDIvIYMQATKFKGfppvdGIQSPrimeegpasaslsfssrartpsnLLNTPAPP 2901
Cdd:PLN02230   316 -------ERGSCESDTSCQLqAPEYKRL-IAIHAGKPKG-----GLRMA-----------------------LKVDPNKI 359

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2902 RRqrsstqlsqelaaeflgsvranatatcyqvTSLNENAAKKLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCW 2981
Cdd:PLN02230   360 RR------------------------------LSLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGW 409

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2982 AHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWDESHlLYNKFLPLSKDIAGHSallLNLTIISGQHV---Y 3058
Cdd:PLN02230   410 MSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGP-NGQDFYPKDNSCPKKT---LKVKVCMGDGWlldF 485

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3059 PNTHYAS-----LYVEIEVIGIHNDCVREKSKvVQRNSVNPIWNHTTQLRIACVDLAFLRIAVCDSGQNGR--VVAHRVV 3131
Cdd:PLN02230   486 KKTHFDSysppdFFVRVGIAGAPVDEVMEKTK-IEYDTWTPIWNKEFIFPLAVPELALLRVEVHEHDINEKddFGGQTCL 564

                          650       660       670
                   ....*....|....*....|....*....|...
gi 1734340688 3132 PVKCIRPGFRHLPLRTPTNLPIDNAMIFLRTRF 3164
Cdd:PLN02230   565 PVSEIRQGIHAVPLFNRKGVKYSSTRLLMRFEF 597
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 2931-3009 1.55e-32

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: 127.95  E-value: 1.55e-32
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340688 2931 YQVTSLNENAAKKLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08558    148 YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 2935-3009 9.51e-24

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: 102.71  E-value: 9.51e-24
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2935 SLNENAAKKLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQS 3009
Cdd:cd08598    157 SLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 1705-1871 1.18e-20

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


Pssm-ID: 459872  Cd Length: 179  Bit Score: 91.88  E-value: 1.18e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1705 EVAFQLSSTEYQLFYSIQPMDYVRYVSCDLTSVPVSENpspVRNLVKRLSEVSSWITHVIVSQPTHDDRKVALTAILRIV 1784
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPN---IEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIA 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1785 ETCWNIGNFNAAVEVLMGLKS---EKLRPFWLSLRQEEKSQFDSLCETLLPANQalpSQAYINAVQRAlrmpQSRVIPFF 1861
Cdd:pfam00617   78 EHCRELNNFNSLMAILSGLNSspiSRLKKTWELVSKKYKKTLEELEKLMSPSRN---FKNYREALSSA----SPPCIPFL 150

                          170
                   ....*....|
gi 1734340688 1862 GIFLRDLYAI 1871
Cdd:pfam00617  151 GLYLTDLTFI 160
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 2930-3008 2.05e-16

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: 81.32  E-value: 2.05e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2930 CYQVTSLNENAAKKLMKR-HPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQ 3008
Cdd:cd08592    149 FYEMSSFPETKAEKYLNRqKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFML 228
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 2558-2669 3.76e-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: 79.02  E-value: 3.76e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2558 NSSHNTYLTGHQlkgPSSSEMYRQVLLTGCRCVELDCWDGDDGLPLIYHGHTL------VSKIGFRQVVEIIKKSAFiTS 2631
Cdd:cd08555      1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLdrttagILPPTLEEVLELIADYLK-NP 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1734340688 2632 DLPVILSIENHCS----LQQQAKMAQMFKTVLGDLLVSNFLF 2669
Cdd:cd08555     77 DYTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGKVVL 118
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 1699-1879 2.05e-15

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


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 78.45  E-value: 2.05e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1699 ILHF-PEEVAFQLSSTEYQLFYSIQPMDYVRYVScDLTSVPVSENPSpVRNLVKRLSEVSSWITHVIVSQPTHDDRKVAL 1777
Cdd:cd00155      1 FLSLdPKELAEQLTLLDFELFRKIEPFELLGSLW-SKKDKNIHLSPN-LERFIERFNNLSNWVASEILLCTNPKKRARLL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 1778 TAILRIVETCWNIGNFNAAVEVLMGLKS---EKLRPFWLSLRQEEKSQFDSLCETLLPANQALPSQAYINAVQralrmPQ 1854
Cdd:cd00155     79 SKFIQVAKHCRELNNFNSLMAIVSALSSspiSRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVG-----PN 153

                          170       180
                   ....*....|....*....|....*
gi 1734340688 1855 SRVIPFFGIFLRDLYAIVNDLPNIV 1879
Cdd:cd00155    154 PPCVPFLGVYLKDLTFLHEGNPDFL 178
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 2931-3006 2.32e-14

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: 75.22  E-value: 2.32e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688 2931 YQVTSLNENAAKKLMKRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMF 3006
Cdd:cd08594    149 WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKF 224
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 2935-3006 2.68e-14

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: 75.10  E-value: 2.68e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340688 2935 SLNENAAKKLM-KRHPAKCVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMF 3006
Cdd:cd08599    153 SLSETQLKKVIeGEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKF 225
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 2933-3006 3.16e-14

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: 75.06  E-value: 3.16e-14
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2933 VTSLNENAAKKLMKRHPAK-CVSYTRDHLIRTYPSAKHYDSSNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMF 3006
Cdd:cd08627    152 MSSFPETKAEKYVNRSKGKkFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 226
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
190-338 4.08e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 75.76  E-value: 4.08e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  190 MNTLHMAVAHKQRDIVELLLKNGYDPNTPASchcKGNctatgnipltsiiprthsmtpelcstcsqlrvvsivdqTPLGV 269
Cdd:COG0666    121 ETPLHLAAYNGNLEIVKLLLEAGADVNAQDN---DGN--------------------------------------TPLHL 159

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340688  270 AVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESplSWPCLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:COG0666    160 AAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENG--HLEIVKLLLEAGADVNAKDNDGKTALDLA 226
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3373-3471 1.42e-13

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: 68.91  E-value: 1.42e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3373 TFLVCVHNVSEDQPYAILRAGIHSTAADIIRQVFVKARRSNVDDSEFVLVEETcddpklnQGQMTPKYPNNRTTSRVLGQ 3452
Cdd:cd17114      3 MFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEV-------QKGWDRKETEKPGSQRILDM 75

                           90
                   ....*....|....*....
gi 1734340688 3453 NENVWKAQSRWKSMGRFVL 3471
Cdd:cd17114     76 DEKILQAQSKWKGSGRFIL 94
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
193-338 1.74e-13

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 74.22  E-value: 1.74e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  193 LHMAVAHKQRDIVELLLKNGYDPNTPASChckgnctatgnipltsiiprthsmtpelcstcsqlrvvsivDQTPLGVAVR 272
Cdd:COG0666     91 LHAAARNGDLEIVKLLLEAGADVNARDKD-----------------------------------------GETPLHLAAY 129

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688  273 SQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESplSWPCLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:COG0666    130 NGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANG--NLEIVKLLLEAGADVNARDNDGETPLHLA 193
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 3046-3145 1.05e-11

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: 63.66  E-value: 1.05e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  3046 LLNLTIISGQHVYP--NTHYASLYVEIEVIGIHNdcVREKSKVVqRNSVNPIWNHTTQLRIACVDLAFLRIAVCDSGQNG 3123
Cdd:smart00239    1 TLTVKIISARNLPPkdKGGKSDPYVKVSLDGDPK--EKKKTKVV-KNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFG 77

                            90       100
                    ....*....|....*....|....
gi 1734340688  3124 R--VVAHRVVPVKCIRPGFRHLPL 3145
Cdd:smart00239   78 RddFIGQVTIPLSDLLLGGRHEKL 101
RA_PLC-epsilon cd17114
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3205-3299 2.66e-11

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: 62.36  E-value: 2.66e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3205 KQIFVLRITGAFADETAITVHSESGSTVKTVMQQALLNAGKNADQVEEYVLIEESLPAPSGED---PIEQRVLPLNEPIM 3281
Cdd:cd17114      1 RRMFFVTVHGVVPEEPYTVLKITQDTTAREVIAQALGKAGKSLERVTDYVLVEEVQKGWDRKEtekPGSQRILDMDEKIL 80

                           90
                   ....*....|....*...
gi 1734340688 3282 DAVACWNGSmRRFVLRKK 3299
Cdd:cd17114     81 QAQSKWKGS-GRFILKKL 97
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3208-3300 3.82e-11

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: 61.93  E-value: 3.82e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  3208 FVLRITGAF-ADETAITVHSESGSTVKTVMQQALLNAGKNaDQVEEYVLIEESlpapsgEDPIEQRVLPLNEPIMDAVAC 3286
Cdd:smart00314    3 FVLRVYVDDlPGGTYKTLRVSSRTTARDVIQQLLEKFHLT-DDPEEYVLVEVL------PDGKERVLPDDENPLQLQKLW 75

                            90
                    ....*....|....*
gi 1734340688  3287 -WNGSMRRFVLRKKG 3300
Cdd:smart00314   76 pRRGPNLRFVLRKRD 90
PLN02223 PLN02223
phosphoinositide phospholipase C
 2480-2663 4.53e-11

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 68.51  E-value: 4.53e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2480 PQMLRAFVNTHQMEQIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDPVN-FAFVPETIEP-----DEEDLRYPLS 2553
Cdd:PLN02223    34 PELLPRFIELLDTEKDEDGAGLNAAEKIAAELKRRKCDILAFRNLRCLELDHLNeFLFSTELNPPigdqvRHHDMHAPLS 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2554 HYYINSSHNTYLTGHQLKGPSSS-EMYRQVLLTGCRCVELDCW-DGDDGLpLIYHGHTLVSKIGFRQVVEIIKKSAFI-T 2630
Cdd:PLN02223   114 HYFIHTSLKSYFTGNNVFGKLYSiEPIIDALEQGVRVVELDLLpDGKDGI-CVRPKWNFEKPLELQECLDAIKEHAFTkC 192

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1734340688 2631 SDLPVILSIENHCSLQQQAKMAQMFKTVLGDLL 2663
Cdd:PLN02223   193 RSYPLIITFKDGLKPDLQSKATQMIDQTFGDMV 225
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1371-1548 1.28e-10

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: 63.47  E-value: 1.28e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1371 YLEFQDQVISGSLPCPKEEAAYLASIQLSVEEQWPSNKRTQtirrhllkgqfgrirdlaqkimvtpwevdqnlyctpprf 1450
Cdd:smart00295   99 YLQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHD--------------------------------------- 139

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  1451 pnesanasraqsvveeiqhrsrtptllrcitntdgLMSEEMQAQCLPVDLRgDRRTIKLVKERKRKLFHSQVYESEIGMK 1530
Cdd:smart00295  140 -----------------------------------LRGELSLKRFLPKQLL-DSRKLKEWRERIVELHKELIGLSPEEAK 183

                           170
                    ....*....|....*...
gi 1734340688  1531 KLYIQTAKKLAAFGCKVF 1548
Cdd:smart00295  184 LKYLELARKLPTYGVELF 201
RA smart00314
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3372-3474 2.25e-10

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: 59.62  E-value: 2.25e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  3372 DTFLVCVHNVS-EDQPYAILRAGIHSTAADIIRQVFVKARRSNvDDSEFVLVEETCDDPKlnqgqmtpkypnnrttsRVL 3450
Cdd:smart00314    1 DTFVLRVYVDDlPGGTYKTLRVSSRTTARDVIQQLLEKFHLTD-DPEEYVLVEVLPDGKE-----------------RVL 62

                            90       100
                    ....*....|....*....|....*..
gi 1734340688  3451 GQNENVWKAQSRWK---SMGRFVLENR 3474
Cdd:smart00314   63 PDDENPLQLQKLWPrrgPNLRFVLRKR 89
PLN02223 PLN02223
phosphoinositide phospholipase C
 2953-3165 8.48e-10

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 64.66  E-value: 8.48e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 2953 VSYTRDHLIRTYPSAKHYDS-SNFNPINCWAHGMQMVALNFQTPDVIMAVNQAMFEQSGNCGYQLKPRCLWD--ESHLLY 3029
Cdd:PLN02223   321 ISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagPSGVFY 400

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3030 NKFLPLSKDIAGHSALLLNLTIISGQHVYPNTHYASLYVEIEVIGIHNDcvrEK--SKVVQRNSVNPIWNHTTQLRIACV 3107
Cdd:PLN02223   401 PTENPVVVKILKVKIYMGDGWIVDFKKRIGRLSKPDLYVRISIAGVPHD---EKimKTTVKNNEWKPTWGEEFTFPLTYP 477

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3108 DLAFLRIAVCD--SGQNGRVVAHRVVPVKCIRPGFRHLPLRTPTNLPIDNAMifLRTRFE 3165
Cdd:PLN02223   478 DLALISFEVYDyeVSTADAFCGQTCLPVSELIEGIRAVPLYDERGKACSSTM--LLTRFK 535
Ank_2 pfam12796
Ankyrin repeats (3 copies);
193-328 1.37e-08

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 54.74  E-value: 1.37e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  193 LHMAVAHKQRDIVELLLKNGYDPNtpaschckgnctatgnipltsiiprthsmtpelcstcsqlrVVSIVDQTPLGVAVR 272
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADAN-----------------------------------------LQDKNGRTALHLAAK 39

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688  273 SQSSELIALLIAYgGDVNLGDeDGNTPLMLAVRESPLSwpCLHTLIFFGAQIEQKN 328
Cdd:pfam12796   40 NGHLEIVKLLLEH-ADVNLKD-NGRTALHYAARSGHLE--IVKLLLEKGADINVKD 91
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
263-338 3.47e-08

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 58.04  E-value: 3.47e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688  263 DQTPLGVAVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESplSWPCLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:COG0666     87 GNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNG--NLEIVKLLLEAGADVNAQDNDGNTPLHLA 160
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 2478-2531 1.36e-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: 53.79  E-value: 1.36e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340688 2478 LTPQMLRAFVNTHQM-----EQI----DEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16200     90 LTLEQLVDFLNEEQRdprlnEILfpfhTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSD 152
PHA03100 PHA03100
ankyrin repeat protein; Provisional
 189-338 4.98e-07

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 55.44  E-value: 4.98e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  189 MMNTLHMAVAHKQRDIVELLLKNGYDPN-------TPASCHCKGNCTATGNIPLTSII---------PRTHSMTPELCST 252
Cdd:PHA03100    35 PVLPLYLAKEARNIDVVKILLDNGADINsstknnsTPLHYLSNIKYNLTDVKEIVKLLleyganvnaPDNNGITPLLYAI 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  253 CSQLRVVSIVD----------------QTPLGVAVRSQSSEL------------------IALLIAYGGDVNLGDEDGNT 298
Cdd:PHA03100   115 SKKSNSYSIVEylldnganvniknsdgENLLHLYLESNKIDLkilkllidkgvdinaknrVNYLLSYGVPINIKDVYGFT 194

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1734340688  299 PLMLAVRESPLSWpcLHTLIFFGAQIEQKNMRGICPLDLA 338
Cdd:PHA03100   195 PLHYAVYNNNPEF--VKYLLDLGANPNLVNKYGDTPLHIA 232
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 2478-2531 1.66e-06

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: 50.30  E-value: 1.66e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2478 LTPQMLRAFVNTHQ-MEQIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16202     85 LTVEELRRFLQEEQkVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSP 139
C2 pfam00168
C2 domain;
3046-3139 2.12e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.77  E-value: 2.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3046 LLNLTIISGQHVYPNTHYASL--YVEIEvigIHNDCVREKSKVVqRNSVNPIWNHTTQLRIACVDLAFLRIAVCDSGQNG 3123
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSdpYVKVY---LLDGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFG 77

                           90
                   ....*....|....*...
gi 1734340688 3124 R--VVAHRVVPVKCIRPG 3139
Cdd:pfam00168   78 RddFIGEVRIPLSELDSG 95
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 2476-2531 4.56e-05

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: 45.74  E-value: 4.56e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340688 2476 SMLTPQMLRAFVNTHQMEQIDEQTAIKLIQDHEPdgiCRQKNQMSFEGFTRFLCDP 2531
Cdd:cd15898     84 DYMTLEEFIRFLREEQGENVSEEECEELIEKYEP---ERENRQLSFEGFTNFLLSP 136
PHA02878 PHA02878
ankyrin repeat protein; Provisional
 193-306 5.27e-05

ankyrin repeat protein; Provisional


Pssm-ID: 222939 [Multi-domain]  Cd Length: 477  Bit Score: 48.72  E-value: 5.27e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  193 LHMAVAHKQRDIVELLLKNGYDPNTPASChckgnctatGNIPLTSIIPRthsmtpelCSTCSQLRVV-----------SI 261
Cdd:PHA02878   205 LHHAVKHYNKPIVHILLENGASTDARDKC---------GNTPLHISVGY--------CKDYDILKLLlehgvdvnaksYI 267

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1734340688  262 VDQTPLGVAVRSQssELIALLIAYGGDVNLGDEDGNTPLMLAVRE 306
Cdd:PHA02878   268 LGLTALHSSIKSE--RKLKLLLEYGADINSLNSYKLTPLSSAVKQ 310
Ank_2 pfam12796
Ankyrin repeats (3 copies);
267-358 8.93e-05

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 43.95  E-value: 8.93e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  267 LGVAVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESPLSwpCLHTLIFFGAQieQKNMRGICPLDLApeLKKLQQ 346
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLE--IVKLLLEHADV--NLKDNGRTALHYA--ARSGHL 74

                           90
                   ....*....|..
gi 1734340688  347 TCVEELFKNACS 358
Cdd:pfam12796   75 EIVKLLLEKGAD 86
PHA02874 PHA02874
ankyrin repeat protein; Provisional
 191-340 1.04e-04

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 48.04  E-value: 1.04e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  191 NTLHMAVAHKQRDIVELLLKNGYDpntpaschckgnctatgniplTSIIPrTHSMTPELCSTCSQLRV-VSIVD---QTP 266
Cdd:PHA02874    70 HPLLTAIKIGAHDIIKLLIDNGVD---------------------TSILP-IPCIEKDMIKTILDCGIdVNIKDaelKTF 127

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340688  267 LGVAVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVRESplSWPCLHTLIFFGAQIEQKNMRGICPLDLAPE 340
Cdd:PHA02874   128 LHYAIKKGDLESIKMLFEYGADVNIEDDNGCYPIHIAIKHN--FFDIIKLLLEKGAYANVKDNNGESPLHNAAE 199
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 2478-2531 1.69e-04

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: 44.47  E-value: 1.69e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2478 LTPQMLRAFVNTHQ-MEQIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16222     88 LDAKDLMLFLEAEQgMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSS 142
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 3047-3124 3.19e-04

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: 42.44  E-value: 3.19e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3047 LNLTIISGQHVYP--NTHYASLYVEIEVIGIHndcvREKSKVVqRNSVNPIWNHTTQLRIACVDLAFLRIAVCDSGQNGR 3124
Cdd:cd00030      1 LRVTVIEARNLPAkdLNGKSDPYVKVSLGGKQ----KFKTKVV-KNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSK 75
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 1362-1401 3.77e-04

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 42.64  E-value: 3.77e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1734340688 1362 ENNEQINDE------YLEFQDQVISGSLPCPKEEAAYLASIQLSVE 1401
Cdd:pfam00373    1 DLELLLQDEvtrhllYLQAKDDILEGRLPCSEEEALLLAALQLQAE 46
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 2483-2528 1.31e-03

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


Pssm-ID: 320034 [Multi-domain]  Cd Length: 142  Bit Score: 41.72  E-value: 1.31e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1734340688 2483 LRAFVNTHQME-QIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFL 2528
Cdd:cd16204     92 LVGFLKKEQFQdEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYM 138
RA2_PLC-epsilon cd01780
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ...
 3230-3299 1.44e-03

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: 40.77  E-value: 1.44e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1734340688 3230 STVKTVMQQALLNAGKNADQVEEYVLIEESLPAPSGEDP--------IEQRVLPLNEPIMDAVACWNGsMRRFVLRKK 3299
Cdd:cd01780     26 STAQDIIAQALVKARRSEDIPSDFVLVEELEKEPTSDKSssksssskTEQRVLGDQENVYQAQSRWKG-AGKFILKLR 102
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3380-3476 1.60e-03

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: 40.39  E-value: 1.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688 3380 NVSEDQPYAILRAGIHSTAADIIRQVFVKARRSNvDDSEFVLVEETCDdpklnqgqmtpkypnnRTTSRVLGQNENVWKA 3459
Cdd:pfam00788   11 DGKPGTTYKTILVSSSTTAEEVIEALLEKFGLED-DPRDYVLVEVLER----------------GGGERRLPDDECPLQI 73

                           90       100
                   ....*....|....*....|
gi 1734340688 3460 QSRWKS---MGRFVLENRKD 3476
Cdd:pfam00788   74 QLQWPRdasDSRFLLRKRDD 93
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 2478-2531 2.11e-03

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: 39.54  E-value: 2.11e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1734340688 2478 LTPQMLRAFVNTHQMEQI-DEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDP 2531
Cdd:pfam09279   25 LSLDELVDFLREEQREEDaSPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSP 79
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 2478-2528 3.35e-03

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: 40.66  E-value: 3.35e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1734340688 2478 LTPQMLRAFVNTHQ-MEQIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFL 2528
Cdd:cd16206     88 LTVDDLMLFLEAEQgMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYL 139
RA pfam00788
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ...
 3223-3299 3.46e-03

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: 39.24  E-value: 3.46e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340688 3223 TVHSESGSTVKTVMQQALLNAGKNADQvEEYVLIEESlpapsgEDPIEQRVLPLNEPIMDAVACW--NGSMRRFVLRKK 3299
Cdd:pfam00788   20 TILVSSSTTAEEVIEALLEKFGLEDDP-RDYVLVEVL------ERGGGERRLPDDECPLQIQLQWprDASDSRFLLRKR 91
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 2478-2531 4.16e-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: 40.11  E-value: 4.16e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1734340688 2478 LTPQMLRAFVNTHQMEQIDEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFLCDP 2531
Cdd:cd16217     85 MSRNNLLNFLQEEQREEVAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSP 138
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 2470-2528 4.77e-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: 40.48  E-value: 4.77e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1734340688 2470 MDTSRSSMLTPQMLRAFVNTHQ----MEQI-----DEQTAIKLIQDHEPDGICRQKNQMSFEGFTRFL 2528
Cdd:cd16211     82 INGDKKDYLTVDQLISFLNEHQrdprLNEIlfpfyDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYL 149
Ank_5 pfam13857
Ankyrin repeats (many copies);
264-303 6.73e-03

Ankyrin repeats (many copies);


Pssm-ID: 433530 [Multi-domain]  Cd Length: 56  Bit Score: 37.33  E-value: 6.73e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1734340688  264 QTPLGVAVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLA 303
Cdd:pfam13857   17 YTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDLA 56
PHA02878 PHA02878
ankyrin repeat protein; Provisional
 193-338 7.41e-03

ankyrin repeat protein; Provisional


Pssm-ID: 222939 [Multi-domain]  Cd Length: 477  Bit Score: 41.79  E-value: 7.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  193 LHMAVAHKQRDIVELLLKNGYDPNTPASChckgnctatgnipltsiiprthsmtpelcstcsqlrvvsivDQTPLGVAVR 272
Cdd:PHA02878   172 LHYATENKDQRLTELLLSYGANVNIPDKT-----------------------------------------NNSPLHHAVK 210

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1734340688  273 SQSSELIALLIAYGGDVNLGDEDGNTPLMLAVrESPLSWPCLHTLIFFGAQIEQKN-MRGICPLDLA 338
Cdd:PHA02878   211 HYNKPIVHILLENGASTDARDKCGNTPLHISV-GYCKDYDILKLLLEHGVDVNAKSyILGLTALHSS 276
PHA03095 PHA03095
ankyrin-like protein; Provisional
 190-305 9.98e-03

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 41.55  E-value: 9.98e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340688  190 MNTL---HMAVAHKQRDIVELLLKNGYDPNTPaschckgncTATGNIPLtsiiprtHSMTpeLCSTCSQLRV-------- 258
Cdd:PHA03095   187 FRSLlhhHLQSFKPRARIVRELIRAGCDPAAT---------DMLGNTPL-------HSMA--TGSSCKRSLVlplliagi 248

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1734340688  259 -VSIVD---QTPLGVAVRSQSSELIALLIAYGGDVNLGDEDGNTPLMLAVR 305
Cdd:PHA03095   249 sINARNrygQTPLHYAAVFNNPRACRRLIALGADINAVSSDGNTPLSLMVR 299
 
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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