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Conserved domains on  [gi|1039767898|ref|XP_017175736|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 isoform X9 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 469-878 3.09e-171

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: 508.43  E-value: 3.09e-171
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKklpanisedaeeg 628
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08633    148 ---------------------------------------------------------------KLSRALSDLVKYTKSVR 164

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 THDVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08633    165 VHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 244

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08633    245 QLNRAKFSAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 317-457 1.34e-97

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


:

Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 307.63  E-value: 1.34e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PLN02228 super family cl31849
Phosphoinositide phospholipase C
 391-1018 1.72e-61

Phosphoinositide phospholipase C


The actual alignment was detected with superfamily member PLN02228:

Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 221.45  E-value: 1.72e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  391 LMLTYSnHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNY----TRSPAgdifnPEHN 466
Cdd:PLN02228    29 LFEAYS-RNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYlfsdTNSPL-----PMSG 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  467 RVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFKDVIE 545
Cdd:PLN02228   103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  546 TINKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdlSSVSSEDATMLPSPQMLKGKILVKGKKlpaniSEDA 625
Cdd:PLN02228   183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGML--FRCTSESTKHFPSPEELKNKILISTKP-----PKEY 255

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  626 EEGEVSDEDSADEMEddckllngdaSTNRKRVENiakkkldsliKESKIRdcEDPNDFSVSTLSPSGKLGRKAEAKKGQS 705
Cdd:PLN02228   256 LESKTVQTTRTPTVK----------ETSWKRVAD----------AENKIL--EEYKDEESEAVGYRDLIAIHAANCKDPL 313

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  706 KveeDVEAGEDSGVSRqnsrlfmssfskrkkkgskikkVASVEEGDETLdspgSQSRGTarqkktmklsralsDLVKYTk 785
Cdd:PLN02228   314 K---DCLSDDPEKPIR----------------------VSMDEQWLETM----VRTRGT--------------DLVRFT- 349

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  786 svgthdveievvsswqvssfsetkahqilqqkptqylrfnQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEG 865
Cdd:PLN02228   350 ----------------------------------------QRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHG 389

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  866 RMLQLNRAKFSANGDCGYVLKPQCMCQ--GVFNPNSEDPlpgqLKKQLALRIISGQ--QLPKPRDSVlgDRGEIIDPFVE 941
Cdd:PLN02228   390 KQLWIMQGMFRANGGCGYVKKPRILLDehTLFDPCKRLP----IKTTLKVKIYTGEgwDLDFHLTHF--DQYSPPDFFVK 463

                          570       580       590       600       610       620       630
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039767898  942 VEVIGLPVDCSKEQTRVVDDNGFnPMW-EETLVFTVHMPEIALVRFLVWDHDP-IGRDFIGQRTLAFSSIMPGYRHVYL 1018
Cdd:PLN02228   464 IGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELKSGVRAVRL 541
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 193-299 6.02e-54

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


:

Pssm-ID: 270170  Cd Length: 109  Bit Score: 183.25  E-value: 6.02e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  193 MQEGTQMVKLRGSSKGLVRFYYLDEHRSCLRWRPSRKN-EKAKISIDSIQEVSEGRQSEIFQRYP-DSSFDPNCCFSIYH 270
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1039767898  271 GSHRESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 1067-1243 3.26e-05

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.78  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1067 LPRPSVSQRLLRRTASAPTKSQKPSRKGFPELALGTQDAGSEGAADDVA---PSSPNPAL--EAPTQE------------ 1129
Cdd:PHA03247  2460 LGAPFSLSLLLGELFPGAPVYRRPAEARFPFAAGAAPDPGGGGPPDPDAppaPSRLAPAIlpDEPVGEpvhprmltwirg 2539

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1130 -------RSGSSSPRGKAPGGEATEERTLAQVRSpnAPEGPGPAGMAATCMKCV-----VGSCAGMDVEGLQREQQPSPG 1197
Cdd:PHA03247  2540 leelasdDAGDPPPPLPPAAPPAAPDRSVPPPRP--APRPSEPAVTSRARRPDAppqsaRPRAPVDDRGDPRGPAPPSPL 2617

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1039767898 1198 PAGSHM--AISHQPRARVDSLGGPCCSPSPraTPGRSKEAPKGPRARR 1243
Cdd:PHA03247  2618 PPDTHApdPPPPSPSPAANEPDPHPPPTVP--PPERPRDDPAPGRVSR 2663
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 469-878 3.09e-171

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: 508.43  E-value: 3.09e-171
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKklpanisedaeeg 628
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08633    148 ---------------------------------------------------------------KLSRALSDLVKYTKSVR 164

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 THDVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08633    165 VHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 244

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08633    245 QLNRAKFSAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 317-457 1.34e-97

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


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 307.63  E-value: 1.34e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 472-614 7.84e-84

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


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 269.76  E-value: 7.84e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  472 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 551
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039767898  552 FIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKG 614
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDML-YTPPLDDDLTELPSPEDLKGKILIKG 142
PLN02952 PLN02952
phosphoinositide phospholipase C
 386-1018 3.61e-68

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 241.83  E-value: 3.61e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  386 RDLYLLMLTYSNHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQF---EPCLENKSKGMLGIDGFTNYTRSPagDIFN 462
Cdd:PLN02952    38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEEVinrRHHVTRYTRHGLNLDDFFHFLLYD--DLNG 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  463 PEHNRVHQDMTQPLSHYFITSSHNTYLVGDQLMSQ-SRVDMYAwVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILF 540
Cdd:PLN02952   116 PITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQRGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPL 194

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  541 KDVIETINKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSsvSSEDATMLPSPQMLKGKILVKGKKlpan 620
Cdd:PLN02952   195 IKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP--ESDSLVQFPSPESLKHRIIISTKP---- 268

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  621 isedaeegevsdedsademeddckllngdastnrkrveniAKKKLDSLIKESKIRDcedpndfsvSTLSPSGKlgrkaea 700
Cdd:PLN02952   269 ----------------------------------------PKEYLESSGPIVIKKK---------NNVSPSGR------- 292

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  701 kkgqSKVEEDVEAgedSGVSRQNSRLfmssfskrkkkgskikkvasveEGDETLDSPGSQSRGTARQKKTMKlsRALSdl 780
Cdd:PLN02952   293 ----NSSEETEEA---QTLESMLFEQ----------------------EADSRSDSDQDDNKSGELQKPAYK--RLIT-- 339

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  781 VKYTKSVGTHDVEIEV-VSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVAL 859
Cdd:PLN02952   340 IHAGKPKGTLKDAMKVaVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAF 419

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  860 NYQSEGRMLQLNRAKFSANGDCGYVLKPQCMCQGVFNPNSEDP---LPgqLKKQLALRIISGQQLPKPRDSVLGDRGEII 936
Cdd:PLN02952   420 NMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPkkkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSPP 497

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  937 DPFVEVEVIGLPVDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSIMPGYRH 1015
Cdd:PLN02952   498 DFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIRS 576


                   ...
gi 1039767898 1016 VYL 1018
Cdd:PLN02952   577 VPL 579
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 472-615 6.14e-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: 210.60  E-value: 6.14e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   472 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 551
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039767898   552 FIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGK 615
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PLN02228 PLN02228
Phosphoinositide phospholipase C
 391-1018 1.72e-61

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 221.45  E-value: 1.72e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  391 LMLTYSnHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNY----TRSPAgdifnPEHN 466
Cdd:PLN02228    29 LFEAYS-RNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYlfsdTNSPL-----PMSG 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  467 RVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFKDVIE 545
Cdd:PLN02228   103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  546 TINKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdlSSVSSEDATMLPSPQMLKGKILVKGKKlpaniSEDA 625
Cdd:PLN02228   183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGML--FRCTSESTKHFPSPEELKNKILISTKP-----PKEY 255

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  626 EEGEVSDEDSADEMEddckllngdaSTNRKRVENiakkkldsliKESKIRdcEDPNDFSVSTLSPSGKLGRKAEAKKGQS 705
Cdd:PLN02228   256 LESKTVQTTRTPTVK----------ETSWKRVAD----------AENKIL--EEYKDEESEAVGYRDLIAIHAANCKDPL 313

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  706 KveeDVEAGEDSGVSRqnsrlfmssfskrkkkgskikkVASVEEGDETLdspgSQSRGTarqkktmklsralsDLVKYTk 785
Cdd:PLN02228   314 K---DCLSDDPEKPIR----------------------VSMDEQWLETM----VRTRGT--------------DLVRFT- 349

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  786 svgthdveievvsswqvssfsetkahqilqqkptqylrfnQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEG 865
Cdd:PLN02228   350 ----------------------------------------QRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHG 389

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  866 RMLQLNRAKFSANGDCGYVLKPQCMCQ--GVFNPNSEDPlpgqLKKQLALRIISGQ--QLPKPRDSVlgDRGEIIDPFVE 941
Cdd:PLN02228   390 KQLWIMQGMFRANGGCGYVKKPRILLDehTLFDPCKRLP----IKTTLKVKIYTGEgwDLDFHLTHF--DQYSPPDFFVK 463

                          570       580       590       600       610       620       630
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039767898  942 VEVIGLPVDCSKEQTRVVDDNGFnPMW-EETLVFTVHMPEIALVRFLVWDHDP-IGRDFIGQRTLAFSSIMPGYRHVYL 1018
Cdd:PLN02228   464 IGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELKSGVRAVRL 541
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 193-299 6.02e-54

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


Pssm-ID: 270170  Cd Length: 109  Bit Score: 183.25  E-value: 6.02e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  193 MQEGTQMVKLRGSSKGLVRFYYLDEHRSCLRWRPSRKN-EKAKISIDSIQEVSEGRQSEIFQRYP-DSSFDPNCCFSIYH 270
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1039767898  271 GSHRESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 908-1033 2.82e-53

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: 182.36  E-value: 2.82e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  908 KKQLALRIISGQQLPKPRDsvlgDRGEIIDPFVEVEVIGLPV-DCSKEQTRVVDDNGFNPMWEETLVFTVHMPEIALVRF 986
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  987 LVWDHDPIGRDFIGQRTLAFSSIMPGYRHVYL-----EGMEEASIFVHVAVS 1033
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 910-1018 5.80e-22

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: 91.78  E-value: 5.80e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   910 QLALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGLPVdcSKEQTRVVDDNGfNPMWEETLVFTVHMPEIALVRFLVW 989
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 1039767898   990 DHDPIGRD-FIGQRTLAFSSIMPGYRHVYL 1018
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
910-1015 3.83e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 86.60  E-value: 3.83e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  910 QLALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGlpvDCSKEQTRVVDdNGFNPMWEETLVFTVHMPEIALVRFLVW 989
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 1039767898  990 DHDPIGRD-FIGQRTLAFSSIMPGYRH 1015
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EF-hand_7 pfam13499
EF-hand domain pair;
315-380 2.17e-13

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 66.12  E-value: 2.17e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039767898  315 DQWLKQTFDEADKNGDGSLSISEVLQLLHKL--NVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYK 380
Cdd:pfam13499    1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDL-DKDGRISFEEFLELYS 67
PH_12 pfam16457
Pleckstrin homology domain;
187-298 1.18e-12

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 66.13  E-value: 1.18e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  187 ERCMSAMQEGTQMVKLRGSSKGL-VRFYYLDEHRSCLRW---------RPSRKNEKAKISIDSIQEVSEGRQSEIF--QR 254
Cdd:pfam16457    3 EQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVreSG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1039767898  255 YPDSSFDPNCCFSIYHGSH-RESLDLVSPSSEEARTWVTGLRYLM 298
Cdd:pfam16457   83 KKSKKTSSTLAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLL 127
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
307-378 9.27e-11

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 60.96  E-value: 9.27e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  307 LARRQRTRDQWLKQTFDEADKNGDGSLSISEVLQLLHKLNVnlPRQRVKQMFREADTdDHQGTLGFEEFCAF 378
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDT-DGDGKISFEEFVAA 128
PTZ00184 PTZ00184
calmodulin; Provisional
 307-385 1.57e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 48.99  E-value: 1.57e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  307 LARRQRTRD--QWLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCafyKMMST 384
Cdd:PTZ00184    73 MARKMKDTDseEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDG-DGQINYEEFV---KMMMS 148


                   .
gi 1039767898  385 R 385
Cdd:PTZ00184   149 K 149
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1067-1243 3.26e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.78  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1067 LPRPSVSQRLLRRTASAPTKSQKPSRKGFPELALGTQDAGSEGAADDVA---PSSPNPAL--EAPTQE------------ 1129
Cdd:PHA03247  2460 LGAPFSLSLLLGELFPGAPVYRRPAEARFPFAAGAAPDPGGGGPPDPDAppaPSRLAPAIlpDEPVGEpvhprmltwirg 2539

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1130 -------RSGSSSPRGKAPGGEATEERTLAQVRSpnAPEGPGPAGMAATCMKCV-----VGSCAGMDVEGLQREQQPSPG 1197
Cdd:PHA03247  2540 leelasdDAGDPPPPLPPAAPPAAPDRSVPPPRP--APRPSEPAVTSRARRPDAppqsaRPRAPVDDRGDPRGPAPPSPL 2617

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1039767898 1198 PAGSHM--AISHQPRARVDSLGGPCCSPSPraTPGRSKEAPKGPRARR 1243
Cdd:PHA03247  2618 PPDTHApdPPPPSPSPAANEPDPHPPPTVP--PPERPRDDPAPGRVSR 2663
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 195-299 1.16e-04

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 42.54  E-value: 1.16e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   195 EGTQMVKLRGSSKGLVRFY-YLdeHRSCLRW-----RPSRKNEKAKISIDSIQeVSEGRqseifqryPDSSFDPNCCFSI 268
Cdd:smart00233    4 EGWLYKKSGGGKKSWKKRYfVL--FNSTLLYykskkDKKSYKPKGSIDLSGCT-VREAP--------DPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|.
gi 1039767898   269 YHGShRESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:smart00233   73 KTSD-RKTLLLQAESEEEREKWVEALRKAIA 102
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 354-382 4.26e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 4.26e-03
                            10        20
                    ....*....|....*....|....*....
gi 1039767898   354 VKQMFREADTdDHQGTLGFEEFCAFYKMM 382
Cdd:smart00054    2 LKEAFRLFDK-DGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 469-878 3.09e-171

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: 508.43  E-value: 3.09e-171
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKklpanisedaeeg 628
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08633    148 ---------------------------------------------------------------KLSRALSDLVKYTKSVR 164

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 THDVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08633    165 VHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 244

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08633    245 QLNRAKFSAN 254
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 469-878 2.85e-144

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: 436.54  E-value: 2.85e-144
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08594      1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKKlpanisedaeeg 628
Cdd:cd08594     81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQLPSPQSLKGKILIKGKK------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08594        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsralsdlvkytksvg 788
Cdd:cd08594        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 thdveievvssWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08594    149 -----------WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRML 217

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08594    218 QLNRAKFRAN 227
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 469-878 9.05e-130

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: 399.40  E-value: 9.05e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08632      1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKklpanisedaeeg 628
Cdd:cd08632     81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08632        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08632    148 ---------------------------------------------------------------KLCRDLSDLVVYTNSVA 164

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 THDVeIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08632    165 AQDI-VDDGSTGNVLSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMM 243

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08632    244 QLNRAKFMVN 253
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 469-878 1.30e-128

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: 394.90  E-value: 1.30e-128
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08558      1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDaTMLPSPQMLKGKILVKGKKlpanisedaeeg 628
Cdd:cd08558     81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENP-VQLPSPEQLKGKILIKGKK------------ 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08558        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsralsdlvkytksvg 788
Cdd:cd08558        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 thdveievvssWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08558    148 -----------YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPM 216

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08558    217 QLNQGKFEQN 226
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 469-878 3.38e-116

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: 363.20  E-value: 3.38e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08593      1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGKKLpanisedaeeg 628
Cdd:cd08593     81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKL-LTQPLDGVLTALPSPEELKGKILVKGKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08593        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08593    149 ---------------------------------------------------------------KLAKELSDLVIYCKSVH 165

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 THDVE--IEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGR 866
Cdd:cd08593    166 FKSFEhsKENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGE 245

                          410
                   ....*....|..
gi 1039767898  867 MLQLNRAKFSAN 878
Cdd:cd08593    246 EMDLNDGLFRQN 257
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 317-457 1.34e-97

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


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 307.63  E-value: 1.34e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 469-878 3.41e-97

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: 311.66  E-value: 3.41e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08597      1 CQDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVsSEDATMLPSPQMLKGKILVKGKKLpanisedaeeg 628
Cdd:cd08597     81 EYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPP-NEGESYLPSPHDLKGKIIIKGKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08597        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkKTMKLSRALSDLVKYTKSVG 788
Cdd:cd08597    149 ------------------------------------------------------------KRRKLCKELSDLVSLCKSVR 168

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 THD--VEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGR 866
Cdd:cd08597    169 FQDfpTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGL 248

                          410
                   ....*....|..
gi 1039767898  867 MLQLNRAKFSAN 878
Cdd:cd08597    249 MMDLNTGKFLEN 260
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 317-457 7.08e-94

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


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 297.37  E-value: 7.08e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16205      1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16205     81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 469-878 3.81e-93

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: 300.41  E-value: 3.81e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 546
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  547 INKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKL---DLSSVSSEDATMLPSPQMLKGKILVKGKKlpanise 623
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLltePLEKYPLEPGVPLPSPNDLKRKILIKNKK------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  624 daeegevsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkg 703
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  704 qskveedveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsraLSDLVKY 783
Cdd:cd08591    154 -------------------------------------------------------------------------LSSLVNY 160

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  784 TKSV--GTHDVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNY 861
Cdd:cd08591    161 IQPVkfQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNF 240

                          410
                   ....*....|....*..
gi 1039767898  862 QSEGRMLQLNRAKFSAN 878
Cdd:cd08591    241 QTPDLPMQLNQGKFEYN 257
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 470-878 1.59e-92

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


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 297.42  E-value: 1.59e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  470 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 549
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  550 YAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGKKLpanisedaeege 629
Cdd:cd08592     82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDML-LTQPVDRNADQLPSPNQLKRKIIIKHKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  630 vsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskvee 709
Cdd:cd08592        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  710 dveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsralsdlvkYTksvgt 789
Cdd:cd08592    149 -------------------------------------------------------------------------FY----- 150

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  790 hdveievvsswQVSSFSETKAHQIL-QQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08592    151 -----------EMSSFPETKAEKYLnRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPM 219

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08592    220 QLNQALFMLN 229
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 469-878 2.18e-90

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: 292.62  E-value: 2.18e-90
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08631      1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKKLpanisedaeeg 628
Cdd:cd08631     81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08631        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08631    150 ---------------------------------------------------------------RLSPELSDCVIYCKSVS 166

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 ----THDVEIEVVssWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSE 864
Cdd:cd08631    167 frsfTHSREHYHF--YEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTA 244

                          410
                   ....*....|....
gi 1039767898  865 GRMLQLNRAKFSAN 878
Cdd:cd08631    245 GLEMDLNDGLFRQN 258
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 469-878 2.41e-86

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: 281.54  E-value: 2.41e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08629      1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGKKLpanisedaeeg 628
Cdd:cd08629     81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPIL-LDQPLDGVTTSLPSPEQLKGKILLKGKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08629        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSV- 787
Cdd:cd08629    149 ---------------------------------------------------------------KLVPELSDMIIYCKSVh 165

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  788 --GTHDVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEG 865
Cdd:cd08629    166 fgGFSSPGTSGQAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPG 245

                          410
                   ....*....|...
gi 1039767898  866 RMLQLNRAKFSAN 878
Cdd:cd08629    246 PEMDVYLGCFQDN 258
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 472-614 7.84e-84

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


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 269.76  E-value: 7.84e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  472 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 551
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039767898  552 FIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKG 614
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDML-YTPPLDDDLTELPSPEDLKGKILIKG 142
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 469-878 4.95e-81

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: 266.42  E-value: 4.95e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08595      1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKKlpanisedaeeg 628
Cdd:cd08595     81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKK------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08595        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSVG 788
Cdd:cd08595    149 ---------------------------------------------------------------KIAKALSDLVIYTKSEK 165

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  789 ----THDVEIEvvSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSE 864
Cdd:cd08595    166 fcsfTHSRDNQ--HSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTL 243

                          410
                   ....*....|....
gi 1039767898  865 GRMLQLNRAKFSAN 878
Cdd:cd08595    244 GAPMDLQNGKFLDN 257
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 469-878 8.66e-80

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: 263.03  E-value: 8.66e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08630      1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEDATMLPSPQMLKGKILVKGKKLpanisedaeeg 628
Cdd:cd08630     81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL----------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  629 evsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskve 708
Cdd:cd08630        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  709 edveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmKLSRALSDLVKYTKSV- 787
Cdd:cd08630    150 ---------------------------------------------------------------QISPELSALAVYCQATr 166

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  788 --GTHDVEIEVVSSwQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEG 865
Cdd:cd08630    167 lrTLEPAPVQPQPC-QVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPG 245

                          410
                   ....*....|...
gi 1039767898  866 RMLQLNRAKFSAN 878
Cdd:cd08630    246 YEMDLNAGRFLVN 258
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 470-878 5.15e-79

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


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 260.76  E-value: 5.15e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  470 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 549
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  550 YAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSVSSEdATMLPSPQMLKGKILVKGKKLPANisedaeege 629
Cdd:cd08628     82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEAS-ADQLPSPTQLKEKIIIKHKKLIAI--------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  630 vsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskvee 709
Cdd:cd08628        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  710 dveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsrALSDLVKYTKSVGT 789
Cdd:cd08628    152 ------------------------------------------------------------------ELSDLVVYCKPTSK 165

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  790 HDVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQ 869
Cdd:cd08628    166 TKDNLENPDFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQ 245


                   ....*....
gi 1039767898  870 LNRAKFSAN 878
Cdd:cd08628    246 LNHALFSLN 254
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 470-878 1.41e-78

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: 258.72  E-value: 1.41e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  470 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 549
Cdd:cd08598      2 EDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  550 YAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKgkklpanisedaeege 629
Cdd:cd08598     82 YAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLL-VTEPLDGLEDELPSPEELRGKILIK---------------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  630 vsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqskvee 709
Cdd:cd08598        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  710 dveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsralsdlVKYTKSVGT 789
Cdd:cd08598    145 -----------------------------------------------------------------------VKKESKTPN 153

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  790 HdveievvsswqVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQ 869
Cdd:cd08598    154 H-----------IFSLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQ 222


                   ....*....
gi 1039767898  870 LNRAKFSAN 878
Cdd:cd08598    223 LNEAMFAGS 231
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 469-878 4.73e-75

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: 249.68  E-value: 4.73e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGP--DGEPIVHHGYTLTSKILFKDVIET 546
Cdd:cd08626      1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  547 INKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKL---DLSSVSSEDATMLPSPQMLKGKILVKGKKlpanise 623
Cdd:cd08626     81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLltkPLESHPLEPGVPLPSPNKLKRKILIKNKR------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  624 daeegevsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkg 703
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  704 qskveedveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsraLSDLVKY 783
Cdd:cd08626    154 -------------------------------------------------------------------------LSSLVNY 160

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  784 TKSVGTH--DVEIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNY 861
Cdd:cd08626    161 AQPVKFQgfDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNF 240

                          410
                   ....*....|....*..
gi 1039767898  862 QSEGRMLQLNRAKFSAN 878
Cdd:cd08626    241 QTPDLGMQLNQGKFEYN 257
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
 317-457 7.04e-72

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


Pssm-ID: 320050 [Multi-domain]  Cd Length: 141  Bit Score: 236.07  E-value: 7.04e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16220      1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQGTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16220     81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSPA 141
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 470-878 2.28e-71

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: 238.98  E-value: 2.28e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  470 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 549
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  550 YAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLD---LSSVSSEDATMLPSPQMLKGKILVKGKKLPanisedae 626
Cdd:cd08596     82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVtkfLFESDFSDDPSLPSPLQLKNKILLKNKKAP-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  627 egevsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkgqsk 706
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  707 veedveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsrALSDLVKYTKS 786
Cdd:cd08596    154 ---------------------------------------------------------------------ELSDLVIYCQA 164

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  787 VGTHDveIEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGR 866
Cdd:cd08596    165 VKFPG--LSTPKCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDL 242

                          410
                   ....*....|..
gi 1039767898  867 MLQLNRAKFSAN 878
Cdd:cd08596    243 PMHLNAAMFEAN 254
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 469-878 4.22e-71

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: 238.80  E-value: 4.22e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 546
Cdd:cd08624      1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  547 INKYAFIKNEYPVILSIENHC-SVVQQKKMAQYLTDILGDKL---DLSSVSSEDATMLPSPQMLKGKILVKGKKLpanis 622
Cdd:cd08624     81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLltePLEKYPLKPGVPLPSPEDLRGKILIKNKKY----- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  623 edaeegevsdedsaDEMeddckllngdastnrkrveniakkkldslikeSKIRDCEDPNDFsvstlspsgklgrkaeakk 702
Cdd:cd08624    156 --------------EEM--------------------------------SSLVNYIQPTKF------------------- 170

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  703 gqskveedveagedsgVSRQNSrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtaRQKKtmklsralsdlvk 782
Cdd:cd08624    171 ----------------VSFEFS-----------------------------------------AQKN------------- 180

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  783 ytksvgthdveievvSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQ 862
Cdd:cd08624    181 ---------------RSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQ 245

                          410
                   ....*....|....*.
gi 1039767898  863 SEGRMLQLNRAKFSAN 878
Cdd:cd08624    246 TMDLPMQQNMALFEFN 261
PLN02952 PLN02952
phosphoinositide phospholipase C
 386-1018 3.61e-68

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 241.83  E-value: 3.61e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  386 RDLYLLMLTYSNHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQF---EPCLENKSKGMLGIDGFTNYTRSPagDIFN 462
Cdd:PLN02952    38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEEVinrRHHVTRYTRHGLNLDDFFHFLLYD--DLNG 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  463 PEHNRVHQDMTQPLSHYFITSSHNTYLVGDQLMSQ-SRVDMYAwVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILF 540
Cdd:PLN02952   116 PITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQRGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPL 194

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  541 KDVIETINKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSsvSSEDATMLPSPQMLKGKILVKGKKlpan 620
Cdd:PLN02952   195 IKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP--ESDSLVQFPSPESLKHRIIISTKP---- 268

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  621 isedaeegevsdedsademeddckllngdastnrkrveniAKKKLDSLIKESKIRDcedpndfsvSTLSPSGKlgrkaea 700
Cdd:PLN02952   269 ----------------------------------------PKEYLESSGPIVIKKK---------NNVSPSGR------- 292

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  701 kkgqSKVEEDVEAgedSGVSRQNSRLfmssfskrkkkgskikkvasveEGDETLDSPGSQSRGTARQKKTMKlsRALSdl 780
Cdd:PLN02952   293 ----NSSEETEEA---QTLESMLFEQ----------------------EADSRSDSDQDDNKSGELQKPAYK--RLIT-- 339

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  781 VKYTKSVGTHDVEIEV-VSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVAL 859
Cdd:PLN02952   340 IHAGKPKGTLKDAMKVaVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAF 419

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  860 NYQSEGRMLQLNRAKFSANGDCGYVLKPQCMCQGVFNPNSEDP---LPgqLKKQLALRIISGQQLPKPRDSVLGDRGEII 936
Cdd:PLN02952   420 NMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPkkkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSPP 497

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  937 DPFVEVEVIGLPVDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSIMPGYRH 1015
Cdd:PLN02952   498 DFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIRS 576


                   ...
gi 1039767898 1016 VYL 1018
Cdd:PLN02952   577 VPL 579
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 470-878 4.55e-67

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: 226.06  E-value: 4.55e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  470 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 549
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  550 YAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGKKLpanisedaeege 629
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDML-LTKPVDINADGLPSPNQLKRKILIKHKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  630 vsdedsademeddckllngdastnrkrveniakkkldslikeskIRDcedpndfsvstlspsgklgrkaeakkgqskvee 709
Cdd:cd08627    149 --------------------------------------------YRD--------------------------------- 151

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  710 dveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsralsdlvkytksvgt 789
Cdd:cd08627        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  790 hdveievvsswqVSSFSETKAHQILQQ-KPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 868
Cdd:cd08627    152 ------------MSSFPETKAEKYVNRsKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPM 219

                          410
                   ....*....|
gi 1039767898  869 QLNRAKFSAN 878
Cdd:cd08627    220 QMNQALFMLG 229
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 471-878 1.51e-65

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: 222.62  E-value: 1.51e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  471 DMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08625      3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHC-SVVQQKKMAQYLTDILGDKL---DLSSVSSEDATMLPSPQMLKGKILVKGKKLpanised 624
Cdd:cd08625     83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALlidPLDKYPLVPGVQLPSPQELMGKILVKNKKM------- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  625 aeegevsdedsademeddckllngdaSTNRKRVENIAKKKLDSLIKESKIrdcedpndfsvstlspsgklgrkaeakkgq 704
Cdd:cd08625    156 --------------------------STLVNYIEPVKFKSFEAAAKRNKF------------------------------ 179

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  705 skveedveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsralsdlvkyt 784
Cdd:cd08625        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  785 ksvgthdveievvssWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSE 864
Cdd:cd08625    180 ---------------FEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTL 244

                          410
                   ....*....|....
gi 1039767898  865 GRMLQLNRAKFSAN 878
Cdd:cd08625    245 DLAMQLNMGVFEYN 258
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 472-615 6.14e-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: 210.60  E-value: 6.14e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   472 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 551
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039767898   552 FIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGK 615
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PLN02228 PLN02228
Phosphoinositide phospholipase C
 391-1018 1.72e-61

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 221.45  E-value: 1.72e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  391 LMLTYSnHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNY----TRSPAgdifnPEHN 466
Cdd:PLN02228    29 LFEAYS-RNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYlfsdTNSPL-----PMSG 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  467 RVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFKDVIE 545
Cdd:PLN02228   103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  546 TINKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLdlSSVSSEDATMLPSPQMLKGKILVKGKKlpaniSEDA 625
Cdd:PLN02228   183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGML--FRCTSESTKHFPSPEELKNKILISTKP-----PKEY 255

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  626 EEGEVSDEDSADEMEddckllngdaSTNRKRVENiakkkldsliKESKIRdcEDPNDFSVSTLSPSGKLGRKAEAKKGQS 705
Cdd:PLN02228   256 LESKTVQTTRTPTVK----------ETSWKRVAD----------AENKIL--EEYKDEESEAVGYRDLIAIHAANCKDPL 313

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  706 KveeDVEAGEDSGVSRqnsrlfmssfskrkkkgskikkVASVEEGDETLdspgSQSRGTarqkktmklsralsDLVKYTk 785
Cdd:PLN02228   314 K---DCLSDDPEKPIR----------------------VSMDEQWLETM----VRTRGT--------------DLVRFT- 349

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  786 svgthdveievvsswqvssfsetkahqilqqkptqylrfnQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEG 865
Cdd:PLN02228   350 ----------------------------------------QRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHG 389

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  866 RMLQLNRAKFSANGDCGYVLKPQCMCQ--GVFNPNSEDPlpgqLKKQLALRIISGQ--QLPKPRDSVlgDRGEIIDPFVE 941
Cdd:PLN02228   390 KQLWIMQGMFRANGGCGYVKKPRILLDehTLFDPCKRLP----IKTTLKVKIYTGEgwDLDFHLTHF--DQYSPPDFFVK 463

                          570       580       590       600       610       620       630
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1039767898  942 VEVIGLPVDCSKEQTRVVDDNGFnPMW-EETLVFTVHMPEIALVRFLVWDHDP-IGRDFIGQRTLAFSSIMPGYRHVYL 1018
Cdd:PLN02228   464 IGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELKSGVRAVRL 541
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 470-878 3.72e-59

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: 204.55  E-value: 3.72e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  470 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETI 547
Cdd:cd08623      2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  548 NKYAFIKNEYPVILSIENHC-SVVQQKKMAQYLTDILGDKL---DLSSVSSEDATMLPSPQMLKGKILVKGKKlpanise 623
Cdd:cd08623     82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALlmePLEKYPLESGVPLPSPMDLMYKILVKNKK------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  624 daeegevsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvstlspsgklgrkaeakkg 703
Cdd:cd08623        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  704 qskveedveagedsgvsrqnsrlfmssfskrkkkgskikkvasveegdetldspgsqsrgtarqkktmklsraLSDLVKY 783
Cdd:cd08623    155 -------------------------------------------------------------------------MSNLVNY 161

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  784 TKSVGTHDVEI--EVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNY 861
Cdd:cd08623    162 IQPVKFESFEAskKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNF 241

                          410
                   ....*....|....*..
gi 1039767898  862 QSEGRMLQLNRAKFSAN 878
Cdd:cd08623    242 QTVDLSMQINMGMYEYN 258
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 407-1018 1.09e-58

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 213.35  E-value: 1.09e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  407 LQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSkgmLGIDGFTNYTrspAGDIFNP-EHNRVHQDMTQPLSHYFITSSH 485
Cdd:PLN02222    45 LHRFLIDVQKQDKATREDAQSIINSASSLLHRNG---LHLDAFFKYL---FGDNNPPlALHEVHHDMDAPISHYFIFTGH 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  486 NTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFKDVIETINKYAFIKNEYPVILSIE 564
Cdd:PLN02222   119 NSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLE 198

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  565 NHCSVVQQKKMAQYLTDILGDKLdLSSVSSEDATMLPSPQMLKGKILVKGKKlpaniseDAEEGEVSDedsaDEMEDDCK 644
Cdd:PLN02222   199 DHLTPDLQSKVAEMVTEIFGEIL-FTPPVGESLKEFPSPNSLKKRIIISTKP-------PKEYKEGKD----DEVVQKGK 266

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  645 LLnGDastnrkrvENIAKKKLDSLIKESKIRDCEDPNdfsvstlspsgklgrkaeakkgqSKVEEDVEAGEDSgvSRQNS 724
Cdd:PLN02222   267 DL-GD--------EEVWGREVPSFIQRNKSVDKNDSN-----------------------GDDDDDDDDGEDK--SKKNA 312

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  725 rlfmssfskrkkkGSKIKKVASVEEGdetldspgsqsrgtarqkktmKLSRALSDLVKytksVGTHDVEIEVVSSWQVSS 804
Cdd:PLN02222   313 -------------PPQYKHLIAIHAG---------------------KPKGGITECLK----VDPDKVRRLSLSEEQLEK 354

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  805 FSETKAHQILqqkptqylRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSANGDCGYV 884
Cdd:PLN02222   355 AAEKYAKQIV--------RFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYI 426

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  885 LKPQCMCQG-----VFNPNSEDPlpgqLKKQLALRIISGQQLPKPRDSVLGDRGEIIDPFVEVEVIGLPVDCSKEQTRVV 959
Cdd:PLN02222   427 KKPDLLLKSgsdsdIFDPKATLP----VKTTLRVTIYMGEGWYFDFRHTHFDQYSPPDFYTRVGIAGVPGDTVMKKTKTL 502

                          570       580       590       600       610       620
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  960 DDNgFNPMWEETLVFTVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSIMPGYRHVYL 1018
Cdd:PLN02222   503 EDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKdDFGGQTCLPVWELSQGIRAFPL 561
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 387-1018 3.98e-56

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 206.09  E-value: 3.98e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  387 DLYLLMLTYSNHKDHLDASDLQRFLEVEQKMNGVT-LESCQNIIEQF---EPCLENKSKGMLGIDGFTNYTRSPagDIFN 462
Cdd:PLN02230    30 DVRDLFEKYADGDAHMSPEQLQKLMAEEGGGEGETsLEEAERIVDEVlrrKHHIAKFTRRNLTLDDFNYYLFST--DLNP 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  463 PEHNRVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKD 542
Cdd:PLN02230   108 PIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRTLTKEVKLGK 187

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  543 VIETINKYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSsvSSEDATMLPSPQMLKGKILVKGKK----LP 618
Cdd:PLN02230   188 CLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYH--DSEGCQEFPSPEELKEKILISTKPpkeyLE 265

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  619 ANISED---AEEGEVSDEDSADEMEDDCKLLNGDASTNRKRVENIAKkkldsliKESKIRDCEdpNDFSVSTLSPsgklg 695
Cdd:PLN02230   266 ANDAKEkdnGEKGKDSDEDVWGKEPEDLISTQSDLDKVTSSVNDLNQ-------DDEERGSCE--SDTSCQLQAP----- 331

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  696 rkaeakkgQSKVEEDVEAGEDSGVSRQNSRLfmssfskrkkkgskikkvasveegdetldSPGSQSRgtarqkktMKLSR 775
Cdd:PLN02230   332 --------EYKRLIAIHAGKPKGGLRMALKV-----------------------------DPNKIRR--------LSLSE 366

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  776 ALSDlvkytKSVGTHDVEIevvsswqvssfsetkahqilqqkptqyLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 855
Cdd:PLN02230   367 QLLE-----KAVASYGADV---------------------------IRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQ 414

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  856 MVALNYQSEGRMLQLNRAKFSANGDCGYVLKPQCMC------QGVFNPNSEDPlpgqlKKQLALRIISGQQLPKPRDSVL 929
Cdd:PLN02230   415 MIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMdagpngQDFYPKDNSCP-----KKTLKVKVCMGDGWLLDFKKTH 489

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  930 GDRGEIIDPFVEVEVIGLPVDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSS 1008
Cdd:PLN02230   490 FDSYSPPDFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNKEFIFPLAVPELALLRVEVHEHDINEKdDFGGQTCLPVSE 568

                          650
                   ....*....|
gi 1039767898 1009 IMPGYRHVYL 1018
Cdd:PLN02230   569 IRQGIHAVPL 578
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 777-889 4.70e-56

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 189.59  E-value: 4.70e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  777 LSDLVKYTKSVGTHDVE-IEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 855
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFStPESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1039767898  856 MVALNYQSEGRMLQLNRAKFSANGDCGYVLKPQC 889
Cdd:pfam00387   81 MVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 469-637 4.12e-54

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: 188.73  E-value: 4.12e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 548
Cdd:cd08599      1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  549 KYAFIKNEYPVILSIENHCSVVQQKKMAQYLTDILGDKLDLSSvSSEDATMLPSPQMLKGKILV--KGKKLPANISEDAE 626
Cdd:cd08599     81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPD-SEDLPEEFPSPEELKGKILIsdKPPVIRNSLSETQL 159

                          170
                   ....*....|.
gi 1039767898  627 EGEVSDEDSAD 637
Cdd:cd08599    160 KKVIEGEHPTD 170
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 193-299 6.02e-54

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


Pssm-ID: 270170  Cd Length: 109  Bit Score: 183.25  E-value: 6.02e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  193 MQEGTQMVKLRGSSKGLVRFYYLDEHRSCLRWRPSRKN-EKAKISIDSIQEVSEGRQSEIFQRYP-DSSFDPNCCFSIYH 270
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1039767898  271 GSHRESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 908-1033 2.82e-53

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: 182.36  E-value: 2.82e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  908 KKQLALRIISGQQLPKPRDsvlgDRGEIIDPFVEVEVIGLPV-DCSKEQTRVVDDNGFNPMWEETLVFTVHMPEIALVRF 986
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  987 LVWDHDPIGRDFIGQRTLAFSSIMPGYRHVYL-----EGMEEASIFVHVAVS 1033
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 778-890 2.80e-50

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: 173.19  E-value: 2.80e-50
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   778 SDLVKYTKSVGTHDVE--IEVVSSWQVSSFSETKAHQILQQKPTQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 855
Cdd:smart00149    1 SDLVIYCAPVKFRSFEsaESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1039767898   856 MVALNYQSEGRMLQLNRAKFSANGDCGYVLKPQCM 890
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 317-456 8.31e-47

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: 164.31  E-value: 8.31e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFRE--ADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLT 394
Cdd:cd16206      1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKElqKKKDGARGRVSSDEFVELFKELATRPEIYFLLVR 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  395 YSNHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16206     81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSE 142
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 469-878 1.15e-45

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: 166.29  E-value: 1.15e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQL-----MSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTsKILFKDV 543
Cdd:cd00137      1 HHPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  544 IETINKYAFIKNEYPVILSIENHCSVV--QQKKMAQYLTDILGDKldLSSVSSEDATMLPSPQMLKGKILVKGKKlpani 621
Cdd:cd00137     80 IEAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDM--LLTPPLKPTVPLPSLEDLRGKILLLNKK----- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  622 sedaeegevsdedsademeddckllngdastnrkrveniakkkldslikeskirdcedpndfsvSTLSPSGklgrkaeak 701
Cdd:cd00137    153 ----------------------------------------------------------------NGFSGPT--------- 159

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  702 kgqskveedveagedsgvsrqnsrlfmssfskrkkkgskikkvasveeGDETLDSPGSQSRGTARQKktmklsralsdlv 781
Cdd:cd00137    160 ------------------------------------------------GSSNDTGFVSFEFSTQKNR------------- 178

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  782 kytksvgthdveievvsSWQVSSFSETKA---HQILQQKPT-QYLRFNQHQLSRIYPS---------SYRVDSSNYNPQP 848
Cdd:cd00137    179 -----------------SYNISSQDEYKAyddEKVKLIKATvQFVDYNKNQLSRNYPSgtsggtawyYYAMDSNNYMPQM 241

                          410       420       430
                   ....*....|....*....|....*....|...
gi 1039767898  849 FWN---AGCQMVALNYQSEGRMLQLNRAKFSAN 878
Cdd:cd00137    242 FWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 317-456 8.54e-42

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: 150.07  E-value: 8.54e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16202      1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSG-EDVLDEEEFVQFYNRLTKRPEIEELFKKYS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16202     80 GDDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSP 139
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 193-298 7.05e-40

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


Pssm-ID: 269952  Cd Length: 108  Bit Score: 143.23  E-value: 7.05e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  193 MQEGTQMVKLRGSSKGLVRFYYLDEHRSCLRWRPSRK-NEKAKISIDSIQEVSEGRQSEIFQRY-PDSSFDPNCCFSIYH 270
Cdd:cd01248      1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKkSEKKSIDISDIKEIRPGKDTDGFKRKkKSNKPKEERCFSIIY 80

                           90       100
                   ....*....|....*....|....*...
gi 1039767898  271 GSHRESLDLVSPSSEEARTWVTGLRYLM 298
Cdd:cd01248     81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 317-457 3.85e-38

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: 139.34  E-value: 3.85e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTY- 395
Cdd:cd15898      1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDT-NGDGTLTFDEFEELYKSLTERPELEPIFKKYa 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  396 SNHKDHLDASDLQRFLEVEQKMNgVTLESCQNIIEQFEPCLENKskgMLGIDGFTNYTRSPA 457
Cdd:cd15898     80 GTNRDYMTLEEFIRFLREEQGEN-VSEEECEELIEKYEPERENR---QLSFEGFTNFLLSPE 137
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 317-456 4.28e-29

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: 113.80  E-value: 4.28e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGT--LGFEEFCAFYKMMSTRRDLYLLMLT 394
Cdd:cd16222      1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTtrVTEEEFCEAYSELCTRPEVYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  395 YSNHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16222     81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSS 142
PLN02223 PLN02223
phosphoinositide phospholipase C
 469-1018 2.20e-28

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 121.67  E-value: 2.20e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  469 HQDMTQPLSHYFITSSHNTYLVGDQLMSQS-RVDMYAWVLQAGCRCVEVDCWdgPDGEP--IVHHGYTLTSKILFKDVIE 545
Cdd:PLN02223   105 HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL--PDGKDgiCVRPKWNFEKPLELQECLD 182

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  546 TINKYAFIK-NEYPVILSIENHCSVVQQKKMAQYLTDILGDKldlssVSSEDAT----MLPSPQMLKGKILVKgKKLPAn 620
Cdd:PLN02223   183 AIKEHAFTKcRSYPLIITFKDGLKPDLQSKATQMIDQTFGDM-----VYHEDPQhsleEFPSPAELQNKILIS-RRPPK- 255

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  621 isedaeegevsdedsademeddcKLLNGDASTNRKRVENiakkkldslikESKIRD-CEDPNDFSV---STLSPSGKLgr 696
Cdd:PLN02223   256 -----------------------ELLYAKADDGGVGVRN-----------ELEIQEgPADKNYQSLvgfHAVEPRGML-- 299

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  697 kaeakkgqskveEDVEAGEDSGVSRqnsrlfmssfskrkkkgskikkvasveegdetldsPGSQSRgtarqkktmklsra 776
Cdd:PLN02223   300 ------------QKALTGKADDIQQ-----------------------------------PGWYER-------------- 318

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  777 lsDLVKYTKSvgthdveievvsswqvssfsetkahQILQQKPtqylrfnQHQLSRIYPSsyrvdssnYNPQPFWNAGCQM 856
Cdd:PLN02223   319 --DIISFTQK-------------------------KFLRTRP-------KKKNLLINAP--------YKPQRAWMHGAQL 356

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  857 VALNYQSEGRMLQLNRAKFSANGDCGYVLKPQCMCQ----GVFNPnSEDPLpgqLKKQLALRIISGQ-----------QL 921
Cdd:PLN02223   357 IALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagpsGVFYP-TENPV---VVKILKVKIYMGDgwivdfkkrigRL 432

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  922 PKPrdsvlgdrgeiiDPFVEVEVIGLPVDcSKEQTRVVDDNGFNPMWEETLVFTVHMPEIALVRFLVWDHDPIGRD-FIG 1000
Cdd:PLN02223   433 SKP------------DLYVRISIAGVPHD-EKIMKTTVKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADaFCG 499

                          570
                   ....*....|....*...
gi 1039767898 1001 QRTLAFSSIMPGYRHVYL 1018
Cdd:PLN02223   500 QTCLPVSELIEGIRAVPL 517
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 317-456 2.58e-26

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


Pssm-ID: 320053 [Multi-domain]  Cd Length: 144  Bit Score: 105.76  E-value: 2.58e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFRE-ADTDDHQGT-LGFEEFCAFYKMMSTRRDLYLLMLT 394
Cdd:cd16223      1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKElHKSKEKGGTeVTKEEFIEVFHELCTRPEIYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  395 YSNHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16223     81 FSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSP 142
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 317-456 7.50e-24

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


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 98.76  E-value: 7.50e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16219      1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSE-SGTLEGEEFVLFYKALTQREDVLKIFQDFS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16219     80 ADGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSP 139
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 910-1018 5.80e-22

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: 91.78  E-value: 5.80e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   910 QLALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGLPVdcSKEQTRVVDDNGfNPMWEETLVFTVHMPEIALVRFLVW 989
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 1039767898   990 DHDPIGRD-FIGQRTLAFSSIMPGYRHVYL 1018
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 193-311 1.73e-21

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


Pssm-ID: 270169  Cd Length: 117  Bit Score: 90.84  E-value: 1.73e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  193 MQEGTQMVKLRGSSKGLVRFYYLDEhrSCLR-WRPSRK---NEKAKISIDSIQEVSEGRQSEIFQRYPDSsFDPNCCFSI 268
Cdd:cd13363      1 LLQGSPLLKVRSRSWKKERFYKLQE--DCKTvWHESKKtrsNSKQTFSIEDIESVREGHQSEGLRKYAEA-FPEDRCFSI 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1039767898  269 -YHGsHRESLDLVSPSSEEARTWVTGLRYLMAGIsdeDSLARRQ 311
Cdd:cd13363     78 vFKG-RRKNLDLIAPSEEEAQRWVRGLEKLIARL---TNMSQRE 117
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 483-588 2.96e-21

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: 92.50  E-value: 2.96e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  483 SSHNTYLVGDQlmsQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLT------SKILFKDVIETINKYAFiKNE 556
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1039767898  557 YPVILSIENHCSVV----QQKKMAQYLTDILGDKLD 588
Cdd:cd08555     78 YTIILSLEIKQDSPeydeFLAKVLKELRVYFDYDLR 113
C2 pfam00168
C2 domain;
910-1015 3.83e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 86.60  E-value: 3.83e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  910 QLALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGlpvDCSKEQTRVVDdNGFNPMWEETLVFTVHMPEIALVRFLVW 989
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 1039767898  990 DHDPIGRD-FIGQRTLAFSSIMPGYRH 1015
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
 186-299 7.22e-20

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


Pssm-ID: 270171  Cd Length: 115  Bit Score: 86.18  E-value: 7.22e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  186 MERCMSAMQEGTQMVKL--RGSSKglVRFYYLDEHRSCLRWRPSRKNEKAKISIDSIQEVSEGRQSEIFQRYPDSSFDpN 263
Cdd:cd13365      3 VIEAITQLKIGSYLLKYgrRGKPH--FRYFWLSPDELTLYWSSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLE-E 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1039767898  264 CCFSIYHGSHRESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:cd13365     80 HSFSIIYADGERSLDLTCKDRQEFDTWFTGLRYLLS 115
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 314-457 2.65e-19

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


Pssm-ID: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 85.76  E-value: 2.65e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  314 RDQWlKQTfDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLML 393
Cdd:cd16207      2 RIHW-KRA-DSKKQDGDERLDFEDVEKLCRRLHINCSESYLRELFDKADT-DKKGYLNFEEFQEFVKLLKRRKDIKAIFK 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1039767898  394 TY-SNHKDHLDASDLQRFLEVEQKMNgVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16207     79 QLtKPGSDGLTLEEFLKFLRDVQKED-VDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
 196-299 1.72e-16

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


Pssm-ID: 270168  Cd Length: 121  Bit Score: 76.93  E-value: 1.72e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  196 GTQMVKLRGSSK-----GLVRFyyldEHRSCLRWRPSRKNEKAKISIDSIQEVSEGRQSEIFQRYPDSS--FDPNCCFSI 268
Cdd:cd13362      4 GTVMTKFYQKKRperrtFQVKL----ETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSKDFERWPDEAkkLDPSCCFVI 79

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1039767898  269 YHGSH--RESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:cd13362     80 LYGTEfrLKTLSVAATSEEECDMWIKGLRYLVE 112
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 317-456 1.04e-15

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: 75.16  E-value: 1.04e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 396
Cdd:cd16217      1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSK-SGFLEGEEIEEFYKLLTKREEIDVIFGEYA 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  397 NHKDHLDASDLQRFLEVEQKmNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16217     80 KSDGTMSRNNLLNFLQEEQR-EEVAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSP 138
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 911-1001 2.24e-14

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: 70.17  E-value: 2.24e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  911 LALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGLpvdcSKEQTRVVDDNgFNPMWEETLVFTVHMPEIALVRFLVWD 990
Cdd:cd00030      1 LRVTVIEARNLPAK------DLNGKSDPYVKVSLGGK----QKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWD 69

                           90
                   ....*....|..
gi 1039767898  991 HDPIGRD-FIGQ 1001
Cdd:cd00030     70 KDRFSKDdFLGE 81
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 317-383 5.34e-14

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


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 67.57  E-value: 5.34e-14
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHqGTLGFEEFCafyKMMS 383
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGD-GKIDFEEFL---ELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
315-380 2.17e-13

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 66.12  E-value: 2.17e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039767898  315 DQWLKQTFDEADKNGDGSLSISEVLQLLHKL--NVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYK 380
Cdd:pfam13499    1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDL-DKDGRISFEEFLELYS 67
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 317-457 5.85e-13

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


Pssm-ID: 320048 [Multi-domain]  Cd Length: 138  Bit Score: 67.46  E-value: 5.85e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADT------DDHQgtlgFEEFCAfyKMMStRRDLYL 390
Cdd:cd16218      1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRsnddrlEEHE----IEEFCR--RLMQ-RPELEE 73

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039767898  391 LMLTYSNHKDHLDASDLQRFLEvEQKMNGvTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:cd16218     74 IFHQYSGEDCVLSAEELREFLK-DQGEDA-SLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
PH_12 pfam16457
Pleckstrin homology domain;
187-298 1.18e-12

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 66.13  E-value: 1.18e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  187 ERCMSAMQEGTQMVKLRGSSKGL-VRFYYLDEHRSCLRW---------RPSRKNEKAKISIDSIQEVSEGRQSEIF--QR 254
Cdd:pfam16457    3 EQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVreSG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1039767898  255 YPDSSFDPNCCFSIYHGSH-RESLDLVSPSSEEARTWVTGLRYLM 298
Cdd:pfam16457   83 KKSKKTSSTLAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLL 127
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 378-462 1.80e-12

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: 64.19  E-value: 1.80e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  378 FYKMMSTRRDLYLLMLTYSNHKDHLDASDLQRFLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSPA 457
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 1039767898  458 GDIFN 462
Cdd:pfam09279   81 GSIFN 85
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 330-455 1.47e-11

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: 63.29  E-value: 1.47e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  330 DGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYSNHKDHLDASDLQR 409
Cdd:cd16204     16 KGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFK-AGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVG 94

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1039767898  410 FLEVEQKMNGVTLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRS 455
Cdd:cd16204     95 FLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTS 140
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
307-378 9.27e-11

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 60.96  E-value: 9.27e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  307 LARRQRTRDQWLKQTFDEADKNGDGSLSISEVLQLLHKLNVnlPRQRVKQMFREADTdDHQGTLGFEEFCAF 378
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDT-DGDGKISFEEFVAA 128
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 336-456 4.06e-09

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: 56.87  E-value: 4.06e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  336 SEVLQLLHKLNvnLPRQRVKQMFREADTDDHqgtlgfeeFCAFYKMMSTRRDLYLLMLTYS-NHKDHLDASDLQRFLEVE 414
Cdd:cd16200     33 KRVLKALKALG--LPDGKNDEIDPEDFTFEK--------FFKLYNKLCPRPDIDEIFKELGgKRKPYLTLEQLVDFLNEE 102

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1039767898  415 Q---KMNGV-----TLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRSP 456
Cdd:cd16200    103 QrdpRLNEIlfpfhTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSD 152
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 910-1019 4.54e-08

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 52.58  E-value: 4.54e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  910 QLALRIISGQQLPkprdsvlgdrGEIIDPFVEVEVIGlpvdcSKEQTRVVDDNGfNPMWEETLVFTVHMP--EI--ALVR 985
Cdd:cd04011      5 QVRVRVIEARQLV----------GGNIDPVVKVEVGG-----QKKYTSVKKGTN-CPFYNEYFFFNFHESpdELfdKIIK 68

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1039767898  986 FLVWDHDPIGRD-FIGQRTLAFSSIMPGYRHVYLE 1019
Cdd:cd04011     69 ISVYDSRSLRSDtLIGSFKLDVGTVYDQPDHAFLR 103
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 317-416 1.92e-07

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


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 51.80  E-value: 1.92e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDdHQGTLGFEEFCAFY-------KMMSTRRDLY 389
Cdd:cd16201      1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTR-RRGELGFDDFAQLYhklmfdqKIIEDFFKKY 79

                           90       100
                   ....*....|....*....|....*..
gi 1039767898  390 llmlTYSNHKDHLDASDLQRFLEVEQK 416
Cdd:cd16201     80 ----SYSSDGQTVTLEDFQRFLLEEQK 102
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 937-1010 2.59e-07

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


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 51.11  E-value: 2.59e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039767898  937 DPFVEVEVIGLPVDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEiaLVRFL---VWDHDPIGR-DFIGQRTLAFSSIM 1010
Cdd:cd04026     35 DPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPAD--KDRRLsieVWDWDRTTRnDFMGSLSFGVSELI 109
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 475-612 3.65e-07

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


Pssm-ID: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 53.25  E-value: 3.65e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  475 PLSHYFITSSHNTYlvgDQLMSQSRVDMYAWV----------LQAGCRCVEVDCW-DGPDGEPIVHHGYTLTSKILFKDV 543
Cdd:cd08557      8 PLSQLSIPGTHNSY---AYTIDGNSPIVSKWSktqdlsitdqLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDV 84

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039767898  544 IETINkyAFIK---NEyPVILSIENHCSV---VQQKKMAQYLTDILGDKLDLSSVSSEDatmlpSP---QMLKGKILV 612
Cdd:cd08557     85 LNEVK--DFLDahpSE-VVILDLEHEYGGdngEDHDELDALLRDVLGDPLYRPPVRAGG-----WPtlgELRAGKRVL 154
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 908-1001 4.58e-07

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


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 49.94  E-value: 4.58e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  908 KKQLALRIISGQQLPkPRDSvlgdrGEIIDPFVEVEVIGLPVDCSKEQTRVVDdNGFNPMWEETLVFTVHMPEIALVRFL 987
Cdd:cd04031     15 TSQLIVTVLQARDLP-PRDD-----GSLRNPYVKVYLLPDRSEKSKRRTKTVK-KTLNPEWNQTFEYSNVRRETLKERTL 87

                           90
                   ....*....|....*...
gi 1039767898  988 ---VWDHDPIG-RDFIGQ 1001
Cdd:cd04031     88 evtVWDYDRDGeNDFLGE 105
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 319-376 5.31e-07

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 47.98  E-value: 5.31e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1039767898  319 KQTFDEADKNGDGSLSISEVLQLLhkLNVNLPRQRVKQMFREADTdDHQGTLGFEEFC 376
Cdd:cd00052      2 DQIFRSLDPDGDGLISGDEARPFL--GKSGLPRSVLAQIWDLADT-DKDGKLDKEEFA 56
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 895-1015 6.50e-07

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 49.89  E-value: 6.50e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  895 FNPNSEdplpgqlkkQLALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGLPVDCSKEQTRVVDDNgFNPMWEETLVF 974
Cdd:cd00276      9 YLPTAE---------RLTVVVLKARNLPPS------DGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSF 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1039767898  975 TV---HMPEIALVrFLVWDHDPIGRD-FIGQRTLAFSSIMPGYRH 1015
Cdd:cd00276     73 DVpaeQLEEVSLV-ITVVDKDSVGRNeVIGQVVLGPDSGGEELEH 116
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
314-387 6.69e-07

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 49.79  E-value: 6.69e-07
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039767898  314 RDQWLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRD 387
Cdd:COG5126     31 FRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDT-DGDGKISADEFRRLLTALGVSEE 103
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 910-1021 7.29e-07

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


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 49.54  E-value: 7.29e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  910 QLALRIISGQQLpKPRDSvlgdRGeIIDPFVEVEVigLP----VDCSKEQTRVVDDNgFNPMWEETLVFTV----HMPEI 981
Cdd:cd04009     17 SLRVEILNARNL-LPLDS----NG-SSDPFVKVEL--LPrhlfPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEG 87

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1039767898  982 ALVRFLVWDHDPIGR-DFIGQRTLAFSSImPGYRHVYLEGM 1021
Cdd:cd04009     88 ALLLFTVKDYDLLGSnDFEGEAFLPLNDI-PGVEDTSSAQG 127
PTZ00184 PTZ00184
calmodulin; Provisional
 307-385 1.57e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 48.99  E-value: 1.57e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  307 LARRQRTRD--QWLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCafyKMMST 384
Cdd:PTZ00184    73 MARKMKDTDseEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDG-DGQINYEEFV---KMMMS 148


                   .
gi 1039767898  385 R 385
Cdd:PTZ00184   149 K 149
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 318-386 1.09e-05

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 46.82  E-value: 1.09e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039767898  318 LKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEF---CAFykMMSTRR 386
Cdd:cd16185     68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDP-DRGGSLGFDDYielCIF--LASARN 136
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 318-380 2.99e-05

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 45.60  E-value: 2.99e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1039767898  318 LKQTFDEADKNGDGSLSISEvLQLLHKLNVNLPRQR--VKQMFREADTDDHqGTLGFEEFCAFYK 380
Cdd:cd16180      2 LRRIFQAVDRDRSGRISAKE-LQRALSNGDWTPFSIetVRLMINMFDRDRS-GTINFDEFVGLWK 64
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1067-1243 3.26e-05

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 48.78  E-value: 3.26e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1067 LPRPSVSQRLLRRTASAPTKSQKPSRKGFPELALGTQDAGSEGAADDVA---PSSPNPAL--EAPTQE------------ 1129
Cdd:PHA03247  2460 LGAPFSLSLLLGELFPGAPVYRRPAEARFPFAAGAAPDPGGGGPPDPDAppaPSRLAPAIlpDEPVGEpvhprmltwirg 2539

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1130 -------RSGSSSPRGKAPGGEATEERTLAQVRSpnAPEGPGPAGMAATCMKCV-----VGSCAGMDVEGLQREQQPSPG 1197
Cdd:PHA03247  2540 leelasdDAGDPPPPLPPAAPPAAPDRSVPPPRP--APRPSEPAVTSRARRPDAppqsaRPRAPVDDRGDPRGPAPPSPL 2617

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1039767898 1198 PAGSHM--AISHQPRARVDSLGGPCCSPSPraTPGRSKEAPKGPRARR 1243
Cdd:PHA03247  2618 PPDTHApdPPPPSPSPAANEPDPHPPPTVP--PPERPRDDPAPGRVSR 2663
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
318-432 4.02e-05

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 44.78  E-value: 4.02e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  318 LKQTFDEADKNGDGSLSISEVLQLLHklnvnlprQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS- 396
Cdd:COG5126      7 LDRRFDLLDADGDGVLERDDFEALFR--------RLWATLFSEADT-DGDGRISREEFVAGMESLFEATVEPFARAAFDl 77

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1039767898  397 ---NHKDHLDASDLQRFLEVEqkmnGVTLESCQNIIEQF 432
Cdd:COG5126     78 ldtDGDGKISADEFRRLLTAL----GVSEEEADELFARL 112
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 937-1056 8.03e-05

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (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: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 44.24  E-value: 8.03e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  937 DPFVeveVIGLpvDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEiALVRFLVWDHD------PIGRDFIGQRTLAFSSIM 1010
Cdd:cd04038     23 DPYV---VLTL--GNQKVKTRVIKKN-LNPVWNEELTLSVPNPM-APLKLEVFDKDtfskddSMGEAEIDLEPLVEAAKL 95

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039767898 1011 PGYRHVYlEGMEEASIF----------VHVAVSDisGKVKQTLGLKglfLRGTKPG 1056
Cdd:cd04038     96 DHLRDTP-GGTQIKKVLpsvenclaseSHITWKD--GKIVQDLVLK---LRNVESG 145
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 318-384 9.05e-05

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 44.51  E-value: 9.05e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039767898  318 LKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMST 384
Cdd:cd16185      2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDR-DGNGTIDFEEFAALHQFLSN 67
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 195-299 1.16e-04

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


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 42.54  E-value: 1.16e-04
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898   195 EGTQMVKLRGSSKGLVRFY-YLdeHRSCLRW-----RPSRKNEKAKISIDSIQeVSEGRqseifqryPDSSFDPNCCFSI 268
Cdd:smart00233    4 EGWLYKKSGGGKKSWKKRYfVL--FNSTLLYykskkDKKSYKPKGSIDLSGCT-VREAP--------DPDSSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|.
gi 1039767898   269 YHGShRESLDLVSPSSEEARTWVTGLRYLMA 299
Cdd:smart00233   73 KTSD-RKTLLLQAESEEEREKWVEALRKAIA 102
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 372-455 1.62e-04

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: 43.56  E-value: 1.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  372 FEEFCAFYKMMSTRRDLYLLMLTYS-NHKDHLDASDLQRFLEVEQK---MNGVTL-----ESCQNIIEQFEPCLENKSKG 442
Cdd:cd16211     59 FEKFYELYHKICPRTDIEELFKKINgDKKDYLTVDQLISFLNEHQRdprLNEILFpfydrKRVMQIIETYEVDEEFKKKE 138

                           90
                   ....*....|...
gi 1039767898  443 MLGIDGFTNYTRS 455
Cdd:cd16211    139 QLSSDGFCRYLMS 151
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 370-452 1.69e-04

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


Pssm-ID: 320043  Cd Length: 154  Bit Score: 43.44  E-value: 1.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  370 LGFEEFCAFYKMMSTRRDLYLLMLTYSN-HKDHLDASDLQRFLEVEQK---MNGV-----TLESCQNIIEQFEPCLENKS 440
Cdd:cd16213     58 FTFEDFFNFYRRLTGRQEVEKIFDELGAkKKPYLTTEQFVDFLNKTQRdprLNEIlypyaNPKRARDLINQYEPNKSFAK 137

                           90
                   ....*....|..
gi 1039767898  441 KGMLGIDGFTNY 452
Cdd:cd16213    138 KGHLSVEGFLRY 149
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 1055-1243 1.69e-04

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 46.32  E-value: 1.69e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1055 PGSLDSHAA-GQPLPRPSVSQRLLRRTASAPTKSQKPSRKGFPELALGTQDAGSEGAADDVAPSSPNPALEAPTQERSGS 1133
Cdd:PHA03307   194 PPSTPPAAAsPRPPRRSSPISASASSPAPAPGRSAADDAGASSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWEAS 273

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1134 ---SSPRGKAPGGEATEERTLAQVRSPNAPEGPGPAGMAATcmkcvVGSCAGMDVEGLQ--REQQPSPGPAGSHmaishq 1208
Cdd:PHA03307   274 gwnGPSSRPGPASSSSSPRERSPSPSPSSPGSGPAPSSPRA-----SSSSSSSRESSSSstSSSSESSRGAAVS------ 342

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1039767898 1209 prarvdslGGPCCSPSPraTPGRSKEAPKGPRARR 1243
Cdd:PHA03307   343 --------PGPSPSRSP--SPSRPPPPADPSSPRK 367
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 913-1014 2.33e-04

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 43.06  E-value: 2.33e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  913 LRIISGQQLPKPRDSVLGDRGEII--DPFVEVEVIGLPVdcskEQTRVVDDNGfNPMWEET-LVFTVHMpeIALVRFLVW 989
Cdd:cd04015     33 FSKLVGCSEPTLKRPSSHRHVGKItsDPYATVDLAGARV----ARTRVIENSE-NPVWNESfHIYCAHY--ASHVEFTVK 105

                           90       100
                   ....*....|....*....|....*
gi 1039767898  990 DHDPIGRDFIGQRTLAFSSIMPGYR 1014
Cdd:cd04015    106 DNDVVGAQLIGRAYIPVEDLLSGEP 130
EF-hand_10 pfam14788
EF hand;
333-382 2.34e-04

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 40.09  E-value: 2.34e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1039767898  333 LSISEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMM 382
Cdd:pfam14788    2 MSFKELKNFLRLINIEVDDSYARKLFQKCDT-SQSGRLEGEEIEEFYKLL 50
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 913-1008 2.41e-04

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 42.25  E-value: 2.41e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  913 LRIISGQQLPKPRDSvlgdrgEIIDPFVEVEVIGLPVDCSKeqTRVVDDNgFNPMWEETLVFTVHMPEIALVRFLVWDHD 992
Cdd:cd04043      5 IRIVRAENLKADSSN------GLSDPYVTLVDTNGKRRIAK--TRTIYDT-LNPRWDEEFELEVPAGEPLWISATVWDRS 75

                           90
                   ....*....|....*..
gi 1039767898  993 PIGR-DFIGQRTLAFSS 1008
Cdd:cd04043     76 FVGKhDLCGRASLKLDP 92
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 913-1010 4.13e-04

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


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 42.23  E-value: 4.13e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  913 LRIISGQQLPKPRDSVL--------GDRGEIIDPFVEVEVIGLpvdcsKEQTRVVDDNgFNPMWEETLVFTVHMPEIA-L 983
Cdd:cd04018      4 FKIYRAEDLPQMDSGIManvkkaflGEKKELVDPYVEVSFAGQ-----KVKTSVKKNS-YNPEWNEQIVFPEMFPPLCeR 77

                           90       100
                   ....*....|....*....|....*...
gi 1039767898  984 VRFLVWDHDPIGRD-FIGQRTLAFSSIM 1010
Cdd:cd04018     78 IKIQIRDWDRVGNDdVIGTHFIDLSKIS 105
PTZ00184 PTZ00184
calmodulin; Provisional
 319-385 4.92e-04

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 42.06  E-value: 4.92e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039767898  319 KQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDHqGTLGFEEFCAfykMMSTR 385
Cdd:PTZ00184    14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 905-1000 5.63e-04

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


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 41.92  E-value: 5.63e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  905 GQLKkqLALRIISGQQLPKPRDSVlGDRGEI------------------IDPFVEVEVigLPVDC--SKEQTRVVDDNGf 964
Cdd:cd04020      2 GELK--VALKYVPPESEGALKSKK-PSTGELhvwvkeaknlpalksggtSDSFVKCYL--LPDKSkkSKQKTPVVKKSV- 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1039767898  965 NPMWEETLVFTVHMPE---IALVRFLVWDHDPIGR-DFIG 1000
Cdd:cd04020     76 NPVWNHTFVYDGVSPEdlsQACLELTVWDHDKLSSnDFLG 115
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 937-1008 6.37e-04

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


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 41.18  E-value: 6.37e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039767898  937 DPFVEVEVIGLPVDCSKEQTRVvDDNGFNPMWEETLVFTVHMPEIAlVRFL---VWDHDpIGR--DFIGQRTLAFSS 1008
Cdd:cd08384     35 DPFVKLYLKPDAGKKSKHKTQV-KKKTLNPEFNEEFFYDIKHSDLA-KKTLeitVWDKD-IGKsnDYIGGLQLGINA 108
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 908-1009 7.02e-04

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc 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.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 40.72  E-value: 7.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  908 KKQLALRIISGqqlpKPRDSVLGDRGeiiDPFVEVEVIGLPVdcskEQTRVVDdNGFNPMWEETlvFTVHMPEIALVRFL 987
Cdd:cd04021      1 KSQLQITVESA----KLKSNSKSFKP---DPYVEVTVDGQPP----KKTEVSK-KTSNPKWNEH--FTVLVTPQSTLEFK 66

                           90       100
                   ....*....|....*....|...
gi 1039767898  988 VWDHDPIGRD-FIGQRTLAFSSI 1009
Cdd:cd04021     67 VWSHHTLKADvLLGEASLDLSDI 89
EFh_PI-PLCgamma1_like cd16216
EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...
 317-416 7.56e-04

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. A second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker.


Pssm-ID: 320046  Cd Length: 150  Bit Score: 41.46  E-value: 7.56e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRV---KQMFREADTDdhqgtLGFEEFCAFYK--MMSTRRDLY-L 390
Cdd:cd16216      1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFlrdKLVEVEARSE-----LTFPHFIQFYKnlMFDAQKSIIeQ 75

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1039767898  391 LMLTYS-NHKD-----HLDASDLQRFLEVEQK 416
Cdd:cd16216     76 LELSFPlRNVDrpelcQISLYDFQKFLQHDQK 107
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 930-1014 8.71e-04

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (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: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 40.32  E-value: 8.71e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  930 GDRGEI-IDPFVEV--EVIGLPVDCskeqTRVVDDNgFNPMWEETLVFTVHMPEIAL---VRFLVWDHDP------IGRD 997
Cdd:cd04041     16 ADFGTGsSDPYVTAsfAKFGKPLYS----TRIIRKD-LNPVWEETWFVLVTPDEVKAgerLSCRLWDSDRftaddrLGRV 90

                           90
                   ....*....|....*..
gi 1039767898  998 FIGQRTLAFSSIMPGYR 1014
Cdd:cd04041     91 EIDLKELIEDRNWMGRR 107
PRK12323 PRK12323
DNA polymerase III subunit gamma/tau;
1064-1241 9.03e-04

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237057 [Multi-domain]  Cd Length: 700  Bit Score: 43.71  E-value: 9.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1064 GQPLPRPSVSQRLLRRTASAPTKSQKPSRKGFPELALGTQDAGSEGAADDVAPSSPNPALEAPTQERSGSSSPRGKAPGG 1143
Cdd:PRK12323   371 GAGPATAAAAPVAQPAPAAAAPAAAAPAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGGAPAP 450

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1144 EATEERT-LAQVRSPNA-PEGPGPAGMAATCMKCVVGSCAGMDVEGLQREQQP-----------SPGPAGSHMAISHQPR 1210
Cdd:PRK12323   451 APAPAAApAAAARPAAAgPRPVAAAAAAAPARAAPAAAPAPADDDPPPWEELPpefaspapaqpDAAPAGWVAESIPDPA 530

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1039767898 1211 ARVDSLGGPCCSPSPRATPGRSKEAPKGPRA 1241
Cdd:PRK12323   531 TADPDDAFETLAPAPAAAPAPRAAAATEPVV 561
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 911-1015 1.43e-03

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


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 40.01  E-value: 1.43e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  911 LALRIISGQQLPKPrdsvlgDRGEIIDPFVEVEVigLPVDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEIALVRFL--- 987
Cdd:cd08386     18 LTLKILKAVELPAK------DFSGTSDPFVKIYL--LPDKKHKLETKVKRKN-LNPHWNETFLFEGFPYEKLQQRVLylq 88

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1039767898  988 VWDH------DPIGRDFIGQRTLAFSSIMPGYRH 1015
Cdd:cd08386     89 VLDYdrfsrnDPIGEVSLPLNKVDLTEEQTFWKD 122
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 318-345 1.44e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 37.38  E-value: 1.44e-03
                           10        20
                   ....*....|....*....|....*...
gi 1039767898  318 LKQTFDEADKNGDGSLSISEVLQLLHKL 345
Cdd:pfam00036    2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
 319-374 1.50e-03

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 42.04  E-value: 1.50e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039767898  319 KQTFDE-ADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADtDDHQGTLGFEE 374
Cdd:cd15899    203 KERFVElRDKDKDGKLDGEELLSWVDPSNQEIALEEAKHLIAESD-ENKDGKLSPEE 258
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 911-1030 1.87e-03

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 39.63  E-value: 1.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  911 LALRIISGQQLPkPRDsvlGDRGeiIDPFVEVEViglpvDCSKEQTRVVDDNgFNPMWEETLVFTVHMPEIALVRFL--- 987
Cdd:cd04022      2 LVVEVVDAQDLM-PKD---GQGS--SSAYVELDF-----DGQKKRTRTKPKD-LNPVWNEKLVFNVSDPSRLSNLVLevy 69

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1039767898  988 VWDH--DPIGRDFIGQRTLAFSSIMPGYRHVYLE-GMEEASIFVHV 1030
Cdd:cd04022     70 VYNDrrSGRRRSFLGRVRISGTSFVPPSEAVVQRyPLEKRGLFSRV 115
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 936-1004 2.19e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. 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 have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 39.62  E-value: 2.19e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1039767898  936 IDPFVEVEviglpvdC-SKEQ-TRVVDDNGFNPMWEETLVFTVHMPEIALVRFL---VWDHDPI-GRDFIGQRTL 1004
Cdd:cd04049     22 IDPYVIIQ-------CrTQERkSKVAKGDGRNPEWNEKFKFTVEYPGWGGDTKLilrIMDKDNFsDDDFIGEATI 89
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1066-1244 2.23e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.62  E-value: 2.23e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1066 PLPRPSVSQRLL----RRTASAPTKSQKPS------RKGFPELALGTQDAGSEGAADDVAPSSPNPALEAPTQERSGSSS 1135
Cdd:PHA03247  2739 PAPPAVPAGPATpggpARPARPPTTAGPPApappaaPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAAL 2818

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898 1136 PRGKAPGGEATEERTLAQVrSPNAPEGPGPAGMAatcmkcVVGSCA-GMDVEGLQREQQPSPGPAGShmaishqPRARVD 1214
Cdd:PHA03247  2819 PPAASPAGPLPPPTSAQPT-APPPPPGPPPPSLP------LGGSVApGGDVRRRPPSRSPAAKPAAP-------ARPPVR 2884

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1039767898 1215 SLGGPCCSPSPR--ATPGRSKEAPKGPRARRQ 1244
Cdd:PHA03247  2885 RLARPAVSRSTEsfALPPDQPERPPQPQAPPP 2916
EF-hand_6 pfam13405
EF-hand domain;
317-346 2.38e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 36.77  E-value: 2.38e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLN 346
Cdd:pfam13405    1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 906-1000 3.02e-03

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 39.19  E-value: 3.02e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  906 QLKKQLALRIISGQQLpKPRDSvlgdrGEIIDPFVEVEVIGLPVDCSKEQTRVVDdNGFNPMWEETLVFTVHMPEIA--- 982
Cdd:cd04035     12 PANSALHCTIIRAKGL-KAMDA-----NGLSDPYVKLNLLPGASKATKLRTKTVH-KTRNPEFNETLTYYGITEEDIqrk 84

                           90
                   ....*....|....*...
gi 1039767898  983 LVRFLVWDHDPIGRDFIG 1000
Cdd:cd04035     85 TLRLLVLDEDRFGNDFLG 102
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 915-1018 3.23e-03

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 38.70  E-value: 3.23e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  915 IISGQQLPKPrdsvlgDRGEIIDPFVEVEVIGLPVDCSKE--QTRVVDDNgFNPMWEETLVFTVHMPEIALVRFLVWDHD 992
Cdd:cd04048      6 SISCRNLLDK------DVLSKSDPFVVVYVKTGGSGQWVEigRTEVIKNN-LNPDFVTTFTVDYYFEEVQKLRFEVYDVD 78

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1039767898  993 PIGR-----DFIGQRTLAFSSIM--PGYRHVYL 1018
Cdd:cd04048     79 SKSKdlsdhDFLGEAECTLGEIVssPGQKLTLP 111
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 315-384 3.79e-03

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 39.43  E-value: 3.79e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039767898  315 DQWlKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEF---CAFYKMMST 384
Cdd:cd16180     67 QDW-RRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRR-RGSISFDDFveaCVTLKRLTD 137
EFh_PI-PLCgamma2 cd16215
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed ...
 317-416 3.81e-03

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, or phospholipase C-IV (PLC-IV), or phospholipase C-gamma-2 (PLC-gamma-2), is highly expressed in cells of hematopoietic origin. It has been implicated in cell motility important to invasion and dissemination of tumor cells. As an important component of the B cell receptor (BCR) signaling pathway, PI-PLC-gamma2 is required for efficient formation of germinal center (GC) and memory B cells. It works as a critical effector stimulating the increase of intracellular Ca2+ and activates various signaling pathways downstream of the BCR. Moreover, PI-PLC-gamma2 has been implicated in Fc receptor-mediated degranulation of mast cells, integrin signaling in platelets, as well as integrin and Fc receptor-mediated neutrophil functions. It also acts as a crucial signaling mediator modifying DC gene expression program to activate DC responses to beta-glucan-containing pathogens. PI-PLC-gamma2 contains 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. Besides, PI-PLC-gamma2 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma2 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 320045  Cd Length: 154  Bit Score: 39.45  E-value: 3.81e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  317 WLKQTFDEADKNGDGSLSISEVLQLLHKLNVNLPRQRV-KQMFREADTddHQGTLGFEEFCAFYKMM----------STR 385
Cdd:cd16215      1 WLRKQIYSVDQTRRNSISVRELKTILPQVNFKVPSAKFlKDKFQEIGA--KKDELTFEQFHLFYKKLmfeqqksildEFK 78

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1039767898  386 RDLYLLMLtysNHKDHLDAS-----DLQRFLEVEQK 416
Cdd:cd16215     79 KDSSVFIL---GNTDRPDASavhlhDFQRFLVHEQK 111
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 354-382 4.26e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.82  E-value: 4.26e-03
                            10        20
                    ....*....|....*....|....*....
gi 1039767898   354 VKQMFREADTdDHQGTLGFEEFCAFYKMM 382
Cdd:smart00054    2 LKEAFRLFDK-DGDGKIDFEEFKDLLKAL 29
PH_PLC_fungal cd13360
Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...
 193-301 5.72e-03

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


Pssm-ID: 241514  Cd Length: 118  Bit Score: 37.93  E-value: 5.72e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  193 MQEGTQMVKLrgSSKGLVRFY-YLDEHRSCLRWRPSRKNekAKISIDSIQEV---SEGRQ-SEIFQryPDSSFDPNCC-- 265
Cdd:cd13360      1 LRQGTPLLKV--TKKKKKRILfKLDPESGKITWDSKKPS--KSLYIDDIKEIrtgEDARNyREEFG--ISEEFEDRWIti 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1039767898  266 -FSIYHGSHRESLDLVSPSSEEARTWVTGLRY-------LMAGI 301
Cdd:cd13360     75 iYFVPKKNKLKTLHLIADTEEDFKLWTTTLEGlvklrreLMESL 118
EF-hand_5 pfam13202
EF hand;
318-342 6.07e-03

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 35.37  E-value: 6.07e-03
                           10        20
                   ....*....|....*....|....*
gi 1039767898  318 LKQTFDEADKNGDGSLSISEVLQLL 342
Cdd:pfam13202    1 LKDTFRQIDLNGDGKISKEELRRLL 25
EFh_NorpA_like cd16212
EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...
 346-455 6.16e-03

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


Pssm-ID: 320042 [Multi-domain]  Cd Length: 153  Bit Score: 38.68  E-value: 6.16e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039767898  346 NVNLPRQRVKQMFREADTddhqgtlgFEEFCAFYKMMSTRRDLYLLMLTYSNHK-DHLDASDLQRFLEVEQK---MNGV- 420
Cdd:cd16212     41 EMGLPSGKGDSIEKEDFT--------FEKFYALYHKICPRNDIEELFTSITKGKgEHISLAQLINFMNDKQRdprLNEIl 112

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1039767898  421 ----TLESCQNIIEQFEPCLENKSKGMLGIDGFTNYTRS 455
Cdd:cd16212    113 yplyDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMS 151
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 353-382 6.27e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 35.45  E-value: 6.27e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 1039767898  353 RVKQMFREADTdDHQGTLGFEEFCAFYKMM 382
Cdd:pfam00036    1 ELKEIFRLFDK-DGDGKIDFEEFKELLKKL 29
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 925-1001 6.30e-03

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 38.23  E-value: 6.30e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1039767898  925 RDSVLGDRGEIIDPFVEVEVIGlpvdcSKEQTRVVDDNGFnPMWEETLVFTVHMPEIALVRFLVWDHDPIGR-DFIGQ 1001
Cdd:cd04025     10 RDLAPKDRNGTSDPFVRVFYNG-----QTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDLVSKnDFLGK 81
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 318-345 6.37e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 35.43  E-value: 6.37e-03
                            10        20
                    ....*....|....*....|....*...
gi 1039767898   318 LKQTFDEADKNGDGSLSISEVLQLLHKL 345
Cdd:smart00054    2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
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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