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Conserved domains on  [gi|1370470037|ref|XP_024306322|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 isoform X1 [Homo sapiens]

Protein Classification

EFh_PI-PLCdelta3 and PI-PLCc_delta3 domain-containing protein( domain architecture ID 11598558)

protein containing domains PH_PLC_delta, EFh_PI-PLCdelta3, PI-PLCc_delta3, and C2_PLC_like

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 336-676 0e+00

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: 526.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08630     1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKLpaarsedgral 495
Cdd:cd08630    81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakQISPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREAgqkrv 575
Cdd:cd08630   150 ---------------------------QISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREA----- 197

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08630   198 ----------------------------------------GNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 237

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08630   238 ALNFQTPGYEMDLNAGRFLVN 258
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 186-324 3.41e-88

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: 275.09  E-value: 3.41e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd16218     1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370470037 266 EDRVLSAPELLEFLEDQGEEgATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16218    81 EDCVLSAEELREFLKDQGED-ASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 65-181 4.26e-67

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: 218.34  E-value: 4.26e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  65 MLRGSRLRKIRSRTWHKERLYRLQEDGLSVWFQRRIPRAPSQHIFFVQHIEAVREGHQSEGLRRFGGAFAPARCLTIAFK 144
Cdd:cd13363     1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKKTRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1370470037 145 GRRKNLDLAAPTAEEAQRWVRGLTKLRARLDAMSQRE 181
Cdd:cd13363    81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 705-832 1.34e-51

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: 176.19  E-value: 1.34e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 705 TTLSIQVLTAQQLPKLNAEKPhSIVDPLVRIEIHGVPA-DCARQETDYVLNNGFNPRWGQTLQFQLRAPELALVRFVVED 783
Cdd:cd00275     2 LTLTIKIISGQQLPKPKGDKG-SIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1370470037 784 YDaTSPNDFVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFIQIRIQ 832
Cdd:cd00275    81 ED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
 
Name Accession Description Interval E-value
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 336-676 0e+00

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: 526.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08630     1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKLpaarsedgral 495
Cdd:cd08630    81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakQISPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREAgqkrv 575
Cdd:cd08630   150 ---------------------------QISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREA----- 197

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08630   198 ----------------------------------------GNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 237

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08630   238 ALNFQTPGYEMDLNAGRFLVN 258
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 186-324 3.41e-88

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: 275.09  E-value: 3.41e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd16218     1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370470037 266 EDRVLSAPELLEFLEDQGEEgATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16218    81 EDCVLSAEELREFLKDQGED-ASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
PLN02228 PLN02228
Phosphoinositide phospholipase C
 255-817 4.41e-86

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 285.01  E-value: 4.41e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 255 ELEEIFHQYSGEDRvLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPEGAALDNTHT 333
Cdd:PLN02228   25 SIKRLFEAYSRNGK-MSFDELLRFVsEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLPMSGQ 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 334 cVFQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGG-EPVIYHGHTLTSKILFRDVVQ 412
Cdd:PLN02228  104 -VHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 413 AVRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTqaLDSPNPEELPSPEQLKGRVLVKGKKlPAARSEDG 492
Cdd:PLN02228  183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFR--CTSESTKHFPSPEELKNKILISTKP-PKEYLESK 259

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 493 RALSDReeeEEDDEEEEEEVEAAAQRRLAKQISPELSALAVYchaTRLRTLHpAPNAPQPCQvSSLSErkakklireaGQ 572
Cdd:PLN02228  260 TVQTTR---TPTVKETSWKRVADAENKILEEYKDEESEAVGY---RDLIAIH-AANCKDPLK-DCLSD----------DP 321

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 573 KRVRsggRVTWGRAWAlfpggyrpglwvrdpRSLSRSHpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGC 652
Cdd:PLN02228  322 EKPI---RVSMDEQWL---------------ETMVRTR-----GTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGA 378

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 653 QLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPACLRQPDSTFDPEYPGPPRTTLSIQVLTAQ----QLPKLNAEKpHSI 728
Cdd:PLN02228  379 QMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPIKTTLKVKIYTGEgwdlDFHLTHFDQ-YSP 457

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 729 VDPLVRIEIHGVPADCARQETDYVLNNGFnPRWG-QTLQFQLRAPELALVRFVVEDYDATSPNDFVGQFTLPLSSLKQGY 807
Cdd:PLN02228  458 PDFFVKIGIAGVPRDTVSYRTETAVDQWF-PIWGnDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGV 536

                         570
                  ....*....|
gi 1370470037 808 RHIHLLSKDG 817
Cdd:PLN02228  537 RAVRLHDRAG 546
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 339-481 2.70e-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: 265.14  E-value: 2.70e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 339 MNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRDHA 418
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370470037 419 FTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKG 481
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLD-DDLTELPSPEDLKGKILIKG 142
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 339-482 3.99e-69

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


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 224.85  E-value: 3.99e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  339 MNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRDHA 418
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370470037  419 FTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKGK 482
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLT-SSLEVLPSPEQLRGKILLKVR 143
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 65-181 4.26e-67

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: 218.34  E-value: 4.26e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  65 MLRGSRLRKIRSRTWHKERLYRLQEDGLSVWFQRRIPRAPSQHIFFVQHIEAVREGHQSEGLRRFGGAFAPARCLTIAFK 144
Cdd:cd13363     1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKKTRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1370470037 145 GRRKNLDLAAPTAEEAQRWVRGLTKLRARLDAMSQRE 181
Cdd:cd13363    81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 705-832 1.34e-51

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: 176.19  E-value: 1.34e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 705 TTLSIQVLTAQQLPKLNAEKPhSIVDPLVRIEIHGVPA-DCARQETDYVLNNGFNPRWGQTLQFQLRAPELALVRFVVED 783
Cdd:cd00275     2 LTLTIKIISGQQLPKPKGDKG-SIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1370470037 784 YDaTSPNDFVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFIQIRIQ 832
Cdd:cd00275    81 ED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 246-329 2.80e-27

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: 105.79  E-value: 2.80e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 246 FLRRLLKRPELEEIFHQYSGEDRVLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLrEEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 1370470037 325 GAALD 329
Cdd:pfam09279  81 GSIFN 85
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 706-812 4.08e-20

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: 86.00  E-value: 4.08e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  706 TLSIQVLTAQQLPKLNaekPHSIVDPLVRIEIHGVPADCARqeTDYVLNNGfNPRWGQTLQFQLRAPELALVRFVVEDYD 785
Cdd:smart00239   1 TLTVKIISARNLPPKD---KGGKSDPYVKVSLDGDPKEKKK--TKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKD 74

                           90       100
                   ....*....|....*....|....*..
gi 1370470037  786 ATSPNDFVGQFTLPLSSLKQGYRHIHL 812
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
706-811 5.16e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 80.06  E-value: 5.16e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 706 TLSIQVLTAQQLPKLNaekPHSIVDPLVRIEIHGvpaDCARQETDyVLNNGFNPRWGQTLQFQLRAPELALVRFVVEDYD 785
Cdd:pfam00168   2 RLTVTVIEAKNLPPKD---GNGTSDPYVKVYLLD---GKQKKKTK-VVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*.
gi 1370470037 786 ATSPNDFVGQFTLPLSSLKQGYRHIH 811
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDG 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 70-170 1.04e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.16  E-value: 1.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  70 RLRKIRSRTWHKeRLYRLQEDGLSVWFQRRIPRAPS-QHIFFVQHIEAVREGHQSEGLRRFGgaFaparCLTIAFKGRRK 148
Cdd:pfam00169   9 KKGGGKKKSWKK-RYFVLFDGSLLYYKDDKSGKSKEpKGSISLSGCEVVEVVASDSPKRKFC--F----ELRTGERTGKR 81

                          90       100
                  ....*....|....*....|..
gi 1370470037 149 NLDLAAPTAEEAQRWVRGLTKL 170
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSA 103
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 69-170 2.92e-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: 40.99  E-value: 2.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037   69 SRLRKIRSRTWHKeRLYRLQEDGLSVWFQRRIPRAPS-QHIFFVQHIEAVREGHQSEGLRRFggafaparCLTIaFKGRR 147
Cdd:smart00233   8 YKKSGGGKKSWKK-RYFVLFNSTLLYYKSKKDKKSYKpKGSIDLSGCTVREAPDPDSSKKPH--------CFEI-KTSDR 77

                           90       100
                   ....*....|....*....|...
gi 1370470037  148 KNLDLAAPTAEEAQRWVRGLTKL 170
Cdd:smart00233  78 KTLLLQAESEEEREKWVEALRKA 100
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
602-806 1.42e-03

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 42.44  E-value: 1.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  602 DPRSLSRSHPNSAPGNSFVRH-NARQLT-RVyplglrMNSANYSPQEMWNSG---CQLVALNFQTPgYEMDLNaGRFLVN 676
Cdd:COG5038    947 SSKAPTRGERNGESGDTFIRElEYSETTfRV------TKNAKKSDKVVCEVTlptLDLVSNAYEKP-SSLNFP-GSAKVL 1018

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  677 GQCGYVLKPACLRQPDSTFDPEYpgpprttLSIQVLTAQQLPKLNaEKPHSivDPLVRIEIHGVPAdcarqETDYVLNNG 756
Cdd:COG5038   1019 VQVSYTPVPVKLPPVEMVENSGY-------LTIMLRSGENLPSSD-ENGYS--DPFVKLFLNEKSV-----YKTKVVKKT 1083

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1370470037  757 FNPRWGQTLQFQLRAPELALVRFVVEDYDATSPNDFVGQFTLPLSSLKQG 806
Cdd:COG5038   1084 LNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLEPG 1133
 
Name Accession Description Interval E-value
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 336-676 0e+00

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: 526.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08630     1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKLpaarsedgral 495
Cdd:cd08630    81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakQISPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREAgqkrv 575
Cdd:cd08630   150 ---------------------------QISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREA----- 197

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08630   198 ----------------------------------------GNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 237

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08630   238 ALNFQTPGYEMDLNAGRFLVN 258
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 336-676 1.73e-164

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: 477.21  E-value: 1.73e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08593     1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKGKKLpaarsedgral 495
Cdd:cd08593    81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLD-GVLTALPSPEELKGKILVKGKKL----------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakQISPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREAgqkrv 575
Cdd:cd08593   149 ---------------------------KLAKELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQES----- 196

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08593   197 ----------------------------------------GNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIV 236

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08593   237 ALNFQTPGEEMDLNDGLFRQN 257
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 336-676 2.49e-131

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: 391.04  E-value: 2.49e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08558     1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpNPEELPSPEQLKGRVLVKGKKlpaarsedgral 495
Cdd:cd08558    81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDE-NPVQLPSPEQLKGKILIKGKK------------ 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakqispelsalavychatrlrtlhpapnapqpCQVSSLSERKAKKLIREAGQKrv 575
Cdd:cd08558   148 ---------------------------------------------------------YHMSSFSETKALKLLKESPEE-- 168

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08558   169 -------------------------------------------FVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMV 205

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08558   206 ALNYQTPDLPMQLNQGKFEQN 226
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 336-676 7.32e-118

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: 357.34  E-value: 7.32e-118
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08631     1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKLpaarsedgral 495
Cdd:cd08631    81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakQISPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREagqkrv 575
Cdd:cd08631   150 ---------------------------RLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIRE------ 196

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsaPGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08631   197 ---------------------------------------AGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMV 237

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08631   238 ALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 336-676 4.55e-116

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: 352.80  E-value: 4.55e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08629     1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpNPEELPSPEQLKGRVLVKGKKLpaarsedgral 495
Cdd:cd08629    81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDG-VTTSLPSPEQLKGKILLKGKKL----------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrRLAKqispELSALAVYCHATRLRTLHPAPNAPQPC-QVSSLSERKAKKLIREAgqkr 574
Cdd:cd08629   149 -----------------------KLVP----ELSDMIIYCKSVHFGGFSSPGTSGQAFyEMASFSESRALRLLQES---- 197

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 575 vrsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQL 654
Cdd:cd08629   198 -----------------------------------------GNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQI 236

                         330       340
                  ....*....|....*....|..
gi 1370470037 655 VALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08629   237 VALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 337-676 5.56e-107

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: 329.38  E-value: 5.56e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08597     2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpNPEELPSPEQLKGRVLVKGKKLpaarsedgrals 496
Cdd:cd08597    82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNE-GESYLPSPHDLKGKIIIKGKKL------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 dreeeeeddeeeeeeveaaAQRRLAKqispELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREagqkrvr 576
Cdd:cd08597   149 -------------------KRRKLCK----ELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANE------- 198

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalFPGgyrpglwvrdprslsrshpnsapgnSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08597   199 -------------FPE-------------------------DFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVA 240

                         330       340
                  ....*....|....*....|
gi 1370470037 657 LNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08597   241 MNYQTPGLMMDLNTGKFLEN 260
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 336-676 7.98e-99

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: 306.66  E-value: 7.98e-99
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08592     1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKGKKLPAarsedgral 495
Cdd:cd08592    81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVD-RNADQLPSPNQLKRKIIIKHKKLFY--------- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlakqispelsalavychatrlrtlhpapnapqpcQVSSLSERKAKKLIreagqkrv 575
Cdd:cd08592   151 ----------------------------------------------------------EMSSFPETKAEKYL-------- 164

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpNSAPGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08592   165 ------------------------------------NRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMV 208

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08592   209 ALNFQTPDKPMQLNQALFMLN 229
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 336-676 2.56e-95

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: 298.77  E-value: 2.56e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08595     1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKklpaarsedgral 495
Cdd:cd08595    81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNK------------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 sdreeeeeddeeeeeeveaaaqrrlaKQISPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREAgqkrv 575
Cdd:cd08595   148 --------------------------KKIAKALSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSS----- 196

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08595   197 ----------------------------------------GADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMV 236

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08595   237 ALNFQTLGAPMDLQNGKFLDN 257
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 336-676 3.56e-94

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: 295.40  E-value: 3.56e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPG--GEPVIYHGHTLTSKILFRDVVQA 413
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGedEEPIITHGKTMCTEILFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 414 VRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpNPEE----LPSPEQLKGRVLVKGKKlpaars 489
Cdd:cd08591    81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEK-YPLEpgvpLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 490 edgralsdreeeeeddeeeeeeveaaaqrrlakqispeLSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIRE 569
Cdd:cd08591   154 --------------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKK 195

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 570 agqkrvrsggrvtwgrawalfpggyrpglwvrdprslsrshpnSAPgnSFVRHNARQLTRVYPLGLRMNSANYSPQEMWN 649
Cdd:cd08591   196 -------------------------------------------SPI--EFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWN 230

                         330       340
                  ....*....|....*....|....*..
gi 1370470037 650 SGCQLVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08591   231 AGCQMVALNFQTPDLPMQLNQGKFEYN 257
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 337-673 3.91e-89

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: 281.44  E-value: 3.91e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08598     2 EDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKGKKLPAARSedgrals 496
Cdd:cd08598    82 YAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLD-GLEDELPSPEELRGKILIKVKKESKTPN------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 dreeeeeddeeeeeeveaaaqrrlakqispelsalavycHatrlrtlhpapnapqpcqVSSLSERKAKKLIREAgqkrvr 576
Cdd:cd08598   154 ---------------------------------------H------------------IFSLSERSLLKLLKDK------ 170

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalfpggyRPGLwvrdprslsrshpnsapgnsfVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08598   171 ------------------RAAL---------------------DKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVA 211

                         330
                  ....*....|....*..
gi 1370470037 657 LNFQTPGYEMDLNAGRF 673
Cdd:cd08598   212 LNWQTYDLGMQLNEAMF 228
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 186-324 3.41e-88

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: 275.09  E-value: 3.41e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd16218     1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370470037 266 EDRVLSAPELLEFLEDQGEEgATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16218    81 EDCVLSAEELREFLKDQGED-ASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 337-676 9.15e-88

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: 277.45  E-value: 9.15e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08594     2 QDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKlpaarsedgrals 496
Cdd:cd08594    82 YAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQLPSPQSLKGKILIKGKK------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 dreeeeeddeeeeeeveaaaqrrlakqispelsalavychatrlrtlhpapnapqpCQVSSLSERKAKKLIREAGQKrvr 576
Cdd:cd08594   149 --------------------------------------------------------WQVSSFSETRAHQIVQQKAAQ--- 169

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08594   170 ------------------------------------------FLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVA 207

                         330       340
                  ....*....|....*....|
gi 1370470037 657 LNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08594   208 LNYQTEGRMLQLNRAKFRAN 227
PLN02228 PLN02228
Phosphoinositide phospholipase C
 255-817 4.41e-86

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 285.01  E-value: 4.41e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 255 ELEEIFHQYSGEDRvLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPEGAALDNTHT 333
Cdd:PLN02228   25 SIKRLFEAYSRNGK-MSFDELLRFVsEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLPMSGQ 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 334 cVFQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGG-EPVIYHGHTLTSKILFRDVVQ 412
Cdd:PLN02228  104 -VHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 413 AVRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTqaLDSPNPEELPSPEQLKGRVLVKGKKlPAARSEDG 492
Cdd:PLN02228  183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFR--CTSESTKHFPSPEELKNKILISTKP-PKEYLESK 259

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 493 RALSDReeeEEDDEEEEEEVEAAAQRRLAKQISPELSALAVYchaTRLRTLHpAPNAPQPCQvSSLSErkakklireaGQ 572
Cdd:PLN02228  260 TVQTTR---TPTVKETSWKRVADAENKILEEYKDEESEAVGY---RDLIAIH-AANCKDPLK-DCLSD----------DP 321

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 573 KRVRsggRVTWGRAWAlfpggyrpglwvrdpRSLSRSHpnsapGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGC 652
Cdd:PLN02228  322 EKPI---RVSMDEQWL---------------ETMVRTR-----GTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGA 378

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 653 QLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPACLRQPDSTFDPEYPGPPRTTLSIQVLTAQ----QLPKLNAEKpHSI 728
Cdd:PLN02228  379 QMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPIKTTLKVKIYTGEgwdlDFHLTHFDQ-YSP 457

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 729 VDPLVRIEIHGVPADCARQETDYVLNNGFnPRWG-QTLQFQLRAPELALVRFVVEDYDATSPNDFVGQFTLPLSSLKQGY 807
Cdd:PLN02228  458 PDFFVKIGIAGVPRDTVSYRTETAVDQWF-PIWGnDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGV 536

                         570
                  ....*....|
gi 1370470037 808 RHIHLLSKDG 817
Cdd:PLN02228  537 RAVRLHDRAG 546
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 337-676 1.86e-85

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: 272.49  E-value: 1.86e-85
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08596     2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQAL---DSPNPEELPSPEQLKGRVLVKGKKlpaarsedgr 493
Cdd:cd08596    82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLfesDFSDDPSLPSPLQLKNKILLKNKK---------- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 494 alsdreeeeeddeeeeeeveaaaqrrlakqiSPELSALAVYCHATRLRTLhpapNAPQPCQVSSLSERKAKKLIREAGQK 573
Cdd:cd08596   152 -------------------------------APELSDLVIYCQAVKFPGL----STPKCYHISSLNENAAKRLCRRYPQK 196

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 574 rvrsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQ 653
Cdd:cd08596   197 ---------------------------------------------LVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQ 231

                         330       340
                  ....*....|....*....|...
gi 1370470037 654 LVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08596   232 LVALNYQTDDLPMHLNAAMFEAN 254
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 339-481 2.70e-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: 265.14  E-value: 2.70e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 339 MNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRDHA 418
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370470037 419 FTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKG 481
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLD-DDLTELPSPEDLKGKILIKG 142
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 337-676 3.16e-84

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: 269.22  E-value: 3.16e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08633     2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKLpaarsedGRALS 496
Cdd:cd08633    82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGKKL-------SRALS 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 DreeeeeddeeeeeeveaaaqrrlakqispelsaLAVYCHATRLRTLHpaPNAPQPCQVSSLSERKAKKLIREagqkrvr 576
Cdd:cd08633   155 D---------------------------------LVKYTKSVRVHDIE--TEATSSWQVSSFSETKAHQILQQ------- 192

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalfpggyRPGlwvrdprslsrshpnsapgnSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08633   193 ------------------KPA--------------------QYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVA 234

                         330       340
                  ....*....|....*....|
gi 1370470037 657 LNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08633   235 LNYQSEGRMLQLNRAKFSAN 254
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 336-676 3.21e-84

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: 269.21  E-value: 3.21e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08632     1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPNPEELPSPEQLKGRVLVKGKKLpaarsedGRAL 495
Cdd:cd08632    81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGKKL-------CRDL 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 496 SDreeeeeddeeeeeeveaaaqrrlakqispelsaLAVYCHATRLRTLhpaPNAPQPCQVSSLSERKAKKLIREAGQKrv 575
Cdd:cd08632   154 SD---------------------------------LVVYTNSVAAQDI---VDDGSTGNVLSFSETRAHQLVQQKAEQ-- 195

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 576 rsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLV 655
Cdd:cd08632   196 -------------------------------------------FMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLV 232

                         330       340
                  ....*....|....*....|.
gi 1370470037 656 ALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08632   233 ALNYQSEGRMMQLNRAKFMVN 253
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 337-676 1.74e-83

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: 267.31  E-value: 1.74e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08628     2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKGKKLpaarsedgrals 496
Cdd:cd08628    82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLE-ASADQLPSPTQLKEKIIIKHKKL------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 dreeeeeddeeeeeeveaaaqrrlakqISPELSALAVYCHATRlRTLHPAPNaPQPCQVSSLSERKAKKLIReagQKRVR 576
Cdd:cd08628   149 ---------------------------IAIELSDLVVYCKPTS-KTKDNLEN-PDFKEIRSFVETKAPSIIR---QKPVQ 196

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08628   197 ------------------------------------------LLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVA 234

                         330       340
                  ....*....|....*....|
gi 1370470037 657 LNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08628   235 LNFQTADKYMQLNHALFSLN 254
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 336-676 1.67e-81

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: 262.01  E-value: 1.67e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPG--GEPVIYHGHTLTSKILFRDVVQA 413
Cdd:cd08626     1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGedQEPIITHGKAMCTDILFKDVIQA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 414 VRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpNPEE----LPSPEQLKGRVLVKGKKlpaars 489
Cdd:cd08626    81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLES-HPLEpgvpLPSPNKLKRKILIKNKR------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 490 edgralsdreeeeeddeeeeeeveaaaqrrlakqispeLSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIRE 569
Cdd:cd08626   154 --------------------------------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKT 195

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 570 agqkrvrsggrvtwgrawalfpggyrpglwvrdprslsrshpnSAPgnSFVRHNARQLTRVYPLGLRMNSANYSPQEMWN 649
Cdd:cd08626   196 -------------------------------------------SAI--EFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWN 230

                         330       340
                  ....*....|....*....|....*..
gi 1370470037 650 SGCQLVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08626   231 AGCQMVSLNFQTPDLGMQLNQGKFEYN 257
PLN02952 PLN02952
phosphoinositide phospholipase C
 255-827 3.53e-81

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 272.64  E-value: 3.53e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 255 ELEEIFHQYSGEDRVLSAPELLEFLED-QGEEGATLARAQQLIQTYelneTAKQHEL-------MTLDGFMMYLLSPE-- 324
Cdd:PLN02952   39 DVKDVFCKFSVGGGHMGADQLRRFLVLhQDELDCTLAEAQRIVEEV----INRRHHVtrytrhgLNLDDFFHFLLYDDln 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 325 GAALDNTHtcvfQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPV-IYHGHTLTS 403
Cdd:PLN02952  115 GPITPQVH----HDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 404 KILFRDVVQAVRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpnPEELPSPEQLKGRVLVKGK- 482
Cdd:PLN02952  191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYPESDS--LVQFPSPESLKHRIIISTKp 268

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 483 -------------KLPAARSEDGRALSDREEEEEDDEEEEEEVEaAAQRRLAKQISPELSALAVYCHaTRLRTLHPApna 549
Cdd:PLN02952  269 pkeylessgpiviKKKNNVSPSGRNSSEETEEAQTLESMLFEQE-ADSRSDSDQDDNKSGELQKPAY-KRLITIHAG--- 343

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 550 pqpcqvsslserKAKKLIREAGQKRVRSGGRVTWGRawalfpggyrpglwvrdpRSLSRShpNSAPGNSFVRHNARQLTR 629
Cdd:PLN02952  344 ------------KPKGTLKDAMKVAVDKVRRLSLSE------------------QELEKA--ATTNGQDVVRFTQRNILR 391

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 630 VYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPACLRQP---DSTFDPEYPGPPRTT 706
Cdd:PLN02952  392 IYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVFDPKKKLPVKKT 471

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 707 LSIQVLTAQQLpKLNAEKPH----SIVDPLVRIEIHGVPADCARQETDYVLNNgFNPRWGQTLQFQLRAPELALVRFVVE 782
Cdd:PLN02952  472 LKVKVYLGDGW-RLDFSHTHfdsySPPDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVR 549

                         570       580       590       600
                  ....*....|....*....|....*....|....*....|....*
gi 1370470037 783 DYDATSPNDFVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFI 827
Cdd:PLN02952  550 EYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLM 594
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 337-676 5.91e-79

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: 254.57  E-value: 5.91e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08627     2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSpNPEELPSPEQLKGRVLVKGKKLpaarsedgrals 496
Cdd:cd08627    82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDI-NADGLPSPNQLKRKILIKHKKL------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 dreeeeeddeeeeeeveaaaqrrlakqispelsalavychatrLRTLhpapnapqpcqvSSLSERKAKKLIreagqkrvr 576
Cdd:cd08627   149 -------------------------------------------YRDM------------SSFPETKAEKYV--------- 164

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalfpggyrpglwvrdprslsrshpNSAPGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08627   165 -----------------------------------NRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVA 209

                         330       340
                  ....*....|....*....|
gi 1370470037 657 LNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08627   210 LNFQTPDKPMQMNQALFMLG 229
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 336-676 2.60e-76

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: 248.43  E-value: 2.60e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 336 FQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG--PGGEPVIYHGHTLTSKILFRDVVQA 413
Cdd:cd08624     1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 414 VRDHAFTLSPYPVILSLENHC-GLEQQAAMARHLCTILGDMLVTQALD----SPNpEELPSPEQLKGRVLVKGKKLpaar 488
Cdd:cd08624    81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEkyplKPG-VPLPSPEDLRGKILIKNKKY---- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 489 sedgralsdreeeeeddeeeeeeveaaaqrrlakqisPELSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIR 568
Cdd:cd08624   156 -------------------------------------EEMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLS 198

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 569 EAGQKrvrsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMW 648
Cdd:cd08624   199 KASVQ---------------------------------------------FVEYNKRQMSRIYPKGTRMDSSNYMPQMFW 233

                         330       340
                  ....*....|....*....|....*...
gi 1370470037 649 NSGCQLVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08624   234 NVGCQMVALNFQTMDLPMQQNMALFEFN 261
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 254-829 1.93e-73

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 251.10  E-value: 1.93e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 254 PELEEIFHQYSgEDRVLSAPELLEFLED-QGEEGATLARAQQLIQTyelNETAKQHELMTLDGFMMYLLSPEGAALDNTH 332
Cdd:PLN02222   25 REIKTIFEKYS-ENGVMTVDHLHRFLIDvQKQDKATREDAQSIINS---ASSLLHRNGLHLDAFFKYLFGDNNPPLALHE 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 333 tcVFQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPV-IYHGHTLTSKILFRDVV 411
Cdd:PLN02222  101 --VHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCL 178

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 412 QAVRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTqaldSPNPE---ELPSPEQLKGRVLVKGK---KLP 485
Cdd:PLN02222  179 KAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFT----PPVGEslkEFPSPNSLKKRIIISTKppkEYK 254

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 486 AARSED----GRALSDREEEEEDDEEEEEEVEAAAQR---------------RLAKQISPElsalavYCHATRLRTLHPA 546
Cdd:PLN02222  255 EGKDDEvvqkGKDLGDEEVWGREVPSFIQRNKSVDKNdsngddddddddgedKSKKNAPPQ------YKHLIAIHAGKPK 328

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 547 PNAPQPCQVS-------SLSERKAKKLIREAGQKRVRsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsF 619
Cdd:PLN02222  329 GGITECLKVDpdkvrrlSLSEEQLEKAAEKYAKQIVR------------------------------------------F 366

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 620 VRHNarqLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPACLRQPDST---FD 696
Cdd:PLN02222  367 TQHN---LLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDsdiFD 443

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 697 PEYPGPPRTTLSIQVLTAQ----QLPKLNAEKpHSIVDPLVRIEIHGVPADCARQETDyVLNNGFNPRWGQTLQFQLRAP 772
Cdd:PLN02222  444 PKATLPVKTTLRVTIYMGEgwyfDFRHTHFDQ-YSPPDFYTRVGIAGVPGDTVMKKTK-TLEDNWIPAWDEVFEFPLTVP 521

                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370470037 773 ELALVRFVVEDYDATSPNDFVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFIQI 829
Cdd:PLN02222  522 ELALLRLEVHEYDMSEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKV 578
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 338-676 5.17e-70

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: 231.48  E-value: 5.17e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 338 DMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG--PGGEPVIYHGHTLTSKILFRDVVQAVR 415
Cdd:cd08625     3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 416 DHAFTLSPYPVILSLENHC-GLEQQAAMARHLCTILGDMLVTQALD----SPNpEELPSPEQLKGRVLVKGKKlpaarse 490
Cdd:cd08625    83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplVPG-VQLPSPQELMGKILVKNKK------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 491 dgralsdreeeeeddeeeeeeveaaaqrrlakqispeLSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKLIREA 570
Cdd:cd08625   155 -------------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKS 197

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 571 GQKrvrsggrvtwgrawalfpggyrpglwvrdprslsrshpnsapgnsFVRHNARQLTRVYPLGLRMNSANYSPQEMWNS 650
Cdd:cd08625   198 PME---------------------------------------------FVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNV 232

                         330       340
                  ....*....|....*....|....*.
gi 1370470037 651 GCQLVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08625   233 GCQMVALNFQTLDLAMQLNMGVFEYN 258
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 339-482 3.99e-69

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


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 224.85  E-value: 3.99e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  339 MNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRDHA 418
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370470037  419 FTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDsPNPEELPSPEQLKGRVLVKGK 482
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLT-SSLEVLPSPEQLRGKILLKVR 143
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 65-181 4.26e-67

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: 218.34  E-value: 4.26e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  65 MLRGSRLRKIRSRTWHKERLYRLQEDGLSVWFQRRIPRAPSQHIFFVQHIEAVREGHQSEGLRRFGGAFAPARCLTIAFK 144
Cdd:cd13363     1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKKTRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1370470037 145 GRRKNLDLAAPTAEEAQRWVRGLTKLRARLDAMSQRE 181
Cdd:cd13363    81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 337-676 1.31e-66

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: 221.09  E-value: 1.31e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVVQAVRD 416
Cdd:cd08599     2 HDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 417 HAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQALDSPnPEELPSPEQLKGRVLVKgKKLPAARsedgrals 496
Cdd:cd08599    82 NAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDL-PEEFPSPEELKGKILIS-DKPPVIR-------- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 497 dreeeeeddeeeeeeveaaaqrrlakqispelsalavychatrlrtlhpapnapqpcqvSSLSERKAKKLIreagqkrvr 576
Cdd:cd08599   152 -----------------------------------------------------------NSLSETQLKKVI--------- 163

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 577 sggrvtwgrawalfpggyrpglWVRDPRSLsrshpnsapgnsfVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVA 656
Cdd:cd08599   164 ----------------------EGEHPTDL-------------IEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVA 208

                         330       340
                  ....*....|....*....|
gi 1370470037 657 LNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08599   209 LNMQGYDRPLWLNRGKFRAN 228
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 255-828 1.32e-64

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 227.28  E-value: 1.32e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 255 ELEEIFHQYSGEDRVLSAPELLEFLEDQGEEGA--TLARAQQLI-----QTYELNETAKQHelMTLDGFMMYLLS----- 322
Cdd:PLN02230   30 DVRDLFEKYADGDAHMSPEQLQKLMAEEGGGEGetSLEEAERIVdevlrRKHHIAKFTRRN--LTLDDFNYYLFStdlnp 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 323 PEGaalDNTHtcvfQDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLT 402
Cdd:PLN02230  108 PIA---DQVH----QNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRTLT 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 403 SKILFRDVVQAVRDHAFTLSPYPVILSLENHCGLEQQAAMARHLCTILGDMLVTQalDSPNPEELPSPEQLKGRVLVKGK 482
Cdd:PLN02230  181 KEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYH--DSEGCQEFPSPEELKEKILISTK 258

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 483 klPAARSEDGRALSDREEEEEDDEEEEEEVEAAAQRRLAKQISPELSALAVYcHATRLRTLHPAPNAPQPCQvssLSERK 562
Cdd:PLN02230  259 --PPKEYLEANDAKEKDNGEKGKDSDEDVWGKEPEDLISTQSDLDKVTSSVN-DLNQDDEERGSCESDTSCQ---LQAPE 332

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 563 AKKLIR-EAGQKRvrsggrvtwgrawalfpGGYRPGLWVrDPRSLSR--------SHPNSAPGNSFVRHNARQLTRVYPL 633
Cdd:PLN02230  333 YKRLIAiHAGKPK-----------------GGLRMALKV-DPNKIRRlslseqllEKAVASYGADVIRFTQKNFLRIYPK 394

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 634 GLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPACLRQPDST---FDPEYPGPPRTTLSIQ 710
Cdd:PLN02230  395 GTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGPNgqdFYPKDNSCPKKTLKVK 474

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 711 VLTAQQLpKLNAEKPH----SIVDPLVRIEIHGVPADCARQETDyVLNNGFNPRWGQTLQFQLRAPELALVRFVVEDYDA 786
Cdd:PLN02230  475 VCMGDGW-LLDFKKTHfdsySPPDFFVRVGIAGAPVDEVMEKTK-IEYDTWTPIWNKEFIFPLAVPELALLRVEVHEHDI 552

                         570       580       590       600
                  ....*....|....*....|....*....|....*....|..
gi 1370470037 787 TSPNDFVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFIQ 828
Cdd:PLN02230  553 NEKDDFGGQTCLPVSEIRQGIHAVPLFNRKGVKYSSTRLLMR 594
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 186-324 2.16e-62

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: 206.31  E-value: 2.16e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd16202     1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTKRPEIEELFKKYSG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 266 EDRVLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16202    81 DDEALTVEELRRFLqEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 337-676 3.82e-61

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: 207.63  E-value: 3.82e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGG--EPVIYHGHTLTSKILFRDVVQAV 414
Cdd:cd08623     2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAeeEPVITHGFTMTTEISFKEVIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 415 RDHAFTLSPYPVILSLENHC-GLEQQAAMARHLCTILGDMLVTQALDSPNPEE---LPSPEQLKGRVLVKGKKlpaarse 490
Cdd:cd08623    82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESgvpLPSPMDLMYKILVKNKK------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 491 dgralsdreeeeeddeeeeeeveaaaqrrlakqispeLSALAVYCHATRLRTLHPAPNAPQPCQVSSLSERKAKKlirea 570
Cdd:cd08623   155 -------------------------------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLE----- 192

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 571 gqkrvrsggrvtwgrawalfpggyrpglwvrdprSLSRSHPnsapgnSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNS 650
Cdd:cd08623   193 ----------------------------------QLTKSPV------EFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNA 232

                         330       340
                  ....*....|....*....|....*.
gi 1370470037 651 GCQLVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd08623   233 GCQMVALNFQTVDLSMQINMGMYEYN 258
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 337-676 2.22e-60

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: 205.96  E-value: 2.22e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 337 QDMNQPLAHYFISSSHNTYLTDSQI-----GGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTsKILFRDVV 411
Cdd:cd00137     2 HPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEVI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 412 QAVRDHAFTLSPYPVILSLENHCGL--EQQAAMARHLCTILGDMLVTQALDSPNPeeLPSPEQLKGRVLVKGKKL----P 485
Cdd:cd00137    81 EAIAQFLKKNPPETIIMSLKNEVDSmdSFQAKMAEYCRTIFGDMLLTPPLKPTVP--LPSLEDLRGKILLLNKKNgfsgP 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 486 AARSEDGRALSDREEEEeddeeeeeeveaaaqrrlaKQISPElsalavychatrlrtlhpapnapqpcqVSSLSERKAkk 565
Cdd:cd00137   159 TGSSNDTGFVSFEFSTQ-------------------KNRSYN---------------------------ISSQDEYKA-- 190

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 566 lireagqkrvrsggrvtwgrawalfpggyrpglwVRDPRSLSrshpnSAPGNSFVRHNARQLTRVYPLGLR--------- 636
Cdd:cd00137   191 ----------------------------------YDDEKVKL-----IKATVQFVDYNKNQLSRNYPSGTSggtawyyya 231

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 1370470037 637 MNSANYSPQEMWN---SGCQLVALNFQTPGYEMDLNAGRFLVN 676
Cdd:cd00137   232 MDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 186-324 1.46e-54

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: 184.94  E-value: 1.46e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd16217     1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370470037 266 EDRVLSAPELLEFLEDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16217    81 SDGTMSRNNLLNFLQEEQREEVAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 705-832 1.34e-51

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: 176.19  E-value: 1.34e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 705 TTLSIQVLTAQQLPKLNAEKPhSIVDPLVRIEIHGVPA-DCARQETDYVLNNGFNPRWGQTLQFQLRAPELALVRFVVED 783
Cdd:cd00275     2 LTLTIKIISGQQLPKPKGDKG-SIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1370470037 784 YDaTSPNDFVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFIQIRIQ 832
Cdd:cd00275    81 ED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 528-687 4.65e-50

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 171.49  E-value: 4.65e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 528 LSALAVYCHATRLRTLHpAPNAPQPCQVSSLSERKAKKLIREagqkrvrsggrvtwgrawalfpggyrpglwvrdprsls 607
Cdd:pfam00387   1 LSDLVVYTQSVKFKSFS-TPESKTPNHIFSFSESKALKLIKS-------------------------------------- 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 608 rshpnsaPGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPAC 687
Cdd:pfam00387  42 -------SSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PLN02223 PLN02223
phosphoinositide phospholipase C
 260-830 2.02e-45

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 171.74  E-value: 2.02e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 260 FHQYsGEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQtyELNETA------KQHELMTLDGFMMYLLS-----PEGAA 327
Cdd:PLN02223   26 FHGY-DDDMPELLPRFIELLDtEKDEDGAGLNAAEKIAA--ELKRRKcdilafRNLRCLELDHLNEFLFStelnpPIGDQ 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 328 LDNthtcvfQDMNQPLAHYFISSSHNTYLTDSQI-GGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKIL 406
Cdd:PLN02223  103 VRH------HDMHAPLSHYFIHTSLKSYFTGNNVfGKLYSIEPIIDALEQGVRVVELDLLPDGKDGICVRPKWNFEKPLE 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 407 FRDVVQAVRDHAFT-LSPYPVILSLENHCGLEQQAAMARHLCTILGDMlVTQALDSPNPEELPSPEQLKGRVLVK---GK 482
Cdd:PLN02223  177 LQECLDAIKEHAFTkCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDM-VYHEDPQHSLEEFPSPAELQNKILISrrpPK 255

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 483 KLPAARSEDGRAlsdreeeeeddeeeeeeveaaaQRRLAKQISPelsalavychatrlrtlHPA-PNAPQPCQVSSLSER 561
Cdd:PLN02223  256 ELLYAKADDGGV----------------------GVRNELEIQE-----------------GPAdKNYQSLVGFHAVEPR 296

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 562 KAKKLIREAGQKRVRsggrvtwgrawalfpggyRPGLWVRDPRSLSRshpnsapgNSFVRhnarqlTRVYPLGLRMNsAN 641
Cdd:PLN02223  297 GMLQKALTGKADDIQ------------------QPGWYERDIISFTQ--------KKFLR------TRPKKKNLLIN-AP 343

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 642 YSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPACLRQ--PDSTFDPEYPGPPRTTLSIQVLTA----- 714
Cdd:PLN02223  344 YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagPSGVFYPTENPVVVKILKVKIYMGdgwiv 423

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 715 ---QQLPKLNaeKPhsivDPLVRIEIHGVPADCARQETDyVLNNGFNPRWGQTLQFQLRAPELALVRFVVEDYDATSPND 791
Cdd:PLN02223  424 dfkKRIGRLS--KP----DLYVRISIAGVPHDEKIMKTT-VKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADA 496

                         570       580       590
                  ....*....|....*....|....*....|....*....
gi 1370470037 792 FVGQFTLPLSSLKQGYRHIHLLSKDGASLSPATLFIQIR 830
Cdd:PLN02223  497 FCGQTCLPVSELIEGIRAVPLYDERGKACSSTMLLTRFK 535
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 529-688 6.72e-43

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: 151.24  E-value: 6.72e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  529 SALAVYCHATRLRTLhPAPNAPQPC-QVSSLSERKAKKLIREAGqkrvrsggrvtwgrawalfpggyrpglwvrdprsls 607
Cdd:smart00149   1 SDLVIYCAPVKFRSF-ESAESKNPFyEMSSFSETKAKKLLKKSP------------------------------------ 43

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  608 rshpnsapgNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVNGQCGYVLKPAC 687
Cdd:smart00149  44 ---------TDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDF 114


                   .
gi 1370470037  688 L 688
Cdd:smart00149 115 L 115
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 186-324 4.02e-40

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: 144.60  E-value: 4.02e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd16219     1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 266 EDRVLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16219    81 DGQKLTLLEFVDFLqQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 186-324 4.20e-35

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: 130.10  E-value: 4.20e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSG 265
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEPIFKKYAG 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 266 EDR-VLSAPELLEFLEDQGEEGATLARAQQLIQTYELNETAKQhelMTLDGFMMYLLSPE 324
Cdd:cd15898    81 TNRdYMTLEEFIRFLREEQGENVSEEECEELIEKYEPERENRQ---LSFEGFTNFLLSPE 137
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 246-329 2.80e-27

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: 105.79  E-value: 2.80e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 246 FLRRLLKRPELEEIFHQYSGEDRVLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLrEEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 1370470037 325 GAALD 329
Cdd:pfam09279  81 GSIFN 85
EF-hand_10 pfam14788
EF hand;
201-250 2.95e-24

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 95.95  E-value: 2.95e-24
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370470037 201 KMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRL 250
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 350-454 1.75e-22

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: 95.58  E-value: 1.75e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 350 SSHNTYltdSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLT------SKILFRDVVQAVRDHAFTlSP 423
Cdd:cd08555     2 LSHRGY---SQNGQENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLKN-PD 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1370470037 424 YPVILSLENHCG----LEQQAAMARHLCTILGDML 454
Cdd:cd08555    78 YTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDL 112
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 706-812 4.08e-20

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: 86.00  E-value: 4.08e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  706 TLSIQVLTAQQLPKLNaekPHSIVDPLVRIEIHGVPADCARqeTDYVLNNGfNPRWGQTLQFQLRAPELALVRFVVEDYD 785
Cdd:smart00239   1 TLTVKIISARNLPPKD---KGGKSDPYVKVSLDGDPKEKKK--TKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKD 74

                           90       100
                   ....*....|....*....|....*..
gi 1370470037  786 ATSPNDFVGQFTLPLSSLKQGYRHIHL 812
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 186-324 6.39e-20

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: 86.88  E-value: 6.39e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNND---RLEGAEIEEFLRRLLKRPELEEIFHQ 262
Cdd:cd16206     1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKELQKKKDGargRVSSDEFVELFKELATRPEIYFLLVR 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370470037 263 YSGEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16206    81 YASNKDYLTVDDLMLFLEaEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 65-170 7.34e-20

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: 85.45  E-value: 7.34e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  65 MLRGSRLRKIRSRTWHKERLYRLQEDGLSVWFQRRIPRAPSQHIFfVQHIEAVREGHQSEGLRRFGGAFAP--ARCLTIA 142
Cdd:cd01248     1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKKSEKKSID-ISDIKEIRPGKDTDGFKRKKKSNKPkeERCFSII 79

                          90       100
                  ....*....|....*....|....*...
gi 1370470037 143 FKGRRKNLDLAAPTAEEAQRWVRGLTKL 170
Cdd:cd01248    80 YGSNNKTLDLVAPSEDEANLWVEGLRAL 107
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 186-324 7.20e-19

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: 83.58  E-value: 7.20e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNND-RLEGAEIEEFLRRLLKRPELEEIFHQYS 264
Cdd:cd16205     1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQgTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370470037 265 GEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16205    81 NKKDYLTLEDLARFLEvEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
C2 pfam00168
C2 domain;
706-811 5.16e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 80.06  E-value: 5.16e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 706 TLSIQVLTAQQLPKLNaekPHSIVDPLVRIEIHGvpaDCARQETDyVLNNGFNPRWGQTLQFQLRAPELALVRFVVEDYD 785
Cdd:pfam00168   2 RLTVTVIEAKNLPPKD---GNGTSDPYVKVYLLD---GKQKKKTK-VVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*.
gi 1370470037 786 ATSPNDFVGQFTLPLSSLKQGYRHIH 811
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDG 100
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 185-323 1.57e-17

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: 79.99  E-value: 1.57e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 185 HWihsylHRADSN---QDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFH 261
Cdd:cd16207     4 HW-----KRADSKkqdGDERLDFEDVEKLCRRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLKRRKDIKAIFK 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370470037 262 QYSGEDR-VLSAPELLEFLED-QGEEgATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSP 323
Cdd:cd16207    79 QLTKPGSdGLTLEEFLKFLRDvQKED-VDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSS 141
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 186-324 3.17e-15

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: 73.31  E-value: 3.17e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHraDSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEgaeIEEF---LRRLLKRPELEEIFHQ 262
Cdd:cd16204     5 WFLSIIQ--DRFRKGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFKAGNIT---IEDFraiYRAIAHRCEIHEIFNT 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370470037 263 YSGEDRVLSAPELLEFL-EDQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16204    80 YSENRKILSAPNLVGFLkKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 707-805 4.71e-12

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: 62.85  E-value: 4.71e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 707 LSIQVLTAQQLPKLNAekpHSIVDPLVRIEIHGVPadcaRQETDYVLNNgFNPRWGQTLQFQLRAPELALVRFVVEDYDA 786
Cdd:cd00030     1 LRVTVIEARNLPAKDL---NGKSDPYVKVSLGGKQ----KFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWDKDR 72

                          90
                  ....*....|....*....
gi 1370470037 787 TSPNDFVGQFTLPLSSLKQ 805
Cdd:cd00030    73 FSKDDFLGEVEIPLSELLD 91
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 186-323 2.36e-11

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: 62.26  E-value: 2.36e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNND-RLEGAEIEEFLRRLLKRPELEEIFHQYS 264
Cdd:cd16221     1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQgTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 265 GEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSP 323
Cdd:cd16221    81 NHKDHLDTNDLQRFLEvEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSP 140
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 207-324 8.50e-11

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: 61.11  E-value: 8.50e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 207 IKSLLRMVNVDMNDMYAYLLFKECD--HSNNDRLEGAE-----IEEFLRRLLKRPELEEIFHQYSGEDR-VLSAPELLEF 278
Cdd:cd16200    19 VKNIIKCFSSDKKRKRVLKALKALGlpDGKNDEIDPEDftfekFFKLYNKLCPRPDIDEIFKELGGKRKpYLTLEQLVDF 98

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370470037 279 LEDQGEE---------GATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16200    99 LNEEQRDprlneilfpFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 65-170 2.54e-10

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: 58.45  E-value: 2.54e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  65 MLRGSRLRKIRSRTWHKERLYRLQEDGLSVWFQ--------RRIPrapsqhiffVQHIEAVREGHQSEGLRR--FGGAFA 134
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKpskkksekAKIP---------ISSIREVREGKTTDIFRScdISGDFP 71

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1370470037 135 PARCLTIAFKGRRKNLDLAAPTAEEAQRWVRGLTKL 170
Cdd:cd13364    72 EECCFSIIYGEEYETLDLVASSPDEANIWITGLRYL 107
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 245-324 3.57e-10

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: 59.24  E-value: 3.57e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 245 EFLRRLLKRPELEEIFHQYSGEDR-VLSAPELLEFLEDQGEEG---------ATLARAQQLIQTYELNETAKQHELMTLD 314
Cdd:cd16213    65 NFYRRLTGRQEVEKIFDELGAKKKpYLTTEQFVDFLNKTQRDPrlneilypyANPKRARDLINQYEPNKSFAKKGHLSVE 144

                          90
                  ....*....|
gi 1370470037 315 GFMMYLLSPE 324
Cdd:cd16213   145 GFLRYLMSED 154
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
 186-323 4.12e-10

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: 58.88  E-value: 4.12e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNND-RLEGAEIEEFLRRLLKRPELEEIFHQYS 264
Cdd:cd16220     1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQgTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 265 GEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSP 323
Cdd:cd16220    81 DKKDHLTVEELAQFLKvEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSP 140
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 186-324 1.42e-09

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: 57.18  E-value: 1.42e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNN---DRLEGAEIEEFLRRLLKRPELEEIFHQ 262
Cdd:cd16222     1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEkltTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370470037 263 YSGEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16222    81 ISKNKEYLDAKDLMLFLEaEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 186-324 1.13e-08

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: 54.53  E-value: 1.13e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECdHSNNDRLeGAEI--EEFLR---RLLKRPELEEIF 260
Cdd:cd16223     1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKEL-HKSKEKG-GTEVtkEEFIEvfhELCTRPEIYFLL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370470037 261 HQYSGEDRVLSAPELLEFLE-DQGEEGATLARAQQLIQTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16223    79 VQFSSNKEFLDTKDLMMFLEaEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPE 143
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 707-803 4.87e-08

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: 52.26  E-value: 4.87e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 707 LSIQVLTAQQLPKLNaekPHSIVDPLVRIEIHGVPADCARQETDYVLNNgFNPRWGQTLQFQLRaPELALVRFVVE--DY 784
Cdd:cd04026    15 LTVEVREAKNLIPMD---PNGLSDPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLK-PADKDRRLSIEvwDW 89

                          90
                  ....*....|....*....
gi 1370470037 785 DATSPNDFVGQFTLPLSSL 803
Cdd:cd04026    90 DRTTRNDFMGSLSFGVSEL 108
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 232-324 9.34e-08

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: 52.04  E-value: 9.34e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 232 HSNNDRLEGAEIE-----EFLRRLLKRPELEEIFHQYSGEDR-VLSAPELLEFLEDQGEEG---------ATLARAQQLI 296
Cdd:cd16211    46 SGKNDEIEPEAFTfekfyELYHKICPRTDIEELFKKINGDKKdYLTVDQLISFLNEHQRDPrlneilfpfYDRKRVMQII 125

                          90       100
                  ....*....|....*....|....*...
gi 1370470037 297 QTYELNETAKQHELMTLDGFMMYLLSPE 324
Cdd:cd16211   126 ETYEVDEEFKKKEQLSSDGFCRYLMSDE 153
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 706-805 1.84e-06

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: 47.86  E-value: 1.84e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 706 TLSIQVLTAQQLpklnAEKPHS-IVDPLVRIEIHGvpadcARQETDYVLNNGFnPRWGQTLQFQLRAPELALVRFVVEDY 784
Cdd:cd04025     1 RLRCHVLEARDL----APKDRNgTSDPFVRVFYNG-----QTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDW 70

                          90       100
                  ....*....|....*....|.
gi 1370470037 785 DATSPNDFVGQFTLPLSSLKQ 805
Cdd:cd04025    71 DLVSKNDFLGKVVFSIQTLQQ 91
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 702-803 2.57e-06

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: 47.62  E-value: 2.57e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 702 PPRTTLSIQVLTAQQLPKLnaeKPHSIVDPLVRIEI--HGVPADCARQETDyVLNNGFNPRWGQTLQFQL----RAPELA 775
Cdd:cd04009    13 ASEQSLRVEILNARNLLPL---DSNGSSDPFVKVELlpRHLFPDVPTPKTQ-VKKKTLFPLFDESFEFNVppeqCSVEGA 88

                          90       100
                  ....*....|....*....|....*...
gi 1370470037 776 LVRFVVEDYDATSPNDFVGQFTLPLSSL 803
Cdd:cd04009    89 LLLFTVKDYDLLGSNDFEGEAFLPLNDI 116
EFh_PI-PLCbeta3 cd16210
EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...
 197-320 6.01e-06

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


Pssm-ID: 320040  Cd Length: 151  Bit Score: 46.84  E-value: 6.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 197 NQDSKMSfkeIKSLLRMVN-----VDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLLKRPELEEIFHQYSGEDR-VL 270
Cdd:cd16210    12 NQDGRIP---VKNILKMFSadkkrVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEIGAKGKpYL 88

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370470037 271 SAPELLEFLEDQGEEG-------ATLARAQ--QLIQTYELNETAKQHELMTLDGFMMYL 320
Cdd:cd16210    89 TLEQLMDFINQKQRDPrlnevlyPPLRPSQvrQLIEKYEPNQQFLERDQMSMEGFSRYL 147
EFh_PI-PLCbeta1 cd16208
EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...
 246-324 8.39e-06

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


Pssm-ID: 320038  Cd Length: 151  Bit Score: 46.41  E-value: 8.39e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 246 FLRRLLKRPELEEIFHQYSGEDR-VLSAPELLEFLEDQGEEGA---------TLARAQQLIQTYELNETAKQHELMTLDG 315
Cdd:cd16208    63 FLNNLCPRPEIDHIFSEFGAKSKpYLSVDQMTEFINSKQRDPRlneilypplKQEQVQQLIEKYEPNSTLAKKGQISVDG 142


                  ....*....
gi 1370470037 316 FMMYLLSPE 324
Cdd:cd16208   143 FMRYLSGEE 151
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
 57-170 6.69e-05

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: 43.04  E-value: 6.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  57 TEDEDVRAMLRGSRLRKIRSRTWHKERLYRLQEDGLSV-WfqrRIPRAPSQHIFFVQHIEAVREGHQSEGLRRFGGAFAP 135
Cdd:cd13365     2 DVIEAITQLKIGSYLLKYGRRGKPHFRYFWLSPDELTLyW---SSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLE 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1370470037 136 ARCLTIAFKGRRKNLDLAAPTAEEAQRWVRGLTKL 170
Cdd:cd13365    79 EHSFSIIYADGERSLDLTCKDRQEFDTWFTGLRYL 113
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 70-170 1.04e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 42.16  E-value: 1.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  70 RLRKIRSRTWHKeRLYRLQEDGLSVWFQRRIPRAPS-QHIFFVQHIEAVREGHQSEGLRRFGgaFaparCLTIAFKGRRK 148
Cdd:pfam00169   9 KKGGGKKKSWKK-RYFVLFDGSLLYYKDDKSGKSKEpKGSISLSGCEVVEVVASDSPKRKFC--F----ELRTGERTGKR 81

                          90       100
                  ....*....|....*....|..
gi 1370470037 149 NLDLAAPTAEEAQRWVRGLTKL 170
Cdd:pfam00169  82 TYLLQAESEEERKDWIKAIQSA 103
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 705-804 1.07e-04

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: 42.70  E-value: 1.07e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 705 TTLSIQVLTAQQLPklnAEKPHSIVDPLVRIEIhgVPaDCARQETDYVLNNGFNPRWGQTLQFQLRAPELALVRFV---V 781
Cdd:cd08386    16 STLTLKILKAVELP---AKDFSGTSDPFVKIYL--LP-DKKHKLETKVKRKNLNPHWNETFLFEGFPYEKLQQRVLylqV 89

                          90       100
                  ....*....|....*....|...
gi 1370470037 782 EDYDATSPNDFVGQFTLPLSSLK 804
Cdd:cd08386    90 LDYDRFSRNDPIGEVSLPLNKVD 112
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 704-802 1.46e-04

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: 42.23  E-value: 1.46e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 704 RTTLSIQVLTAQQL-PKLNAEKPhsivDPLVRIEIHGVPADCARQETDYVlNNGFNPRWGQTLQFQ-LRAPELaLVRFV- 780
Cdd:cd04031    15 TSQLIVTVLQARDLpPRDDGSLR----NPYVKVYLLPDRSEKSKRRTKTV-KKTLNPEWNQTFEYSnVRRETL-KERTLe 88

                          90       100
                  ....*....|....*....|....
gi 1370470037 781 --VEDYDATSPNDFVGQFTLPLSS 802
Cdd:cd04031    89 vtVWDYDRDGENDFLGEVVIDLAD 112
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 186-324 2.28e-04

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: 42.17  E-value: 2.28e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 186 WIHSYLHRADSNQDSKMSFKEIKSLLRMVNVDMNDMYAYLLFKECDHSNNDRLEGAEIEEFLRRLL-KRPELEEIFHQYS 264
Cdd:cd16201     1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTRRRGELGFDDFAQLYHKLMfDQKIIEDFFKKYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370470037 265 G--EDRVLSAPELLEFLEDQGEE--GATLARAQQLIQTY---ELNETAKQHelMTLDGFMMYLLSPE 324
Cdd:cd16201    81 YssDGQTVTLEDFQRFLLEEQKEpwANDPNAVREFMRDFlqdPLRDVQEPY--FTLDEFLDYLFSKE 145
EFh_NorpA_like cd16212
EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...
 253-324 2.33e-04

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: 42.15  E-value: 2.33e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 253 RPELEEIFHQYS-GEDRVLSAPELLEFLEDQGEEGA---------TLARAQQLIQTYELNETAKQHELMTLDGFMMYLLS 322
Cdd:cd16212    72 RNDIEELFTSITkGKGEHISLAQLINFMNDKQRDPRlneilyplyDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMS 151


                  ..
gi 1370470037 323 PE 324
Cdd:cd16212   152 DE 153
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 711-803 2.55e-04

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 41.47  E-value: 2.55e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 711 VLTAQQLPKLNAeKPhsivDPLVRIEIHGVPadcarQETDyVLNNGFNPRWGQTLQFQLRAP-----ELALvrfVVEDYD 785
Cdd:cd08373     2 VVSLKNLPGLKG-KG----DRIAKVTFRGVK-----KKTR-VLENELNPVWNETFEWPLAGSpdpdeSLEI---VVKDYE 67

                          90
                  ....*....|....*...
gi 1370470037 786 ATSPNDFVGQFTLPLSSL 803
Cdd:cd08373    68 KVGRNRLIGSATVSLQDL 85
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 69-170 2.92e-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: 40.99  E-value: 2.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037   69 SRLRKIRSRTWHKeRLYRLQEDGLSVWFQRRIPRAPS-QHIFFVQHIEAVREGHQSEGLRRFggafaparCLTIaFKGRR 147
Cdd:smart00233   8 YKKSGGGKKSWKK-RYFVLFNSTLLYYKSKKDKKSYKpKGSIDLSGCTVREAPDPDSSKKPH--------CFEI-KTSDR 77

                           90       100
                   ....*....|....*....|...
gi 1370470037  148 KNLDLAAPTAEEAQRWVRGLTKL 170
Cdd:smart00233  78 KTLLLQAESEEEREKWVEALRKA 100
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
 114-179 2.95e-04

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: 41.11  E-value: 2.95e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370470037 114 IEAVREGHQSEGLRRF---GGAFAPARCLTIaFKG---RRKNLDLAAPTAEEAQRWVRGLTKLRArlDAMSQ 179
Cdd:cd13362    49 IKEIRPGKNSKDFERWpdeAKKLDPSCCFVI-LYGtefRLKTLSVAATSEEECDMWIKGLRYLVE--DTLSA 117
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 338-465 3.95e-04

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


Pssm-ID: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 43.24  E-value: 3.95e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 338 DMNQPLAHYFISSSHNTYltdSQIGGPSSTEAYVRAFAQ----------GCRCVELDCWEGP-GGEPVIYHGHTLTSKIL 406
Cdd:cd08557     4 LDDLPLSQLSIPGTHNSY---AYTIDGNSPIVSKWSKTQdlsitdqldaGVRYLDLRVAYDPdDGDLYVCHGLFLLNGQT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370470037 407 FRDVVQAVRDhaFtLSPYP---VILSLENHCGLEQQAAMARhLCTILGDMLVTQALDSPNPE 465
Cdd:cd08557    81 LEDVLNEVKD--F-LDAHPsevVILDLEHEYGGDNGEDHDE-LDALLRDVLGDPLYRPPVRA 138
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
602-806 1.42e-03

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 42.44  E-value: 1.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  602 DPRSLSRSHPNSAPGNSFVRH-NARQLT-RVyplglrMNSANYSPQEMWNSG---CQLVALNFQTPgYEMDLNaGRFLVN 676
Cdd:COG5038    947 SSKAPTRGERNGESGDTFIRElEYSETTfRV------TKNAKKSDKVVCEVTlptLDLVSNAYEKP-SSLNFP-GSAKVL 1018

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  677 GQCGYVLKPACLRQPDSTFDPEYpgpprttLSIQVLTAQQLPKLNaEKPHSivDPLVRIEIHGVPAdcarqETDYVLNNG 756
Cdd:COG5038   1019 VQVSYTPVPVKLPPVEMVENSGY-------LTIMLRSGENLPSSD-ENGYS--DPFVKLFLNEKSV-----YKTKVVKKT 1083

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1370470037  757 FNPRWGQTLQFQLRAPELALVRFVVEDYDATSPNDFVGQFTLPLSSLKQG 806
Cdd:COG5038   1084 LNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLEPG 1133
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 758-805 2.33e-03

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH 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. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 38.90  E-value: 2.33e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1370470037 758 NPRWGQTLQFQLRAPELALVRFVVEDYDATSPNDFVGQFTLPLSSLKQ 805
Cdd:cd08375    59 NPKWNSSMQFFVKDLEQDVLCITVFDRDFFSPDDFLGRTEIRVADILK 106
GDPD_GDE4_like cd08575
Glycerophosphodiester phosphodiesterase domain of mammalian glycerophosphodiester ...
 368-401 2.67e-03

Glycerophosphodiester phosphodiesterase domain of mammalian glycerophosphodiester phosphodiesterase GDE4-like proteins; This subfamily corresponds to the glycerophosphodiester phosphodiesterase domain (GDPD) present in mammalian GDE4 (also known as glycerophosphodiester phosphodiesterase domain-containing protein 1 (GDPD1)) and similar proteins. Mammalian GDE4 is a transmembrane protein whose cellular function is not elucidated. It is expressed widely, including in placenta, liver, kidney, pancreas, spleen, thymus, ovary, small intestine and peripheral blood leukocytes. It is also expressed in the growth cones in neuroblastoma Neuro2a cells, which suggests mammalian GDE4 may play some distinct role from other members of mammalian GDEs family. Also included in this subfamily are uncharacterized mammalian glycerophosphodiester phosphodiesterase domain-containing protein 3 (GDPD3) and similar proteins which display very high sequence homology to mammalian GDE4.


Pssm-ID: 176517 [Multi-domain]  Cd Length: 264  Bit Score: 40.66  E-value: 2.67e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1370470037 368 EAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTL 401
Cdd:cd08575    19 AAFRHAVKNGADMLELDVQLTKDGQVVVFHDWDL 52
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 730-803 5.32e-03

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 37.55  E-value: 5.32e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370470037 730 DPLVRIEIHGVPadCARQETdyvLNNGFNPRWGQTLQFQLRAPELALVRFVVEDYDATSPNDFVGQFTLPLSSL 803
Cdd:cd04040    21 DPFVKFYLNGEK--VFKTKT---IKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDLLGSAYIDLSDL 89
PH_PLC_fungal cd13360
Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...
 65-174 5.43e-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: 37.55  E-value: 5.43e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037  65 MLRGSRLRKIRSRTwHKERLYRLQEDGLSVWFQRRIPRapsqHIFFVQHIEAVREG----------HQSEglrrfggAFA 134
Cdd:cd13360     1 LRQGTPLLKVTKKK-KKRILFKLDPESGKITWDSKKPS----KSLYIDDIKEIRTGedarnyreefGISE-------EFE 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1370470037 135 PaRCLTI----AFKGRRKNLDLAAPTAEEAQRWV---RGLTKLRARL 174
Cdd:cd13360    69 D-RWITIiyfvPKKNKLKTLHLIADTEEDFKLWTttlEGLVKLRREL 114
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 706-809 7.98e-03

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 37.41  E-value: 7.98e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370470037 706 TLSIQVLTAQQLPKLNAEKPhsiVDPLVRIEIHGVPADCARQETdYVLNNGFNPRWGQTLQFQLRAPEL--ALVRFVVED 783
Cdd:cd08404    16 RLTVVVLKARHLPKMDVSGL---ADPYVKVNLYYGKKRISKKKT-HVKKCTLNPVFNESFVFDIPSEELedISVEFLVLD 91

                          90       100
                  ....*....|....*....|....*.
gi 1370470037 784 YDATSPNDFVGQFTLPLSSLKQGYRH 809
Cdd:cd08404    92 SDRVTKNEVIGRLVLGPKASGSGGHH 117
 
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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