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Conserved domains on  [gi|2031723591|ref|XP_041067920|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [Carcharodon carcharias]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 316-686 3.65e-179

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: 527.68  E-value: 3.65e-179
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSpKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08591    154 ---------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKR 206

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08591    207 QLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257
EFh_PI-PLCbeta1 cd16208
EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...
 155-304 2.38e-88

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: 282.15  E-value: 2.38e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADRKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSEYG 234
Cdd:cd16208      2 KAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEFG 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  235 AKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16208     82 AKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151
PH_PLC_beta cd13361
Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...
 22-149 5.65e-65

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


:

Pssm-ID: 270167  Cd Length: 127  Bit Score: 215.51  E-value: 5.65e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   22 LKKGSKFMKWDDDSTTVTPVTLKVDPQGLFLYWTDQNKETDLLEISHVKDARTGKYARNPKDTKLRElLDVGNQGNRLEN 101
Cdd:cd13361      1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKERE-VNVGGSDEDLED 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2031723591  102 RMVTVVYGPDLVNISYLNFMAFQEDVAKEWTDALFSLATNLLAQNRSR 149
Cdd:cd13361     80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 720-839 8.74e-37

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


:

Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 134.98  E-value: 8.74e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  720 TLSVKVLSGQFLSD------KKVGTYVEIDMFGLPVDTRRKaFKTKTSQNNAVNPVWeDDPIVFKkVVLPSLSSLRISVY 793
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVW-NETFEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2031723591  794 EEGG---KFIGHRILPVQAIRPGYHYICLRNERNQPLMLPALFVYIEVK 839
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
PLC-beta_C super family cl25592
PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...
 1067-1216 8.37e-35

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


The actual alignment was detected with superfamily member pfam08703:

Pssm-ID: 462571 [Multi-domain]  Cd Length: 176  Bit Score: 131.34  E-value: 8.37e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1067 YYSEKYQKREHVKQLVQKLTEVAEECQANQLKKLRELCEKEKKELKKKMDKKRQEKITEAKSKDKNQMEEE--KTEIIRS 1144
Cdd:pfam08703   22 YEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQEAKKRTSDKAAQErlKKEINNS 101

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591 1145 YIHEVVQSIKRLEDAQCKRQEKLVDKHKEVRQQILDEKPKLQSDLDQEYQDKFKRLPLEIQEFVQDTLKGKF 1216
Cdd:pfam08703  102 HIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAEVRESVKSCLKEGF 173
DUF1154 super family cl05918
Protein of unknown function (DUF1154); This family represents a small conserved region of ...
 947-982 4.33e-06

Protein of unknown function (DUF1154); This family represents a small conserved region of unknown function within eukaryotic phospholipase C (EC:3.1.4.3). All members also contain pfam00387 and pfam00388.


The actual alignment was detected with superfamily member pfam06631:

Pssm-ID: 461969  Cd Length: 45  Bit Score: 44.56  E-value: 4.33e-06
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 2031723591  947 EVEAQTVEELRQQKAFVKLQKKHYKEMKELVKKHHK 982
Cdd:pfam06631    3 KFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSK 38
 
Name Accession Description Interval E-value
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 316-686 3.65e-179

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: 527.68  E-value: 3.65e-179
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSpKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08591    154 ---------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKR 206

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08591    207 QLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257
EFh_PI-PLCbeta1 cd16208
EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...
 155-304 2.38e-88

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: 282.15  E-value: 2.38e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADRKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSEYG 234
Cdd:cd16208      2 KAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEFG 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  235 AKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16208     82 AKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 319-467 5.53e-74

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


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 241.64  E-value: 5.53e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  319 MTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSteEEPVITHGFTMTTEICFKEVIEAIAE 398
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPD--GEPVVYHGYTLTSKIPFRDVLEAIKD 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2031723591  399 CAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEkyplESGVPLPSPHDMIGKILIKN 467
Cdd:pfam00388   79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLD----DDLTELPSPEDLKGKILIKG 142
PH_PLC_beta cd13361
Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...
 22-149 5.65e-65

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


Pssm-ID: 270167  Cd Length: 127  Bit Score: 215.51  E-value: 5.65e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   22 LKKGSKFMKWDDDSTTVTPVTLKVDPQGLFLYWTDQNKETDLLEISHVKDARTGKYARNPKDTKLRElLDVGNQGNRLEN 101
Cdd:cd13361      1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKERE-VNVGGSDEDLED 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2031723591  102 RMVTVVYGPDLVNISYLNFMAFQEDVAKEWTDALFSLATNLLAQNRSR 149
Cdd:cd13361     80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127
PLN02952 PLN02952
phosphoinositide phospholipase C
 217-827 1.91e-63

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 227.57  E-value: 1.91e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  217 LNNICPRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQrdprlNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGF 296
Cdd:PLN02952    31 ITEAEPPDDVKDVFCKF-SVGGGHMGADQLRRFLVLHQ-----DELDCTLAEAQRIVEEVINRRHHVTRYTRHGLNLDDF 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  297 KKYLSGDE-NGVIPPEkldLSEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrSTEEEP 375
Cdd:PLN02952   105 FHFLLYDDlNGPITPQ---VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPG-STKDEI 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  376 VITHGFTMTTEICFKEVIEAIAECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLmedlekYPLESG-VPLP 454
Cdd:PLN02952   181 LVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFP 253

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  455 SPHDMIGKILIKNKK-KGHKSSDGSAKKKLSEqasntysdsssvfePSSPGAASSNPEepdtaqqsnidgsDKPVEKIGK 533
Cdd:PLN02952   254 SPESLKHRIIISTKPpKEYLESSGPIVIKKKN--------------NVSPSGRNSSEE-------------TEEAQTLES 306

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  534 EVTEQKASGRkSIGDGEAESEEEEDDDEDSKKSSMDEGT-AGCEASATEEMSNLVTYIqpvkfesfevakknnksfemsS 612
Cdd:PLN02952   307 MLFEQEADSR-SDSDQDDNKSGELQKPAYKRLITIHAGKpKGTLKDAMKVAVDKVRRL---------------------S 364

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  613 FVETKALEQLTKSPVEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHNGKSGFR 692
Cdd:PLN02952   365 LSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYL 444

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  693 LKPEFMRRTDKH---FDPFTETTvdgiVANTLSVKVLSG----------QFLSDKKVGTYVEIDMFGLPVDTRRKafKTK 759
Cdd:PLN02952   445 KKPDFLMKKGFHdevFDPKKKLP----VKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK--KTK 518

                          570       580       590       600       610       620       630
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591  760 TSQNNAvNPVWeDDPIVFKKVVlPSLSSLRISVYE----EGGKFIGHRILPVQAIRPGYHYICLRNERNQPL 827
Cdd:PLN02952   519 IIEDNW-YPAW-NEEFSFPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 584-698 1.54e-62

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: 208.25  E-value: 1.54e-62
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   584 SNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAGCH 663
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 2031723591   664 LVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEFM 698
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PH_14 pfam17787
PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...
 17-146 1.91e-56

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


Pssm-ID: 465506  Cd Length: 131  Bit Score: 191.44  E-value: 1.91e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   17 SVPENLKKGSKFMKWDDDSTTVTP-VTLKVDPQGLFLYWTDQNKETDLLEISHVKDARTGKYARNPKDTKLRELLDVGNQ 95
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591   96 GNRLENRMVTVVYGPDLVNISYLNFMAFQEDVAKEWTDALFSLATNLLAQN 146
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 720-839 8.74e-37

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 134.98  E-value: 8.74e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  720 TLSVKVLSGQFLSD------KKVGTYVEIDMFGLPVDTRRKaFKTKTSQNNAVNPVWeDDPIVFKkVVLPSLSSLRISVY 793
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVW-NETFEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2031723591  794 EEGG---KFIGHRILPVQAIRPGYHYICLRNERNQPLMLPALFVYIEVK 839
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
PLC-beta_C pfam08703
PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...
 1067-1216 8.37e-35

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


Pssm-ID: 462571 [Multi-domain]  Cd Length: 176  Bit Score: 131.34  E-value: 8.37e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1067 YYSEKYQKREHVKQLVQKLTEVAEECQANQLKKLRELCEKEKKELKKKMDKKRQEKITEAKSKDKNQMEEE--KTEIIRS 1144
Cdd:pfam08703   22 YEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQEAKKRTSDKAAQErlKKEINNS 101

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591 1145 YIHEVVQSIKRLEDAQCKRQEKLVDKHKEVRQQILDEKPKLQSDLDQEYQDKFKRLPLEIQEFVQDTLKGKF 1216
Cdd:pfam08703  102 HIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAEVRESVKSCLKEGF 173
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 223-304 4.21e-09

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: 54.56  E-value: 4.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  223 RPEIDIIFSEYGAKGRSyLTADQMTEFINSKQRDPRlneilyppVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSG 302
Cdd:pfam09279    8 REEIDEIFQEYSGDGQK-LSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCS 78


                   ..
gi 2031723591  303 DE 304
Cdd:pfam09279   79 PD 80
DUF1154 pfam06631
Protein of unknown function (DUF1154); This family represents a small conserved region of ...
 947-982 4.33e-06

Protein of unknown function (DUF1154); This family represents a small conserved region of unknown function within eukaryotic phospholipase C (EC:3.1.4.3). All members also contain pfam00387 and pfam00388.


Pssm-ID: 461969  Cd Length: 45  Bit Score: 44.56  E-value: 4.33e-06
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 2031723591  947 EVEAQTVEELRQQKAFVKLQKKHYKEMKELVKKHHK 982
Cdd:pfam06631    3 KFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSK 38
PTZ00121 PTZ00121
MAEBL; Provisional
 949-1198 2.68e-03

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 42.44  E-value: 2.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  949 EAQTVEELRQQKAFVKLQKKHYKEMKELVKKHH--KKTTDLIKEHTAKSSEFQNEYLRRRVLLEKSAKRDGKKRPESASP 1026
Cdd:PTZ00121  1481 EAKKADEAKKKAEEAKKKADEAKKAAEAKKKADeaKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKA 1560

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1027 EHPSSSIEQELTGLDAEMTQKLAELKEQQQQQLLNLRQEQYYSEKYQKREHVKQLVQKLTEVAEECQANQLKKLRELCEK 1106
Cdd:PTZ00121  1561 EEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKK 1640

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1107 EKKELKKKMDKKRQE----KITEAKSKDKNQMEEEKTEIIRSYIHEvvqsiKRLEDAQCKRQEKLVDKHKEVRQQILDEK 1182
Cdd:PTZ00121  1641 KEAEEKKKAEELKKAeeenKIKAAEEAKKAEEDKKKAEEAKKAEED-----EKKAAEALKKEAEEAKKAEELKKKEAEEK 1715

                          250
                   ....*....|....*.
gi 2031723591 1183 PKLQSDLDQEYQDKFK 1198
Cdd:PTZ00121  1716 KKAEELKKAEEENKIK 1731
 
Name Accession Description Interval E-value
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 316-686 3.65e-179

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: 527.68  E-value: 3.65e-179
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSpKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSS-KQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08591    154 ---------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKR 206

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08591    207 QLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 316-686 2.27e-156

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: 468.38  E-value: 2.27e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08625      1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEEEPFITHGFTMTTEIPFKDVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSPKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08625     81 IAESAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK------ 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08625        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08625    155 ---------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEFVEYNKK 207

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08625    208 QLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 316-686 2.73e-153

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: 460.32  E-value: 2.73e-153
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08623      1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSPKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08623     81 IAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK------ 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08623        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08623    155 ---------------------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKM 207

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08623    208 QLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 316-686 5.68e-149

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: 449.12  E-value: 5.68e-149
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08624      1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSPKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08624     81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08624        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasaTEEMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08624    155 ------------------------YEEMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKR 210

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08624    211 QMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 317-686 1.62e-130

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: 399.13  E-value: 1.62e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRstEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08558      2 QDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGP--DGEPVVYHGHTLTSKILFKDVIEAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEKYPlesgVPLPSPHDMIGKILIKNKKkghkssd 476
Cdd:cd08558     80 KEYAFVTSPYPVILSLENHC-SLEQQKKMAQILKEIFGDKLLTPPLDENP----VQLPSPEQLKGKILIKGKK------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08558        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasateemsnlvtyiqpvkfesfevakknnksFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08558    148 ---------------------------------------------------YHMSSFSETKALKLLKESPEEFVKYNKRQ 176

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08558    177 LSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 318-686 1.67e-125

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: 387.20  E-value: 1.67e-125
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  318 DMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPVITHGFTMTTEICFKEVIEAIA 397
Cdd:cd08626      3 DMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQAIK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  398 ECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkssdg 477
Cdd:cd08626     83 DTAFVTSDYPVILSFENHC-SKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKR-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  478 sakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseeee 557
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  558 dddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQL 637
Cdd:cd08626    154 -------------------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQM 208

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 2031723591  638 SRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08626    209 SRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 317-686 5.73e-106

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: 334.69  E-value: 5.73e-106
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSteEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08593      2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPD--GEPIIYHGHTLTSKILFKDVIQAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEkyplESGVPLPSPHDMIGKILIKNKkkghkssd 476
Cdd:cd08593     80 REYAFKVSPYPVILSLENHC-SVEQQKVMAQHLKSILGDKLLTQPLD----GVLTALPSPEELKGKILVKGK-------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsaKKKLSeqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08593    147 ---KLKLA------------------------------------------------------------------------ 151

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasatEEMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08593    152 ------------------------KELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQ 207

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08593    208 LSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 317-686 1.68e-93

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: 300.88  E-value: 1.68e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08597      2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDG--PNGEPVIYHGHTLTSKISFRSVIEAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEdlekYPLESGVPLPSPHDMIGKILIKNKKKGHkssd 476
Cdd:cd08597     80 NEYAFVASEYPLILCIENHC-SEKQQLVMAQYLKEIFGDKLYTE----PPNEGESYLPSPHDLKGKIIIKGKKLKR---- 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakKKLseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08597    151 ----RKL------------------------------------------------------------------------- 153

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasaTEEMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08597    154 -----------------------CKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKKF 210

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08597    211 LSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260
EFh_PI-PLCbeta1 cd16208
EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...
 155-304 2.38e-88

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: 282.15  E-value: 2.38e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADRKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSEYG 234
Cdd:cd16208      2 KAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEFG 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  235 AKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16208     82 AKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 317-686 8.48e-82

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: 267.37  E-value: 8.48e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPIIYHGHTLTSKIKFMDVLKTI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVDSPkQQAKMAEYCRSIFGDALLMEDLEKypleSGVPLPSPHDMIGKILIKNKKkghkssd 476
Cdd:cd08592     80 KEHAFVTSEYPVILSIENHCSLP-QQRNMAQAFKEVFGDMLLTQPVDR----NADQLPSPNQLKRKIIIKHKK------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08592        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasateemsnLVTyiqpvkfesfevakknnksfEMSSFVETKALEQLTKS-PVEFVEYNKR 635
Cdd:cd08592    148 -----------------------------LFY--------------------EMSSFPETKAEKYLNRQkGKIFLKYNRR 178

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08592    179 QLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 316-683 1.62e-80

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: 263.72  E-value: 1.62e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSteEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDD--GEPVVTHGYTLTSSVPFRDVCRA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDsPKQQAKMAEYCRSIFGDALLMEDLEkyPLESGvpLPSPHDMIGKILIKnkkkghkss 475
Cdd:cd08598     79 IKKYAFVTSPYPLILSLEVHCD-AEQQERMVEIMKETFGDLLVTEPLD--GLEDE--LPSPEELRGKILIK--------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08598        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasateemsnlvtyiqpvkfesfevAKKNNKSFE-MSSFVETKALEQLTKSPVEFVEYNK 634
Cdd:cd08598    145 ---------------------------------------------VKKESKTPNhIFSLSERSLLKLLKDKRAALDKHNR 179

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 2031723591  635 RQLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMF 683
Cdd:cd08598    180 RHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 317-686 1.81e-79

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: 261.89  E-value: 1.81e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVLRAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEkyplESGVPLPSPHDMIGKILIKNKKKghkssd 476
Cdd:cd08629     80 RDYAFKASPYPVILSLENHC-SLEQQRVMARHLRAILGPILLDQPLD----GVTTSLPSPEQLKGKILLKGKKL------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpveKIGKevteqkasgrksigdgeaeseee 556
Cdd:cd08629    149 -----------------------------------------------------KLVP----------------------- 152

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasateEMSNLVTYIQPVKFESFEVAKKNNKSF-EMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08629    153 -------------------------ELSDMIIYCKSVHFGGFSSPGTSGQAFyEMASFSESRALRLLQESGNGFVRHNVS 207

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08629    208 CLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 317-686 5.55e-79

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: 260.65  E-value: 5.55e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTeeEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNG--EPIVYHGHTFTSKILFKDVVAAV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLE-KYPlesgVPLPSPHDMIGKILIKNKkkghkss 475
Cdd:cd08631     80 AQYAFQVSDYPVILSLENHC-GVEQQQTMAQHLTEILGEKLLSTTLDgVLP----TQLPSPEELRGKILLKGK------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsaKKKLSeqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08631    148 ----KIRLS----------------------------------------------------------------------- 152

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasatEEMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08631    153 -------------------------PELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTW 207

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08631    208 QLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 317-686 7.12e-78

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: 257.56  E-value: 7.12e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08595      2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDG--ADNEPVVYHGYTLTSKILFKEVITTV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEKYPLESgvpLPSPHDMIGKILIKNKKKGHKSsd 476
Cdd:cd08595     80 EKYAFEKSDYPVVLSLENHC-STEQQEIMAHYLVSILGEKLLRAPIDDPATGE---LPSPEALKFKILVKNKKKIAKA-- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08595        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasateeMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08595    154 --------------------------LSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRF 207

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08595    208 ITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 317-686 1.99e-77

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: 256.10  E-value: 1.99e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08630      2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG--PGGEPVIYHGHTLTSKILFRDVIQAV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEKYPLESgvpLPSPHDMIGKILIKNKkkghkssd 476
Cdd:cd08630     80 RQHAFTASPYPVILSLENHC-GLEQQAAMARHLQTILGDMLVTQPLDSLNPEE---LPSPEELKGRVLVKGK-------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsaKKKLSeqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08630    148 ---KLQIS------------------------------------------------------------------------ 152

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasatEEMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08630    153 ------------------------PELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQ 208

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08630    209 LTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 317-686 7.61e-76

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: 251.69  E-value: 7.61e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDG--DDGMPIIYHGHTLTTKIPFKDVVEAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVDSPkQQAKMAEYCRSIFGDALLMEDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkssd 476
Cdd:cd08596     80 NRSAFITSDYPVILSIENHCSLQ-QQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasaTEEMSNLVTYIQPVKFESFEVAkknnKSFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08596    152 -----------------------APELSDLVIYCQAVKFPGLSTP----KCYHISSLNENAAKRLCRRYPQKLVQHTRCQ 204

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08596    205 LLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 316-686 3.92e-75

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: 249.57  E-value: 3.92e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  316 SEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEA 395
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAFKTSPYPVILSFENHVDSPkQQAKMAEYCRSIFGDALlmeDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkss 475
Cdd:cd08633     79 INKYAFIKNEYPVILSIENHCSVP-QQKKMAQYLTEILGDKL---DLSSVISNDCTRLPSPEILKGKILVKGKK------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  476 dgsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaesee 555
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  556 eedddedskkssmdegtagceasATEEMSNLVTYIQPVKFESFEVAKKNnkSFEMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08633    149 -----------------------LSRALSDLVKYTKSVRVHDIETEATS--SWQVSSFSETKAHQILQQKPAQYLRFNQR 203

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08633    204 QLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 319-467 5.53e-74

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


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 241.64  E-value: 5.53e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  319 MTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSteEEPVITHGFTMTTEICFKEVIEAIAE 398
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPD--GEPVVYHGYTLTSKIPFRDVLEAIKD 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2031723591  399 CAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEkyplESGVPLPSPHDMIGKILIKN 467
Cdd:pfam00388   79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLD----DDLTELPSPEDLKGKILIKG 142
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 317-686 2.20e-73

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: 243.56  E-value: 2.20e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRstEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08594      2 QDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGP--DGEPVVHHGYTLTSKILFRDVIETI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALlmeDLEKYPLESGVPLPSPHDMIGKILIKNKKkghkssd 476
Cdd:cd08594     80 NKYAFIKNEYPVILSIENHC-SVQQQKKMAQYLKEILGDKL---DLSSVISGDSKQLPSPQSLKGKILIKGKK------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08594        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasateemsnlvtyiqpvkfesfevakknnksFEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08594    149 ---------------------------------------------------WQVSSFSETRAHQIVQQKAAQFLRFNQRQ 177

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08594    178 LSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 318-686 1.67e-71

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: 240.24  E-value: 1.67e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  318 DMTQPLSHYFINSSHNTYLTAGQLA-----GNSSVEMYRQVLLAGCRCVELDCWKGRstEEEPVITHGFTMTtEICFKEV 392
Cdd:cd00137      3 PDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDGK--PEEPIIYHGPTFL-DIFLKEV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  393 IEAIAECAFKTSPYPVILSFENHVDS-PKQQAKMAEYCRSIFGDALLmedleKYPLESGVPLPSPHDMIGKILIKNKKKG 471
Cdd:cd00137     80 IEAIAQFLKKNPPETIIMSLKNEVDSmDSFQAKMAEYCRTIFGDMLL-----TPPLKPTVPLPSLEDLRGKILLLNKKNG 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  472 hkssdgsakkklseqasntysdsssvfepSSPGAASSNPEEPDtaqqsnidgsdkpvekigkevteqkasgrksigdgea 551
Cdd:cd00137    155 -----------------------------FSGPTGSSNDTGFV------------------------------------- 168

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  552 eseeeedddedskkssmdegtagceasateemsnlvtyiqpvkFESFEVAKknNKSFEMSSFVETKALE----QLTKSPV 627
Cdd:cd00137    169 -------------------------------------------SFEFSTQK--NRSYNISSQDEYKAYDdekvKLIKATV 203

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  628 EFVEYNKRQLSRIYPKGTRV---------DSSNYMPQVFWN---AGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd00137    204 QFVDYNKNQLSRNYPSGTSGgtawyyyamDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 317-686 2.95e-70

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: 235.72  E-value: 2.95e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDG--PDGKPIIYHGWTRTTKIKFDDVVQAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVDSpKQQAKMAEYCRSIFGDALLMEDLEKypleSGVPLPSPHDMIGKILIKNKKkghkssd 476
Cdd:cd08628     80 KDHAFVTSEYPVILSIEEHCSV-EQQRHMAKVFKEVFGDKLLMKPLEA----SADQLPSPTQLKEKIIIKHKK------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08628        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceaSATEEMSNLVTYIQPvkfESFEVAKKNNKSF-EMSSFVETKALEQLTKSPVEFVEYNKR 635
Cdd:cd08628    148 ---------------------LIAIELSDLVVYCKP---TSKTKDNLENPDFkEIRSFVETKAPSIIRQKPVQLLKYNRK 203

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08628    204 GLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254
EFh_PI-PLCbeta3 cd16210
EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...
 155-304 8.15e-67

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: 221.72  E-value: 8.15e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADRKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSEYG 234
Cdd:cd16210      2 KAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEIG 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  235 AKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16210     82 AKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151
PH_PLC_beta cd13361
Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...
 22-149 5.65e-65

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


Pssm-ID: 270167  Cd Length: 127  Bit Score: 215.51  E-value: 5.65e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   22 LKKGSKFMKWDDDSTTVTPVTLKVDPQGLFLYWTDQNKETDLLEISHVKDARTGKYARNPKDTKLRElLDVGNQGNRLEN 101
Cdd:cd13361      1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKERE-VNVGGSDEDLED 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2031723591  102 RMVTVVYGPDLVNISYLNFMAFQEDVAKEWTDALFSLATNLLAQNRSR 149
Cdd:cd13361     80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 317-686 2.89e-64

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: 218.75  E-value: 2.89e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08632      2 QDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKITFRDVIETI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALlmeDLEKYPLESGVPLPSPHDMIGKILIKNkkkghkssd 476
Cdd:cd08632     80 NKYAFVKNEFPVILSIENHC-SIQQQKKIAQYLKEIFGDKL---DLSSVLTGDPKQLPSPQLLKGKILVKG--------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakKKLSEQASNTYSDSSSVfepsspgaassnpeepdTAQQsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08632    147 ----KKLCRDLSDLVVYTNSV-----------------AAQD-------------------------------------- 167

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskksSMDEGTAGceasateemsnlvtyiqpvkfesfevakknnksfEMSSFVETKALEQLTKSPVEFVEYNKRQ 636
Cdd:cd08632    168 ----------IVDDGSTG----------------------------------NVLSFSETRAHQLVQQKAEQFMTYNQKQ 203

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 2031723591  637 LSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08632    204 LTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253
PLN02952 PLN02952
phosphoinositide phospholipase C
 217-827 1.91e-63

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 227.57  E-value: 1.91e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  217 LNNICPRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQrdprlNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGF 296
Cdd:PLN02952    31 ITEAEPPDDVKDVFCKF-SVGGGHMGADQLRRFLVLHQ-----DELDCTLAEAQRIVEEVINRRHHVTRYTRHGLNLDDF 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  297 KKYLSGDE-NGVIPPEkldLSEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrSTEEEP 375
Cdd:PLN02952   105 FHFLLYDDlNGPITPQ---VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPG-STKDEI 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  376 VITHGFTMTTEICFKEVIEAIAECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLmedlekYPLESG-VPLP 454
Cdd:PLN02952   181 LVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQFP 253

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  455 SPHDMIGKILIKNKK-KGHKSSDGSAKKKLSEqasntysdsssvfePSSPGAASSNPEepdtaqqsnidgsDKPVEKIGK 533
Cdd:PLN02952   254 SPESLKHRIIISTKPpKEYLESSGPIVIKKKN--------------NVSPSGRNSSEE-------------TEEAQTLES 306

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  534 EVTEQKASGRkSIGDGEAESEEEEDDDEDSKKSSMDEGT-AGCEASATEEMSNLVTYIqpvkfesfevakknnksfemsS 612
Cdd:PLN02952   307 MLFEQEADSR-SDSDQDDNKSGELQKPAYKRLITIHAGKpKGTLKDAMKVAVDKVRRL---------------------S 364

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  613 FVETKALEQLTKSPVEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHNGKSGFR 692
Cdd:PLN02952   365 LSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYL 444

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  693 LKPEFMRRTDKH---FDPFTETTvdgiVANTLSVKVLSG----------QFLSDKKVGTYVEIDMFGLPVDTRRKafKTK 759
Cdd:PLN02952   445 KKPDFLMKKGFHdevFDPKKKLP----VKKTLKVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK--KTK 518

                          570       580       590       600       610       620       630
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591  760 TSQNNAvNPVWeDDPIVFKKVVlPSLSSLRISVYE----EGGKFIGHRILPVQAIRPGYHYICLRNERNQPL 827
Cdd:PLN02952   519 IIEDNW-YPAW-NEEFSFPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 584-698 1.54e-62

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: 208.25  E-value: 1.54e-62
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   584 SNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETKALEQLTKSPVEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAGCH 663
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 2031723591   664 LVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEFM 698
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 154-304 4.95e-62

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: 208.25  E-value: 4.95e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  154 HKVYTKLKLQMNQDARIPVKNIFRMFSAD--RKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFS 231
Cdd:cd16200      1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDkkRKRVLKALKALGLPDGKNDEIDPEDFTFEKFFKLYNKLCPRPDIDEIFK 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2031723591  232 EYGAKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16200     81 ELGGKRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153
EFh_PI-PLCbeta2 cd16209
EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...
 155-304 3.45e-61

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


Pssm-ID: 320039  Cd Length: 151  Bit Score: 205.88  E-value: 3.45e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADRKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSEYG 234
Cdd:cd16209      2 KIYVKLKMQLNSEGKIPVKNFFQMFPADRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSYH 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  235 AKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16209     82 AKAKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 317-686 4.91e-60

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: 205.65  E-value: 4.91e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  317 EDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGrsTEEEPVITHGFTMTTEICFKEVIEAI 396
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  397 AECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEKypleSGVPLPSPHDMIGKILIKNKKkghkssd 476
Cdd:cd08627     80 KEHAFVTSEYPIILSIEDHC-SIVQQRNMAQHFKKVFGDMLLTKPVDI----NADGLPSPNQLKRKILIKHKK------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  477 gsakkklseqasnTYSDsssvfepsspgaassnpeepdtaqqsnidgsdkpvekigkevteqkasgrksigdgeaeseee 556
Cdd:cd08627    148 -------------LYRD--------------------------------------------------------------- 151

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  557 edddedskkssmdegtagceasateemsnlvtyiqpvkfesfevakknnksfeMSSFVETKALEQLTKSP-VEFVEYNKR 635
Cdd:cd08627    152 -----------------------------------------------------MSSFPETKAEKYVNRSKgKKFLQYNRR 178

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591  636 QLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08627    179 QLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 583-697 9.37e-60

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 199.99  E-value: 9.37e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  583 MSNLVTYIQPVKFESFEvaKKNNKSF-EMSSFVETKALEQLTKSPVEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAG 661
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFS--TPESKTPnHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCG 78

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 2031723591  662 CHLVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEF 697
Cdd:pfam00387   79 VQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 155-304 2.50e-59

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: 200.61  E-value: 2.50e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSA---DRKRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFS 231
Cdd:cd16213      2 KAYTKLTLQTDKEGKIPVKNIVKMFAQhkdDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIFD 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2031723591  232 EYGAKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16213     82 ELGAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154
PLN02228 PLN02228
Phosphoinositide phospholipase C
 222-813 3.20e-59

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 214.51  E-value: 3.20e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  222 PRPEIDIIFSEYGAKGRsyLTADQMTEFINSKQRDpRLNEILYppvkpeqVQQLVEKYEPNVTLAKRGHISIDGFKKYLS 301
Cdd:PLN02228    22 PPVSIKRLFEAYSRNGK--MSFDELLRFVSEVQGE-RHAGLDY-------VQDIFHSVKHHNVFHHHGLVHLNAFYRYLF 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  302 GDENGVIPPEKlDLSEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSTEEEPViTHGF 381
Cdd:PLN02228    92 SDTNSPLPMSG-QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAEV-RHGR 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  382 TMTTEICFKEVIEAIAECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLmedleKYPLESGVPLPSPHDMIG 461
Cdd:PLN02228   170 TLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL-PPNLQAQVAKMLTKTFRGMLF-----RCTSESTKHFPSPEELKN 243

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  462 KILIKNKkkghkssdgSAKKKLSEQASNTysdsssvfepsspgaaSSNPEEPDTAQQSNIDGSDKPVEKIGKEvtEQKAS 541
Cdd:PLN02228   244 KILISTK---------PPKEYLESKTVQT----------------TRTPTVKETSWKRVADAENKILEEYKDE--ESEAV 296

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  542 GRKSIGDGEAeseeeedddedskkssmdegtAGCEASATEEMSNlvtyiQPvkfesfevakknNKSFEMSsfVETKALEQ 621
Cdd:PLN02228   297 GYRDLIAIHA---------------------ANCKDPLKDCLSD-----DP------------EKPIRVS--MDEQWLET 336

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  622 LTKSP-VEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEFMRR 700
Cdd:PLN02228   337 MVRTRgTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLD 416

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  701 TDKHFDPFTETTVDgivaNTLSVKVLSGQ----------FLSDKKVGTYVEIDMFGLPVDTrrKAFKTKTSQNNAVnPVW 770
Cdd:PLN02228   417 EHTLFDPCKRLPIK----TTLKVKIYTGEgwdldfhlthFDQYSPPDFFVKIGIAGVPRDT--VSYRTETAVDQWF-PIW 489

                          570       580       590       600
                   ....*....|....*....|....*....|....*....|....*..
gi 2031723591  771 EDDPIVFKKVVlPSLSSLRISV--YEEGGK--FIGHRILPVQAIRPG 813
Cdd:PLN02228   490 GNDEFLFQLRV-PELALLWFKVqdYDNDTQndFAGQTCLPLPELKSG 535
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 319-468 4.56e-59

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: 199.43  E-value: 4.56e-59
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   319 MTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSteEEPVITHGFTMTTEICFKEVIEAIAE 398
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPD--GEPVIYHGHTFTLPIKLSEVLEAIKD 78

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   399 CAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEkyplESGVPLPSPHDMIGKILIKNK 468
Cdd:smart00148   79 FAFVTSPYPVILSLENHC-SPDQQAKMAQMFKEIFGDMLYTPPLT----SSLEVLPSPEQLRGKILLKVR 143
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 224-837 2.23e-58

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 212.58  E-value: 2.23e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  224 PEIDIIFSEYGAKGrsYLTADQMTEFINSKQRDPRLNEilyppvkpEQVQQLVEKYEpnvTLAKRGHISIDGFKKYLSGD 303
Cdd:PLN02222    25 REIKTIFEKYSENG--VMTVDHLHRFLIDVQKQDKATR--------EDAQSIINSAS---SLLHRNGLHLDAFFKYLFGD 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  304 ENgviPPEKL-DLSEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKgRSTEEEPVITHGFT 382
Cdd:PLN02222    92 NN---PPLALhEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWP-NSDKDDIDVLHGMT 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  383 MTTEICFKEVIEAIAECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEkyplESGVPLPSPHDMIGK 462
Cdd:PLN02222   168 LTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHL-TPDLQSKVAEMVTEIFGEILFTPPVG----ESLKEFPSPNSLKKR 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  463 ILIKNKKkghkssdgsakkklseqasntysdsssvfepsspgaassnPEEPDtaqqsniDGSDKPVEKIGKEVTEQKASG 542
Cdd:PLN02222   243 IIISTKP----------------------------------------PKEYK-------EGKDDEVVQKGKDLGDEEVWG 275

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  543 RKSIGDGEAESEEEEDDDEDSKKSSMDEGTAGCEASATEEMSNLVTyIQPVK-----FESFEVAKKNNKSFEMSSFVETK 617
Cdd:PLN02222   276 REVPSFIQRNKSVDKNDSNGDDDDDDDDGEDKSKKNAPPQYKHLIA-IHAGKpkggiTECLKVDPDKVRRLSLSEEQLEK 354

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  618 ALEQLTKSPVEFVEYNkrqLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEF 697
Cdd:PLN02222   355 AAEKYAKQIVRFTQHN---LLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDL 431

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  698 MRRTDKH---FDPftETTVDgiVANTLSVKVLSGQ----------FLSDKKVGTYVEIDMFGLPVDTRRKafKTKTSQNN 764
Cdd:PLN02222   432 LLKSGSDsdiFDP--KATLP--VKTTLRVTIYMGEgwyfdfrhthFDQYSPPDFYTRVGIAGVPGDTVMK--KTKTLEDN 505

                          570       580       590       600       610       620       630
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2031723591  765 AVnPVWEDdpiVFK-KVVLPSLSSLRISVYE----EGGKFIGHRILPVQAIRPGYHYICLRNERNQPLMLPALFVYIE 837
Cdd:PLN02222   506 WI-PAWDE---VFEfPLTVPELALLRLEVHEydmsEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKVE 579
PH_14 pfam17787
PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...
 17-146 1.91e-56

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


Pssm-ID: 465506  Cd Length: 131  Bit Score: 191.44  E-value: 1.91e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   17 SVPENLKKGSKFMKWDDDSTTVTP-VTLKVDPQGLFLYWTDQNKETDLLEISHVKDARTGKYARNPKDTKLRELLDVGNQ 95
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2031723591   96 GNRLENRMVTVVYGPDLVNISYLNFMAFQEDVAKEWTDALFSLATNLLAQN 146
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 318-686 2.08e-53

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


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 186.42  E-value: 2.08e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  318 DMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKGRSteEEPVITHGFTMTTEICFKEVIEAIA 397
Cdd:cd08599      3 DMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGR--GDICVLHGGTLTKPVKFEDCIKAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  398 ECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDLEKYPLEsgvpLPSPHDMIGKILIknkkkghkssdg 477
Cdd:cd08599     81 ENAFTASEYPVIITLENHL-SPELQAKAAQILRETLGDKLFYPDSEDLPEE----FPSPEELKGKILI------------ 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  478 sakkklseqasntysdsssvfepsspgaassnpeepdtaqqsnidgSDKPvekigkevteqkasgrKSIGdgeaeseeee 557
Cdd:cd08599    144 ----------------------------------------------SDKP----------------PVIR---------- 151

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  558 dddedskkssmdegtagceASATEemsnlvtyiqpvkfesfevaKKNNKSFEMSsfvetkaleqltkSPVEFVEYNKRQL 637
Cdd:cd08599    152 -------------------NSLSE--------------------TQLKKVIEGE-------------HPTDLIEFTQKNL 179

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 2031723591  638 SRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHN 686
Cdd:cd08599    180 LRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 222-823 1.02e-51

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 193.00  E-value: 1.02e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  222 PRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQR---DPRLNEilyppvkPEQVQQLVEKYEPNVTLAKRGHISIDGFKK 298
Cdd:PLN02230    27 PVADVRDLFEKY-ADGDAHMSPEQLQKLMAEEGGgegETSLEE-------AERIVDEVLRRKHHIAKFTRRNLTLDDFNY 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  299 YL-SGDENgviPPEKLDLSEDMTQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLAGCRCVELDCWKgRSTeEEPVI 377
Cdd:PLN02230    99 YLfSTDLN---PPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWP-RGT-DDVCV 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  378 THGFTMTTEICFKEVIEAIAECAFKTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDlekypLESGVPLPSPH 457
Cdd:PLN02230   174 KHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHL-TPKLQFKVAKMITQTFGDMLYYHD-----SEGCQEFPSPE 247

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  458 DMIGKILIKNKKKGHKSSDGSAKKKlseqasntysDSSSVFEPSSPGAASSNPEEPdTAQQSNIDGSDKPVEKIGKEVTE 537
Cdd:PLN02230   248 ELKEKILISTKPPKEYLEANDAKEK----------DNGEKGKDSDEDVWGKEPEDL-ISTQSDLDKVTSSVNDLNQDDEE 316

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  538 QKASgrksigdgeaeseeeedddedskkssmdEGTAGCEASATEEMSNLVTYIQPVKFESFEVAKKNNKSFEMSSFVETK 617
Cdd:PLN02230   317 RGSC----------------------------ESDTSCQLQAPEYKRLIAIHAGKPKGGLRMALKVDPNKIRRLSLSEQL 368

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  618 ALEQLTKSPVEFVEYNKRQLSRIYPKGTRVDSSNYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEF 697
Cdd:PLN02230   369 LEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDF 448

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  698 MRRTDKHFDPFTETTvDGIVANTLSVKVLSG----------QFLSDKKVGTYVEIDMFGLPVDTRRKafKTKTsQNNAVN 767
Cdd:PLN02230   449 LMDAGPNGQDFYPKD-NSCPKKTLKVKVCMGdgwlldfkktHFDSYSPPDFFVRVGIAGAPVDEVME--KTKI-EYDTWT 524

                          570       580       590       600       610       620
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  768 PVWEDDPIVfkKVVLPSLSSLRISVYE----EGGKFIGHRILPVQAIRPGYHYICLRNER 823
Cdd:PLN02230   525 PIWNKEFIF--PLAVPELALLRVEVHEhdinEKDDFGGQTCLPVSEIRQGIHAVPLFNRK 582
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 155-304 1.44e-43

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: 155.27  E-value: 1.44e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADR--KRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSE 232
Cdd:cd16211      2 KHWMRLCFLVNPNGKIPVRSITRTFASGKteKIVFQSLKELGLPSGKNDEIEPEAFTFEKFYELYHKICPRTDIEELFKK 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591  233 YGAKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16211     82 INGDKKDYLTVDQLISFLNEHQRDPRLNEILFPFYDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 720-839 8.74e-37

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 134.98  E-value: 8.74e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  720 TLSVKVLSGQFLSD------KKVGTYVEIDMFGLPVDTRRKaFKTKTSQNNAVNPVWeDDPIVFKkVVLPSLSSLRISVY 793
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVW-NETFEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 2031723591  794 EEGG---KFIGHRILPVQAIRPGYHYICLRNERNQPLMLPALFVYIEVK 839
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128
PLC-beta_C pfam08703
PLC-beta C terminal; This domain corresponds to the alpha helical C terminal domain of ...
 1067-1216 8.37e-35

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


Pssm-ID: 462571 [Multi-domain]  Cd Length: 176  Bit Score: 131.34  E-value: 8.37e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1067 YYSEKYQKREHVKQLVQKLTEVAEECQANQLKKLRELCEKEKKELKKKMDKKRQEKITEAKSKDKNQMEEE--KTEIIRS 1144
Cdd:pfam08703   22 YEQEKKRKEQHLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLESIQEAKKRTSDKAAQErlKKEINNS 101

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591 1145 YIHEVVQSIKRLEDAQCKRQEKLVDKHKEVRQQILDEKPKLQSDLDQEYQDKFKRLPLEIQEFVQDTLKGKF 1216
Cdd:pfam08703  102 HIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQIKEEEPQLQAELNAEYEEKLKGLPAEVRESVKSCLKEGF 173
EFh_NorpA_like cd16212
EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...
 155-304 2.33e-33

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: 126.12  E-value: 2.33e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  155 KVYTKLKLQMNQDARIPVKNIFRMFSADR--KRVETALDACGLPSGRNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSE 232
Cdd:cd16212      2 KHWMRLGFMVDSGGKIPVKHIARTFASGKteKLVYQCLAEMGLPSGKGDSIEKEDFTFEKFYALYHKICPRNDIEELFTS 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2031723591  233 YGAKGRSYLTADQMTEFINSKQRDPRLNEILYPPVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16212     82 ITKGKGEHISLAQLINFMNDKQRDPRLNEILYPLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153
PLN02223 PLN02223
phosphoinositide phospholipase C
 318-825 1.23e-25

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 113.19  E-value: 1.23e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  318 DMTQPLSHYFINSSHNTYLTAGQLAGNS-SVEMYRQVLLAGCRCVELDCWK-GRSTeeePVITHGFTMTTEICFKEVIEA 395
Cdd:PLN02223   107 DMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLPdGKDG---ICVRPKWNFEKPLELQECLDA 183

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  396 IAECAF-KTSPYPVILSFENHVdSPKQQAKMAEYCRSIFGDALLMEDlekyPLESGVPLPSPHDMIGKILIKNKKKGH-- 472
Cdd:PLN02223   184 IKEHAFtKCRSYPLIITFKDGL-KPDLQSKATQMIDQTFGDMVYHED----PQHSLEEFPSPAELQNKILISRRPPKEll 258

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  473 --KSSDGSAKKKLSEQASNTYSDsssvfePSSPGAASSNPEEPDTAQQSNIDGSDKPVEkigkevteqkasgrksigdge 550
Cdd:PLN02223   259 yaKADDGGVGVRNELEIQEGPAD------KNYQSLVGFHAVEPRGMLQKALTGKADDIQ--------------------- 311

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  551 aeseeeedddedskkssmdegtagceasateemsnlvtyiQPVKFESFEVakknnkSFEMSSFVETKAleqltkspvefv 630
Cdd:PLN02223   312 ----------------------------------------QPGWYERDII------SFTQKKFLRTRP------------ 333

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  631 eynKRQLSRIYPKgtrvdssnYMPQVFWNAGCHLVALNFQTLDLAMQLNMGMFEHNGKSGFRLKPEFMRRTDKH--FDPf 708
Cdd:PLN02223   334 ---KKKNLLINAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNAGPSgvFYP- 401

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  709 tetTVDGIVANTLSVKVLSGQ-FLSD--KKVGT------YVEIDMFGLPVDtrRKAFKTkTSQNNAVNPVWEDD---PIV 776
Cdd:PLN02223   402 ---TENPVVVKILKVKIYMGDgWIVDfkKRIGRlskpdlYVRISIAGVPHD--EKIMKT-TVKNNEWKPTWGEEftfPLT 475

                          490       500       510       520       530
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2031723591  777 FkkvvlPSLSSLRISVYE----EGGKFIGHRILPVQAIRPGYHYICLRNERNQ 825
Cdd:PLN02223   476 Y-----PDLALISFEVYDyevsTADAFCGQTCLPVSELIEGIRAVPLYDERGK 523
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 329-438 7.59e-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: 94.04  E-value: 7.59e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  329 NSSHNTYLTAGQLagnSSVEMYRQVLLAGCRCVELDCWKGRstEEEPVITHGFTMT------TEICFKEVIEAIAECAFk 402
Cdd:cd08555      1 VLSHRGYSQNGQE---NTLEAFYRALDAGARGLELDVRLTK--DGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK- 74

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2031723591  403 TSPYPVILSFENHVDS---PKQQAKMAEYCRSIFGDALL 438
Cdd:cd08555     75 NPDYTIILSLEIKQDSpeyDEFLAKVLKELRVYFDYDLR 113
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 22-138 9.71e-12

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


Pssm-ID: 269952  Cd Length: 108  Bit Score: 62.72  E-value: 9.71e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   22 LKKGSKFMKWDDDSTTvTPVTLKVDPQGLFLYWTDQNK--ETDLLEISHVKDARTGKYARNPKDTKlrelldvgNQGNRL 99
Cdd:cd01248      1 LQQGTLLLKYREGSKP-KERTFYLDPDGTRITWESSKKksEKKSIDISDIKEIRPGKDTDGFKRKK--------KSNKPK 71

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2031723591  100 ENRMVTVVYGPdlvNISYLNFMAFQEDVAKEWTDALFSL 138
Cdd:cd01248     72 EERCFSIIYGS---NNKTLDLVAPSEDEANLWVEGLRAL 107
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 159-304 1.04e-10

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: 60.70  E-value: 1.04e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  159 KLKLQMNqdARIPVKNIFRMFSADRKRVETALDAcglpsgrndsipqENFTTevfqaFLNNICPRPEIDIIFSEYGAKGR 238
Cdd:cd16202     24 KLLKKLN--VKVDKDYAKKLFQEADTSGEDVLDE-------------EEFVQ-----FYNRLTKRPEIEELFKKYSGDDE 83

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2031723591  239 sYLTADQMTEFINSKQRDPRlneilyppVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16202     84 -ALTVEELRRFLQEEQKVKD--------VTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 157-304 5.45e-10

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: 58.83  E-value: 5.45e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  157 YTKLKLQMNQDARIPVKNIFRM-----FSADRKRVETALDACGlpSGRNDSIpqenfTTEVFQAFLNNICPRPEIDIIFS 231
Cdd:cd15898      4 RQWIKADKDGDGKLSLKEIKKLlkrlnIRVSEKELKKLFKEVD--TNGDGTL-----TFDEFEELYKSLTERPELEPIFK 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2031723591  232 EYGAKGRSYLTADQMTEFinskqrdprLNEILYPPVKPEQVQQLVEKYEPNVtlaKRGHISIDGFKKYLSGDE 304
Cdd:cd15898     77 KYAGTNRDYMTLEEFIRF---------LREEQGENVSEEECEELIEKYEPER---ENRQLSFEGFTNFLLSPE 137
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 214-304 1.59e-09

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: 57.44  E-value: 1.59e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  214 QAFLNNICPRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQRDPrlneilyppVKPEQVQQLVEKYEPNVTLAKRGHISI 293
Cdd:cd16217     59 EEFYKLLTKREEIDVIFGEY-AKSDGTMSRNNLLNFLQEEQREE---------VAPAYALSLIEKYEPDETAKAQRQMTK 128

                           90
                   ....*....|.
gi 2031723591  294 DGFKKYLSGDE 304
Cdd:cd16217    129 DGFLMYLLSPE 139
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 223-304 4.21e-09

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: 54.56  E-value: 4.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  223 RPEIDIIFSEYGAKGRSyLTADQMTEFINSKQRDPRlneilyppVKPEQVQQLVEKYEPNVTLAKRGHISIDGFKKYLSG 302
Cdd:pfam09279    8 REEIDEIFQEYSGDGQK-LSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCS 78


                   ..
gi 2031723591  303 DE 304
Cdd:pfam09279   79 PD 80
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 209-304 5.34e-09

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: 56.06  E-value: 5.34e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  209 TTEVFQAFLNNICPRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQRDPRLNEilyppvkpEQVQQLVEKYEPNVTLAKR 288
Cdd:cd16206     57 SSDEFVELFKELATRPEIYFLLVRY-ASNKDYLTVDDLMLFLEAEQGMTGVTK--------EKCLEIINKYEPSEEGREK 127

                           90
                   ....*....|....*.
gi 2031723591  289 GHISIDGFKKYLSGDE 304
Cdd:cd16206    128 GQLGIDGFTRYLLSEE 143
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 211-300 1.68e-07

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: 51.61  E-value: 1.68e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  211 EVFQAFLNNICPRPEIDIIFSEYGAKGrSYLTADQMTEFINSKQRdprLNEilyppVKPEQVQQLVEKYEPNVTLAKRGH 290
Cdd:cd16205     57 EEFCAFYKMMSTRRELYLLLLSYSNKK-DYLTLEDLARFLEVEQK---MTN-----VTLEYCLDIIEKFEPSEENKKNGL 127

                           90
                   ....*....|
gi 2031723591  291 ISIDGFKKYL 300
Cdd:cd16205    128 LGIDGFTNYM 137
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 204-304 4.30e-06

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: 47.59  E-value: 4.30e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  204 PQENFTTEVFQAFLNNICPRPEIDIIFSEYGAKgRSYLTADQMTEFINSKQRDPRLNEilyppvkpEQVQQLVEKYEPNV 283
Cdd:cd16223     52 GGTEVTKEEFIEVFHELCTRPEIYFLLVQFSSN-KEFLDTKDLMMFLEAEQGMAHVTE--------EISLDIIHKYEPSK 122

                           90       100
                   ....*....|....*....|.
gi 2031723591  284 TLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16223    123 EGQEKGWLSLDGFTNYLMSPE 143
DUF1154 pfam06631
Protein of unknown function (DUF1154); This family represents a small conserved region of ...
 947-982 4.33e-06

Protein of unknown function (DUF1154); This family represents a small conserved region of unknown function within eukaryotic phospholipase C (EC:3.1.4.3). All members also contain pfam00387 and pfam00388.


Pssm-ID: 461969  Cd Length: 45  Bit Score: 44.56  E-value: 4.33e-06
                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 2031723591  947 EVEAQTVEELRQQKAFVKLQKKHYKEMKELVKKHHK 982
Cdd:pfam06631    3 KFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSK 38
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 211-304 4.83e-06

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


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 47.53  E-value: 4.83e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  211 EVFQAFLNNICPRPEIDIIFSEYGAKGRSyLTADQMTEFINSKQRDPRLNEilyppvkpEQVQQLVEKYEPNVTLAKRGH 290
Cdd:cd16219     56 EEFVLFYKALTQREDVLKIFQDFSADGQK-LTLLEFVDFLQQEQLERENTE--------ELAMELIDRYEPSDTAKKLHA 126

                           90
                   ....*....|....
gi 2031723591  291 ISIDGFKKYLSGDE 304
Cdd:cd16219    127 LSIDGFLMYLCSPE 140
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 199-304 5.78e-06

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: 47.50  E-value: 5.78e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  199 RNDSIPQENFTTEVFQAFLNNICPRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQRDPRLNEILyppvkpeqVQQLVEK 278
Cdd:cd16204     46 KNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTY-SENRKILSAPNLVGFLKKEQFQDEADETI--------ASELIAK 116

                           90       100
                   ....*....|....*....|....*.
gi 2031723591  279 YEPNVTLAKRGHISIDGFKKYLSGDE 304
Cdd:cd16204    117 YEPIEEVRKRKQMSFEGFIRYMTSED 142
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 213-301 1.82e-04

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: 43.01  E-value: 1.82e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  213 FQAFLNNICPRPEIDIIFSEYGAKGRSYLTADQMTEFINSKQRDprlneilypPVKPEQVQQLVEKYEPNVTLAKRGHIS 292
Cdd:cd16207     60 FQEFVKLLKRRKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVQKE---------DVDRETWEKIFEKFARRIDDSDSLTMT 130


                   ....*....
gi 2031723591  293 IDGFKKYLS 301
Cdd:cd16207    131 LEGFTSFLL 139
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 216-304 3.42e-04

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


Pssm-ID: 320048 [Multi-domain]  Cd Length: 138  Bit Score: 42.04  E-value: 3.42e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  216 FLNNICPRPEIDIIFSEYGAKGRsYLTADQMTEFINSKQRDPRLneilyppvkpEQVQQLVEKYEPNVTLAKRGHISIDG 295
Cdd:cd16218     61 FCRRLMQRPELEEIFHQYSGEDC-VLSAEELREFLKDQGEDASL----------VHAKELIQTYELNEKAKQHQLMTLDG 129


                   ....*....
gi 2031723591  296 FKKYLSGDE 304
Cdd:cd16218    130 FTMYMLSKD 138
PH_PLC_fungal cd13360
Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...
 40-138 4.34e-04

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: 41.40  E-value: 4.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591   40 PVTLKVDPQGLFLYWtDQNKETDLLEISHVKDARTGKYARNpkdtkLRELLDVGNQgnrLENRMVTVVYG-PDLVNISYL 118
Cdd:cd13360     17 RILFKLDPESGKITW-DSKKPSKSLYIDDIKEIRTGEDARN-----YREEFGISEE---FEDRWITIIYFvPKKNKLKTL 87

                           90       100
                   ....*....|....*....|
gi 2031723591  119 NFMAFQEDVAKEWTDALFSL 138
Cdd:cd13360     88 HLIADTEEDFKLWTTTLEGL 107
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 209-304 1.88e-03

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


Pssm-ID: 320052 [Multi-domain]  Cd Length: 143  Bit Score: 40.23  E-value: 1.88e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  209 TTEVFQAFLNNICPRPEIDIIFSEYgAKGRSYLTADQMTEFINSKQRDPRLNEilyppvkpEQVQQLVEKYEPNVTLAKR 288
Cdd:cd16222     57 TEEEFCEAYSELCTRPEVYFLLVQI-SKNKEYLDAKDLMLFLEAEQGMTHITE--------EMCLDIIRRYEPSQEGRLK 127

                           90
                   ....*....|....*.
gi 2031723591  289 GHISIDGFKKYLSGDE 304
Cdd:cd16222    128 GFLGIDGFTQYLLSSE 143
PTZ00121 PTZ00121
MAEBL; Provisional
 949-1198 2.68e-03

MAEBL; Provisional


Pssm-ID: 173412 [Multi-domain]  Cd Length: 2084  Bit Score: 42.44  E-value: 2.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591  949 EAQTVEELRQQKAFVKLQKKHYKEMKELVKKHH--KKTTDLIKEHTAKSSEFQNEYLRRRVLLEKSAKRDGKKRPESASP 1026
Cdd:PTZ00121  1481 EAKKADEAKKKAEEAKKKADEAKKAAEAKKKADeaKKAEEAKKADEAKKAEEAKKADEAKKAEEKKKADELKKAEELKKA 1560

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1027 EHPSSSIEQELTGLDAEMTQKLAELKEQQQQQLLNLRQEQYYSEKYQKREHVKQLVQKLTEVAEECQANQLKKLRELCEK 1106
Cdd:PTZ00121  1561 EEKKKAEEAKKAEEDKNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEKKKVEQLKK 1640

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2031723591 1107 EKKELKKKMDKKRQE----KITEAKSKDKNQMEEEKTEIIRSYIHEvvqsiKRLEDAQCKRQEKLVDKHKEVRQQILDEK 1182
Cdd:PTZ00121  1641 KEAEEKKKAEELKKAeeenKIKAAEEAKKAEEDKKKAEEAKKAEED-----EKKAAEALKKEAEEAKKAEELKKKEAEEK 1715

                          250
                   ....*....|....*.
gi 2031723591 1183 PKLQSDLDQEYQDKFK 1198
Cdd:PTZ00121  1716 KKAEELKKAEEENKIK 1731
 
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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