NCBI Conserved Domain Search

Conserved domains on [gi|922580920|ref|NP_001300030|]

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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase [Caenorhabditis elegans]

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 ...

311-727

3.96e-171

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: 507.65 E-value: 3.96e-171

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGEnKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGE-DEEPIITHGKTMCTEILFKDVIE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08591    80 AIAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08591   154 -------------------------------------------------------------------------LSSLVNY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08591   161 IQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNF 240

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08591   241 QTPDLPMQLNQGKFEYN 257

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

147-299

2.01e-64

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: 215.19 E-value: 2.01e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKeREELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16200     1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKKRKRVLKALKALGLPDGK-NDEIDPEDFTFEKFFKLYNKLCPRPDIDEIF 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLSG-QKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16200    80 KELGGkRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

17-142

5.80e-45

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: 158.50 E-value: 5.80e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   17 LLHGSVFDRYDDEStCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGGLPKDGRIMFELE--QRGASETIAE 94
Cdd:cd13361     1 LLKGSKFDKWDEDS-SLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREvnVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 922580920   95 RTIWITHGQDLVNVQSFFLVAESVELAKTCRAGINDILKSSRIRHVCP 142
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

761-881

2.84e-41

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 148.07 E-value: 2.84e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  761 HCSVRVISGQFLSD------RKIGTYVEVEMYGLPTDTiRKEHKTKVIPGNGLNPVYNEdPFVFrKVVLPELAVLRFAVY 834
Cdd:cd00275     3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNE-TFEF-DVTVPELAFLRFVVY 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 922580920  835 DENGKQ---LGQRILPLDGLQAGYRHISLRSDTNQSFILSpVLFVQIVIK 881
Cdd:cd00275    80 DEDSGDddfLGQACLPLDSLRQGYRHVPLLDSKGEPLELS-TLFVHIDIT 128

DUF1154

pfam06631

Protein of unknown function (DUF1154); This family represents a small conserved region of ...

986-1030

2.32e-16

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: 73.83 E-value: 2.32e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 922580920   986 KFKVDPIEVDDLRRDKAFAKLLKRFQKELDDLRKKHQKQRDSIQK 1030
Cdd:pfam06631    1 DIKFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

PLC-beta_C super family

cl25592

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

1157-1296

4.60e-07

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: 51.22 E-value: 4.60e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  1157 EFELKKVQ--LKEQFDLLRKLMSEAQKNQMLALKLRLEAEGKDLKQTQTKKSMEdaKVIQLDKGIKTKAERDRRVKELNE 1234
Cdd:pfam08703   23 EQEKKRKEqhLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLE--SIQEAKKRTSDKAAQERLKKEINN 100

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 922580920  1235 KNLKMFVEERKRLAMKAQKHEEQLTKRHLDQLEQLdKDFHKALDAEVGNYKEEQLAAQPTSV 1296
Cdd:pfam08703  101 SHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQI-KEEEPQLQAELNAEYEEKLKGLPAEV 161

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

311-727

3.96e-171

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 507.65 E-value: 3.96e-171

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGEnKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGE-DEEPIITHGKTMCTEILFKDVIE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08591    80 AIAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08591   154 -------------------------------------------------------------------------LSSLVNY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08591   161 IQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNF 240

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08591   241 QTPDLPMQLNQGKFEYN 257

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

314-462

1.29e-72

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: 237.79 E-value: 1.29e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   314 MDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQIR 393
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG---PDGEPVVYHGYTLTSKIPFRDVLEAIK 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 922580920   394 DTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgVSLPSPNRLRKKILIKN 462
Cdd:pfam00388   78 DYAFVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDL----TELPSPEDLKGKILIKG 142

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

147-299

2.01e-64

Pssm-ID: 320030 [Multi-domain] Cd Length: 153 Bit Score: 215.19 E-value: 2.01e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKeREELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16200     1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKKRKRVLKALKALGLPDGK-NDEIDPEDFTFEKFFKLYNKLCPRPDIDEIF 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLSG-QKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16200    80 KELGGkRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

625-739

6.72e-61

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: 203.62 E-value: 6.72e-61

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    625 SSLVNYTHPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQ 704
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 922580920    705 MVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFL 739
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PLN02952

phosphoinositide phospholipase C

206-860

6.37e-56

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 205.62 E-value: 6.37e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  206 FEKFQRLY--NKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQrdprlNEILFPFFDSQRIV-ALLKKHENDIKYQE 282
Cdd:PLN02952   22 FNLFNRKFkiTEAEPPDDVKDVFCKFSVGGGHMGADQLRRFLVLHQ-----DELDCTLAEAQRIVeEVINRRHHVTRYTR 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  283 DGkMSGDGFLRFLMSDE-NPPVFldrIEMFMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCW 361
Cdd:PLN02952   97 HG-LNLDDFFHFLLYDDlNGPIT---PQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLW 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  362 DGTgeNKGEPIITHGKAMCTDVFFKDVLVQIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSkPFEDAP 441
Cdd:PLN02952  173 PGS--TKDEILVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYY-PESDSL 249

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  442 ldpgVSLPSPNRLRKKILIKNKRLKTDIERHQLDQFLREGKLDEEDElNETPEvvgEDSVSPPGDQRAHPEVEQPVSSSS 521
Cdd:PLN02952  250 ----VQFPSPESLKHRIIISTKPPKEYLESSGPIVIKKKNNVSPSGR-NSSEE---TEEAQTLESMLFEQEADSRSDSDQ 321

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  522 PATPSisgpppcatssgstssititttgcsTSSSGPSKHILGGEMPAKENDEAHPELKqnfIAKNlkgfgfSKKQPVLTK 601
Cdd:PLN02952  322 DDNKS-------------------------GELQKPAYKRLITIHAGKPKGTLKDAMK---VAVD------KVRRLSLSE 367

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  602 EEEERifaeyhytGATTNihpllsslvnythpvkfsGFDVaeannlhfhmssfsestglgylkqsapefVNYNKRQSSRI 681
Cdd:PLN02952  368 QELEK--------AATTN------------------GQDV-----------------------------VRFTQRNILRI 392

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  682 YPKGARVDSSNFLPQIFWNAGCQMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFLRRP---DRTFDPFSESPVDGVI 758
Cdd:PLN02952  393 YPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVFDPKKKLPVKKTL 472

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  759 aahcSVRVISG----------QFLSDRKIGTYVEVEMYGLPTDTIRKehKTKVIPGNgLNPVYNEDpFVFrKVVLPELAV 828
Cdd:PLN02952  473 ----KVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK--KTKIIEDN-WYPAWNEE-FSF-PLTVPELAL 543

                         650       660       670
                  ....*....|....*....|....*....|....*.
gi 922580920  829 LRFAV--YDENGKQL--GQRILPLDGLQAGYRHISL 860
Cdd:PLN02952  544 LRIEVreYDMSEKDDfgGQTCLPVSELRPGIRSVPL 579

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

17-142

5.80e-45

Pssm-ID: 270167 Cd Length: 127 Bit Score: 158.50 E-value: 5.80e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   17 LLHGSVFDRYDDEStCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGGLPKDGRIMFELE--QRGASETIAE 94
Cdd:cd13361     1 LLKGSKFDKWDEDS-SLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREvnVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 922580920   95 RTIWITHGQDLVNVQSFFLVAESVELAKTCRAGINDILKSSRIRHVCP 142
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

761-881

2.84e-41

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 148.07 E-value: 2.84e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  761 HCSVRVISGQFLSD------RKIGTYVEVEMYGLPTDTiRKEHKTKVIPGNGLNPVYNEdPFVFrKVVLPELAVLRFAVY 834
Cdd:cd00275     3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNE-TFEF-DVTVPELAFLRFVVY 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 922580920  835 DENGKQ---LGQRILPLDGLQAGYRHISLRSDTNQSFILSpVLFVQIVIK 881
Cdd:cd00275    80 DEDSGDddfLGQACLPLDSLRQGYRHVPLLDSKGEPLELS-TLFVHIDIT 128

PH_14

pfam17787

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

14-122

3.10e-17

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: 79.34 E-value: 3.10e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    14 IPELL-HGSVFDRYDDESTCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGG---LPKDGRIMFELEQRGAS 89
Cdd:pfam17787    2 VPEKLqKGELFIKWDEESTVAEPNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKfakIPKDPKLREVLSMGGSD 81

                           90       100       110
                   ....*....|....*....|....*....|...
gi 922580920    90 ETIAERTIWITHGQDLVNVQSFFLVAESVELAK 122
Cdd:pfam17787   82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAK 114

DUF1154

pfam06631

Protein of unknown function (DUF1154); This family represents a small conserved region of ...

986-1030

2.32e-16

Pssm-ID: 461969 Cd Length: 45 Bit Score: 73.83 E-value: 2.32e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 922580920   986 KFKVDPIEVDDLRRDKAFAKLLKRFQKELDDLRKKHQKQRDSIQK 1030
Cdd:pfam06631    1 DIKFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

764-860

3.02e-14

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 69.82 E-value: 3.02e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    764 VRVISGQFLSDRKIGT----YVEVEMYGLPtdtiRKEHKTKVIPGNgLNPVYNEDpFVFrKVVLPELAVLRFAVYDENG- 838
Cdd:smart00239    4 VKIISARNLPPKDKGGksdpYVKVSLDGDP----KEKKKTKVVKNT-LNPVWNET-FEF-EVPPPELAELEIEVYDKDRf 76

                            90       100
                    ....*....|....*....|....*
gi 922580920    839 ---KQLGQRILPLDGLQAGYRHISL 860
Cdd:smart00239   77 grdDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

763-857

1.82e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 53.48 E-value: 1.82e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   763 SVRVISGQFLSDRKIG----TYVEVEMYGLptdtiRKEHKTKVIPgNGLNPVYNEDpFVFrKVVLPELAVLRFAVYDENG 838
Cdd:pfam00168    4 TVTVIEAKNLPPKDGNgtsdPYVKVYLLDG-----KQKKKTKVVK-NTLNPVWNET-FTF-SVPDPENAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|...
gi 922580920   839 KQ----LGQRILPLDGLQAGYRH 857
Cdd:pfam00168   76 FGrddfIGEVRIPLSELDSGEGL 98

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

212-299

3.51e-07

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: 49.17 E-value: 3.51e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   212 LYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRlneilfpfFDSQRIVALLKKHENDIKYQEDGKMSGDGF 291
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKDGF 72


                   ....*...
gi 922580920   292 LRFLMSDE 299
Cdd:pfam09279   73 LMYLCSPD 80

PLC-beta_C

pfam08703

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

1157-1296

4.60e-07

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: 51.22 E-value: 4.60e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  1157 EFELKKVQ--LKEQFDLLRKLMSEAQKNQMLALKLRLEAEGKDLKQTQTKKSMEdaKVIQLDKGIKTKAERDRRVKELNE 1234
Cdd:pfam08703   23 EQEKKRKEqhLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLE--SIQEAKKRTSDKAAQERLKKEINN 100

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 922580920  1235 KNLKMFVEERKRLAMKAQKHEEQLTKRHLDQLEQLdKDFHKALDAEVGNYKEEQLAAQPTSV 1296
Cdd:pfam08703  101 SHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQI-KEEEPQLQAELNAEYEEKLKGLPAEV 161

PTZ00121

MAEBL; Provisional

1152-1289

8.69e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 47.06 E-value: 8.69e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920 1152 RHDEEEFELKKVQLKeqfdllRKLMSEAQKnqmlALKLRLEAEGKDLKQTQTKKSMEDA-KVIQLDKGI---KTKAERDR 1227
Cdd:PTZ00121 1653 KKAEEENKIKAAEEA------KKAEEDKKK----AEEAKKAEEDEKKAAEALKKEAEEAkKAEELKKKEaeeKKKAEELK 1722

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 922580920 1228 RVKELNE---KNLKMFVEERKRLAMKAQKHEEQltKRHLDQLEQLDKDFHKALDAEVGNYKEEQL 1289
Cdd:PTZ00121 1723 KAEEENKikaEEAKKEAEEDKKKAEEAKKDEEE--KKKIAHLKKEEEKKAEEIRKEKEAVIEEEL 1785

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

311-727

3.96e-171

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 507.65 E-value: 3.96e-171

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGEnKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGE-DEEPIITHGKTMCTEILFKDVIE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08591    80 AIAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08591   154 -------------------------------------------------------------------------LSSLVNY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08591   161 IQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNF 240

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08591   241 QTPDLPMQLNQGKFEYN 257

PI-PLCc_beta4

cd08626

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...

311-727

8.56e-162

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: 483.50 E-value: 8.56e-162

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGEnKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08626     1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGE-DQEPIITHGKAMCTDILFKDVIQ 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08626    80 AIKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKR------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08626       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08626   154 -------------------------------------------------------------------------LSSLVNY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08626   161 AQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNF 240

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08626   241 QTPDLGMQLNQGKFEYN 257

PI-PLCc_eukaryota

cd08558

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...

311-727

3.92e-115

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: 358.69 E-value: 3.92e-115

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08558     1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG---PDGEPVVYHGHTLTSKILFKDVIE 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgVSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08558    78 AIKEYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENP----VQLPSPEQLKGKILIKGKK------ 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08558       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihpllsslvny 630
Cdd:cd08558       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 thpvkfsgfdvaeannlhFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08558   148 ------------------YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNY 209

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08558   210 QTPDLPMQLNQGKFEQN 226

PI-PLCc_beta2

cd08624

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...

313-727

9.40e-98

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: 313.15 E-value: 9.40e-98

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGENKgEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08624     3 DMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDE-EPIITHGFTMTTEILFKDAIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHC-SKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKrlktdier 471
Cdd:cd08624    82 AESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNK-------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  472 hqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcs 551
Cdd:cd08624       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  552 tsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltKEEEerifaeyhytgattnihplLSSLVNYT 631
Cdd:cd08624   154 -------------------------------------------------KYEE-------------------MSSLVNYI 165

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  632 HPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQ 711
Cdd:cd08624   166 QPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQ 245

                         410
                  ....*....|....*.
gi 922580920  712 TPDVYMQLNMGKFEYN 727
Cdd:cd08624   246 TMDLPMQQNMALFEFN 261

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

313-727

7.69e-97

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: 310.45 E-value: 7.69e-97

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGENKgEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08625     3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEE-EPFITHGFTMTTEIPFKDVIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHC-SKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRlktdier 471
Cdd:cd08625    82 AESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  472 hqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcs 551
Cdd:cd08625       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  552 tsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNYT 631
Cdd:cd08625   155 ------------------------------------------------------------------------MSTLVNYI 162

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  632 HPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQ 711
Cdd:cd08625   163 EPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQ 242

                         410
                  ....*....|....*.
gi 922580920  712 TPDVYMQLNMGKFEYN 727
Cdd:cd08625   243 TLDLAMQLNMGVFEYN 258

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

311-727

2.19e-95

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 306.19 E-value: 2.19e-95

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08593     1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDG---PDGEPIIYHGHTLTSKILFKDVIQ 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEdaplDPGVSLPSPNRLRKKILIKNKRLKtdie 470
Cdd:cd08593    78 AIREYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLD----GVLTALPSPEELKGKILVKGKKLK---- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08593       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvLTKEeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08593   150 ------------------------------------------------LAKE---------------------LSDLVIY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08593   161 CKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNF 240

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08593   241 QTPGEEMDLNDGLFRQN 257

PI-PLCc_beta1

cd08623

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...

313-727

8.74e-85

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: 276.96 E-value: 8.74e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDG-TGENkgEPIITHGKAMCTDVFFKDVLVQ 391
Cdd:cd08623     3 DMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrTAEE--EPVITHGFTMTTEISFKEVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  392 IRDTAFARSDFPVVLSFENHC-SKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08623    81 IAECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08623       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08623   155 -------------------------------------------------------------------------MSNLVNY 161

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08623   162 IQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNF 241

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08623   242 QTVDLSMQINMGMYEYN 258

PI-PLCc_gamma

cd08592

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...

311-727

5.91e-81

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: 265.06 E-value: 5.91e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08592     1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGP---DGMPIIYHGHTLTSKIKFMDVLK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKpfedaPLDP-GVSLPSPNRLRKKILIKNKRLKTDi 469
Cdd:cd08592    78 TIKEHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQ-----PVDRnADQLPSPNQLKRKIIIKHKKLFYE- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  470 erhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttg 549
Cdd:cd08592       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  550 cstsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihpllsslvn 629
Cdd:cd08592       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  630 ythpvkfsgfdvaeannlhfhMSSFSESTGLGYL-KQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSL 708
Cdd:cd08592   152 ---------------------MSSFPETKAEKYLnRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVAL 210

                         410
                  ....*....|....*....
gi 922580920  709 NFQTPDVYMQLNMGKFEYN 727
Cdd:cd08592   211 NFQTPDKPMQLNQALFMLN 229

PI-PLCc_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

313-727

2.19e-76

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: 253.50 E-value: 2.19e-76

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08597     3 DMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDG---PNGEPVIYHGHTLTSKISFRSVIEAI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLlskpFEDAPLDPGVSLPSPNRLRKKILIKNKRLKTdierh 472
Cdd:cd08597    80 NEYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKL----YTEPPNEGESYLPSPHDLKGKIIIKGKKLKR----- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  473 qldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcst 552
Cdd:cd08597       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  553 sssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqPVLTKEeeerifaeyhytgattnihplLSSLVNYTH 632
Cdd:cd08597   151 --------------------------------------------RKLCKE---------------------LSDLVSLCK 165

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  633 PVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQT 712
Cdd:cd08597   166 SVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQT 245

                         410
                  ....*....|....*
gi 922580920  713 PDVYMQLNMGKFEYN 727
Cdd:cd08597   246 PGLMMDLNTGKFLEN 260

PI-PLCc_delta3

cd08630

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...

311-727

9.10e-75

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: 248.78 E-value: 9.10e-75

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08630     1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG---PGGEPVIYHGHTLTSKILFRDVIQ 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDpgvSLPSPNRLRKKILIKNKRLKtdie 470
Cdd:cd08630    78 AVRQHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPE---ELPSPEELKGRVLVKGKKLQ---- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08630       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnIHPLLSSLVNY 630
Cdd:cd08630   151 ---------------------------------------------------------------------ISPELSALAVY 161

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08630   162 CQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNF 241

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08630   242 QTPGYEMDLNAGRFLVN 258

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

314-462

1.29e-72

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: 237.79 E-value: 1.29e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   314 MDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQIR 393
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG---PDGEPVVYHGYTLTSKIPFRDVLEAIK 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 922580920   394 DTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgVSLPSPNRLRKKILIKN 462
Cdd:pfam00388   78 DYAFVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDL----TELPSPEDLKGKILIKG 142

PI-PLC1c_yeast

cd08598

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...

313-724

1.12e-69

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: 233.29 E-value: 1.12e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGenkGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08598     3 DLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDD---GEPVVTHGYTLTSSVPFRDVCRAI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDpgvsLPSPNRLRKKILIKNKRlktdierh 472
Cdd:cd08598    80 KKYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDE----LPSPEELRGKILIKVKK-------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  473 qldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssSPATPSisgpppcatssgstssititttgcst 552
Cdd:cd08598   148 ------------------------------------------------ESKTPN-------------------------- 153

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  553 sssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihpllsslvnyth 632
Cdd:cd08598       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  633 pvkfsgfdvaeannlhfHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQT 712
Cdd:cd08598   154 -----------------HIFSLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQT 216

                         410
                  ....*....|..
gi 922580920  713 PDVYMQLNMGKF 724
Cdd:cd08598   217 YDLGMQLNEAMF 228

PI-PLCc_epsilon

cd08596

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...

313-727

2.83e-68

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: 230.12 E-value: 2.83e-68

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08596     3 DLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDG---DDGMPIIYHGHTLTTKIPFKDVVEAI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSK-PFE-DAPLDPgvSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08596    80 NRSAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKfLFEsDFSDDP--SLPSPLQLKNKILLKNKK------ 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelneTPEvvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08596   152 ---------------------APE-------------------------------------------------------- 154

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08596   155 -------------------------------------------------------------------------LSDLVIY 161

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEAnnlhFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08596   162 CQAVKFPGLSTPKC----YHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNY 237

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08596   238 QTDDLPMHLNAAMFEAN 254

PI-PLCc_zeta

cd08595

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...

311-727

2.96e-68

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: 230.21 E-value: 2.96e-68

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08595     1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGA---DNEPVVYHGYTLTSKILFKEVIT 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDpgvSLPSPNRLRKKILIKNKRlktdie 470
Cdd:cd08595    78 TVEKYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATG---ELPSPEALKFKILVKNKK------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08595       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpsKHILGgempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08595   149 --------KIAKA------------------------------------------------------------LSDLVIY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNF 710
Cdd:cd08595   161 TKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNF 240

                         410
                  ....*....|....*..
gi 922580920  711 QTPDVYMQLNMGKFEYN 727
Cdd:cd08595   241 QTLGAPMDLQNGKFLDN 257

PI-PLCc_delta1

cd08629

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...

311-727

6.44e-67

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: 226.45 E-value: 6.44e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08629     1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGP---NQEPIIYHGYTFTSKILFCDVLR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgVSLPSPNRLRKKILIKNKRLKtdie 470
Cdd:cd08629    78 AIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVT----TSLPSPEQLKGKILLKGKKLK---- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  471 rhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgc 550
Cdd:cd08629       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  551 stsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvLTKEeeerifaeyhytgattnihplLSSLVNY 630
Cdd:cd08629   150 ------------------------------------------------LVPE---------------------LSDMIIY 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  631 THPVKFSGF-DVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLN 709
Cdd:cd08629   161 CKSVHFGGFsSPGTSGQAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALN 240

                         410
                  ....*....|....*...
gi 922580920  710 FQTPDVYMQLNMGKFEYN 727
Cdd:cd08629   241 FQTPGPEMDVYLGCFQDN 258

PI-PLCc_delta4

cd08631

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...

311-727

1.94e-65

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: 222.52 E-value: 1.94e-65

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08631     1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGP---NGEPIVYHGHTFTSKILFKDVVA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFED-APldpgVSLPSPNRLRKKILIKNKRLKtdi 469
Cdd:cd08631    78 AVAQYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGvLP----TQLPSPEELRGKILLKGKKIR--- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  470 erhqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttg 549
Cdd:cd08631       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  550 cstsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvLTKEeeerifaeyhytgattnihplLSSLVN 629
Cdd:cd08631   151 -------------------------------------------------LSPE---------------------LSDCVI 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  630 YTHPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLN 709
Cdd:cd08631   161 YCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALN 240

                         410
                  ....*....|....*...
gi 922580920  710 FQTPDVYMQLNMGKFEYN 727
Cdd:cd08631   241 FQTAGLEMDLNDGLFRQN 258

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

147-299

2.01e-64

Pssm-ID: 320030 [Multi-domain] Cd Length: 153 Bit Score: 215.19 E-value: 2.01e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKeREELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16200     1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKKRKRVLKALKALGLPDGK-NDEIDPEDFTFEKFFKLYNKLCPRPDIDEIF 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLSG-QKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16200    80 KELGGkRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

PI-PLCc_eta

cd08594

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...

313-727

6.89e-62

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: 210.81 E-value: 6.89e-62

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08594     3 DMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGP---DGEPVVHHGYTLTSKILFRDVIETI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDML-LSKPfedaPLDPGVSLPSPNRLRKKILIKNKRlktdier 471
Cdd:cd08594    80 NKYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLdLSSV----ISGDSKQLPSPQSLKGKILIKGKK------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  472 hqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcs 551
Cdd:cd08594       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  552 tsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihpllsslvnyt 631
Cdd:cd08594       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  632 hpvkfsgfdvaeannlhFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQ 711
Cdd:cd08594   149 -----------------WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQ 211

                         410
                  ....*....|....*.
gi 922580920  712 TPDVYMQLNMGKFEYN 727
Cdd:cd08594   212 TEGRMLQLNRAKFRAN 227

PI-PLC-Y

pfam00387

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...

624-738

1.53e-61

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 205.39 E-value: 1.53e-61

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   624 LSSLVNYTHPVKFSGFDVAEANNlHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGC 703
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTPESKT-PNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 922580920   704 QMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDF 738
Cdd:pfam00387   80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

625-739

6.72e-61

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 203.62 E-value: 6.72e-61

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    625 SSLVNYTHPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQ 704
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 922580920    705 MVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFL 739
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_eta2

cd08633

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...

313-727

7.30e-61

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: 209.13 E-value: 7.30e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08633     3 DMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGP---DGEPIVHHGYTLTSKILFKDVIETI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDML-LSKPFEdaplDPGVSLPSPNRLRKKILIKNKRLktdier 471
Cdd:cd08633    80 NKYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdLSSVIS----NDCTRLPSPEILKGKILVKGKKL------ 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  472 hqldqflregkldeedelnetpevvgedsvsppgdQRAhpeveqpvsssspatpsisgpppcatssgstssititttgcs 551
Cdd:cd08633   150 -----------------------------------SRA------------------------------------------ 152

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  552 tsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihplLSSLVNYT 631
Cdd:cd08633   153 ------------------------------------------------------------------------LSDLVKYT 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  632 HPVKFSGFDVAEANNlhFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQ 711
Cdd:cd08633   161 KSVRVHDIETEATSS--WQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQ 238

                         410
                  ....*....|....*.
gi 922580920  712 TPDVYMQLNMGKFEYN 727
Cdd:cd08633   239 SEGRMLQLNRAKFSAN 254

PI-PLCc_gamma2

cd08628

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...

312-727

8.44e-61

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: 208.76 E-value: 8.44e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  312 MDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLVQ 391
Cdd:cd08628     2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGP---DGKPIIYHGWTRTTKIKFDDVVQA 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  392 IRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEdAPLDpgvSLPSPNRLRKKILIKNKRLktdier 471
Cdd:cd08628    79 IKDHAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLE-ASAD---QLPSPTQLKEKIIIKHKKL------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  472 hqldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcs 551
Cdd:cd08628       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  552 tsssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnIHPLLSSLVNYT 631
Cdd:cd08628   149 --------------------------------------------------------------------IAIELSDLVVYC 160

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  632 HPVKFS--GFDvaeaNNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLN 709
Cdd:cd08628   161 KPTSKTkdNLE----NPDFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALN 236

                         410
                  ....*....|....*...
gi 922580920  710 FQTPDVYMQLNMGKFEYN 727
Cdd:cd08628   237 FQTADKYMQLNHALFSLN 254

PI-PLCc_eta1

cd08632

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...

313-727

1.05e-60

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: 208.73 E-value: 1.05e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08632     3 DMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGP---DGEPVVHHGYTLTSKITFRDVIETI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDML-LSKPFEDAPldpgVSLPSPNRLRKKILIKNKRLKTDIer 471
Cdd:cd08632    80 NKYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLdLSSVLTGDP----KQLPSPQLLKGKILVKGKKLCRDL-- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  472 hqldqflregkldeEDELNETPEVVGEDSVsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcs 551
Cdd:cd08632   154 --------------SDLVVYTNSVAAQDIV-------------------------------------------------- 169

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  552 tsssgpskhilggempakenDEahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytGATTNIhpllsslvnyt 631
Cdd:cd08632   170 --------------------DD-----------------------------------------GSTGNV----------- 177

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  632 hpvkfsgfdvaeannlhfhmSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQ 711
Cdd:cd08632   178 --------------------LSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQ 237

                         410
                  ....*....|....*.
gi 922580920  712 TPDVYMQLNMGKFEYN 727
Cdd:cd08632   238 SEGRMMQLNRAKFMVN 253

PI-PLCc_gamma1

cd08627

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...

313-727

4.11e-58

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: 200.25 E-value: 4.11e-58

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08627     3 EMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGP---DGMPVIYHGHTLTTKIKFSDVLHTI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFeDAPLDpgvSLPSPNRLRKKILIKNKRLKTDierh 472
Cdd:cd08627    80 KEHAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPV-DINAD---GLPSPNQLKRKILIKHKKLYRD---- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  473 qldqflregkldeedelnetpevvgedsvsppgdqrahpeveqpvsssspatpsisgpppcatssgstssititttgcst 552
Cdd:cd08627       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  553 sssgpskhilggempakendeahpelkqnfiaknlkgfgfskkqpvltkeeeerifaeyhytgattnihpllsslvnyth 632
Cdd:cd08627       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  633 pvkfsgfdvaeannlhfhMSSFSESTGLGYL-KQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQ 711
Cdd:cd08627   152 ------------------MSSFPETKAEKYVnRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQ 213

                         410
                  ....*....|....*.
gi 922580920  712 TPDVYMQLNMGKFEYN 727
Cdd:cd08627   214 TPDKPMQMNQALFMLG 229

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

314-463

8.69e-57

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: 192.88 E-value: 8.69e-57

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    314 MDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQIR 393
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDG---PDGEPVIYHGHTFTLPIKLSEVLEAIK 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    394 DTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLdpgvSLPSPNRLRKKILIKNK 463
Cdd:smart00148   78 DFAFVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLE----VLPSPEQLRGKILLKVR 143

PLN02952

phosphoinositide phospholipase C

206-860

6.37e-56

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 205.62 E-value: 6.37e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  206 FEKFQRLY--NKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQrdprlNEILFPFFDSQRIV-ALLKKHENDIKYQE 282
Cdd:PLN02952   22 FNLFNRKFkiTEAEPPDDVKDVFCKFSVGGGHMGADQLRRFLVLHQ-----DELDCTLAEAQRIVeEVINRRHHVTRYTR 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  283 DGkMSGDGFLRFLMSDE-NPPVFldrIEMFMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCW 361
Cdd:PLN02952   97 HG-LNLDDFFHFLLYDDlNGPIT---PQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLW 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  362 DGTgeNKGEPIITHGKAMCTDVFFKDVLVQIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSkPFEDAP 441
Cdd:PLN02952  173 PGS--TKDEILVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYY-PESDSL 249

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  442 ldpgVSLPSPNRLRKKILIKNKRLKTDIERHQLDQFLREGKLDEEDElNETPEvvgEDSVSPPGDQRAHPEVEQPVSSSS 521
Cdd:PLN02952  250 ----VQFPSPESLKHRIIISTKPPKEYLESSGPIVIKKKNNVSPSGR-NSSEE---TEEAQTLESMLFEQEADSRSDSDQ 321

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  522 PATPSisgpppcatssgstssititttgcsTSSSGPSKHILGGEMPAKENDEAHPELKqnfIAKNlkgfgfSKKQPVLTK 601
Cdd:PLN02952  322 DDNKS-------------------------GELQKPAYKRLITIHAGKPKGTLKDAMK---VAVD------KVRRLSLSE 367

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  602 EEEERifaeyhytGATTNihpllsslvnythpvkfsGFDVaeannlhfhmssfsestglgylkqsapefVNYNKRQSSRI 681
Cdd:PLN02952  368 QELEK--------AATTN------------------GQDV-----------------------------VRFTQRNILRI 392

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  682 YPKGARVDSSNFLPQIFWNAGCQMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFLRRP---DRTFDPFSESPVDGVI 758
Cdd:PLN02952  393 YPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVFDPKKKLPVKKTL 472

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  759 aahcSVRVISG----------QFLSDRKIGTYVEVEMYGLPTDTIRKehKTKVIPGNgLNPVYNEDpFVFrKVVLPELAV 828
Cdd:PLN02952  473 ----KVKVYLGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK--KTKIIEDN-WYPAWNEE-FSF-PLTVPELAL 543

                         650       660       670
                  ....*....|....*....|....*....|....*.
gi 922580920  829 LRFAV--YDENGKQL--GQRILPLDGLQAGYRHISL 860
Cdd:PLN02952  544 LRIEVreYDMSEKDDfgGQTCLPVSELRPGIRSVPL 579

PLN02228

Phosphoinositide phospholipase C

218-872

2.39e-54

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 200.26 E-value: 2.39e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  218 PRTEVQELFVKLSgQKEYLTKERLINFLNEEQ--RDPRLNEIlfpffdsQRIVALLKKHEndiKYQEDGKMSGDGFLRFL 295
Cdd:PLN02228   22 PPVSIKRLFEAYS-RNGKMSFDELLRFVSEVQgeRHAGLDYV-------QDIFHSVKHHN---VFHHHGLVHLNAFYRYL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  296 MSDENPPVFLDRiEMFMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGENKGEpiITH 375
Cdd:PLN02228   91 FSDTNSPLPMSG-QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAE--VRH 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  376 GKAMCTDVFFKDVLVQIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgvSLPSPNRLR 455
Cdd:PLN02228  168 GRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSESTK-----HFPSPEELK 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  456 KKILIKNKrlktdierhqldqflregkldeedelnetpevvgedsvsPPgdqrahPEVEQPVSSSSPATPSISgpppcat 535
Cdd:PLN02228  243 NKILISTK---------------------------------------PP------KEYLESKTVQTTRTPTVK------- 270

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  536 ssgstssititttgcstsssgpskhilggEMPAKENDEAHPELKQNfiaknlkgfgfskkqpvltKEEEERIFAEYHytg 615
Cdd:PLN02228  271 -----------------------------ETSWKRVADAENKILEE-------------------YKDEESEAVGYR--- 299

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  616 ATTNIHPllsslVNYTHPVKfsgfDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLP 695
Cdd:PLN02228  300 DLIAIHA-----ANCKDPLK----DCLSDDPEKPIRVSMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDP 370

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  696 QIFWNAGCQMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFLRRPDRTFDPFSESPVDGVIaahcSVRVISGQ----- 770
Cdd:PLN02228  371 HVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKRLPIKTTL----KVKIYTGEgwdld 446

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  771 -----FLSDRKIGTYVEVEMYGLPTDTIRKEHKTKVipgNGLNPVYNEDPFVFRKVVlPELAVLRFAV--YDENGKQ--L 841
Cdd:PLN02228  447 fhlthFDQYSPPDFFVKIGIAGVPRDTVSYRTETAV---DQWFPIWGNDEFLFQLRV-PELALLWFKVqdYDNDTQNdfA 522

                         650       660       670       680
                  ....*....|....*....|....*....|....*....|
gi 922580920  842 GQRILPLDGLQAGYRHISLRSDTNQ---------SFILSP 872
Cdd:PLN02228  523 GQTCLPLPELKSGVRAVRLHDRAGKaykntrllvSFALDP 562

EFh_PI-PLCbeta4

cd16211

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...

153-299

8.43e-53

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: 181.85 E-value: 8.43e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  153 LTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKErEELDVDILTFEKFQRLYNKICPRTEVQELFVKLSG- 231
Cdd:cd16211     7 LCFLVNPNGKIPVRSITRTFASGKTEKIVFQSLKELGLPSGKN-DEIEPEAFTFEKFYELYHKICPRTDIEELFKKINGd 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 922580920  232 QKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16211    86 KKDYLTVDQLISFLNEHQRDPRLNEILFPFYDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153

PLN02222

phosphoinositide phospholipase C 2

209-862

6.05e-51

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 190.63 E-value: 6.05e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  209 FQRLYN---KICPRtEVQELFVKLSgQKEYLTKERLINFLNEEQRDPRLNEIlfpffDSQRIV----ALLkkHENDIKYq 281
Cdd:PLN02222   12 FRRRFRytaSEAPR-EIKTIFEKYS-ENGVMTVDHLHRFLIDVQKQDKATRE-----DAQSIInsasSLL--HRNGLHL- 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  282 edgkmsgDGFLRFLMSDENPPVFLDRIEMfmDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCW 361
Cdd:PLN02222   82 -------DAFFKYLFGDNNPPLALHEVHH--DMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIW 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  362 DGTgeNKGEPIITHGKAMCTDVFFKDVLVQIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAP 441
Cdd:PLN02222  153 PNS--DKDDIDVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESL 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  442 LDpgvsLPSPNRLRKKILIKNKRLKtDIERHQLDQFLREGKL--DEEDELNETPEVVGEDSVSPPGDQRAHPEVEqpvSS 519
Cdd:PLN02222  231 KE----FPSPNSLKKRIIISTKPPK-EYKEGKDDEVVQKGKDlgDEEVWGREVPSFIQRNKSVDKNDSNGDDDDD---DD 302

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  520 SSPATPSISGPPpcatssgstssititttgcstsssgPSKHILGgempakendeAHPELKQNFIAKNLKGFGFSKKQPVL 599
Cdd:PLN02222  303 DGEDKSKKNAPP-------------------------QYKHLIA----------IHAGKPKGGITECLKVDPDKVRRLSL 347

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  600 TKEEEERIFAEYhytgattnihpllsslvnythpvkfsgfdvaeannlhfhmssfsestglgylkqsAPEFVNYNKRQSS 679
Cdd:PLN02222  348 SEEQLEKAAEKY-------------------------------------------------------AKQIVRFTQHNLL 372

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  680 RIYPKGARVDSSNFLPQIFWNAGCQMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFLRRPD---RTFDPFSESPVDG 756
Cdd:PLN02222  373 RIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGsdsDIFDPKATLPVKT 452

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  757 VIaaHCSVRVISGQFLSDRKI--------GTYVEVEMYGLPTDTIRKehKTKVIPGNGLnPVYNEdpfVFR-KVVLPELA 827
Cdd:PLN02222  453 TL--RVTIYMGEGWYFDFRHThfdqysppDFYTRVGIAGVPGDTVMK--KTKTLEDNWI-PAWDE---VFEfPLTVPELA 524

                         650       660       670
                  ....*....|....*....|....*....|....*....
gi 922580920  828 VLRFAV--YDENGKQ--LGQRILPLDGLQAGYRHISLRS 862
Cdd:PLN02222  525 LLRLEVheYDMSEKDdfGGQTCLPVWELSQGIRAFPLHS 563

PI-PLCc

cd00137

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...

313-727

1.27e-49

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: 177.46 E-value: 1.27e-49

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYL-----TGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGEnkgEPIITHGKAMcTDVFFKD 387
Cdd:cd00137     3 PDTQPLAHYSIPGTHDTYLtagqfTIKQVWGLTQTEMYRQQLLSGCRCVDIRCWDGKPE---EPIIYHGPTF-LDIFLKE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  388 VLVQIRDTAFARSDFPVVLSFENHCS--KSNQLKMAKYCMDIFGDMLLskpfeDAPLDPGVSLPSPNRLRKKILIKNKRL 465
Cdd:cd00137    79 VIEAIAQFLKKNPPETIIMSLKNEVDsmDSFQAKMAEYCRTIFGDMLL-----TPPLKPTVPLPSLEDLRGKILLLNKKN 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  466 KTdierhqldqflregkldeedelnetpevvgedsvSPPGdqrahpeveqpvsssspatpsisgpppcatssgstssiti 545
Cdd:cd00137   154 GF----------------------------------SGPT---------------------------------------- 159

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  546 tttgcstsssgpskhilggempakendeahpelkqnfIAKNLKGFGFSKKqpvltkeeeerifaeyhytGATTNIHPlls 625
Cdd:cd00137   160 -------------------------------------GSSNDTGFVSFEF-------------------STQKNRSY--- 180

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  626 slvnythpvkfsgfdvaeannlhfHMSSFSESTGLGYLK----QSAPEFVNYNKRQSSRIYPKGARV---------DSSN 692
Cdd:cd00137   181 ------------------------NISSQDEYKAYDDEKvkliKATVQFVDYNKNQLSRNYPSGTSGgtawyyyamDSNN 236

                         410       420       430
                  ....*....|....*....|....*....|....*...
gi 922580920  693 FLPQIFWN---AGCQMVSLNFQTPDVYMQLNMGKFEYN 727
Cdd:cd00137   237 YMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274

EFh_NorpA_like

cd16212

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...

147-299

5.81e-46

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: 162.33 E-value: 5.81e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKErEELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16212     1 KKHWMRLGFMVDSGGKIPVKHIARTFASGKTEKLVYQCLAEMGLPSGKG-DSIEKEDFTFEKFYALYHKICPRNDIEELF 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLS-GQKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16212    80 TSITkGKGEHISLAQLINFMNDKQRDPRLNEILYPLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

17-142

5.80e-45

Pssm-ID: 270167 Cd Length: 127 Bit Score: 158.50 E-value: 5.80e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   17 LLHGSVFDRYDDEStCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGGLPKDGRIMFELE--QRGASETIAE 94
Cdd:cd13361     1 LLKGSKFDKWDEDS-SLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREvnVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 922580920   95 RTIWITHGQDLVNVQSFFLVAESVELAKTCRAGINDILKSSRIRHVCP 142
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PI-PLCc_plant

cd08599

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...

313-463

5.28e-43

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: 156.76 E-value: 5.28e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08599     3 DMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPG---GRGDICVLHGGTLTKPVKFEDCIKAI 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 922580920  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLlskpFEDAPLDPGVSLPSPNRLRKKILIKNK 463
Cdd:cd08599    80 KENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKL----FYPDSEDLPEEFPSPEELKGKILISDK 146

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

761-881

2.84e-41

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 148.07 E-value: 2.84e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  761 HCSVRVISGQFLSD------RKIGTYVEVEMYGLPTDTiRKEHKTKVIPGNGLNPVYNEdPFVFrKVVLPELAVLRFAVY 834
Cdd:cd00275     3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNE-TFEF-DVTVPELAFLRFVVY 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 922580920  835 DENGKQ---LGQRILPLDGLQAGYRHISLRSDTNQSFILSpVLFVQIVIK 881
Cdd:cd00275    80 DEDSGDddfLGQACLPLDSLRQGYRHVPLLDSKGEPLELS-TLFVHIDIT 128

PLN02230

phosphoinositide phospholipase C 4

218-860

5.89e-41

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 160.64 E-value: 5.89e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  218 PRTEVQELFVKLSGQKEYLTKERLINFLNEEQR---DPRLNEilfpffdSQRIVALLKKHENDIKYQEDGKMSGDGFLRF 294
Cdd:PLN02230   27 PVADVRDLFEKYADGDAHMSPEQLQKLMAEEGGgegETSLEE-------AERIVDEVLRRKHHIAKFTRRNLTLDDFNYY 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  295 LMS-DENPPVFlDRIEMfmDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDgtgENKGEPII 373
Cdd:PLN02230  100 LFStDLNPPIA-DQVHQ--NMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWP---RGTDDVCV 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  374 THGKAMCTDVFFKDVLVQIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgvSLPSPNR 453
Cdd:PLN02230  174 KHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHDSEGCQ-----EFPSPEE 248

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  454 LRKKILIKNKRLKTDIERHQLDQ--FLREGKLDEEDELNETPevvgEDSVSPPGDqrahpeVEQPVSSSspatpsisgpp 531
Cdd:PLN02230  249 LKEKILISTKPPKEYLEANDAKEkdNGEKGKDSDEDVWGKEP----EDLISTQSD------LDKVTSSV----------- 307

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  532 pcatssgstssititttgcstsssgpskhilggempakeNDeahpelkqnfiaknlkgfgfskkqpvLTKEEEERIFAEy 611
Cdd:PLN02230  308 ---------------------------------------ND--------------------------LNQDDEERGSCE- 321

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  612 hyTGATTNIH-PLLSSLVNYTHPVKFSGFDVA-EANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVD 689
Cdd:PLN02230  322 --SDTSCQLQaPEYKRLIAIHAGKPKGGLRMAlKVDPNKIRRLSLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFN 399

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  690 SSNFLPQIFWNAGCQMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFLRRPDRTFDPFseSPVDGVIAAHC-SVRVIS 768
Cdd:PLN02230  400 SSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGPNGQDF--YPKDNSCPKKTlKVKVCM 477

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  769 G----------QFLSDRKIGTYVEVEMYGLPTDTIRKEHKtkvIPGNGLNPVYNEDpFVFrKVVLPELAVLRFAVYDENG 838
Cdd:PLN02230  478 GdgwlldfkktHFDSYSPPDFFVRVGIAGAPVDEVMEKTK---IEYDTWTPIWNKE-FIF-PLAVPELALLRVEVHEHDI 552

                         650       660
                  ....*....|....*....|....*.
gi 922580920  839 KQL----GQRILPLDGLQAGYRHISL 860
Cdd:PLN02230  553 NEKddfgGQTCLPVSEIRQGIHAVPL 578

EFh_PI-PLC21

cd16213

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...

148-299

5.72e-40

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: 145.14 E-value: 5.72e-40

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  148 KYHTWLTMNVNERRKIPIKLIIKTFSSGKPE-KMVQKCLNDLGLGGDKErEELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16213     2 KAYTKLTLQTDKEGKIPVKNIVKMFAQHKDDrKRVEKALEAIGLPSGKN-DAIDPKKFTFEDFFNFYRRLTGRQEVEKIF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLSGQKE-YLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16213    81 DELGAKKKpYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

147-299

3.87e-29

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: 114.25 E-value: 3.87e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKpeKMVQKCLNDLGLGGDKErEELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16210     1 RKAYTKLKLQVNQDGRIPVKNILKMFSADK--KRVETALESCGLKFNRS-ESIKPDEFTLEIFERFLNKLCLRPDIDKIL 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLSGQ-KEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16210    78 LEIGAKgKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

EFh_PI-PLCbeta1

cd16208

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...

148-299

2.67e-24

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: 100.34 E-value: 2.67e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  148 KYHTWLTMNVNERRKIPIKLIIKTFSSGKpeKMVQKCLNDLGLGGDKErEELDVDILTFEKFQRLYNKICPRTEVQELFV 227
Cdd:cd16208     2 KAYTKLKLQVNPEGRIPVKNIYRLFSADR--KRVETALEACNLPSSRN-DSIPQEDFTPEVYRVFLNNLCPRPEIDHIFS 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 922580920  228 KL-SGQKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16208    79 EFgAKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

EFh_PI-PLCbeta2

cd16209

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...

148-299

1.44e-22

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: 95.33 E-value: 1.44e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  148 KYHTWLTMNVNERRKIPIKLIIKTFSSGKpeKMVQKCLNDLGLGGDKErEELDVDILTFEKFQRLYNKICPRTEVQELFV 227
Cdd:cd16209     2 KIYVKLKMQLNSEGKIPVKNFFQMFPADR--KRVEAALSACHLPKGKN-DAINPEDFPEAVFKTFLMQLCPRPEIDEIFT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 922580920  228 KLSGQ-KEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16209    79 SYHAKaKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151

PLN02223

phosphoinositide phospholipase C

264-860

2.20e-20

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 96.63 E-value: 2.20e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  264 SQRIVALLKKHENDI-KYQEDGKMSGDGFLRFLMSDE-NPPVFlDRIEmFMDMDQPLCHYYINSSHNTYLTGRQYGGKSS 341
Cdd:PLN02223   58 AEKIAAELKRRKCDIlAFRNLRCLELDHLNEFLFSTElNPPIG-DQVR-HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLY 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  342 S-EIYRQVLLSGCRCIELDCW-DGTGENKGEPIITHGKAMctdvFFKDVLVQIRDTAFARSD-FPVVLSFENHCSKSNQL 418
Cdd:PLN02223  136 SiEPIIDALEQGVRVVELDLLpDGKDGICVRPKWNFEKPL----ELQECLDAIKEHAFTKCRsYPLIITFKDGLKPDLQS 211

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  419 KMAKYCMDIFGDMLLSKpfedaplDPGVSL---PSPNRLRKKILIkNKRLKTDIERHQLDqflrEGKLDEEDELnetpev 495
Cdd:PLN02223  212 KATQMIDQTFGDMVYHE-------DPQHSLeefPSPAELQNKILI-SRRPPKELLYAKAD----DGGVGVRNEL------ 273

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  496 vgedsvsppgdqrahpEVEQpvSSSSPATPSISGpppcatssgstssititttgcstsssgpskhilggempakendeah 575
Cdd:PLN02223  274 ----------------EIQE--GPADKNYQSLVG---------------------------------------------- 289

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  576 pelkqnFIAKNLKGFgfskKQPVLTKEEEerifaeyhytgattnihpllsslvnythpvkfsgfDVAEANNLHFHMSSFS 655
Cdd:PLN02223  290 ------FHAVEPRGM----LQKALTGKAD-----------------------------------DIQQPGWYERDIISFT 324

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  656 ESTGLgylkQSAPefvnynKRQSSRIYPKgarvdssnFLPQIFWNAGCQMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLK 735
Cdd:PLN02223  325 QKKFL----RTRP------KKKNLLINAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKK 386

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  736 PDFLRR--PDRTFDPfSESPvdgVIAAHCSVRVISGQ-FLSD--RKIGT------YVEVEMYGLPTDtiRKEHKTKViPG 804
Cdd:PLN02223  387 PDFLLNagPSGVFYP-TENP---VVVKILKVKIYMGDgWIVDfkKRIGRlskpdlYVRISIAGVPHD--EKIMKTTV-KN 459

                         570       580       590       600       610       620
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  805 NGLNPVYNEDpFVFrKVVLPELAVLRFAVYDENGKQ----LGQRILPLDGLQAGYRHISL 860
Cdd:PLN02223  460 NEWKPTWGEE-FTF-PLTYPDLALISFEVYDYEVSTadafCGQTCLPVSELIEGIRAVPL 517

PH_14

pfam17787

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

14-122

3.10e-17

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: 79.34 E-value: 3.10e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    14 IPELL-HGSVFDRYDDESTCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGG---LPKDGRIMFELEQRGAS 89
Cdd:pfam17787    2 VPEKLqKGELFIKWDEESTVAEPNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKfakIPKDPKLREVLSMGGSD 81

                           90       100       110
                   ....*....|....*....|....*....|...
gi 922580920    90 ETIAERTIWITHGQDLVNVQSFFLVAESVELAK 122
Cdd:pfam17787   82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAK 114

DUF1154

pfam06631

Protein of unknown function (DUF1154); This family represents a small conserved region of ...

986-1030

2.32e-16

Pssm-ID: 461969 Cd Length: 45 Bit Score: 73.83 E-value: 2.32e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 922580920   986 KFKVDPIEVDDLRRDKAFAKLLKRFQKELDDLRKKHQKQRDSIQK 1030
Cdd:pfam06631    1 DIKFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

PI-PLCc_GDPD_SF

cd08555

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...

324-435

1.86e-14

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: 72.85 E-value: 1.86e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  324 NSSHNTYLtgrQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGenkGEPIITHG------KAMCTDVFFKDVLVQIRDTAF 397
Cdd:cd08555     1 VLSHRGYS---QNGQENTLEAFYRALDAGARGLELDVRLTKD---GELVVYHGptldrtTAGILPPTLEEVLELIADYLK 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 922580920  398 ArSDFPVVLSFENHCS----KSNQLKMAKYCMDIFGDMLLSK 435
Cdd:cd08555    75 N-PDYTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGK 115

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

764-860

3.02e-14

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 69.82 E-value: 3.02e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920    764 VRVISGQFLSDRKIGT----YVEVEMYGLPtdtiRKEHKTKVIPGNgLNPVYNEDpFVFrKVVLPELAVLRFAVYDENG- 838
Cdd:smart00239    4 VKIISARNLPPKDKGGksdpYVKVSLDGDP----KEKKKTKVVKNT-LNPVWNET-FEF-EVPPPELAELEIEVYDKDRf 76

                            90       100
                    ....*....|....*....|....*
gi 922580920    839 ---KQLGQRILPLDGLQAGYRHISL 860
Cdd:smart00239   77 grdDFIGQVTIPLSDLLLGGRHEKL 101

EFh_PI-PLCdelta

cd16202

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...

202-299

5.24e-14

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: 70.33 E-value: 5.24e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  202 DILTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRdprlneilFPFFDSQRIVALLKKHENDIKYQ 281
Cdd:cd16202    51 DVLDEEEFVQFYNRLTKRPEIEELFKKYSGDDEALTVEELRRFLQEEQK--------VKDVTLEWAEQLIETYEPSEDLK 122

                          90
                  ....*....|....*...
gi 922580920  282 EDGKMSGDGFLRFLMSDE 299
Cdd:cd16202   123 AQGLMSLDGFTLFLLSPD 140

EFh_PI-PLC

cd15898

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...

150-299

2.25e-11

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 62.69 E-value: 2.25e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  150 HTWLTMNVNERRKIP---IKLIIKTFSSGKPEKMVQKCLNDLGLGGDKEreeldvdiLTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd15898     4 RQWIKADKDGDGKLSlkeIKKLLKRLNIRVSEKELKKLFKEVDTNGDGT--------LTFDEFEELYKSLTERPELEPIF 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 922580920  227 VKLSG-QKEYLTKERLINFLNEEQRDPRlneilfpffDSQRIVALLKKHENDikyQEDGKMSGDGFLRFLMSDE 299
Cdd:cd15898    76 KKYAGtNRDYMTLEEFIRFLREEQGENV---------SEEECEELIEKYEPE---RENRQLSFEGFTNFLLSPE 137

EFh_PRIP2

cd16223

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...

194-299

5.02e-10

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: 59.15 E-value: 5.02e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  194 KEREELDVDIlTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRLNEilfpffdsQRIVALLKK 273
Cdd:cd16223    47 KSKEKGGTEV-TKEEFIEVFHELCTRPEIYFLLVQFSSNKEFLDTKDLMMFLEAEQGMAHVTE--------EISLDIIHK 117

                          90       100
                  ....*....|....*....|....*.
gi 922580920  274 HENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16223   118 YEPSKEGQEKGWLSLDGFTNYLMSPE 143

EFh_PRIP

cd16206

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...

165-299

1.16e-08

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: 55.29 E-value: 1.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  165 IKLIIKTFSSGKPEKMVQKcLNDLGLGGDKEREELdvdilTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINF 244
Cdd:cd16206    23 VQLIKQLNPGLSTSRIKQK-LKELQKKKDGARGRV-----SSDEFVELFKELATRPEIYFLLVRYASNKDYLTVDDLMLF 96

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 922580920  245 LNEEQRDPRLNEilfpffdsQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16206    97 LEAEQGMTGVTK--------EKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

202-299

1.76e-08

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: 54.36 E-value: 1.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  202 DILTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPrlneilfpffDSQRIV-ALLKKHENDIKY 280
Cdd:cd16217    51 GFLEGEEIEEFYKLLTKREEIDVIFGEYAKSDGTMSRNNLLNFLQEEQREE----------VAPAYAlSLIEKYEPDETA 120

                          90
                  ....*....|....*....
gi 922580920  281 QEDGKMSGDGFLRFLMSDE 299
Cdd:cd16217   121 KAQRQMTKDGFLMYLLSPE 139

pfam00168

C2 domain;

763-857

1.82e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 53.48 E-value: 1.82e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   763 SVRVISGQFLSDRKIG----TYVEVEMYGLptdtiRKEHKTKVIPgNGLNPVYNEDpFVFrKVVLPELAVLRFAVYDENG 838
Cdd:pfam00168    4 TVTVIEAKNLPPKDGNgtsdPYVKVYLLDG-----KQKKKTKVVK-NTLNPVWNET-FTF-SVPDPENAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|...
gi 922580920   839 KQ----LGQRILPLDGLQAGYRH 857
Cdd:pfam00168   76 FGrddfIGEVRIPLSELDSGEGL 98

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

763-837

6.21e-08

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 51.68 E-value: 6.21e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 922580920  763 SVRVISGQFLSDRKIG----TYVEVEMYGlptdtiRKEHKTKVIPGNgLNPVYNEDpFVFrKVVLPELAVLRFAVYDEN 837
Cdd:cd00030     2 RVTVIEARNLPAKDLNgksdPYVKVSLGG------KQKFKTKVVKNT-LNPVWNET-FEF-PVLDPESDTLTVEVWDKD 71

EFh_PRIP1

cd16222

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...

194-299

6.35e-08

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: 52.94 E-value: 6.35e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  194 KEREELDVDIlTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRLNEilfpffdsQRIVALLKK 273
Cdd:cd16222    47 KSKEKLTTRV-TEEEFCEAYSELCTRPEVYFLLVQISKNKEYLDAKDLMLFLEAEQGMTHITE--------EMCLDIIRR 117

                          90       100
                  ....*....|....*....|....*.
gi 922580920  274 HENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16222   118 YEPSQEGRLKGFLGIDGFTQYLLSSE 143

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

212-299

3.51e-07

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 49.17 E-value: 3.51e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920   212 LYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRlneilfpfFDSQRIVALLKKHENDIKYQEDGKMSGDGF 291
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKDGF 72


                   ....*...
gi 922580920   292 LRFLMSDE 299
Cdd:pfam09279   73 LMYLCSPD 80

PLC-beta_C

pfam08703

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

1157-1296

4.60e-07

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: 51.22 E-value: 4.60e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  1157 EFELKKVQ--LKEQFDLLRKLMSEAQKNQMLALKLRLEAEGKDLKQTQTKKSMEdaKVIQLDKGIKTKAERDRRVKELNE 1234
Cdd:pfam08703   23 EQEKKRKEqhLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLE--SIQEAKKRTSDKAAQERLKKEINN 100

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 922580920  1235 KNLKMFVEERKRLAMKAQKHEEQLTKRHLDQLEQLdKDFHKALDAEVGNYKEEQLAAQPTSV 1296
Cdd:pfam08703  101 SHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQI-KEEEPQLQAELNAEYEEKLKGLPAEV 161

EFh_PI-PLCeta

cd16205

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...

204-297

1.10e-06

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: 49.30 E-value: 1.10e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  204 LTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQrdpRLNEIlfpffDSQRIVALLKKHENDIKYQED 283
Cdd:cd16205    54 LDFEEFCAFYKMMSTRRELYLLLLSYSNKKDYLTLEDLARFLEVEQ---KMTNV-----TLEYCLDIIEKFEPSEENKKN 125

                          90
                  ....*....|....
gi 922580920  284 GKMSGDGFLRFLMS 297
Cdd:cd16205   126 GLLGIDGFTNYMRS 139

EFh_ScPlc1p_like

cd16207

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...

204-297

1.77e-05

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: 46.09 E-value: 1.77e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  204 LTFEKFQRLYNKICPRTEVQELFVKLSGQ-KEYLTKERLINFLNEEQRDPrlneilfpfFDSQRIVALLKKHENDIKYQE 282
Cdd:cd16207    55 LNFEEFQEFVKLLKRRKDIKAIFKQLTKPgSDGLTLEEFLKFLRDVQKED---------VDRETWEKIFEKFARRIDDSD 125

                          90
                  ....*....|....*
gi 922580920  283 DGKMSGDGFLRFLMS 297
Cdd:cd16207   126 SLTMTLEGFTSFLLS 140

EFh_PI-PLCdelta4

cd16219

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...

207-299

8.12e-05

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: 44.06 E-value: 8.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  207 EKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRLNEilfpffdsQRIVALLKKHENDIKYQEDGKM 286
Cdd:cd16219    56 EEFVLFYKALTQREDVLKIFQDFSADGQKLTLLEFVDFLQQEQLERENTE--------ELAMELIDRYEPSDTAKKLHAL 127

                          90
                  ....*....|...
gi 922580920  287 SGDGFLRFLMSDE 299
Cdd:cd16219   128 SIDGFLMYLCSPE 140

PTZ00121

MAEBL; Provisional

1152-1289

8.69e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 47.06 E-value: 8.69e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920 1152 RHDEEEFELKKVQLKeqfdllRKLMSEAQKnqmlALKLRLEAEGKDLKQTQTKKSMEDA-KVIQLDKGI---KTKAERDR 1227
Cdd:PTZ00121 1653 KKAEEENKIKAAEEA------KKAEEDKKK----AEEAKKAEEDEKKAAEALKKEAEEAkKAEELKKKEaeeKKKAEELK 1722

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 922580920 1228 RVKELNE---KNLKMFVEERKRLAMKAQKHEEQltKRHLDQLEQLDKDFHKALDAEVGNYKEEQL 1289
Cdd:PTZ00121 1723 KAEEENKikaEEAKKEAEEDKKKAEEAKKDEEE--KKKIAHLKKEEEKKAEEIRKEKEAVIEEEL 1785

EFh_PI-PLCzeta

cd16204

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...

194-299

1.42e-04

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

Pssm-ID: 320034 [Multi-domain] Cd Length: 142 Bit Score: 43.26 E-value: 1.42e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  194 KEREELDVDILTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRLNEilfpffdsQRIVALLKK 273
Cdd:cd16204    45 KKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVGFLKKEQFQDEADE--------TIASELIAK 116

                          90       100
                  ....*....|....*....|....*.
gi 922580920  274 HENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16204   117 YEPIEEVRKRKQMSFEGFIRYMTSED 142

EFh_PI-PLCdelta3

cd16218

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...

219-299

5.74e-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: 41.65 E-value: 5.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  219 RTEVQELFVKLSGQKEYLTKERLINFLNEEQRDPRLneilfpffdsQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSD 298
Cdd:cd16218    68 RPELEEIFHQYSGEDCVLSAEELREFLKDQGEDASL----------VHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSK 137


                  .
gi 922580920  299 E 299
Cdd:cd16218   138 D 138

EFh_PI-PLCeta1

cd16220

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...

197-297

9.64e-04

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

Pssm-ID: 320050 [Multi-domain] Cd Length: 141 Bit Score: 40.78 E-value: 9.64e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  197 EELDVD----ILTFEKFQRLYNKICPRTEVQELFVKLSGQKEYLTKERLINFLNEEQrdpRLNEILFPFfdsqrIVALLK 272
Cdd:cd16220    43 QEADTDenqgTLTFEEFCVFYKMMSLRRDLYLLLLSYSDKKDHLTVEELAQFLKVEQ---KMNNVTTEY-----CLDIIK 114

                          90       100
                  ....*....|....*....|....*
gi 922580920  273 KHENDIKYQEDGKMSGDGFLRFLMS 297
Cdd:cd16220   115 KFEVSEENKEQNVLGIEGFTNFMRS 139

PTZ00121

MAEBL; Provisional

1159-1288

1.17e-03

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 43.59 E-value: 1.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920 1159 ELKKVQlKEQFDLLRKLMSEAQKnqMLALKLRLEAEGKdLKQTQTKKSMEDAKVIQLDKGI----KTKAERDRRVKELNE 1234
Cdd:PTZ00121 1585 EAKKAE-EARIEEVMKLYEEEKK--MKAEEAKKAEEAK-IKAEELKKAEEEKKKVEQLKKKeaeeKKKAEELKKAEEENK 1660

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 922580920 1235 ---KNLKMFVEERKRLAMKAQKHEEQLTKRHldqlEQLDKDFHKALDAEVGNYKEEQ 1288
Cdd:PTZ00121 1661 ikaAEEAKKAEEDKKKAEEAKKAEEDEKKAA----EALKKEAEEAKKAEELKKKEAE 1713

PI-PLCc_bacteria_like

cd08557

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...

312-439

1.75e-03

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

Pssm-ID: 176500 [Multi-domain] Cd Length: 271 Bit Score: 41.69 E-value: 1.75e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  312 MDMDQPLCHYYINSSHNTY---LTGRQYGGKSSSE-----IYRQvLLSGCRCIELDCWdgTGENKGEPIITHGKAMCTDV 383
Cdd:cd08557     3 LLDDLPLSQLSIPGTHNSYaytIDGNSPIVSKWSKtqdlsITDQ-LDAGVRYLDLRVA--YDPDDGDLYVCHGLFLLNGQ 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 922580920  384 FFKDVLVQIRDtaF--ARSDFPVVLSFENHCS---KSNQLKMAKYCMDIFGDMLLSKPFED 439
Cdd:cd08557    80 TLEDVLNEVKD--FldAHPSEVVILDLEHEYGgdnGEDHDELDALLRDVLGDPLYRPPVRA 138

C2A_Synaptotagmin-1-5-6-9-10

cd08385

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...

783-848

1.97e-03

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

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 39.56 E-value: 1.97e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 922580920  783 VEMYGLPtDTiRKEHKTKVIPGNgLNPVYNEDpFVFrKVVLPELA--VLRFAVYDEN----GKQLGQRILPL 848
Cdd:cd08385    41 VKVYLLP-DK-KKKFETKVHRKT-LNPVFNET-FTF-KVPYSELGnkTLVFSVYDFDrfskHDLIGEVRVPL 107

TPH

pfam13868

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of ...

1156-1292

4.29e-03

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

Pssm-ID: 464007 [Multi-domain] Cd Length: 341 Bit Score: 41.06 E-value: 4.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  1156 EEFELKKVQLKEQFDLLRKLMSEAQknQMLALKLRLEAEGKDLKQTQTKKSMEDAKVIQldkgIKTKAERDRRVKELNEK 1235
Cdd:pfam13868   83 EEREQKRQEEYEEKLQEREQMDEIV--ERIQEEDQAEAEEKLEKQRQLREEIDEFNEEQ----AEWKELEKEEEREEDER 156

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 922580920  1236 NL-----KMFVEERKRLAMKAQKHE-EQLTKRHLDQLEQL--DKDFHKALDAEvgNYKEEQLAAQ 1292
Cdd:pfam13868  157 ILeylkeKAEREEEREAEREEIEEEkEREIARLRAQQEKAqdEKAERDELRAK--LYQEEQERKE 219

PI-PLCc_Rv2075c_like

cd08590

Catalytic domain of uncharacterized Mycobacterium tuberculosis Rv2075c-like proteins; This ...

312-461

6.19e-03

Catalytic domain of uncharacterized Mycobacterium tuberculosis Rv2075c-like proteins; This subfamily corresponds to the catalytic domain present in uncharacterized Mycobacterium tuberculosis Rv2075c and its homologs. Members in this family are more closely related to the Streptomyces antibioticus phosphatidylinositol-specific phospholipase C1(SaPLC1)-like proteins rather than the typical bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), which participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). In contrast, SaPLC1-like proteins have two Ca2+-chelating amino acid substitutions which convert them to metal-dependent bacterial PI-PLC. Rv2075c and its homologs have the same amino acid substitutions as well, which might suggest they have metal-dependent PI-PLC activity.

Pssm-ID: 176532 Cd Length: 267 Bit Score: 40.08 E-value: 6.19e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  312 MDMDQPLCHYYINSSHNTYLTgRQYG-GKSSSEIYR----------QVLLSGCRCIELDCWDGTGENK---GEPIITHGK 377
Cdd:cd08590     4 LDSNAPLCQAQILGTHNSYNS-RAYGyGNRYHGVRYldpnqelsitDQLDLGARFLELDVHWTTGDLRlchGGDHGYLGV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 922580920  378 AMCTDVFFKDVLVQIRDTAFARSDFPVVLSFENHCS-KSNQLKMAKYcMDIFGDMLLSkpfedaPLDPGVSLPSPNRLRK 456
Cdd:cd08590    83 CSSEDRLFEDGLNEIADWLNANPDEVVILYLEDHGDgGKDDELNALL-NDAFGDLLYT------PSDCDDLQGLPNWPTK 155


                  ....*
gi 922580920  457 KILIK 461
Cdd:cd08590   156 EDMLN 160

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