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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  730 LSSLVNYTHPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGC 809
Cdd:cd08591    154 LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGC 233

                           90       100
                   ....*....|....*....|....
gi 1831515685  810 QMVSLNFQTPDVYMQLNMGKFEYN 833
Cdd:cd08591    234 QMVALNFQTPDLPMQLNQGKFEYN 257

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   17 LLHGSVFDRYDDEStCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGGLPKDGRIMFELE--QRGASETIAE 94
Cdd:cd13361      1 LLKGSKFDKWDEDS-SLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREvnVGGSDEDLED 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1831515685   95 RTIWITHGQDLVNVQSFFLVAESVELAKTCRAGINDILKSSRIRHVCP 142
Cdd:cd13361     80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1831515685 1092 KFKVDPIEVDDLRRDKAFAKLLKRFQKELDDLRKKHQKQRDSIQK 1136
Cdd:pfam06631    1 DIKFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  500 SVSPRSGGSGgTGAPEEVDDDTSDDDDDPSVqTSLNVMRTIPTVNTTSNNGSNRSARSSLDTPSPSGGSlmvPDRATST- 578
Cdd:pfam05109  491 SPSPRDNGTE-SKAPDMTSPTSAVTTPTPNA-TSPTPAVTTPTPNATSPTLGKTSPTSAVTTPTPNATS---PTPAVTTp 565

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1831515685  579 ----------ATSIKNAVLARSPNFSSlrqklsfkrrqsPLAGDQRAHPEVEQPVSSSSPATPSISGPPPCA 640
Cdd:pfam05109  566 tpnatiptlgKTSPTSAVTTPTPNATS------------PTVGETSPQANTTNHTLGGTSSTPVVTSPPKNA 625

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  314 MDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQIR 393
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG---PDGEPVVYHGYTLTSKIPFRDVLEAIK 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1831515685  394 DTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgVSLPSPNRLRKKILIKN 462
Cdd:pfam00388   78 DYAFVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDL----TELPSPEDLKGKILIKG 142

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKeREELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16200      1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKKRKRVLKALKALGLPDGK-NDEIDPEDFTFEKFFKLYNKLCPRPDIDEIF 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1831515685  227 VKLSG-QKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16200     80 KELGGkRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   731 SSLVNYTHPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGCQ 810
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1831515685   811 MVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDFL 845
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   17 LLHGSVFDRYDDEStCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGGLPKDGRIMFELE--QRGASETIAE 94
Cdd:cd13361      1 LLKGSKFDKWDEDS-SLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREvnVGGSDEDLED 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1831515685   95 RTIWITHGQDLVNVQSFFLVAESVELAKTCRAGINDILKSSRIRHVCP 142
Cdd:cd13361     80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  867 HCSVRVISGQFLSD------RKIGTYVEVEMYGLPTDTiRKEHKTKVIPGNGLNPVYNEdPFVFrKVVLPELAVLRFAVY 940
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNE-TFEF-DVTVPELAFLRFVVY 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1831515685  941 DENGKQ---LGQRILPLDGLQAGYRHISLRSDTNQSFILSpVLFVQIVIK 987
Cdd:cd00275     80 DEDSGDddfLGQACLPLDSLRQGYRHVPLLDSKGEPLELS-TLFVHIDIT 128

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   14 IPELLH-GSVFDRYDDESTCLELNAQVRIDENGFFLRWLIEGKDAVVLDMGQIWEARTGG---LPKDGRIMFELEQRGAS 89
Cdd:pfam17787    2 VPEKLQkGELFIKWDEESTVAEPNVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKfakIPKDPKLREVLSMGGSD 81

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1831515685   90 ETIAERTIWITHGQDLVNVQSFFLVAESVELAK 122
Cdd:pfam17787   82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAK 114

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   870 VRVISGQFLSDRKIGT----YVEVEMYGLPtdtiRKEHKTKVIPGNgLNPVYNEDpFVFrKVVLPELAVLRFAVYDENG- 944
Cdd:smart00239    4 VKIISARNLPPKDKGGksdpYVKVSLDGDP----KEKKKTKVVKNT-LNPVWNET-FEF-EVPPPELAELEIEVYDKDRf 76

                            90       100
                    ....*....|....*....|....*
gi 1831515685   945 ---KQLGQRILPLDGLQAGYRHISL 966
Cdd:smart00239   77 grdDFIGQVTIPLSDLLLGGRHEKL 101

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685 1251 EFELKKVQ--LKEQFDLLRKLMSEAQKNQMLALKLRLEAEGKDLKQTQTKKSMEdaKVIQLDKGIKTKAERDRRVKELNE 1328
Cdd:pfam08703   23 EQEKKRKEqhLTEQIQKLKELAREKQAAELKALKESSESEKKEMKKKLERKRLE--SIQEAKKRTSDKAAQERLKKEINN 100

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1831515685 1329 KNLKMFVEERKRLAMKAQKHEEQLTKRHLDQLEQLdKDFHKALDAEVGNYKEEQLAAQPTSV 1390
Cdd:pfam08703  101 SHIQEVVQSIKQLEEKQKRRQEKLEEKQAECLQQI-KEEEPQLQAELNAEYEEKLKGLPAEV 161

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685 1246 RHDEEEFELKKVQLKeqfdllRKLMSEAQKnqmlALKLRLEAEGKDLKQTQTKKSMEDA-KVIQLDKGI---KTKAERDR 1321
Cdd:PTZ00121  1653 KKAEEENKIKAAEEA------KKAEEDKKK----AEEAKKAEEDEKKAAEALKKEAEEAkKAEELKKKEaeeKKKAEELK 1722

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1831515685 1322 RVKELNE---KNLKMFVEERKRLAMKAQKHEEQltKRHLDQLEQLDKDFHKALDAEVGNYKEEQL 1383
Cdd:PTZ00121  1723 KAEEENKikaEEAKKEAEEDKKKAEEAKKDEEE--KKKIAHLKKEEEKKAEEIRKEKEAVIEEEL 1785

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGEnKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08626      1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGE-DQEPIITHGKAMCTDILFKDVIQ 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1831515685  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDPGVSLPSPNRLRKKILIKNKRLKT 467
Cdd:cd08626     80 AIKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKRLSS 156

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  314 MDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQIR 393
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG---PDGEPVVYHGYTLTSKIPFRDVLEAIK 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1831515685  394 DTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPldpgVSLPSPNRLRKKILIKN 462
Cdd:pfam00388   78 DYAFVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDL----TELPSPEDLKGKILIKG 142

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  730 LSSLVNYTHPVKFSGFDVAEANNLHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGC 809
Cdd:cd08626    154 LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGC 233

                           90       100
                   ....*....|....*....|....
gi 1831515685  810 QMVSLNFQTPDVYMQLNMGKFEYN 833
Cdd:cd08626    234 QMVSLNFQTPDLGMQLNQGKFEYN 257

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  311 FMDMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTgenKGEPIITHGKAMCTDVFFKDVLV 390
Cdd:cd08592      1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGP---DGMPIIYHGHTLTSKIKFMDVLK 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  391 QIRDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKpfedaPLDP-GVSLPSPNRLRKKILIKNKRLKTDI 469
Cdd:cd08592     78 TIKEHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQ-----PVDRnADQLPSPNQLKRKIIIKHKKLFYEM 152

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  147 MKYHTWLTMNVNERRKIPIKLIIKTFSSGKPEKMVQKCLNDLGLGGDKeREELDVDILTFEKFQRLYNKICPRTEVQELF 226
Cdd:cd16200      1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDKKRKRVLKALKALGLPDGK-NDEIDPEDFTFEKFFKLYNKLCPRPDIDEIF 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1831515685  227 VKLSG-QKEYLTKERLINFLNEEQRDPRLNEILFPFFDSQRIVALLKKHENDIKYQEDGKMSGDGFLRFLMSDE 299
Cdd:cd16200     80 KELGGkRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  730 LSSLVNYTHPVKFSGFDVAEANNlHFHMSSFSESTGLGYLKQSAPEFVNYNKRQSSRIYPKGARVDSSNFLPQIFWNAGC 809
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTPESKT-PNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1831515685  810 QMVSLNFQTPDVYMQLNMGKFEYNGGSGYLLKPDF 844
Cdd:pfam00387   80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGTGenkGEPIITHGKAMCTDVFFKDVLVQI 392
Cdd:cd08598      3 DLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDD---GEPVVTHGYTLTSSVPFRDVCRAI 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1831515685  393 RDTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLDpgvsLPSPNRLRKKILIKNKR 464
Cdd:cd08598     80 KKYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDE----LPSPEELRGKILIKVKK 147

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   314 MDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDGtgeNKGEPIITHGKAMCTDVFFKDVLVQIR 393
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDG---PDGEPVIYHGHTFTLPIKLSEVLEAIK 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685   394 DTAFARSDFPVVLSFENHCSKSNQLKMAKYCMDIFGDMLLSKPFEDAPLdpgvSLPSPNRLRKKILIKNK 463
Cdd:smart00148   78 DFAFVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLE----VLPSPEQLRGKILLKVR 143

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831515685  313 DMDQPLCHYYINSSHNTYLTGRQYGGKSSSEIYRQVLLSGCRCIELDCWDG-TGENkgEPIITHGKAMCTDVFFKDVLVQ 391
Cdd:cd08623      3 DMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrTAEE--EPVITHGFTMTTEISFKEVIEA 80