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 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08595    1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFP-DTLPSPEALKFKILVKNRKvgtlsetherig 210
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPAtGELPSPEALKFKILVKNKK------------ 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 211 tdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmKIAMALSDLVIYTKAEKFRN 290
Cdd:cd08595  149 ------------------------------------------------------------KIAKALSDLVIYTKSEKFCS 168

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 291 FQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPMD 370
Cdd:cd08595  169 FTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMD 248

                 ....*....
gi 568944095 371 LQNGKFLDN 379
Cdd:cd08595  249 LQNGKFLDN 257

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.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 568944095   2 EIDHSDSVEIINKYEPIEEVKGERQMSIEGFARYMFSSE 40
Cdd:cd16204  104 EADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08595    1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFP-DTLPSPEALKFKILVKNRKvgtlsetherig 210
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPAtGELPSPEALKFKILVKNKK------------ 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 211 tdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmKIAMALSDLVIYTKAEKFRN 290
Cdd:cd08595  149 ------------------------------------------------------------KIAKALSDLVIYTKSEKFCS 168

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 291 FQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPMD 370
Cdd:cd08595  169 FTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMD 248

                 ....*....
gi 568944095 371 LQNGKFLDN 379
Cdd:cd08595  249 LQNGKFLDN 257

phosphoinositide phospholipase C

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  51 VYQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGS-QNEPIVYHGYTFTSKLLFKTVVQA 129
Cdd:PLN02952 121 VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGStKDEILVLHGRTLTTPVPLIKCLKS 200

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 130 INKYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLL---SDMLEEFPdtlpSPEALKFKILVKNRKVGTLSETH 206
Cdd:PLN02952 201 IRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYypeSDSLVQFP----SPESLKHRIIISTKPPKEYLESS 276

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 207 ERIGTDKSGQVLEWKEVIYEDGDEDSGMDPETWDV-FLSRIKEEREADPSTLSGIAGVK--------KRKRKMKIAMALS 277
Cdd:PLN02952 277 GPIVIKKKNNVSPSGRNSSEETEEAQTLESMLFEQeADSRSDSDQDDNKSGELQKPAYKrlitihagKPKGTLKDAMKVA 356

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 278 dlviytkAEKFRNFqysrvyqqfnetnSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQM 357
Cdd:PLN02952 357 -------VDKVRRL-------------SLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQM 416

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 358 VALNFQTPGLPMDLQNGKFLDNGGSGYILKPDILRDTtlgfNPNEPEYDDH---PVTLTIRII----SGIQLPVS----S 426
Cdd:PLN02952 417 IAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKK----GFHDEVFDPKkklPVKKTLKVKvylgDGWRLDFShthfD 492

                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568944095 427 SSNTPDIVVIIEVYGVPNDHVKQQTRVVKNNaFSPKWNETFTFLIQVPELALIRfvVETQQGLLS-GNELLGQYTLPVL 504
Cdd:PLN02952 493 SYSPPDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLR--IEVREYDMSeKDDFGGQTCLPVS 568

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 568944095 409 PVTLTIRIISGIQLPVS--SSSNTPDIVVIIEVYGVPNDH-VKQQTRVVKNNAFSPKWNETFTFLIQVPELALIRFVVET 485
Cdd:cd00275    1 PLTLTIKIISGQQLPKPkgDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 568944095 486 QQGllSGNELLGQYTLPVLCMNKvGN-HERMHTAD--PRVHATLF 527
Cdd:cd00275   81 EDS--GDDDFLGQACLPLDSLRQ-GYrHVPLLDSKgePLELSTLF 122

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  411 TLTIRIISGIQLPVSSSSNTPDIVVIIEVYGvpnDHVKQQTRVVKNNaFSPKWNETFTFLIQVPELALIRFVVETqQGLL 490
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLD---GKQKKKTKVVKNT-LNPVWNETFTFSVPDPENAVLEIEVYD-YDRF 76

                          90
                  ....*....|...
gi 568944095  491 SGNELLGQYTLPV 503
Cdd:pfam00168  77 GRDDFIGEVRIPL 89

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568944095    1 MEIDHS--DSVEIINKYEPIEEVKGERQMSIEGFARYMFSSECLLF 44
Cdd:pfam09279  39 REEDASpaLALSLIERYEPSETAKKQHAMTKDGFLMYLCSPDGSIF 84

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08595    1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFP-DTLPSPEALKFKILVKNRKvgtlsetherig 210
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPAtGELPSPEALKFKILVKNKK------------ 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 211 tdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmKIAMALSDLVIYTKAEKFRN 290
Cdd:cd08595  149 ------------------------------------------------------------KIAKALSDLVIYTKSEKFCS 168

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 291 FQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPMD 370
Cdd:cd08595  169 FTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMD 248

                 ....*....
gi 568944095 371 LQNGKFLDN 379
Cdd:cd08595  249 LQNGKFLDN 257

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08558    1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFPDTLPSPEALKFKILVKNRKvgtlsetherigt 211
Cdd:cd08558   81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQLKGKILIKGKK------------- 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 212 dksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmkiamalsdlviytkaekfrnf 291
Cdd:cd08558      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 292 qysrvyqqfNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPMDL 371
Cdd:cd08558  148 ---------YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQL 218

                 ....*...
gi 568944095 372 QNGKFLDN 379
Cdd:cd08558  219 NQGKFEQN 226

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08631    1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLE-EFPDTLPSPEALKFKILVKNRKVgtlsetherig 210
Cdd:cd08631   81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDgVLPTQLPSPEELRGKILLKGKKI----------- 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 211 tdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmKIAMALSDLVIYTKAEKFRN 290
Cdd:cd08631  150 ------------------------------------------------------------RLSPELSDCVIYCKSVSFRS 169

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 291 FQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPMD 370
Cdd:cd08631  170 FTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMD 249

                 ....*....
gi 568944095 371 LQNGKFLDN 379
Cdd:cd08631  250 LNDGLFRQN 258

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08630    1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFP-DTLPSPEALKFKILVKNrkvgtlsetherig 210
Cdd:cd08630   81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNpEELPSPEELKGRVLVKG-------------- 146

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 211 tdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkRKMKIAMALSDLVIYTKAEKFRN 290
Cdd:cd08630  147 ---------------------------------------------------------KKLQISPELSALAVYCQATRLRT 169

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 291 FQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPMD 370
Cdd:cd08630  170 LEPAPVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMD 249

                 ....*....
gi 568944095 371 LQNGKFLDN 379
Cdd:cd08630  250 LNAGRFLVN 258

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGS--QNEPIVYHGYTFTSKLLFKTVVQA 129
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKgeDEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 130 INKYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFP----DTLPSPEALKFKILVKNRKvgtlset 205
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPlepgVPLPSPNDLKRKILIKNKK------- 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 206 herigtdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmkiamaLSDLVIYTKA 285
Cdd:cd08591  154 ----------------------------------------------------------------------LSSLVNYIQP 163

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 286 EKFRNFQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTP 365
Cdd:cd08591  164 VKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTP 243

                        330
                 ....*....|.
gi 568944095 366 GLPMDLQNGKF 376
Cdd:cd08591  244 DLPMQLNQGKF 254

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  53 QDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAINK 132
Cdd:cd08633    2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 133 YAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFL-LSDMLEEFPDTLPSPEALKFKILVKNRKvgtlsetherigt 211
Cdd:cd08633   82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdLSSVISNDCTRLPSPEILKGKILVKGKK------------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 212 dksgqvlewkeviyedgdedsgmdpetwdvfLSRikeereadpstlsgiagvkkrkrkmkiamALSDLVIYTKAEKFRNF 291
Cdd:cd08633  149 -------------------------------LSR-----------------------------ALSDLVKYTKSVRVHDI 168

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 292 --QYSRVYQqfneTNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLPM 369
Cdd:cd08633  169 etEATSSWQ----VSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 244

                        330
                 ....*....|
gi 568944095 370 DLQNGKFLDN 379
Cdd:cd08633  245 QLNRAKFSAN 254

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  53 QDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAINK 132
Cdd:cd08596    2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 133 YAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEE--FPD--TLPSPEALKFKILVKNRKVgtlsether 208
Cdd:cd08596   82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFEsdFSDdpSLPSPLQLKNKILLKNKKA--------- 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 209 igtdksgqvlewkeviyedgdedsgmdPEtwdvflsrikeereadpstlsgiagvkkrkrkmkiamaLSDLVIYTKAEKF 288
Cdd:cd08596  153 ---------------------------PE--------------------------------------LSDLVIYCQAVKF 167

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 289 RNFQYSRVYQqfneTNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGLP 368
Cdd:cd08596  168 PGLSTPKCYH----ISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLP 243

                        330
                 ....*....|.
gi 568944095 369 MDLQNGKFLDN 379
Cdd:cd08596  244 MHLNAAMFEAN 254

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  52 YQDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08632    1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFL-LSDMLEEFPDTLPSPEALKFKILVKNRKvgtlsetherig 210
Cdd:cd08632   81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLdLSSVLTGDPKQLPSPQLLKGKILVKGKK------------ 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 211 tdksgqvlewkeviyedgdedsgmdpetwdvfLSRikeereadpstlsgiagvkkrkrkmkiamALSDLVIYTKaekfrn 290
Cdd:cd08632  149 --------------------------------LCR-----------------------------DLSDLVVYTN------ 161

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 291 fqySRVYQQFNETNSIG------ESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQT 364
Cdd:cd08632  162 ---SVAAQDIVDDGSTGnvlsfsETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQS 238

                        330
                 ....*....|....*
gi 568944095 365 PGLPMDLQNGKFLDN 379
Cdd:cd08632  239 EGRMMQLNRAKFMVN 253

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  53 QDMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDGSQNEPIVYHGYTFTSKLLFKTVVQAINK 132
Cdd:cd08628    2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 133 YAFVTSDYPVVLSLENHCSPGQQEVMASILQSTFGDFLLSDMLEEFPDTLPSPEALKFKILVKNRKVgtlsetherigtd 212
Cdd:cd08628   82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQLKEKIIIKHKKL------------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 213 ksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmkIAMALSDLVIYTK-----AEK 287
Cdd:cd08628  149 -----------------------------------------------------------IAIELSDLVVYCKptsktKDN 169

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 288 FRNFqysrvyqQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPGL 367
Cdd:cd08628  170 LENP-------DFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADK 242

                 ....*....
gi 568944095 368 PMDLQNGKF 376
Cdd:cd08628  243 YMQLNHALF 251

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095  54 DMNHPLSDYFISSSHNTYLISDQILGPSDIWGYVSALVKGCRCLEIDCWDG--SQNEPIVYHGYTFTSKLLFKTVVQAIN 131
Cdd:cd08625    3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 132 KYAFVTSDYPVVLSLENHC-SPGQQEVMASILQSTFGDFLLSDMLEEFP----DTLPSPEALKFKILVKNRKVGTlseth 206
Cdd:cd08625   83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPlvpgVQLPSPQELMGKILVKNKKMST----- 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 207 erigtdksgqvlewkeviyedgdedsgmdpetwdvflsrikeereadpstlsgiagvkkrkrkmkiamalsdLVIYTKAE 286
Cdd:cd08625  158 ------------------------------------------------------------------------LVNYIEPV 165

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568944095 287 KFRNFQYSRVYQQFNETNSIGESRARKLSKLRVHEFIFHTAAFITRVYPKMMRADSSNFNPQEFWNVGCQMVALNFQTPG 366
Cdd:cd08625  166 KFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLD 245

                        330
                 ....*....|
gi 568944095 367 LPMDLQNGKF 376
Cdd:cd08625  246 LAMQLNMGVF 255