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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  153 EKAYTKLKLQVTPEGRIPLKNIYRLFSADRKRVETALEACSLPSSRNDSIPQEDFTPDVYRVFLNNLCPRPEIDNIFSEF 232
Cdd:cd16208      1 EKAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1938920293  233 GAKSKPYLTVDQMMDFINLKQRDPRLNEILYPPLKQEQVQVLIEKYEPNSSLAKKGQISVDGFMRYLSGEE 303
Cdd:cd16208     81 GAKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

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 1938920293  677 TLSVKIISGQFLSD------KKVGTYVEVDMFGLPVDTRRKaFKTKTSQGNAVNPVWEEEpIVFKkVVLPTLACLRIAVY 750
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1938920293  751 EEGG---KFIGHRILPVQAIRPGYHYICLRNERNQPLMLPAVFVYIEVK 796
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

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
                   ....*....|....*....|....*....|....*..
gi 1938920293  903 TEVEAQTIEELKQQKSFVKLQKKHYKEMKDLVKRHHK 939
Cdd:pfam06631    2 IKFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSK 38

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  153 EKAYTKLKLQVTPEGRIPLKNIYRLFSADRKRVETALEACSLPSSRNDSIPQEDFTPDVYRVFLNNLCPRPEIDNIFSEF 232
Cdd:cd16208      1 EKAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1938920293  233 GAKSKPYLTVDQMMDFINLKQRDPRLNEILYPPLKQEQVQVLIEKYEPNSSLAKKGQISVDGFMRYLSGEE 303
Cdd:cd16208     81 GAKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

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 1938920293   22 LKKGIKFVKWDDDSTIVTPIILRTDPQGFFFYWTDQNKETELLDLSLVKDARCGRHAKAPKDPKLRELLDVGNIGRLEQR 101
Cdd:cd13361      1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREVNVGGSDEDLEDR 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1938920293  102 MITVVYGPDLVNISHLNLVAFQEEVAKEWTNEVFSLATNLLAQNMSR 148
Cdd:cd13361     81 TLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

phosphoinositide phospholipase C

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  216 LNNLCPRPEIDNIFSEFgAKSKPYLTVDQMMDFINLKQ--RDPRLNEilypplKQEQVQVLIEKYEPNSSLAKKGqISVD 293
Cdd:PLN02952    31 ITEAEPPDDVKDVFCKF-SVGGGHMGADQLRRFLVLHQdeLDCTLAE------AQRIVEEVINRRHHVTRYTRHG-LNLD 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  294 GFMRYLSGEE-NGVVSPEkldLNEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEE 372
Cdd:PLN02952   103 DFFHFLLYDDlNGPITPQ---VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDE 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  373 EPVItHGFTMTTEISFKEVIEAIAECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLmeplekYPLESG-VP 451
Cdd:PLN02952   180 ILVL-HGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLY------YPESDSlVQ 251

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  452 LPSPMDLMYKILVKNKKKSHKSsEGSGKkkLSEQASNTCSDSSsmfEPSSPGAGEADTESDDDDDDDDCKKSSMDEGTAG 531
Cdd:PLN02952   252 FPSPESLKHRIIISTKPPKEYL-ESSGP--IVIKKKNNVSPSG---RNSSEETEEAQTLESMLFEQEADSRSDSDQDDNK 325

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  532 SEAMATEEMSNLVNyIQPVK-----FESFEISKKRNKSFEMSsfvETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDS 606
Cdd:PLN02952   326 SGELQKPAYKRLIT-IHAGKpkgtlKDAMKVAVDKVRRLSLS---EQELEKAATTNGQDVVRFTQRNILRIYPKGTRITS 401

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  607 SNYMPQLFWNAGCQMVALNFQTMDLAMQINMGMYEYNGKSGYRLKPEFMRRPDKH---FDPFTEgivdGIVANTLSVKII 683
Cdd:PLN02952   402 SNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHdevFDPKKK----LPVKKTLKVKVY 477

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  684 SG----------QFLSDKKVGTYVEVDMFGLPVDTRRKafKTKTSQGNAvNPVWEEEpIVFKKVVlPTLACLRIAVYE-- 751
Cdd:PLN02952   478 LGdgwrldfshtHFDSYSPPDFYTKMYIVGVPADNAKK--KTKIIEDNW-YPAWNEE-FSFPLTV-PELALLRIEVREyd 552

                          570       580       590
                   ....*....|....*....|....*....|....*
gi 1938920293  752 --EGGKFIGHRILPVQAIRPGYHYICLRNERNQPL 784
Cdd:PLN02952   553 msEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKL 587

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 1938920293  677 TLSVKIISGQFLSD------KKVGTYVEVDMFGLPVDTRRKaFKTKTSQGNAVNPVWEEEpIVFKkVVLPTLACLRIAVY 750
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1938920293  751 EEGG---KFIGHRILPVQAIRPGYHYICLRNERNQPLMLPAVFVYIEVK 796
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

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 1938920293   677 TLSVKIISGQFLSDKKVGT----YVEVDMFGLPvdtrRKAFKTKTSQGNaVNPVWEEEpIVFkKVVLPTLACLRIAVYEE 752
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGksdpYVKVSLDGDP----KEKKKTKVVKNT-LNPVWNET-FEF-EVPPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 1938920293   753 GG----KFIGHRILPVQAIRPGYHYICL 776
Cdd:smart00239   74 DRfgrdDFIGQVTIPLSDLLLGGRHEKL 101

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  676 NTLSVKIISGQFLSDKKVG----TYVEVDMfglpvDTRRKAFKTKTSQGNaVNPVWEEEpIVFkKVVLPTLACLRIAVYE 751
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNgtsdPYVKVYL-----LDGKQKKKTKVVKNT-LNPVWNET-FTF-SVPDPENAVLEIEVYD 72

                           90       100
                   ....*....|....*....|....*.
gi 1938920293  752 EGG----KFIGHRILPVQAIRPGYHY 773
Cdd:pfam00168   73 YDRfgrdDFIGEVRIPLSELDSGEGL 98

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 1938920293  315 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEA 394
Cdd:cd08623      1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  395 IAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKnkkkshkss 474
Cdd:cd08623     81 IAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVK--------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  475 egsgkkklseqasntcsdsssmfepsspgageadtesddddddddckkssmdegtagseamaTEEMSNLVNYIQPVKFES 554
Cdd:cd08623    152 --------------------------------------------------------------NKKMSNLVNYIQPVKFES 169

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  555 FEISKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTMDLAMQ 634
Cdd:cd08623    170 FEASKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQ 249

                   ....*....
gi 1938920293  635 INMGMYEYN 643
Cdd:cd08623    250 INMGMYEYN 258

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  316 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEAI 395
Cdd:cd08624      2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  396 AECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKnkkkshksse 475
Cdd:cd08624     82 AESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIK---------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  476 gsgKKKLseqasntcsdsssmfepsspgageadtesddddddddckkssmdegtagseamatEEMSNLVNYIQPVKFESF 555
Cdd:cd08624    152 ---NKKY-------------------------------------------------------EEMSSLVNYIQPTKFVSF 173

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  556 EISKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTMDLAMQI 635
Cdd:cd08624    174 EFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQ 253

                   ....*...
gi 1938920293  636 NMGMYEYN 643
Cdd:cd08624    254 NMALFEFN 261

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 1938920293  317 DMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEAIA 396
Cdd:cd08626      3 DMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQAIK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  397 ECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKnkkkshksseg 476
Cdd:cd08626     83 DTAFVTSDYPVILSFENHC-SKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIK----------- 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  477 sgKKKLseqasntcsdsssmfepsspgageadtesddddddddckkssmdegtagseamateemSNLVNYIQPVKFESFE 556
Cdd:cd08626    151 --NKRL----------------------------------------------------------SSLVNYAQPVKFQGFD 170

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  557 ISKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTMDLAMQIN 636
Cdd:cd08626    171 VAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLN 250

                   ....*..
gi 1938920293  637 MGMYEYN 643
Cdd:cd08626    251 QGKFEYN 257

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  153 EKAYTKLKLQVTPEGRIPLKNIYRLFSADRKRVETALEACSLPSSRNDSIPQEDFTPDVYRVFLNNLCPRPEIDNIFSEF 232
Cdd:cd16208      1 EKAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1938920293  233 GAKSKPYLTVDQMMDFINLKQRDPRLNEILYPPLKQEQVQVLIEKYEPNSSLAKKGQISVDGFMRYLSGEE 303
Cdd:cd16208     81 GAKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

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 1938920293  315 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEA 394
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDG--DDGEPVVTHGYTLTSSVPFRDVCRA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  395 IAECAFKTSPFPILLSFENHVDsPKQQAKMAEYCRLIFGDALLMEPLEkyPLESGvpLPSPMDLMYKILVKnkkkshkss 474
Cdd:cd08598     79 IKKYAFVTSPYPLILSLEVHCD-AEQQERMVEIMKETFGDLLVTEPLD--GLEDE--LPSPEELRGKILIK--------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  475 egsgkkklseqasntcsdsssmfepsspgageadtesddddddddckkssmdegtagseamateemsnlvnyiqpVKFEs 554
Cdd:cd08598    145 ---------------------------------------------------------------------------VKKE- 148

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  555 feiSKKRNKSFemsSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTMDLAMQ 634
Cdd:cd08598    149 ---SKTPNHIF---SLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQ 222

                   ....*.
gi 1938920293  635 INMGMY 640
Cdd:cd08598    223 LNEAMF 228

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  316 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 395
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVLRAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  396 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEkyplESGVPLPSPMDLMYKILVknkkkshksse 475
Cdd:cd08629     80 RDYAFKASPYPVILSLENHC-SLEQQRVMARHLRAILGPILLDQPLD----GVTTSLPSPEQLKGKILL----------- 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  476 gSGKK-KLSeqasntcsdsssmfepsspgageadtesddddddddckkssmdegtagseamatEEMSNLVNYIQPVKFES 554
Cdd:cd08629    144 -KGKKlKLV------------------------------------------------------PELSDMIIYCKSVHFGG 168

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  555 FEISKKRNKSF-EMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTMDLAM 633
Cdd:cd08629    169 FSSPGTSGQAFyEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEM 248

                          330
                   ....*....|
gi 1938920293  634 QINMGMYEYN 643
Cdd:cd08629    249 DVYLGCFQDN 258

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 1938920293  316 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 395
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDG--PNGEPIVYHGHTFTSKILFKDVVAAV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  396 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLE-KYPlesgVPLPSPMDLMYKILVknkkkshkss 474
Cdd:cd08631     80 AQYAFQVSDYPVILSLENHC-GVEQQQTMAQHLTEILGEKLLSTTLDgVLP----TQLPSPEELRGKILL---------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  475 egSGKK-KLSeqasntcsdsssmfepsspgageadtesddddddddckkssmdegtagseamatEEMSNLVNYIQPVKFE 553
Cdd:cd08631    145 --KGKKiRLS------------------------------------------------------PELSDCVIYCKSVSFR 168

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938920293  554 SFEISKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTMDLAM 633
Cdd:cd08631    169 SFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEM 248

                          330
                   ....*....|
gi 1938920293  634 QINMGMYEYN 643
Cdd:cd08631    249 DLNDGLFRQN 258