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 1624434001  154 EKIYTRLKLQLNPDGCIPVKNIFRMFSADRKRVETALENCNLSSGRNDAIPQDDFTTEIFKAFLNSICPRPDIDTIFSEV 233
Cdd:cd16208      1 EKAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1624434001  234 GAKSRPYLTVEQLTDFINNKQRDPRLNEILYPPLKVEQVQTLVEKYEPNAMLSQRGQISVEGFTRYLSGEE 304
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 1624434001  706 TLSVKIISGQFLSD------RKVGTYVEVDMFGLPVDTKRKaFRTKTSPGNSVNPVWEEEpIVFKkVVLPTLASLRIAVY 779
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1624434001  780 EDGG---KFIGHRIIPVSAIRPGYHYVGLRNEKNQSLTLPALFIYIEVK 825
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

Transcriptional activator LAG-3; The C.elegans Notch pathway, involved in the control of growth, differentiation and patterning in animal development, relies on either of the receptors GLP-1 or LIN-12. Both these receptors promote signalling by the recruitment of LAG-3 to target promoters, where it then acts as a transcriptional activator. LAG-3 works as a ternary complex together with the DNA binding protein, LAG-1. Its N-terminal region adopts an elongated kinked helix that is required for complex assembly.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  881 SEPKTDPKPAPTENGMSHAPLIAPKPASLVSHQPQPSVKSEDVIQSVLTDLEAQSMEELKQQKVFVREQRRQYKElkelv 960
Cdd:pfam11498  290 MEPEGETKKSPMEAGGDRMPQSAPPPAMNPQHIAQLAQQQNKMRLLQQQEMEMQRIEQQRQQQIMHQHQQQQQQE----- 364

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1624434001  961 krHHKKTTDMIKEHTARQNEQH----------SQHLRHRASMQKSAKRDGQEQ 1003
Cdd:pfam11498  365 --HQQQQMLLQQQQQMHQLQQHhqmngggqfaTQAHQHAAYLQQMQHMRLQEQ 415

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 1624434001  154 EKIYTRLKLQLNPDGCIPVKNIFRMFSADRKRVETALENCNLSSGRNDAIPQDDFTTEIFKAFLNSICPRPDIDTIFSEV 233
Cdd:cd16208      1 EKAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1624434001  234 GAKSRPYLTVEQLTDFINNKQRDPRLNEILYPPLKVEQVQTLVEKYEPNAMLSQRGQISVEGFTRYLSGEE 304
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 1624434001   22 LKKGSKFMKWDDDSTSVTPVTLRVDPQGYFLYWTDQNKETDVLDISTIKDTRNGKYAKLPKDTKLRElLDVGAMVGKMEN 101
Cdd:cd13361      1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKERE-VNVGGSDEDLED 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1624434001  102 RVLTVVFGPDMVNISFLNFVAFQEDLAKEWTGELFSLASNLLAQNMSR 149
Cdd:cd13361     80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

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 1624434001   18 VPESLKKGSKFMKWDDDSTSVTP-VTLRVDPQGYFLYWTDQNKETDVLDISTIKDTRNGKYAKLPKDTKLRELLDVGAMV 96
Cdd:pfam17787    2 VPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGSD 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1624434001   97 GKMENRVLTVVFGPDMVNISFLNFVAFQEDLAKEWTGELFSLASNLLAQN 146
Cdd:pfam17787   82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

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 1624434001  706 TLSVKIISGQFLSD------RKVGTYVEVDMFGLPVDTKRKaFRTKTSPGNSVNPVWEEEpIVFKkVVLPTLASLRIAVY 779
Cdd:cd00275      3 TLTIKIISGQQLPKpkgdkgSIVDPYVEVEIHGLPADDSAK-FKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1624434001  780 EDGG---KFIGHRIIPVSAIRPGYHYVGLRNEKNQSLTLPALFIYIEVK 825
Cdd:cd00275     80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  705 NTLSVKIISGQFLSDRKVG----TYVEVDMfglpvDTKRKAFRTKTSPgNSVNPVWEEEpIVFkKVVLPTLASLRIAVYE 780
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNgtsdPYVKVYL-----LDGKQKKKTKVVK-NTLNPVWNET-FTF-SVPDPENAVLEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1624434001  781 DGG----KFIGHRIIPVSAIRPGYHYVGLRN 807
Cdd:pfam00168   73 YDRfgrdDFIGEVRIPLSELDSGEGLDGWYP 103

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 1624434001  929 TDLEAQSMEELKQQKVFVREQRRQYKELKELVKRHHKKTTDMIK 972
Cdd:pfam06631    2 IKFPPITLESLRQDKAYLKLLKKQQKELESLKKKHSKERSAMQK 45

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 1624434001  316 SEDMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTTEEEPVITHGFTMTSEISFKEVIEA 395
Cdd:cd08623      1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  396 IAESAFKTSPFPVILSFENHVDSPKQQAKMAEYCKSIFGDALLTEALEKFPLEQGVALPSPMDLMGKILIKNKKksqkad 475
Cdd:cd08623     81 IAECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK------ 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  476 gstkkklteqtsntysdtssmcepsspstgsnhqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeckksid 555
Cdd:cd08623        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  556 edtagsetfateeMSNLVNYIQPVKFTSFVAAKETNRSYEMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDS 635
Cdd:cd08623    155 -------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDS 221

                          330       340       350
                   ....*....|....*....|....*....|....*..
gi 1624434001  636 SNYMPQVFWNAGCQLVALNFQVIDLSMQLNLGMYEYN 672
Cdd:cd08623    222 SNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 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 1624434001  316 SEDMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTTEEEPVITHGFTMTSEISFKEVIEA 395
Cdd:cd08624      1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  396 IAESAFKTSPFPVILSFENHVDSPKQQAKMAEYCKSIFGDALLTEALEKFPLEQGVALPSPMDLMGKILIKNKKksqkad 475
Cdd:cd08624     81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  476 gstkkklteqtsntysdtssmcepsspstgsnhqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeckksid 555
Cdd:cd08624        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  556 edtagsetfaTEEMSNLVNYIQPVKFTSFVAAKETNRSYEMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDS 635
Cdd:cd08624    155 ----------YEEMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDS 224

                          330       340       350
                   ....*....|....*....|....*....|....*..
gi 1624434001  636 SNYMPQVFWNAGCQLVALNFQVIDLSMQLNLGMYEYN 672
Cdd:cd08624    225 SNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 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 1624434001  318 DMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTTEEEPVITHGFTMTSEISFKEVIEAIA 397
Cdd:cd08626      3 DMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQAIK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  398 ESAFKTSPFPVILSFENHVdSPKQQAKMAEYCKSIFGDALLTEALEKFPLEQGVALPSPMDLMGKILIKNKKksqkadgs 477
Cdd:cd08626     83 DTAFVTSDYPVILSFENHC-SKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKR-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  478 tkkklteqtsntysdtssmcepsspstgsnhqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeckksided 557
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  558 tagsetfateeMSNLVNYIQPVKFTSFVAAKETNRSYEMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDSSN 637
Cdd:cd08626    154 -----------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSN 222

                          330       340       350
                   ....*....|....*....|....*....|....*
gi 1624434001  638 YMPQVFWNAGCQLVALNFQVIDLSMQLNLGMYEYN 672
Cdd:cd08626    223 YMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  317 EDMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtTEEEPVITHGFTMTSEISFKEVIEAI 396
Cdd:cd08597      2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDG--PNGEPVIYHGHTLTSKISFRSVIEAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  397 AESAFKTSPFPVILSFENHVdSPKQQAKMAEYCKSIFGDALLTEalekFPLEQGVALPSPMDLMGKILIKNKKksqkadg 476
Cdd:cd08597     80 NEYAFVASEYPLILCIENHC-SEKQQLVMAQYLKEIFGDKLYTE----PPNEGESYLPSPHDLKGKIIIKGKK------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  477 sTKK-KLteqtsntysdtssmcepsspstgsnhqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeCKksid 555
Cdd:cd08597    148 -LKRrKL-------------------------------------------------------------------CK---- 155

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  556 edtagsetfateEMSNLVNYIQPVKFTSFVAAKETNRSYEMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDS 635
Cdd:cd08597    156 ------------ELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDS 223

                          330       340       350
                   ....*....|....*....|....*....|....*..
gi 1624434001  636 SNYMPQVFWNAGCQLVALNFQVIDLSMQLNLGMYEYN 672
Cdd:cd08597    224 SNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

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 1624434001  316 SEDMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRttEEEPVITHGFTMTSEISFKEVIEA 395
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGD--DGEPVVTHGYTLTSSVPFRDVCRA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  396 IAESAFKTSPFPVILSFENHVDsPKQQAKMAEYCKSIFGDALLTEALEkfplEQGVALPSPMDLMGKILIKNKKksqkad 475
Cdd:cd08598     79 IKKYAFVTSPYPLILSLEVHCD-AEQQERMVEIMKETFGDLLVTEPLD----GLEDELPSPEELRGKILIKVKK------ 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  476 gstkkklteqtsntysdtssmcEPSSPstgsNHqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeckksid 555
Cdd:cd08598    148 ----------------------ESKTP----NH----------------------------------------------- 154

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  556 edtagsetfateemsnlvnyiqpvkftsfvaaketnrsyeMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDS 635
Cdd:cd08598    155 ----------------------------------------IFSLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISS 194

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1624434001  636 SNYMPQVFWNAGCQLVALNFQVIDLSMQLNLGMY 669
Cdd:cd08598    195 SNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228

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 1624434001  317 EDMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtTEEEPVITHGFTMTSEISFKEVIEAI 396
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDG--DDGMPIIYHGHTLTTKIPFKDVVEAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  397 AESAFKTSPFPVILSFENHVDSPkQQAKMAEYCKSIFGDALLTEALEKFPLEQGVALPSPMDLMGKILIKNKKksqkadg 476
Cdd:cd08596     80 NRSAFITSDYPVILSIENHCSLQ-QQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLKNKILLKNKK------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  477 stkkklteqtsntysdtssmcepsspstgsnhqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeckkside 556
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  557 dtagsetfaTEEMSNLVNYIQPVKFTSFVAAKetnrSYEMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDSS 636
Cdd:cd08596    152 ---------APELSDLVIYCQAVKFPGLSTPK----CYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSS 218

                          330       340       350
                   ....*....|....*....|....*....|....*.
gi 1624434001  637 NYMPQVFWNAGCQLVALNFQVIDLSMQLNLGMYEYN 672
Cdd:cd08596    219 NPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

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 1624434001  317 EDMTLPLSHYLINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtTEEEPVITHGFTMTSEISFKEVIEAI 396
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVLRAI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  397 AESAFKTSPFPVILSFENHVdSPKQQAKMAEYCKSIFGDALLTEALEkfplEQGVALPSPMDLMGKILIKNKkksqkadg 476
Cdd:cd08629     80 RDYAFKASPYPVILSLENHC-SLEQQRVMARHLRAILGPILLDQPLD----GVTTSLPSPEQLKGKILLKGK-------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  477 stKKKLteqtsntysdtssmcepsspstgsnhqetsdqtnhgpgeggdgkqqgtksngepeaeseedededdeckkside 556
Cdd:cd08629    147 --KLKL-------------------------------------------------------------------------- 150

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1624434001  557 dtagsetfaTEEMSNLVNYIQPVKFTSFVAAKETNRS-YEMSSFVETKALEQLTKSPVEFVEYNKLQLSRIYPKGTRYDS 635
Cdd:cd08629    151 ---------VPELSDMIIYCKSVHFGGFSSPGTSGQAfYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDS 221