NCBI Conserved Domain Search

Conserved domains on [gi|45552167|ref|NP_995606|]

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phospholipase C at 21C, isoform C [Drosophila melanogaster]

Protein Classification

EFh_PI-PLC21 and PI-PLCc_beta domain-containing protein( domain architecture ID 11598292)

protein containing domains PH_PLC_beta, EFh_PI-PLC21, PI-PLCc_beta, and C2_PLC_like

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

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

317-702

8.58e-162

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 483.76 E-value: 8.58e-162

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRT--EEPVIVHGYTFVPEIFAKDVLEA 394
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGedEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  395 IAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLRRkiiiknkkkhhhhhh 474
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKR--------------- 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  475 hhhhkkpaqvgtpaannKLTTANSvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqssk 554
Cdd:cd08591  146 -----------------KILIKNK-------------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  555 dstgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQA 634
Cdd:cd08591  153 -------------------------------------------KLSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKG 189

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  635 TTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08591  190 LGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

EFh_PI-PLC21

cd16213

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

151-305

2.41e-91

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family includes invertebrate homologs of phosphoinositide phospholipase C beta (PI-PLC-beta) named PLC21 from cephalopod retina. It also includes PLC21 encoded by plc-21 gene, which is expressed in the central nervous system of Drosophila. Like beta-class of vertebrate PI-PLCs, PLC21 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320043 Cd Length: 154 Bit Score: 291.13 E-value: 2.41e-91

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAQNKEDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16213    1 EKAYTKLTLQTDKEGKIPVKNIVKMFAQHKDDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIF 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 DSIvGNSKRKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16213   81 DEL-GAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

PH_PLC_beta

cd13361

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

20-145

3.31e-56

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is regulated by heterotrimeric G protein-coupled receptors through their C2 domain and long C-terminal extension which forms an autoinhibitory helix. There are four isoforms: PLC-beta1-4. The PH domain of PLC-beta2 and PLC-beta3 plays a dual role, much like PLC-delta1, by binding to the plasma membrane, as well as the interaction site for the catalytic activator. However, PLC-beta binds to the lipid surface independent of PIP2. PLC-beta1 seems to play unspecified roles in cellular proliferation and differentiation. PLC-beta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, a C2 domain and a C-terminal PDZ. Members of the Rho GTPase family (e.g., Rac1, Rac2, Rac3, and cdc42) have been implicated in their activation by binding to an alternate site on the N-terminal PH domain. A basic amino acid region within the enzyme's long C-terminal tail appears to function as a Nuclear Localization Signal for import into the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

Pssm-ID: 270167 Cd Length: 127 Bit Score: 190.47 E-value: 3.31e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   20 LQDGEKFIRWDDDSGTGTPVTMRVDAKGFFLYWVDQNNELDILDIATIRDVRTGQYAKRPKDNKLRQIVTLGPQDTLEEK 99
Cdd:cd13361    1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREVNVGGSDEDLEDR 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 45552167  100 TVTVCHGSDFVNMTFVNFCCTRRDIAQLWTDGLIKLAYSLAQLNGS 145
Cdd:cd13361   81 TLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNAS 126

C2_PLC_like

cd00275

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

736-855

1.34e-36

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 134.59 E-value: 1.34e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  736 TVSITVLSGQFL------TDKRANTFVEVDMYGLPADTvRKKFRTKTVRDNGMNPLYDEEpFVFKkVVLPELASIRIAAY 809
Cdd:cd00275    3 TLTIKIISGQQLpkpkgdKGSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 45552167  810 EEGG---KLIGHRVLPVIGLCPGYRHVNLRSEVGQPIALASLFLCVVVK 855
Cdd:cd00275   80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

SMC_prok_B super family

cl37069

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

1005-1244

3.89e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

The actual alignment was detected with superfamily member TIGR02168:

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 48.13 E-value: 3.89e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1005 KSVKEKRLEMEKKLESLRKKHDKEKIKIAGQKSSpLEGKKPKFAITNKLVKRLSNKSLEPGVEIPACPLDLGDSSEESAA 1084
Cdd:TIGR02168  701 AELRKELEELEEELEQLRKELEELSRQISALRKD-LARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAE 779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1085 ADAG-----EDLAGGSSSLDgrTQESRLRSACREYTSQYRELQEKY-----HEAIYSAAEKVLKTSQtGQTKQLKASLDK 1154
Cdd:TIGR02168  780 AEAEieeleAQIEQLKEELK--ALREALDELRAELTLLNEEAANLRerlesLERRIAATERRLEDLE-EQIEELSEDIES 856

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1155 VTGEvMHQLQEARRNEVKNL--ATVHRDRDELIRMKREVASSVVERGVAERVRLKQTFDRRTDELQKQHDSVRNALAEHR 1232
Cdd:TIGR02168  857 LAAE-IEELEELIEELESELeaLLNERASLEEALALLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGLE 935

                          250
                   ....*....|..
gi 45552167   1233 SKARQILDKEAE 1244
Cdd:TIGR02168  936 VRIDNLQERLSE 947

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

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

317-702

8.58e-162

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 483.76 E-value: 8.58e-162

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRT--EEPVIVHGYTFVPEIFAKDVLEA 394
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGedEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  395 IAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLRRkiiiknkkkhhhhhh 474
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKR--------------- 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  475 hhhhkkpaqvgtpaannKLTTANSvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqssk 554
Cdd:cd08591  146 -----------------KILIKNK-------------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  555 dstgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQA 634
Cdd:cd08591  153 -------------------------------------------KLSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKG 189

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  635 TTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08591  190 LGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

EFh_PI-PLC21

cd16213

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

151-305

2.41e-91

Pssm-ID: 320043 Cd Length: 154 Bit Score: 291.13 E-value: 2.41e-91

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAQNKEDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16213    1 EKAYTKLTLQTDKEGKIPVKNIVKMFAQHKDDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIF 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 DSIvGNSKRKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16213   81 DEL-GAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

PI-PLC-X

pfam00388

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

320-459

3.42e-70

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

Pssm-ID: 459795 [Multi-domain] Cd Length: 142 Bit Score: 231.24 E-value: 3.42e-70

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    320 MDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAESA 399
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    400 FKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDshplEPNMDLPPPAMLRR 459
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLD----DDLTELPSPEDLKG 136

PLCXc

smart00148

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

320-459

3.43e-67

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 222.54 E-value: 3.43e-67

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     320 MDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAESA 399
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     400 FKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEpnmdLPPPAMLRR 459
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQLRG 136

PLN02222

phosphoinositide phospholipase C 2

213-850

2.07e-57

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 209.50 E-value: 2.07e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   213 FYNLYKYLTQRS--EVERLFDSIvgnSKRKCMSIAQLVEFLNKTQRDPRlneilypyANPARAKELIQQYEPNkfnAQKG 290
Cdd:PLN02222   12 FRRRFRYTASEAprEIKTIFEKY---SENGVMTVDHLHRFLIDVQKQDK--------ATREDAQSIINSASSL---LHRN 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   291 QLSLDGFLRYLMGDDNPIMAPSKLDlcDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGR 370
Cdd:PLN02222   78 GLHLDAFFKYLFGDNNPPLALHEVH--HDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNS 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   371 TEEPV-IVHGYTFVPEIFAKDVLEAIAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDshplEPNM 449
Cdd:PLN02222  156 DKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVG----ESLK 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   450 DLPPPAMLRRkiiiknkkkhhhhhHHHHHKKPAQVGTPAANNKLTTA--NSVDAKAAQQVGLSASHEDGGVTRSTANGDV 527
Cdd:PLN02222  232 EFPSPNSLKK--------------RIIISTKPPKEYKEGKDDEVVQKgkDLGDEEVWGREVPSFIQRNKSVDKNDSNGDD 297

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   528 ATGTGTGSaagtaghapplQQIRQsskdstgssdsdsssedeslpnttpnlpsgNEPPPEKAQKETEAGAEISALVNYVQ 607
Cdd:PLN02222  298 DDDDDDGE-----------DKSKK------------------------------NAPPQYKHLIAIHAGKPKGGITECLK 336

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   608 PihfssfeNAEKKNRCyemsSFDEKQATTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQT 687
Cdd:PLN02222  337 V-------DPDKVRRL----SLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQG 405

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   688 LDLAMQLNLGIFEYNARSGYLLKPEFMRRSDRRLDPF-AESTVDgiIAGTVSITVLSGQ-FLTDKRANTF---------V 756
Cdd:PLN02222  406 YGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDSDIFdPKATLP--VKTTLRVTIYMGEgWYFDFRHTHFdqysppdfyT 483

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   757 EVDMYGLPADTVRKKfrTKTVRDNGMnPLYDEepfVFK-KVVLPELASIRIAAYE----EGGKLIGHRVLPVIGLCPGYR 831
Cdd:PLN02222  484 RVGIAGVPGDTVMKK--TKTLEDNWI-PAWDE---VFEfPLTVPELALLRLEVHEydmsEKDDFGGQTCLPVWELSQGIR 557

                         650
                  ....*....|....*....
gi 45552167   832 HVNLRSEVGQPIALASLFL 850
Cdd:PLN02222  558 AFPLHSRKGEKYKSVKLLV 576

PH_PLC_beta

cd13361

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

20-145

3.31e-56

Pssm-ID: 270167 Cd Length: 127 Bit Score: 190.47 E-value: 3.31e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   20 LQDGEKFIRWDDDSGTGTPVTMRVDAKGFFLYWVDQNNELDILDIATIRDVRTGQYAKRPKDNKLRQIVTLGPQDTLEEK 99
Cdd:cd13361    1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREVNVGGSDEDLEDR 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 45552167  100 TVTVCHGSDFVNMTFVNFCCTRRDIAQLWTDGLIKLAYSLAQLNGS 145
Cdd:cd13361   81 TLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNAS 126

PH_14

pfam17787

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

15-143

1.75e-50

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

Pssm-ID: 465506 Cd Length: 131 Bit Score: 174.49 E-value: 1.75e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     15 EVPQALQDGEKFIRWDDDSGTGTP-VTMRVDAKGFFLYWVDQNNELDILDIATIRDVRTGQYAKRPKDNKLRQIVTL-GP 92
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMgGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 45552167     93 QDTLEEKTVTVCHGSDFVNMTFVNFCCTRRDIAQLWTDGLIKLAYSLAQLN 143
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

C2_PLC_like

cd00275

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

736-855

1.34e-36

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 134.59 E-value: 1.34e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  736 TVSITVLSGQFL------TDKRANTFVEVDMYGLPADTvRKKFRTKTVRDNGMNPLYDEEpFVFKkVVLPELASIRIAAY 809
Cdd:cd00275    3 TLTIKIISGQQLpkpkgdKGSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 45552167  810 EEGG---KLIGHRVLPVIGLCPGYRHVNLRSEVGQPIALASLFLCVVVK 855
Cdd:cd00275   80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

EF-hand_like

pfam09279

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

216-308

3.87e-17

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme.

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 77.29 E-value: 3.87e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    216 LYKYLTQRSEVERLFDSIVGNSKRkcMSIAQLVEFLNKTQRDPRlneilypyANPARAKELIQQYEPNKFNAQKGQLSLD 295
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQK--LSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKD 70

                           90
                   ....*....|...
gi 45552167    296 GFLRYLMGDDNPI 308
Cdd:pfam09279   71 GFLMYLCSPDGSI 83

smart00239

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

736-835

9.08e-12

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

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 62.89 E-value: 9.08e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     736 TVSITVLSGQFLTDKR----ANTFVEVDMYGLPadtvRKKFRTKTVRDNGmNPLYDEEpFVFkKVVLPELASIRIAAYEE 811
Cdd:smart00239    1 TLTVKIISARNLPPKDkggkSDPYVKVSLDGDP----KEKKKTKVVKNTL-NPVWNET-FEF-EVPPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 45552167     812 GG----KLIGHRVLPVIGLCPGYRHVNL 835
Cdd:smart00239   74 DRfgrdDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

735-823

1.59e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 45.00 E-value: 1.59e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    735 GTVSITVLSGQFLTDK----RANTFVEVDMyglpaDTVRKKFRTKTVRDNGmNPLYDEEpFVFkKVVLPELASIRIAAYE 810
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKdgngTSDPYVKVYL-----LDGKQKKKTKVVKNTL-NPVWNET-FTF-SVPDPENAVLEIEVYD 72

                           90
                   ....*....|....*..
gi 45552167    811 EGG----KLIGHRVLPV 823
Cdd:pfam00168   73 YDRfgrdDFIGEVRIPL 89

SMC_prok_B

TIGR02168

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

1005-1244

3.89e-05

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 48.13 E-value: 3.89e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1005 KSVKEKRLEMEKKLESLRKKHDKEKIKIAGQKSSpLEGKKPKFAITNKLVKRLSNKSLEPGVEIPACPLDLGDSSEESAA 1084
Cdd:TIGR02168  701 AELRKELEELEEELEQLRKELEELSRQISALRKD-LARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAE 779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1085 ADAG-----EDLAGGSSSLDgrTQESRLRSACREYTSQYRELQEKY-----HEAIYSAAEKVLKTSQtGQTKQLKASLDK 1154
Cdd:TIGR02168  780 AEAEieeleAQIEQLKEELK--ALREALDELRAELTLLNEEAANLRerlesLERRIAATERRLEDLE-EQIEELSEDIES 856

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1155 VTGEvMHQLQEARRNEVKNL--ATVHRDRDELIRMKREVASSVVERGVAERVRLKQTFDRRTDELQKQHDSVRNALAEHR 1232
Cdd:TIGR02168  857 LAAE-IEELEELIEELESELeaLLNERASLEEALALLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGLE 935

                          250
                   ....*....|..
gi 45552167   1233 SKARQILDKEAE 1244
Cdd:TIGR02168  936 VRIDNLQERLSE 947

PTZ00121

MAEBL; Provisional

981-1246

4.16e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 48.21 E-value: 4.16e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   981 RQVESSQFDVDLVLAEPLEKILDHKSVKE-KRLEMEKKLESLRKKHDKEKI----KIAGQKSSPLEGKKPKFAITNKLVK 1055
Cdd:PTZ00121 1176 KKAEAARKAEEVRKAEELRKAEDARKAEAaRKAEEERKAEEARKAEDAKKAeavkKAEEAKKDAEEAKKAEEERNNEEIR 1255

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1056 RLSNKSLEPGVEIPACP-------LDLGDSSEESAAADAGE--DLAGGSSSLDGRTQESR----LRSACREYTSQYRELQ 1122
Cdd:PTZ00121 1256 KFEEARMAHFARRQAAIkaeearkADELKKAEEKKKADEAKkaEEKKKADEAKKKAEEAKkadeAKKKAEEAKKKADAAK 1335

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1123 EKYHEAiySAAEKVLKTSQTGQTKQLKASLDKV------TGEVMHQLQEARRN--EVKNLATVHRDRDELIRMKREVASS 1194
Cdd:PTZ00121 1336 KKAEEA--KKAAEAAKAEAEAAADEAEAAEEKAeaaekkKEEAKKKADAAKKKaeEKKKADEAKKKAEEDKKKADELKKA 1413

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 45552167  1195 VVERGVAERVRLKQTFDRRTDELQKQHDSVRNA-----LAEHRSKARQILDKEAESR 1246
Cdd:PTZ00121 1414 AAAKKKADEAKKKAEEKKKADEAKKKAEEAKKAdeakkKAEEAKKAEEAKKKAEEAK 1470

Name

Accession

Description

Interval

E-value

PI-PLCc_beta

cd08591

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

317-702

8.58e-162

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 483.76 E-value: 8.58e-162

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRT--EEPVIVHGYTFVPEIFAKDVLEA 394
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGedEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  395 IAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLRRkiiiknkkkhhhhhh 474
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKR--------------- 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  475 hhhhkkpaqvgtpaannKLTTANSvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqssk 554
Cdd:cd08591  146 -----------------KILIKNK-------------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  555 dstgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQA 634
Cdd:cd08591  153 -------------------------------------------KLSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKG 189

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  635 TTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08591  190 LGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

PI-PLCc_eukaryota

cd08558

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

317-702

9.54e-119

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.

Pssm-ID: 176501 [Multi-domain] Cd Length: 226 Bit Score: 368.70 E-value: 9.54e-119

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIA 396
Cdd:cd08558    1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  397 ESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEpnmdLPPPAMLRrkiiiknkkkhhhhhhhh 476
Cdd:cd08558   81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQ----LPSPEQLK------------------ 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  477 hhkkpaqvgtpaanNKLttansvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskds 556
Cdd:cd08558  139 --------------GKI--------------------------------------------------------------- 141

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  557 tgssdsdsssedeslpnttpnlpsgnepppekaqketeagaeisaLVnyvqpihfssfenaekKNRCYEMSSFDEKQATT 636
Cdd:cd08558  142 ---------------------------------------------LI----------------KGKKYHMSSFSETKALK 160

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45552167  637 LLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08558  161 LLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_beta4

cd08626

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

319-702

2.35e-116

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.

Pssm-ID: 176563 [Multi-domain] Cd Length: 257 Bit Score: 363.70 E-value: 2.35e-116

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTE--EPVIVHGYTFVPEIFAKDVLEAIA 396
Cdd:cd08626    3 DMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEdqEPIITHGKAMCTDILFKDVIQAIK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  397 ESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLRRkiiiknkkkhhhhhhhh 476
Cdd:cd08626   83 DTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKR----------------- 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  477 hhkkpaqvgtpaannKLTTANSvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskds 556
Cdd:cd08626  146 ---------------KILIKNK---------------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  557 tgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATT 636
Cdd:cd08626  153 -----------------------------------------RLSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLG 191

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45552167  637 LLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08626  192 YLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

PI-PLCc_beta3

cd08625

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

318-702

6.82e-112

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.

Pssm-ID: 176562 [Multi-domain] Cd Length: 258 Bit Score: 351.66 E-value: 6.82e-112

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  318 DDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGR--TEEPVIVHGYTFVPEIFAKDVLEAI 395
Cdd:cd08625    2 DDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRppEEEPFITHGFTMTTEIPFKDVIEAI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  396 AESAFKTSEYPVILSFENHCN-PRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLrrkiiiknkkkhhhhhh 474
Cdd:cd08625   82 AESAFKTSPYPVILSFENHVDsAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQEL----------------- 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  475 hhhhkkpaqVGTPAANNKlttansvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqssk 554
Cdd:cd08625  145 ---------MGKILVKNK-------------------------------------------------------------- 153

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  555 dstgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQA 634
Cdd:cd08625  154 -------------------------------------------KMSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKA 190

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  635 TTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08625  191 MEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

PI-PLCc_beta2

cd08624

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

319-702

2.51e-111

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.

Pssm-ID: 176561 [Multi-domain] Cd Length: 261 Bit Score: 350.13 E-value: 2.51e-111

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGR--TEEPVIVHGYTFVPEIFAKDVLEAIA 396
Cdd:cd08624    3 DMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMTTEILFKDAIEAIA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  397 ESAFKTSEYPVILSFENHCN-PRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLRrkiiiknkkkhhhhhhh 475
Cdd:cd08624   83 ESAFKTSPYPVILSFENHVDsPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLR----------------- 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  476 hhhkkpaqvgtpaanNKLTTANsvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskd 555
Cdd:cd08624  146 ---------------GKILIKN---------------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  556 stgssdsdsssedeslpnttpnlpsgnepppekaqKETEagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQAT 635
Cdd:cd08624  153 -----------------------------------KKYE---EMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAY 194

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552167  636 TLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08624  195 DLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261

PI-PLCc_delta

cd08593

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

317-702

2.82e-100

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

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 320.05 E-value: 2.82e-100

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIA 396
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  397 ESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDShplePNMDLPPPAMLRRKIIIKnkkkhhhhhhhh 476
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDG----VLTALPSPEELKGKILVK------------ 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  477 hhkkpaqvgtpaaNNKLTTANsvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskds 556
Cdd:cd08593  145 -------------GKKLKLAK----------------------------------------------------------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  557 tgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATT 636
Cdd:cd08593  153 -----------------------------------------ELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALK 191

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45552167  637 LLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08593  192 LAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

PI-PLCc_beta1

cd08623

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

318-702

6.60e-99

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.

Pssm-ID: 176560 [Multi-domain] Cd Length: 258 Bit Score: 316.25 E-value: 6.60e-99

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  318 DDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRT--EEPVIVHGYTFVPEIFAKDVLEAI 395
Cdd:cd08623    2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTaeEEPVITHGFTMTTEISFKEVIEAI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  396 AESAFKTSEYPVILSFENHCN-PRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLrrkiiiknkkkhhhhhh 474
Cdd:cd08623   82 AECAFKTSPFPILLSFENHVDsPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDL----------------- 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  475 hhhhkkpaqVGTPAANNKlttansvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqssk 554
Cdd:cd08623  145 ---------MYKILVKNK-------------------------------------------------------------- 153

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  555 dstgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQA 634
Cdd:cd08623  154 -------------------------------------------KMSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKG 190

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  635 TTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08623  191 LEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258

EFh_PI-PLC21

cd16213

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

151-305

2.41e-91

Pssm-ID: 320043 Cd Length: 154 Bit Score: 291.13 E-value: 2.41e-91

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAQNKEDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16213    1 EKAYTKLTLQTDKEGKIPVKNIVKMFAQHKDDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIF 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 DSIvGNSKRKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16213   81 DEL-GAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

PI-PLCc_PRIP_metazoa

cd08597

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

317-702

3.11e-81

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

Pssm-ID: 176539 [Multi-domain] Cd Length: 260 Bit Score: 267.36 E-value: 3.11e-81

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIA 396
Cdd:cd08597    1 CQDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  397 ESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPldshPLEPNMDLPPPAMLRRKIiiknkkkhhhhhhhh 476
Cdd:cd08597   81 EYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEP----PNEGESYLPSPHDLKGKI--------------- 141

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  477 hhkkpaqvgtpaannklttanSVDAKAAQQVGLsashedggvtrstangdvatgtgtgsaagtaghapplqqIRqsskds 556
Cdd:cd08597  142 ---------------------IIKGKKLKRRKL---------------------------------------CK------ 155

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  557 tgssdsdsssedeslpnttpnlpsgnepppekaqketeagaEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATT 636
Cdd:cd08597  156 -----------------------------------------ELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARR 194

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45552167  637 LLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08597  195 LANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLCc_gamma

cd08592

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

317-702

5.54e-76

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.

Pssm-ID: 176534 [Multi-domain] Cd Length: 229 Bit Score: 251.19 E-value: 5.54e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  317 CDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIA 396
Cdd:cd08592    1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  397 ESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDshplePNMD-LPPPAMLRRkiiiknkkkhhhhhhh 475
Cdd:cd08592   81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVD-----RNADqLPSPNQLKR---------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  476 hhhkkpaqvgtpaannKLTTANsvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskd 555
Cdd:cd08592  140 ----------------KIIIKH---------------------------------------------------------- 145

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  556 stgssdsdsssedeslpnttpnlpsgnepppekaqketeagaeisalvnyvqpihfssfenaekKNRCYEMSSFDEKQAT 635
Cdd:cd08592  146 ----------------------------------------------------------------KKLFYEMSSFPETKAE 161

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  636 TLL-KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08592  162 KYLnRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLC1c_yeast

cd08598

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

319-699

1.75e-73

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.

Pssm-ID: 176540 [Multi-domain] Cd Length: 231 Bit Score: 244.08 E-value: 1.75e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08598    3 DLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKKY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEpnmdLPPPAMLRrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08598   83 AFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDE----LPSPEELR-------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaannklttansvdakaaqqvglsashedggvtrstanGDVATgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08598  139 ----------------------------------------------GKILI----------------------------- 143

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnlpsgnepppeKAQKEteagaeisalvnyvqpihfssfenAEKKNRCYemsSFDEKQATTLL 638
Cdd:cd08598  144 -----------------------------KVKKE------------------------SKTPNHIF---SLSERSLLKLL 167

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45552167  639 KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIF 699
Cdd:cd08598  168 KDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228

PI-PLCc_epsilon

cd08596

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

318-702

1.28e-72

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.

Pssm-ID: 176538 [Multi-domain] Cd Length: 254 Bit Score: 242.83 E-value: 1.28e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  318 DDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAE 397
Cdd:cd08596    2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  398 SAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEPNMDLPPPAMLRrkiiiknkkkhhhhhhhhh 477
Cdd:cd08596   82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSDDPSLPSPLQLK------------------- 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  478 hkkpaqvgtpaanNKLTTANsvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskdst 557
Cdd:cd08596  143 -------------NKILLKN------------------------------------------------------------ 149

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  558 gssdsdsssedeslpnttpnlpsgnepppEKAQketeagaEISALVNYVQPIHFSSFENAekknRCYEMSSFDEKQATTL 637
Cdd:cd08596  150 -----------------------------KKAP-------ELSDLVIYCQAVKFPGLSTP----KCYHISSLNENAAKRL 189

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  638 LKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08596  190 CRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PI-PLCc_delta4

cd08631

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

319-702

3.11e-71

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.

Pssm-ID: 176568 [Multi-domain] Cd Length: 258 Bit Score: 239.08 E-value: 3.11e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08631    3 DMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSH-PLEpnmdLPPPAMLRRkiiiknkkkhhhhhhhhh 477
Cdd:cd08631   83 AFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVlPTQ----LPSPEELRG------------------ 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  478 hkkpaqvgtpaannklttansvdakaaqQVGLSAshedggvtrstangdvatgtgtgsaagtaghapplqqirqsskdst 557
Cdd:cd08631  141 ----------------------------KILLKG---------------------------------------------- 146

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  558 gssdsdsssedeslpnttpnlpsgnepppekaqKETEAGAEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATTL 637
Cdd:cd08631  147 ---------------------------------KKIRLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKL 193

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  638 LKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08631  194 IREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_delta1

cd08629

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

319-702

4.58e-71

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.

Pssm-ID: 176566 [Multi-domain] Cd Length: 258 Bit Score: 238.40 E-value: 4.58e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08629    3 DMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRDY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEpnmdLPPPAMLRrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08629   83 AFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVTTS----LPSPEQLK-------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaannklttansvdakaaqqvglsashedggvTRSTANGdvatgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08629  139 ----------------------------------------GKILLKG--------------------------------- 145

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnlpsgnepppekaqKETEAGAEISALVNYVQPIHFSSFENA-EKKNRCYEMSSFDEKQATTL 637
Cdd:cd08629  146 --------------------------------KKLKLVPELSDMIIYCKSVHFGGFSSPgTSGQAFYEMASFSESRALRL 193

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  638 LKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08629  194 LQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLCc_delta3

cd08630

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

319-702

9.68e-71

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.

Pssm-ID: 176567 [Multi-domain] Cd Length: 258 Bit Score: 237.61 E-value: 9.68e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08630    3 DMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQH 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEpnmDLPPPAMLRrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08630   83 AFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPE---ELPSPEELK-------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaannklttansvdakaaqqvglsashedggvTRSTANGdvatgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08630  140 ----------------------------------------GRVLVKG--------------------------------- 146

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnlpsgnepppekaqKETEAGAEISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATTLL 638
Cdd:cd08630  147 --------------------------------KKLQISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLI 194

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552167  639 KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08630  195 REAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

PI-PLC-X

pfam00388

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

320-459

3.42e-70

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

Pssm-ID: 459795 [Multi-domain] Cd Length: 142 Bit Score: 231.24 E-value: 3.42e-70

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    320 MDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAESA 399
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    400 FKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDshplEPNMDLPPPAMLRR 459
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLD----DDLTELPSPEDLKG 136

PLCXc

smart00148

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

320-459

3.43e-67

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 222.54 E-value: 3.43e-67

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     320 MDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAESA 399
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     400 FKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHPLEpnmdLPPPAMLRR 459
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQLRG 136

PI-PLCc_zeta

cd08595

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

319-702

9.87e-67

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.

Pssm-ID: 176537 [Multi-domain] Cd Length: 257 Bit Score: 225.97 E-value: 9.87e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08595    3 DMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEKY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDsHPlePNMDLPPPAMLRrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08595   83 AFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPID-DP--ATGELPSPEALK-------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaanNKLTTANsvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08595  140 ------------FKILVKN------------------------------------------------------------- 146

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnlpsgnepppekaQKETEAGaeISALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATTLL 638
Cdd:cd08595  147 -------------------------------KKKIAKA--LSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLL 193

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552167  639 KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08595  194 KSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLCc_eta

cd08594

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

319-702

2.61e-66

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.

Pssm-ID: 176536 [Multi-domain] Cd Length: 227 Bit Score: 223.53 E-value: 2.61e-66

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08594    3 DMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINKY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLdkpLDSHPLEPNMDLPPPAMLRrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08594   83 AFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLD---LSSVISGDSKQLPSPQSLK-------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaannklttansvdakaaqqvglsashedggvtrstanGDVatgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08594  140 ----------------------------------------------GKI------------------------------- 142

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnlpsgnepppekaqketeagaeisaLVnyvqpihfssfenaekKNRCYEMSSFDEKQATTLL 638
Cdd:cd08594  143 -------------------------------------------LI----------------KGKKWQVSSFSETRAHQIV 163

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552167  639 KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08594  164 QQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

PLCYc

smart00149

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

600-714

9.85e-65

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 214.41 E-value: 9.85e-65

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     600 SALVNYVQPIHFSSFENAEKKNRCYEMSSFDEKQATTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQ 679
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 45552167     680 LVALNFQTLDLAMQLNLGIFEYNARSGYLLKPEFM 714
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_gamma2

cd08628

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

319-702

1.57e-63

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.

Pssm-ID: 176565 [Multi-domain] Cd Length: 254 Bit Score: 216.85 E-value: 1.57e-63

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08628    3 DMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKDH 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKpldshPLEPNMD-LPPPAMLRRKIIIKnkkkhhhhhhhhh 477
Cdd:cd08628   83 AFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMK-----PLEASADqLPSPTQLKEKIIIK------------- 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  478 hkkpaqvgtpaaNNKLTtansvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskdst 557
Cdd:cd08628  145 ------------HKKLI--------------------------------------------------------------- 149

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  558 gssdsdsssedeslpnttpnlpsgnepppekaqketeaGAEISALVNYVQPIHFS--SFENAEKKnrcyEMSSFDEKQAT 635
Cdd:cd08628  150 --------------------------------------AIELSDLVVYCKPTSKTkdNLENPDFK----EIRSFVETKAP 187

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552167  636 TLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08628  188 SIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254

PI-PLCc_eta2

cd08633

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

319-702

1.77e-63

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.

Pssm-ID: 176570 [Multi-domain] Cd Length: 254 Bit Score: 216.44 E-value: 1.77e-63

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08633    3 DMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLldkPLDSHPLEPNMDLPPPAMLRrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08633   83 AFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKL---DLSSVISNDCTRLPSPEILK-------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaannklttansvdakaaqqvglsashedggvtrstanGDVATgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08633  140 ----------------------------------------------GKILV----------------------------- 144

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnlpsgnepppeKAQKETEAgaeISALVNYVQPIHFSSFENaeKKNRCYEMSSFDEKQATTLL 638
Cdd:cd08633  145 -----------------------------KGKKLSRA---LSDLVKYTKSVRVHDIET--EATSSWQVSSFSETKAHQIL 190

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552167  639 KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08633  191 QQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

EFh_PI-PLCbeta

cd16200

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

151-305

5.85e-61

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta isozymes; PI-PLC-beta isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors (EC 3.1.4.11). They have been implicated in numerous processes relevant to central nervous system (CNS), including chemotaxis, cardiovascular function, neuronal signaling, and opioid sensitivity. Like other PI-PLC isozymes, PI-PLC-beta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, they have a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PI-PLC-beta isozymes (1-4). PI-PLC-beta1 and PI-PLC-beta3 are expressed in a wide range of tissues and cell types, whereas PI-PLC-beta2 and PI-PLC-beta4 have been found only in hematopoietic and neuronal tissues, respectively. All PI-PLC-beta isozymes are activated by the heterotrimeric G protein alpha subunits of the Gq class through their C2 domain and long C-terminal extension. They are GTPase-activating proteins (GAPs) for these G alpha(q) proteins. PI-PLC-beta2 and PI-PLC-beta3 can also be activated by beta-gamma subunits of the G alpha(i/o) family of heterotrimeric G proteins and the small GTPases such as Rac and Cdc42. This family also includes two invertebrate homologs of PI-PLC-beta, PLC21 from cephalopod retina and No receptor potential A protein (NorpA) from Drosophila melanogaster.

Pssm-ID: 320030 [Multi-domain] Cd Length: 153 Bit Score: 205.17 E-value: 5.85e-61

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAqNKEDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16200    1 KKLYTKLKLSVNITGKIPVKNIIKCFS-SDKKRKRVLKALKALGLPDGKNDEIDPEDFTFEKFFKLYNKLCPRPDIDEIF 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 DSIVGNSKRKcMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16200   80 KELGGKRKPY-LTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

PI-PLC-Y

pfam00387

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

600-713

2.34e-60

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 201.92 E-value: 2.34e-60

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    600 SALVNYVQPIHFSSFENAEKKnRCYEMSSFDEKQATTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQ 679
Cdd:pfam00387    2 SDLVVYTQSVKFKSFSTPESK-TPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 45552167    680 LVALNFQTLDLAMQLNLGIFEYNARSGYLLKPEF 713
Cdd:pfam00387   81 MVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PI-PLCc_eta1

cd08632

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

319-702

5.63e-59

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.

Pssm-ID: 176569 [Multi-domain] Cd Length: 253 Bit Score: 203.72 E-value: 5.63e-59

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAES 398
Cdd:cd08632    3 DMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINKY 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  399 AFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLldkpldshplepnmDLpppamlrrkiiiknkkkhhhhhhhhhh 478
Cdd:cd08632   83 AFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKL--------------DL--------------------------- 121

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  479 kkpaqvgtpaannklttaNSVDAKAAQQvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskdstg 558
Cdd:cd08632  122 ------------------SSVLTGDPKQ---------------------------------------------------- 131

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  559 ssdsdsssedeslpnttpnLPSGNEPPPEKAQKETEAGAEISALVNYVQPIhfSSFENAEKKNRCyEMSSFDEKQATTLL 638
Cdd:cd08632  132 -------------------LPSPQLLKGKILVKGKKLCRDLSDLVVYTNSV--AAQDIVDDGSTG-NVLSFSETRAHQLV 189

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552167  639 KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08632  190 QQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PI-PLCc

cd00137

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

319-702

1.31e-57

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.

Pssm-ID: 176497 [Multi-domain] Cd Length: 274 Bit Score: 200.57 E-value: 1.31e-57

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTYLTGHQLT-----GKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVpEIFAKDVLE 393
Cdd:cd00137    3 PDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEVIE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  394 AIAESAFKTSEYPVILSFENHCN--PRQQAKIANYCREIFGDMLLDKPLDshplePNMDLPPPAMLRrkiiiknkkkhhh 471
Cdd:cd00137   82 AIAQFLKKNPPETIIMSLKNEVDsmDSFQAKMAEYCRTIFGDMLLTPPLK-----PTVPLPSLEDLR------------- 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  472 hhhhhhhkkpaqvgtpaanNKLTTANSvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirq 551
Cdd:cd00137  144 -------------------GKILLLNK----------------------------------------------------- 151

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  552 sskdstgssdsdsssedeslpNTTPNLPSGNEPPPEkaqketeagaeisalvnyvqpihFSSFENAEKKNRCYEMSSFDE 631
Cdd:cd00137  152 ---------------------KNGFSGPTGSSNDTG-----------------------FVSFEFSTQKNRSYNISSQDE 187

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  632 KQATTLLKERPIE----FVNYNKHQLSRVYPAGTRF---------DSSNFMPQLFWN---AGCQLVALNFQTLDLAMQLN 695
Cdd:cd00137  188 YKAYDDEKVKLIKatvqFVDYNKNQLSRNYPSGTSGgtawyyyamDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQY 267


                 ....*..
gi 45552167  696 LGIFEYN 702
Cdd:cd00137  268 MAVIEFN 274

PLN02222

phosphoinositide phospholipase C 2

213-850

2.07e-57

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 209.50 E-value: 2.07e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   213 FYNLYKYLTQRS--EVERLFDSIvgnSKRKCMSIAQLVEFLNKTQRDPRlneilypyANPARAKELIQQYEPNkfnAQKG 290
Cdd:PLN02222   12 FRRRFRYTASEAprEIKTIFEKY---SENGVMTVDHLHRFLIDVQKQDK--------ATREDAQSIINSASSL---LHRN 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   291 QLSLDGFLRYLMGDDNPIMAPSKLDlcDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGR 370
Cdd:PLN02222   78 GLHLDAFFKYLFGDNNPPLALHEVH--HDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNS 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   371 TEEPV-IVHGYTFVPEIFAKDVLEAIAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDshplEPNM 449
Cdd:PLN02222  156 DKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVG----ESLK 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   450 DLPPPAMLRRkiiiknkkkhhhhhHHHHHKKPAQVGTPAANNKLTTA--NSVDAKAAQQVGLSASHEDGGVTRSTANGDV 527
Cdd:PLN02222  232 EFPSPNSLKK--------------RIIISTKPPKEYKEGKDDEVVQKgkDLGDEEVWGREVPSFIQRNKSVDKNDSNGDD 297

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   528 ATGTGTGSaagtaghapplQQIRQsskdstgssdsdsssedeslpnttpnlpsgNEPPPEKAQKETEAGAEISALVNYVQ 607
Cdd:PLN02222  298 DDDDDDGE-----------DKSKK------------------------------NAPPQYKHLIAIHAGKPKGGITECLK 336

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   608 PihfssfeNAEKKNRCyemsSFDEKQATTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQT 687
Cdd:PLN02222  337 V-------DPDKVRRL----SLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQG 405

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   688 LDLAMQLNLGIFEYNARSGYLLKPEFMRRSDRRLDPF-AESTVDgiIAGTVSITVLSGQ-FLTDKRANTF---------V 756
Cdd:PLN02222  406 YGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDSDIFdPKATLP--VKTTLRVTIYMGEgWYFDFRHTHFdqysppdfyT 483

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   757 EVDMYGLPADTVRKKfrTKTVRDNGMnPLYDEepfVFK-KVVLPELASIRIAAYE----EGGKLIGHRVLPVIGLCPGYR 831
Cdd:PLN02222  484 RVGIAGVPGDTVMKK--TKTLEDNWI-PAWDE---VFEfPLTVPELALLRLEVHEydmsEKDDFGGQTCLPVWELSQGIR 557

                         650
                  ....*....|....*....
gi 45552167   832 HVNLRSEVGQPIALASLFL 850
Cdd:PLN02222  558 AFPLHSRKGEKYKSVKLLV 576

PH_PLC_beta

cd13361

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

20-145

3.31e-56

Pssm-ID: 270167 Cd Length: 127 Bit Score: 190.47 E-value: 3.31e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   20 LQDGEKFIRWDDDSGTGTPVTMRVDAKGFFLYWVDQNNELDILDIATIRDVRTGQYAKRPKDNKLRQIVTLGPQDTLEEK 99
Cdd:cd13361    1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREVNVGGSDEDLEDR 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 45552167  100 TVTVCHGSDFVNMTFVNFCCTRRDIAQLWTDGLIKLAYSLAQLNGS 145
Cdd:cd13361   81 TLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNAS 126

PI-PLCc_gamma1

cd08627

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

318-702

2.94e-55

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.

Pssm-ID: 176564 [Multi-domain] Cd Length: 229 Bit Score: 192.17 E-value: 2.94e-55

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  318 DDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAE 397
Cdd:cd08627    2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  398 SAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDShplepNMD-LPPPAMLRRkiiiknkkkhhhhhhhh 476
Cdd:cd08627   82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDI-----NADgLPSPNQLKR----------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  477 hhkkpaqvgtpaannklttansvdakaaqqvglsashedggvtrstangdvatgtgtgsaagtaghapplqqirqsskds 556
Cdd:cd08627      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  557 tgssdsdsssedeslpnttpnlpsgnepppekaqketeagaeiSALVnyvqpihfssfenaeKKNRCY-EMSSFDEKQAT 635
Cdd:cd08627  140 -------------------------------------------KILI---------------KHKKLYrDMSSFPETKAE 161

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  636 TLL-KERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08627  162 KYVnRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

EFh_PI-PLCbeta4

cd16211

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

151-305

9.44e-51

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, or phospholipase C-beta-4 (PLC-beta4), is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It may play a critical role in linking anxiety behaviors and theta rhythm heterogeneity. PI-PLC-beta4 is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta4 functions as a downstream signaling molecule of type 1 metabotropic glutamate receptors (mGluR1s). The thalamic mGluR1-PI-PLC-beta4 cascade is essential for formalin-induced inflammatory pain by regulating the response of ventral posterolateral thalamic nucleus (VPL) neurons. Moreover, PI-PLC-beta4 is essential for long-term depression (LTD) in the rostral cerebellum, which may be required for the acquisition of the conditioned eyeblink response. Besides, PI-PLC-beta4 may play an important role in maintenance of the status epilepticus. The mutations of PI-PLC-beta4 has been identified as the major cause of autosomal dominant auriculocondylar syndrome (ACS). PI-PLC-beta4 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320041 Cd Length: 153 Bit Score: 176.07 E-value: 9.44e-51

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAQNKEDrKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16211    1 KKHWMRLCFLVNPNGKIPVRSITRTFASGKTE-KIVFQSLKELGLPSGKNDEIEPEAFTFEKFYELYHKICPRTDIEELF 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 DSIVGNSKrKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16211   80 KKINGDKK-DYLTVDQLISFLNEHQRDPRLNEILFPFYDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153

PI-PLCc_plant

cd08599

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

318-702

1.32e-50

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.

Pssm-ID: 176541 [Multi-domain] Cd Length: 228 Bit Score: 178.72 E-value: 1.32e-50

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  318 DDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAE 397
Cdd:cd08599    2 HDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  398 SAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLldkpLDSHPLEPNMDLPPPAMLRrkiiiknkkkhhhhhhhhh 477
Cdd:cd08599   82 NAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKL----FYPDSEDLPEEFPSPEELK------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  478 hkkpaqvgtpaannklttansvdakaaqqvglsashedGGVTRSTangdvatgtgtgsaagtaghAPPLQQIrqsskdst 557
Cdd:cd08599  139 --------------------------------------GKILISD--------------------KPPVIRN-------- 152

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  558 gssdsdsssedeslpnttpnlpSGNEpPPEKAQKETEAGAEIsalvnyvqpihfssfenaekknrcyemssfdekqattl 637
Cdd:cd08599  153 ----------------------SLSE-TQLKKVIEGEHPTDL-------------------------------------- 171

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  638 lkerpIEFVNYNkhqLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYN 702
Cdd:cd08599  172 -----IEFTQKN---LLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

PH_14

pfam17787

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

15-143

1.75e-50

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

Pssm-ID: 465506 Cd Length: 131 Bit Score: 174.49 E-value: 1.75e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     15 EVPQALQDGEKFIRWDDDSGTGTP-VTMRVDAKGFFLYWVDQNNELDILDIATIRDVRTGQYAKRPKDNKLRQIVTL-GP 92
Cdd:pfam17787    1 EVPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMgGS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 45552167     93 QDTLEEKTVTVCHGSDFVNMTFVNFCCTRRDIAQLWTDGLIKLAYSLAQLN 143
Cdd:pfam17787   81 DNSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

PLN02952

phosphoinositide phospholipase C

292-850

3.39e-50

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 188.67 E-value: 3.39e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   292 LSLDGFLRYLMGDD-NPIMAPSkldLCDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGR 370
Cdd:PLN02952   99 LNLDDFFHFLLYDDlNGPITPQ---VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGS 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   371 TEEPVIV-HGYTFVPEIFAKDVLEAIAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLDKPLDSHplepnM 449
Cdd:PLN02952  176 TKDEILVlHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYPESDSL-----V 250

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   450 DLPPPAMLRRKIIiknkkkhhhhhhhhhhkkpaqVGTPAANNKLTTANSVDAKaaQQVGLSASHEDggvtrSTANGDVAT 529
Cdd:PLN02952  251 QFPSPESLKHRII---------------------ISTKPPKEYLESSGPIVIK--KKNNVSPSGRN-----SSEETEEAQ 302

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   530 GTGTGSAAGTAGHapplqqiRQSSKDSTGSSDSDSSSEDESLPNTTPNLPSGnepppekAQKEteagaEISALVNYVQPI 609
Cdd:PLN02952  303 TLESMLFEQEADS-------RSDSDQDDNKSGELQKPAYKRLITIHAGKPKG-------TLKD-----AMKVAVDKVRRL 363

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   610 HFSSFENaekknrcyemssfdEKQATTllkeRPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLD 689
Cdd:PLN02952  364 SLSEQEL--------------EKAATT----NGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYG 425

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   690 LAMQLNLGIFEYNARSGYLLKPEFMRR---SDRRLDPFAESTVdgiiAGTVSITVLSG----------QFLTDKRANTFV 756
Cdd:PLN02952  426 KSLWLMHGMFRANGGCGYLKKPDFLMKkgfHDEVFDPKKKLPV----KKTLKVKVYLGdgwrldfshtHFDSYSPPDFYT 501

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   757 EVDMYGLPADTVRKKfrTKTVRDNgMNPLYDEEpFVFKKVVlPELASIRIAAYE----EGGKLIGHRVLPVIGLCPGYRH 832
Cdd:PLN02952  502 KMYIVGVPADNAKKK--TKIIEDN-WYPAWNEE-FSFPLTV-PELALLRIEVREydmsEKDDFGGQTCLPVSELRPGIRS 576

                         570
                  ....*....|....*...
gi 45552167   833 VNLRSEVGQPIALASLFL 850
Cdd:PLN02952  577 VPLHDKKGEKLKNVRLLM 594

PLN02228

Phosphoinositide phospholipase C

225-841

5.97e-50

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 187.17 E-value: 5.97e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   225 EVERLFDSIVGNSKrkcMSIAQLVEFLNKTQRDPrlneilypYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGD 304
Cdd:PLN02228   25 SIKRLFEAYSRNGK---MSFDELLRFVSEVQGER--------HAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   305 DNPIMaPSKLDLCDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFW-NGRTEEPVIVHGYTFV 383
Cdd:PLN02228   94 TNSPL-PMSGQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWpNPSGNAAEVRHGRTLT 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   384 PEIFAKDVLEAIAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLdkpldSHPLEPNMDLPPPAMLRRkiii 463
Cdd:PLN02228  173 SHEDLQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-----RCTSESTKHFPSPEELKN---- 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   464 knkkkhhhhhHHHHHKKPAQVGTPAANNKLTTANSVDAKAAQQVglsASHEDGGVTRSTANGDVATGTGTGSAAGTAGHA 543
Cdd:PLN02228  244 ----------KILISTKPPKEYLESKTVQTTRTPTVKETSWKRV---ADAENKILEEYKDEESEAVGYRDLIAIHAANCK 310

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   544 PPLQqirqsskdstgssdsdsssedeslpnttpNLPSGNeppPEKAQKeteagaeisalvnyvqpihfssfenaekknrc 623
Cdd:PLN02228  311 DPLK-----------------------------DCLSDD---PEKPIR-------------------------------- 326

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   624 yemSSFDEKQATTLLKERPIEFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYNA 703
Cdd:PLN02228  327 ---VSMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANG 403

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   704 RSGYLLKPEFMRRSDRRLDPFAESTvdgiIAGTVSITVLSGQ----------FLTDKRANTFVEVDMYGLPADTVrkKFR 773
Cdd:PLN02228  404 GCGYVKKPRILLDEHTLFDPCKRLP----IKTTLKVKIYTGEgwdldfhlthFDQYSPPDFFVKIGIAGVPRDTV--SYR 477

                         570       580       590       600       610       620       630
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 45552167   774 TKTVRDNGMnPLYDEEPFVFKKVVlPELA--SIRIAAYEEGGK--LIGHRVLPVIGLCPGYRHVNLRSEVGQ 841
Cdd:PLN02228  478 TETAVDQWF-PIWGNDEFLFQLRV-PELAllWFKVQDYDNDTQndFAGQTCLPLPELKSGVRAVRLHDRAGK 547

EFh_PI-PLCbeta1

cd16208

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

151-305

5.27e-47

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, or PLC-154, or phospholipase C-I (PLC-I), or phospholipase C-beta-1 (PLC-beta1), is expressed at highest levels in specific regions of the brain, as well as in the cardiovascular system. It has two splice variants, PI-PLC-beta1a and PI-PLC-beta1b, both of which are present within the nucleus. Nuclear PI-PLC-beta1 is a key molecule for nuclear inositide signaling, where it plays a role in cell cycle progression, proliferation and differentiation. It also contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta1 acts as an effector and a GTPase activating protein (GAP) specifically activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It regulates neuronal activity in the cerebral cortex and hippocampus, and has been implicated for participations in diverse critical functions related to forebrain diseases such as schizophrenia. It may play an important role in maintenance of the status epilepticus, and in osteosarcoma-related signal transduction pathways. PI-PLC-beta1 also functions as a regulator of erythropoiesis in kinamycin F, a potent inducer of gamma-globin production in K562 cells. The G protein activation and the degradation of PI-PLC-beta1 can be regulated by the interaction of alpha-synuclein. As a result, it may reduce cell damage under oxidative stress. Moreover, PI-PLC-beta1 works as a new intermediate in the HIV-1 gp120-triggered phosphatidylcholine-specific phospholipase C (PC-PLC)-driven signal transduction pathway leading to cytoplasmic CCL2 secretion in macrophages. PI-PLC-beta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320038 Cd Length: 151 Bit Score: 165.44 E-value: 5.27e-47

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAQnkeDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16208    1 EKAYTKLKLQVNPEGRIPVKNIYRLFSA---DRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIF 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 dSIVGNSKRKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16208   78 -SEFGAKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

EFh_NorpA_like

cd16212

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

156-305

1.41e-45

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and similar proteins; NorpA, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, is an eye-specific phosphoinositide phospholipase C (PI-PLC) encoded by norpA gene in Drosophila. It is expressed predominantly in photoreceptors and plays an essential role in the phototransduction pathway of Drosophila. A mutation within the norpA gene can render the fly blind without affecting any of the obvious structures of the eye. Like beta-class of vertebrate PI-PLCs, NorpA contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320042 [Multi-domain] Cd Length: 153 Bit Score: 161.18 E-value: 1.41e-45

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  156 KLCLQVDKSGRIPVKNIIKLFAQNKEDrKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLFDSIVg 235
Cdd:cd16212    6 RLGFMVDSGGKIPVKHIARTFASGKTE-KLVYQCLAEMGLPSGKGDSIEKEDFTFEKFYALYHKICPRNDIEELFTSIT- 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  236 NSKRKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16212   84 KGKGEHISLAQLINFMNDKQRDPRLNEILYPLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153

EFh_PI-PLCbeta3

cd16210

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

151-305

6.67e-42

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, or phospholipase C-beta-3 (PLC-beta3), is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta3 associates with CXC chemokine receptor 2 (CXCR2) and Na+/H+ exchanger regulatory factor-1 (NHERF1) to form macromolecular complexes at the plasma membrane of pancreatic cancer cells, which functionally couple chemokine signaling to PI-PLC-beta3-mediated signaling cascade. Moreover, PI-PLC-beta3 directly interacts with the M3 muscarinic receptor (M3R), a prototypical G alpha-q-coupled receptor that promotes PI-PLC-beta3 localization to the plasma membrane. This binding can alter G alpha-q-dependent PLC activation. Furthermore, PI-PLC-beta3 inhibits the proliferation of hematopoietic stem cells (HSCs) and myeloid cells through the interaction of SH2-domain-containing protein phosphatase 1 (SHP-1) and signal transducer and activator of transcription 5 (Stat5), and the augment of the dephosphorylating activity of SHP-1 toward Stat5, leading to the inactivation of Stat5. It is also involved in atopic dermatitis (AD) pathogenesis via regulating the expression of periostin in fibroblasts and thymic stromal lymphopoietin (TSLP) in keratinocytes. In addition, PI-PLC-beta3 mediates the thrombin-induced Ca2+ response in glial cells. PI-PLC-beta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320040 Cd Length: 151 Bit Score: 150.84 E-value: 6.67e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAqnkEDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16210    1 RKAYTKLKLQVNQDGRIPVKNILKMFS---ADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKIL 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45552167  231 DSIvGNSKRKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16210   78 LEI-GAKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PLN02230

phosphoinositide phospholipase C 4

292-840

4.23e-41

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 161.41 E-value: 4.23e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   292 LSLDGFLRYLMGDD-NPimaPSKLDLCDDMDQPMSHYFINSSHNTYLTGHQLTGKSSVEIYRQCLLAGCRCVELDFWNGR 370
Cdd:PLN02230   91 LTLDDFNYYLFSTDlNP---PIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRG 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   371 TEEPVIVHGYTFVPEIFAKDVLEAIAESAFKTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLLdkpldSHPLEPNMD 450
Cdd:PLN02230  168 TDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLY-----YHDSEGCQE 242

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   451 LPPPAMLRRKIIiknkkkhhhhhhhhhhkkpaqVGTPAANNKLtTANsvDAKaaqqvglsasHEDGGVTRSTANGDVatg 530
Cdd:PLN02230  243 FPSPEELKEKIL---------------------ISTKPPKEYL-EAN--DAK----------EKDNGEKGKDSDEDV--- 285

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   531 tgtgsaagtAGHAPplqqirqsskdstgssdSDSSSEDESLPNTTPNLPSGNEPPPEKAQKETEAGAEISA-LVNYVQPI 609
Cdd:PLN02230  286 ---------WGKEP-----------------EDLISTQSDLDKVTSSVNDLNQDDEERGSCESDTSCQLQApEYKRLIAI 339

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   610 HFSSFENAEKKNRCYEMSSFDEKQATTLLKERPI-----EFVNYNKHQLSRVYPAGTRFDSSNFMPQLFWNAGCQLVALN 684
Cdd:PLN02230  340 HAGKPKGGLRMALKVDPNKIRRLSLSEQLLEKAVasygaDVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFN 419

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   685 FQTLDLAMQLNLGIFEYNARSGYLLKPEFMRRSDRRLDPFAESTvDGIIAGTVSITVLSG----------QFLTDKRANT 754
Cdd:PLN02230  420 MQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGPNGQDFYPKD-NSCPKKTLKVKVCMGdgwlldfkktHFDSYSPPDF 498

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   755 FVEVDMYGLPADTVRKKfrTKTVRDNgMNPLYDEEpFVFkKVVLPELASIRIAAYE----EGGKLIGHRVLPVIGLCPGY 830
Cdd:PLN02230  499 FVRVGIAGAPVDEVMEK--TKIEYDT-WTPIWNKE-FIF-PLAVPELALLRVEVHEhdinEKDDFGGQTCLPVSEIRQGI 573

                         570
                  ....*....|
gi 45552167   831 RHVNLRSEVG 840
Cdd:PLN02230  574 HAVPLFNRKG 583

C2_PLC_like

cd00275

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

736-855

1.34e-36

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 134.59 E-value: 1.34e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  736 TVSITVLSGQFL------TDKRANTFVEVDMYGLPADTvRKKFRTKTVRDNGMNPLYDEEpFVFKkVVLPELASIRIAAY 809
Cdd:cd00275    3 TLTIKIISGQQLpkpkgdKGSIVDPYVEVEIHGLPADD-SAKFKTKVVKNNGFNPVWNET-FEFD-VTVPELAFLRFVVY 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 45552167  810 EEGG---KLIGHRVLPVIGLCPGYRHVNLRSEVGQPIALASLFLCVVVK 855
Cdd:cd00275   80 DEDSgddDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

EFh_PI-PLCbeta2

cd16209

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

151-303

7.60e-36

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, or phospholipase C-beta-2 (PLC-beta2), is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits (G alpha(q)) through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta2 has two cellular binding partners, alpha- and gamma-synuclein. The binding of either alpha- and gamma-synuclein inhibits PI-PLC-beta2 activity through preventing the binding of its activator G alpha(q). However, the binding of gamma-synuclein to PI-PLC-beta2 does not affect its binding to G beta(gamma) subunits or small G proteins, but enhances these signals. Meanwhile, gamma-synuclein may protect PI-PLC-beta2 from protease degradation and contribute to its over-expression in breast cancer. In leukocytes, the G beta(gamma)-mediated activation of PI-PLC-beta2 can be promoted by a scaffolding protein WDR26, which is also required for the translocation of PI-PLC-beta2 from the cytosol to the membrane in polarized leukocytes. PI-PLC-beta2 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320039 Cd Length: 151 Bit Score: 133.47 E-value: 7.60e-36

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  151 QKAHTKLCLQVDKSGRIPVKNIIKLFAQnkeDRKRVEKALDVTGLPSGKVDSISVSKFQFEDFYNLYKYLTQRSEVERLF 230
Cdd:cd16209    1 EKIYVKLKMQLNSEGKIPVKNFFQMFPA---DRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIF 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 45552167  231 DSIVGNSKrKCMSIAQLVEFLNKTQRDPRLNEILYPYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMG 303
Cdd:cd16209   78 TSYHAKAK-PYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCG 149

PLN02223

phosphoinositide phospholipase C

319-841

1.00e-22

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 103.95 E-value: 1.00e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   319 DMDQPMSHYFINSSHNTYLTGHQLTGKS-SVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPEIFAKDVLEAIAE 397
Cdd:PLN02223  107 DMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLPDGKDGICVRPKWNFEKPLELQECLDAIKE 186

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   398 SAF-KTSEYPVILSFENHCNPRQQAKIANYCREIFGDMLL-DKPldSHPLEpnmDLPPPAMLRRkiiiknkkkhhhhhHH 475
Cdd:PLN02223  187 HAFtKCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYhEDP--QHSLE---EFPSPAELQN--------------KI 247

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   476 HHHKKPAQvgtpaannKLTTANSVDAKAAQQVGLsashedggvtrstangdvatgtgtgsaagtaghapplqQIRQSskd 555
Cdd:PLN02223  248 LISRRPPK--------ELLYAKADDGGVGVRNEL--------------------------------------EIQEG--- 278

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   556 stgssdsdsssedeslpNTTPNLPS-----GNEPPPEKAQKETEAGAEISalvnyvQPIHFSSfenaekknrcyEMSSFD 630
Cdd:PLN02223  279 -----------------PADKNYQSlvgfhAVEPRGMLQKALTGKADDIQ------QPGWYER-----------DIISFT 324

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   631 EKQattLLKERPiefvnynKHQLSRVYPAgtrfdssnFMPQLFWNAGCQLVALNFQTLDLAMQLNLGIFEYNARSGYLLK 710
Cdd:PLN02223  325 QKK---FLRTRP-------KKKNLLINAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKK 386

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   711 PEFMRRSDRrlDPFAESTVDGIIAGTVSITVLSGQ-FLTD--KRANTFVEVDMY------GLPADtvrKKFRTKTVRDNG 781
Cdd:PLN02223  387 PDFLLNAGP--SGVFYPTENPVVVKILKVKIYMGDgWIVDfkKRIGRLSKPDLYvrisiaGVPHD---EKIMKTTVKNNE 461

                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45552167   782 MNPLYDEEpFVFkKVVLPELASIRIAAYE----EGGKLIGHRVLPVIGLCPGYRHVNLRSEVGQ 841
Cdd:PLN02223  462 WKPTWGEE-FTF-PLTYPDLALISFEVYDyevsTADAFCGQTCLPVSELIEGIRAVPLYDERGK 523

EF-hand_like

pfam09279

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

216-308

3.87e-17

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 77.29 E-value: 3.87e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    216 LYKYLTQRSEVERLFDSIVGNSKRkcMSIAQLVEFLNKTQRDPRlneilypyANPARAKELIQQYEPNKFNAQKGQLSLD 295
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQK--LSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKD 70

                           90
                   ....*....|...
gi 45552167    296 GFLRYLMGDDNPI 308
Cdd:pfam09279   71 GFLMYLCSPDGSI 83

EFh_PI-PLC

cd15898

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

160-305

8.73e-17

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

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 78.09 E-value: 8.73e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  160 QVDKSGRIPVKNIIKLFAQ-----NKEDRKRVEKALDVTGlpSGKVDsisvskfqFEDFYNLYKYLTQRSEVERLFDSIV 234
Cdd:cd15898   10 DKDGDGKLSLKEIKKLLKRlnirvSEKELKKLFKEVDTNG--DGTLT--------FDEFEELYKSLTERPELEPIFKKYA 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45552167  235 GNsKRKCMSIAQLVEFLNKTQRDPRLneilypyanPARAKELIQQYEPNKfnaQKGQLSLDGFLRYLMGDD 305
Cdd:cd15898   80 GT-NRDYMTLEEFIRFLREEQGENVS---------EEECEELIEKYEPER---ENRQLSFEGFTNFLLSPE 137

PI-PLCc_GDPD_SF

cd08555

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

330-438

1.04e-16

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.

Pssm-ID: 176498 [Multi-domain] Cd Length: 179 Bit Score: 79.40 E-value: 1.04e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  330 NSSHNTYLTGHQltgKSSVEIYRQCLLAGCRCVELDFWNGRTEEPVIVHGYTFVPE------IFAKDVLEAIAESAFkTS 403
Cdd:cd08555    1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDRTtagilpPTLEEVLELIADYLK-NP 76

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 45552167  404 EYPVILSFENHCN----PRQQAKIANYCREIFGDMLLDK 438
Cdd:cd08555   77 DYTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGK 115

EFh_PI-PLCdelta

cd16202

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

161-305

1.66e-16

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.

Pssm-ID: 320032 [Multi-domain] Cd Length: 140 Bit Score: 77.65 E-value: 1.66e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  161 VDKSGRIPVKNIIKLFAQ-----NKEDRKRVEKALDVTGlpSGKVDsisvskfqFEDFYNLYKYLTQRSEVERLFDSIVG 235
Cdd:cd16202   11 KNGDGKLSFKECKKLLKKlnvkvDKDYAKKLFQEADTSG--EDVLD--------EEEFVQFYNRLTKRPEIEELFKKYSG 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  236 NSKRkcMSIAQLVEFLNKTQRDPrlneilypYANPARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16202   81 DDEA--LTVEELRRFLQEEQKVK--------DVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140

EFh_PI-PLCdelta1

cd16217

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

211-305

1.52e-13

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (PLCD1), or phospholipase C-III (PLC-III), or phospholipase C-delta-1 (PLC-delta-1), is present in high abundancy in the brain, heart, lung, skeletal muscle and testis. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. PI-PLC-delta1 is required for maintenance of homeostasis in skin and metabolic tissues. Moreover, it is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta1 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta1 can be positively or negatively regulated by several binding partners, including p122/Rho GTPase activating protein (RhoGAP), Gha/Transglutaminase II, RalA, and calmodulin. It is involved in Alzheimer's disease and hypertension. Furthermore, PI-PLC-delta1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity and p27 levels. It can be activated by alpha1-adrenoreceptors (AR) in a calcium-dependent manner and may be important for G protein-coupled receptors (GPCR) responses in vascular smooth muscle (VSM). PI-PLC-delta1 may also be involved in noradrenaline (NA)-induced phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and modulate sustained contraction of mesenteric small arteries. In addition, it inhibits thermogenesis and induces lipid accumulation, and therefore contributes to the development of obesity. PI-PLC-delta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. In addition, PI-PLC-delta1 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, as well as a nuclear localization signal within its linker region, both of which may be responsible for translocating PI-PLC-delta1 into and out of the cell nucleus.

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 69.00 E-value: 1.52e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  211 EDFYNLykyLTQRSEVERLFDSIVGnsKRKCMSIAQLVEFLNKTQRDPrlneilypyANPARAKELIQQYEPNKFNAQKG 290
Cdd:cd16217   59 EEFYKL---LTKREEIDVIFGEYAK--SDGTMSRNNLLNFLQEEQREE---------VAPAYALSLIEKYEPDETAKAQR 124

                         90
                 ....*....|....*
gi 45552167  291 QLSLDGFLRYLMGDD 305
Cdd:cd16217  125 QMTKDGFLMYLLSPE 139

smart00239

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

736-835

9.08e-12

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 62.89 E-value: 9.08e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167     736 TVSITVLSGQFLTDKR----ANTFVEVDMYGLPadtvRKKFRTKTVRDNGmNPLYDEEpFVFkKVVLPELASIRIAAYEE 811
Cdd:smart00239    1 TLTVKIISARNLPPKDkggkSDPYVKVSLDGDP----KEKKKTKVVKNTL-NPVWNET-FEF-EVPPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 45552167     812 GG----KLIGHRVLPVIGLCPGYRHVNL 835
Cdd:smart00239   74 DRfgrdDFIGQVTIPLSDLLLGGRHEKL 101

EFh_PI-PLCdelta4

cd16219

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

211-301

1.26e-11

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4.

Pssm-ID: 320049 [Multi-domain] Cd Length: 140 Bit Score: 63.71 E-value: 1.26e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  211 EDFYNLYKYLTQRSEVERLFDSIVGNSKRkcMSIAQLVEFLNKTQRDPRLNEILypyanparAKELIQQYEPNKFNAQKG 290
Cdd:cd16219   56 EEFVLFYKALTQREDVLKIFQDFSADGQK--LTLLEFVDFLQQEQLERENTEEL--------AMELIDRYEPSDTAKKLH 125

                         90
                 ....*....|.
gi 45552167  291 QLSLDGFLRYL 301
Cdd:cd16219  126 ALSIDGFLMYL 136

EFh_PI-PLCzeta

cd16204

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

199-305

2.40e-10

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

Pssm-ID: 320034 [Multi-domain] Cd Length: 142 Bit Score: 59.82 E-value: 2.40e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  199 KVDSISVSKFQFEDFYNLYKYLTQRSEVERLFDSIVGNskRKCMSIAQLVEFLNKTQRDPRLNEilypyanpARAKELIQ 278
Cdd:cd16204   46 KNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSEN--RKILSAPNLVGFLKKEQFQDEADE--------TIASELIA 115

                         90       100
                 ....*....|....*....|....*..
gi 45552167  279 QYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16204  116 KYEPIEEVRKRKQMSFEGFIRYMTSED 142

PH_PLC_ELMO1

cd01248

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...

20-132

9.49e-10

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. 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 which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. 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.

Pssm-ID: 269952 Cd Length: 108 Bit Score: 57.33 E-value: 9.49e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   20 LQDGEKFIRWDDdSGTGTPVTMRVDAKGFFLYWVD--QNNELDILDIATIRDVRTGQYAKRPKDNKlrqivtlGPQDTLE 97
Cdd:cd01248    1 LQQGTLLLKYRE-GSKPKERTFYLDPDGTRITWESskKKSEKKSIDISDIKEIRPGKDTDGFKRKK-------KSNKPKE 72

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 45552167   98 EKTVTVCHGSdfvNMTFVNFCCTRRDIAQLWTDGL 132
Cdd:cd01248   73 ERCFSIIYGS---NNKTLDLVAPSEDEANLWVEGL 104

EFh_PI-PLCeta

cd16205

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

210-301

3.68e-09

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.

Pssm-ID: 320035 [Multi-domain] Cd Length: 141 Bit Score: 56.62 E-value: 3.68e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  210 FEDFYNLYKYLTQRSEVERLFDSIvGNSKRKcMSIAQLVEFLNKTQRdprLNEILYPYAnparaKELIQQYEPNKFNAQK 289
Cdd:cd16205   56 FEEFCAFYKMMSTRRELYLLLLSY-SNKKDY-LTLEDLARFLEVEQK---MTNVTLEYC-----LDIIEKFEPSEENKKN 125

                         90
                 ....*....|..
gi 45552167  290 GQLSLDGFLRYL 301
Cdd:cd16205  126 GLLGIDGFTNYM 137

EFh_PRIP

cd16206

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

161-305

1.61e-08

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); This family represents a class of metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(also known as p130 or PLC-L1), which is predominantly expressed in the brain, and PRIP-2 (also known as PLC-L2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.

Pssm-ID: 320036 [Multi-domain] Cd Length: 143 Bit Score: 54.91 E-value: 1.61e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  161 VDKSGRIPVKNIIKLFAQNKEDRK--RVEKALDVTGLPSGKVDSiSVSKfqfEDFYNLYKYLTQRSEVERLFDSIVGNSK 238
Cdd:cd16206   11 TNKSGFLDEEEAVQLIKQLNPGLStsRIKQKLKELQKKKDGARG-RVSS---DEFVELFKELATRPEIYFLLVRYASNKD 86

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552167  239 RkcMSIAQLVEFLNKTQRDPRLNEilypyanpARAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16206   87 Y--LTVDDLMLFLEAEQGMTGVTK--------EKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143

EFh_PI-PLCepsilon

cd16203

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...

232-302

3.15e-07

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal 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 only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases.

Pssm-ID: 320033 Cd Length: 174 Bit Score: 51.94 E-value: 3.15e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45552167  232 SIVGN------SKRKCMSIAQLVEFLNKTQRDPRLNEilypyanpaRAKELIQQYEPNKFNAQKGQLSLDGFLRYLM 302
Cdd:cd16203  104 SIVTNgagvdsSRSSVLTISQLKDFLENHQMEHITEE---------EAIKIIQRHEPDPILRSKNCLSFEGFARYLM 171

EFh_PI-PLCdelta3

cd16218

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

220-305

1.39e-06

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLCD3), phospholipase C-delta-3 (PLC-delta-3), is expressed abundantly in brain, skeletal muscle and heart. PI-PLC-delta3 gene expression is down-regulation by cAMP and calcium. PI-PLC-delta3 acts as anchoring of myosin VI on plasma membrane, and further modulates Myosin IV expression and microvilli formation in enterocytes. It negatively regulates RhoA expression, inhibits RhoA/Rho kinase signaling, and plays an essential role in normal neuronal migration by promoting neuronal outgrowth in the developing brain. Moreover, PI-PLC-delta3 is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta3 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. In addition, PI-PLC-delta3 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, which may be responsible transporting PI-PLC-delta3 from the cell nucleus.

Pssm-ID: 320048 [Multi-domain] Cd Length: 138 Bit Score: 48.97 E-value: 1.39e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  220 LTQRSEVERLFDSIVGNSKrkCMSIAQLVEFLNKTQRDPRLneilypyanpARAKELIQQYEPNKFNAQKGQLSLDGFLR 299
Cdd:cd16218   65 LMQRPELEEIFHQYSGEDC--VLSAEELREFLKDQGEDASL----------VHAKELIQTYELNEKAKQHQLMTLDGFTM 132


                 ....*.
gi 45552167  300 YLMGDD 305
Cdd:cd16218  133 YMLSKD 138

EFh_PRIP2

cd16223

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

159-305

4.40e-06

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); PRIP-2, also termed phospholipase C-L2, or phospholipase C-epsilon-2 (PLC-epsilon-2), or inactive phospholipase C-like protein 2 (PLC-L2), is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that exhibits a relatively ubiquitous expression. It functions as a novel negative regulator of B-cell receptor (BCR) signaling and immune responses. PRIP-2 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-2 does not have PLC enzymatic activity.

Pssm-ID: 320053 [Multi-domain] Cd Length: 144 Bit Score: 47.59 E-value: 4.40e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  159 LQVDKSGRIPVKNIIKLFAQNKEDRKRVEKALDVTGLPSGKVD-SISVSKfqfEDFYNLYKYLTQRSEVERLFdsIVGNS 237
Cdd:cd16223    9 ADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKELHKSKEKgGTEVTK---EEFIEVFHELCTRPEIYFLL--VQFSS 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45552167  238 KRKCMSIAQLVEFLNKTQRDPRLNEILypyanparAKELIQQYEPNKFNAQKGQLSLDGFLRYLMGDD 305
Cdd:cd16223   84 NKEFLDTKDLMMFLEAEQGMAHVTEEI--------SLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPE 143

pfam00168

C2 domain;

735-823

1.59e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 45.00 E-value: 1.59e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167    735 GTVSITVLSGQFLTDK----RANTFVEVDMyglpaDTVRKKFRTKTVRDNGmNPLYDEEpFVFkKVVLPELASIRIAAYE 810
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKdgngTSDPYVKVYL-----LDGKQKKKTKVVKNTL-NPVWNET-FTF-SVPDPENAVLEIEVYD 72

                           90
                   ....*....|....*..
gi 45552167    811 EGG----KLIGHRVLPV 823
Cdd:pfam00168   73 YDRfgrdDFIGEVRIPL 89

SMC_prok_B

TIGR02168

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...

1005-1244

3.89e-05

Pssm-ID: 274008 [Multi-domain] Cd Length: 1179 Bit Score: 48.13 E-value: 3.89e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1005 KSVKEKRLEMEKKLESLRKKHDKEKIKIAGQKSSpLEGKKPKFAITNKLVKRLSNKSLEPGVEIPACPLDLGDSSEESAA 1084
Cdd:TIGR02168  701 AELRKELEELEEELEQLRKELEELSRQISALRKD-LARLEAEVEQLEERIAQLSKELTELEAEIEELEERLEEAEEELAE 779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1085 ADAG-----EDLAGGSSSLDgrTQESRLRSACREYTSQYRELQEKY-----HEAIYSAAEKVLKTSQtGQTKQLKASLDK 1154
Cdd:TIGR02168  780 AEAEieeleAQIEQLKEELK--ALREALDELRAELTLLNEEAANLRerlesLERRIAATERRLEDLE-EQIEELSEDIES 856

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   1155 VTGEvMHQLQEARRNEVKNL--ATVHRDRDELIRMKREVASSVVERGVAERVRLKQTFDRRTDELQKQHDSVRNALAEHR 1232
Cdd:TIGR02168  857 LAAE-IEELEELIEELESELeaLLNERASLEEALALLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGLE 935

                          250
                   ....*....|..
gi 45552167   1233 SKARQILDKEAE 1244
Cdd:TIGR02168  936 VRIDNLQERLSE 947

PTZ00121

MAEBL; Provisional

981-1246

4.16e-05

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 48.21 E-value: 4.16e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   981 RQVESSQFDVDLVLAEPLEKILDHKSVKE-KRLEMEKKLESLRKKHDKEKI----KIAGQKSSPLEGKKPKFAITNKLVK 1055
Cdd:PTZ00121 1176 KKAEAARKAEEVRKAEELRKAEDARKAEAaRKAEEERKAEEARKAEDAKKAeavkKAEEAKKDAEEAKKAEEERNNEEIR 1255

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1056 RLSNKSLEPGVEIPACP-------LDLGDSSEESAAADAGE--DLAGGSSSLDGRTQESR----LRSACREYTSQYRELQ 1122
Cdd:PTZ00121 1256 KFEEARMAHFARRQAAIkaeearkADELKKAEEKKKADEAKkaEEKKKADEAKKKAEEAKkadeAKKKAEEAKKKADAAK 1335

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1123 EKYHEAiySAAEKVLKTSQTGQTKQLKASLDKV------TGEVMHQLQEARRN--EVKNLATVHRDRDELIRMKREVASS 1194
Cdd:PTZ00121 1336 KKAEEA--KKAAEAAKAEAEAAADEAEAAEEKAeaaekkKEEAKKKADAAKKKaeEKKKADEAKKKAEEDKKKADELKKA 1413

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 45552167  1195 VVERGVAERVRLKQTFDRRTDELQKQHDSVRNA-----LAEHRSKARQILDKEAESR 1246
Cdd:PTZ00121 1414 AAAKKKADEAKKKAEEKKKADEAKKKAEEAKKAdeakkKAEEAKKAEEAKKKAEEAK 1470

EFh_PRIP1

cd16222

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

211-302

1.51e-04

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); PRIP-1, also termed phospholipase C-deleted in lung carcinoma, or inactive phospholipase C-like protein 1 (PLC-L1), or p130, is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that is predominantly expressed in the brain. It is involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. It interacts with the catalytic subunits of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), and functions as a scaffold to regulate the activities and subcellular localizations of both PP1 and PP2A in phospho-dependent cellular signaling. It also promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of hormone-sensitive lipase (HSL) and perilipin A, thus reducing protein kinase A (PKA)-mediated lipolysis. Moreover, PRIP-1 plays an important role in insulin granule exocytosis through the association with GABAA-receptor-associated protein (GABARAP) to form a complex to regulate KIF5B-mediated insulin secretion. It also inhibits regulated exocytosis through direct interactions with syntaxin 1 and synaptosomal-associated protein 25 (SNAP-25) via its C2 domain. Furthermore, PRIP-1 has been implicated in the negative regulation of bone formation. PRIP-1 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-1 does not have PLC enzymatic activity.

Pssm-ID: 320052 [Multi-domain] Cd Length: 143 Bit Score: 43.31 E-value: 1.51e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  211 EDFYNLYKYLTQRSEVERLFDSIVGNskRKCMSIAQLVEFLNKTQRDPRLNEILypyanparAKELIQQYEPNKFNAQKG 290
Cdd:cd16222   59 EEFCEAYSELCTRPEVYFLLVQISKN--KEYLDAKDLMLFLEAEQGMTHITEEM--------CLDIIRRYEPSQEGRLKG 128

                         90
                 ....*....|..
gi 45552167  291 QLSLDGFLRYLM 302
Cdd:cd16222  129 FLGIDGFTQYLL 140

EFh_ScPlc1p_like

cd16207

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

199-302

1.81e-04

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.

Pssm-ID: 320037 [Multi-domain] Cd Length: 142 Bit Score: 43.01 E-value: 1.81e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  199 KVDSISVSKFQFEDFYNLYKYLTQRSEVERLFDSIVGNSKRKcMSIAQLVEFLNKTQRDPRlneilypyaNPARAKELIQ 278
Cdd:cd16207   46 KADTDKKGYLNFEEFQEFVKLLKRRKDIKAIFKQLTKPGSDG-LTLEEFLKFLRDVQKEDV---------DRETWEKIFE 115

                         90       100
                 ....*....|....*....|....
gi 45552167  279 QYEPNKFNAQKGQLSLDGFLRYLM 302
Cdd:cd16207  116 KFARRIDDSDSLTMTLEGFTSFLL 139

PTZ00121

MAEBL; Provisional

995-1246

3.25e-04

MAEBL; Provisional

Pssm-ID: 173412 [Multi-domain] Cd Length: 2084 Bit Score: 45.52 E-value: 3.25e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   995 AEPLEKILDHKSVKE---KRLEMEKKLESLRKKHDkEKIKIAGQKSSPLEGKKPKFAITNKLVKRLSNKSLEPGVEIPAC 1071
Cdd:PTZ00121 1420 ADEAKKKAEEKKKADeakKKAEEAKKADEAKKKAE-EAKKAEEAKKKAEEAKKADEAKKKAEEAKKADEAKKKAEEAKKK 1498

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1072 PLDLGDSSEESAAADAGEDLAGGSSSLDGRTQESRLRSacreytSQYRELQEKYHEAIYSAAEKVLKTSQTGQTKQLKAS 1151
Cdd:PTZ00121 1499 ADEAKKAAEAKKKADEAKKAEEAKKADEAKKAEEAKKA------DEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKA 1572

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1152 LDKvTGEVMHQLQEARRNEVKNLATVHRDRDELIRMKREVASSvvergvAERVRLKQTFDRRTDELQKQHDSVRNALAEH 1231
Cdd:PTZ00121 1573 EED-KNMALRKAEEAKKAEEARIEEVMKLYEEEKKMKAEEAKK------AEEAKIKAEELKKAEEEKKKVEQLKKKEAEE 1645

                         250
                  ....*....|....*
gi 45552167  1232 RSKARQILDKEAESR 1246
Cdd:PTZ00121 1646 KKKAEELKKAEEENK 1660

EFh_PI-PLCeta2

cd16221

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...

210-301

2.65e-03

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also 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. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320051 [Multi-domain] Cd Length: 141 Bit Score: 39.53 E-value: 2.65e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  210 FEDFYNLYKYLTQRSEVERLFDSIVGNskRKCMSIAQLVEFLNKTQRdprlneilypYANPAR--AKELIQQYEPNKFNA 287
Cdd:cd16221   56 FEEFCAFYKMMSTRRDLYLLMLTYSNH--KDHLDTNDLQRFLEVEQK----------MAGVTRehCLEIISQFEPCSENK 123

                         90
                 ....*....|....
gi 45552167  288 QKGQLSLDGFLRYL 301
Cdd:cd16221  124 QNGALGIDGFTNYM 137

PI-PLCc_bacteria_like

cd08557

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

319-439

4.95e-03

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

Pssm-ID: 176500 [Multi-domain] Cd Length: 271 Bit Score: 40.54 E-value: 4.95e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  319 DMDQPMSHYFINSSHNTY---LTGHQLTGKSSVE-----IYRQcLLAGCRCVELDFW-NGRTEEPVIVHGYTFVPEIFAK 389
Cdd:cd08557    4 LDDLPLSQLSIPGTHNSYaytIDGNSPIVSKWSKtqdlsITDQ-LDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLE 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 45552167  390 DVLEAIAesAFkTSEYP---VILSFENHCNP---RQQAKIANYCREIFGDMLLDKP 439
Cdd:cd08557   83 DVLNEVK--DF-LDAHPsevVILDLEHEYGGdngEDHDELDALLRDVLGDPLYRPP 135

PRK03918

DNA double-strand break repair ATPase Rad50;

994-1230

9.03e-03

DNA double-strand break repair ATPase Rad50;

Pssm-ID: 235175 [Multi-domain] Cd Length: 880 Bit Score: 40.43 E-value: 9.03e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167   994 LAEPLEKILDHKSVKEKRL--------EMEKKLESLRKKHDKekikiagqksspLEGKKPKFAITNKLVKRLSNKSLEpg 1065
Cdd:PRK03918  322 EINGIEERIKELEEKEERLeelkkklkELEKRLEELEERHEL------------YEEAKAKKEELERLKKRLTGLTPE-- 387

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1066 vEIPACPLDLGDSSEEsaAADAGEDLAGGSSSLDGRTQE-----SRLRSA---C----REYTSQYR-ELQEKYHEAIYSA 1132
Cdd:PRK03918  388 -KLEKELEELEKAKEE--IEEEISKITARIGELKKEIKElkkaiEELKKAkgkCpvcgRELTEEHRkELLEEYTAELKRI 464

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45552167  1133 AEKVLKTSQtgQTKQLKASLDKVTG------------EVMHQLQEAR-RNEVKNLATVHRDRDELIRMKREVASSVVE-R 1198
Cdd:PRK03918  465 EKELKEIEE--KERKLRKELRELEKvlkkeseliklkELAEQLKELEeKLKKYNLEELEKKAEEYEKLKEKLIKLKGEiK 542

                         250       260       270
                  ....*....|....*....|....*....|..
gi 45552167  1199 GVAERVRLKQTFDRRTDELQKQHDSVRNALAE 1230
Cdd:PRK03918  543 SLKKELEKLEELKKKLAELEKKLDELEEELAE 574

Blast search parameters

Data Source:	Precalculated data, version = cdd.v.3.21
Preset Options:	Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01