NCBI Conserved Domain Search

Conserved domains on [gi|1907136685|ref|XP_036015459|]

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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X3 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_GDPD_SF super family

cl14615

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

311-585

1.33e-119

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.

The actual alignment was detected with superfamily member cd08624:

Pssm-ID: 472694 [Multi-domain] Cd Length: 261 Bit Score: 355.52 E-value: 1.33e-119

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08624     1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 391 IAESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKKnqfsgp 470
Cdd:cd08624    81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 471 aspskkpggvaegslpssvpveedtgwtaedrteveeeevveeeeeeesgnldeeeikkmqsdegtaglevtaYEEMSSL 550
Cdd:cd08624   155 -------------------------------------------------------------------------YEEMSSL 161

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1907136685 551 VNYIQPTKFISFEFSAR-----VQTRLFQLRAPAALSPSA 585
Cdd:cd08624   162 VNYIQPTKFVSFEFSAQknrsyVISSFTELKAYDLLSKAS 201

EFh_PI-PLCbeta2

cd16209

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

149-299

1.40e-102

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: 307.58 E-value: 1.40e-102

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 149 DKILVKLKMQLNPEGKIPVKNFFQMFPADRKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSY 228
Cdd:cd16209     1 EKIYVKLKMQLNSEGKIPVKNFFQMFPADRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSY 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907136685 229 HSKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16209    81 HAKAKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151

PH_14

pfam17787

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

13-141

3.12e-67

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: 215.32 E-value: 3.12e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  13 VKAYLSQGERFIKWDDETSIASP-VILRVDPKGYYLYWTYQNQEMEFLDVTSIRDTRFGKFAKIPKSQKLREVFNMDFPD 91
Cdd:pfam17787   2 VPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGSD 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907136685  92 NHFLLKTLTVVSGPDMVDLTFYNFVSYKENVGKDWAEDVLALAKHPMTVN 141
Cdd:pfam17787  82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

Name

Accession

Description

Interval

E-value

PI-PLCc_beta2

cd08624

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

311-585

1.33e-119

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: 355.52 E-value: 1.33e-119

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08624     1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 391 IAESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKKnqfsgp 470
Cdd:cd08624    81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 471 aspskkpggvaegslpssvpveedtgwtaedrteveeeevveeeeeeesgnldeeeikkmqsdegtaglevtaYEEMSSL 550
Cdd:cd08624   155 -------------------------------------------------------------------------YEEMSSL 161

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1907136685 551 VNYIQPTKFISFEFSAR-----VQTRLFQLRAPAALSPSA 585
Cdd:cd08624   162 VNYIQPTKFVSFEFSAQknrsyVISSFTELKAYDLLSKAS 201

EFh_PI-PLCbeta2

cd16209

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

149-299

1.40e-102

Pssm-ID: 320039 Cd Length: 151 Bit Score: 307.58 E-value: 1.40e-102

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 149 DKILVKLKMQLNPEGKIPVKNFFQMFPADRKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSY 228
Cdd:cd16209     1 EKIYVKLKMQLNSEGKIPVKNFFQMFPADRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSY 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907136685 229 HSKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16209    81 HAKAKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151

PI-PLC-X

pfam00388

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

314-462

2.05e-79

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: 247.42 E-value: 2.05e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 314 MTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAIAE 393
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGYTLTSKIPFRDVLEAIKD 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136685 394 SAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENfplkPGIPLPSPEDLRGKILIKN 462
Cdd:pfam00388  79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPEDLKGKILIKG 142

PH_14

pfam17787

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

13-141

3.12e-67

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: 215.32 E-value: 3.12e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  13 VKAYLSQGERFIKWDDETSIASP-VILRVDPKGYYLYWTYQNQEMEFLDVTSIRDTRFGKFAKIPKSQKLREVFNMDFPD 91
Cdd:pfam17787   2 VPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGSD 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907136685  92 NHFLLKTLTVVSGPDMVDLTFYNFVSYKENVGKDWAEDVLALAKHPMTVN 141
Cdd:pfam17787  82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

PLCXc

smart00148

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

314-463

2.49e-63

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: 205.21 E-value: 2.49e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  314 MTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAIAE 393
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDG--PDGEPVIYHGHTFTLPIKLSEVLEAIKD 78

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  394 SAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgipLPSPEDLRGKILIKNK 463
Cdd:smart00148  79 FAFVTSPYPVILSLENHC-SPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQLRGKILLKVR 143

PH_PLC_beta

cd13361

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

17-144

2.01e-53

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: 178.53 E-value: 2.01e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  17 LSQGERFIKWDDETSIASPVILRVDPKGYYLYWTYQNQEMEFLDVTSIRDTRFGKFAKIPKSQKLREVfNMDFPDNHFLL 96
Cdd:cd13361     1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907136685  97 KTLTVVSGPDMVDLTFYNFVSYKENVGKDWAEDVLALAKHPMTVNAPR 144
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

PLN02222

phosphoinositide phospholipase C 2

219-463

1.02e-31

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 130.15 E-value: 1.02e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 219 PEIDEIFTSYHSKAkpYMTKEHLTKFINQKQRDPRlnsllfppARPEQVQVLIDKyepSGINVQRGQLSPEGMVWFLCGP 298
Cdd:PLN02222   25 REIKTIFEKYSENG--VMTVDHLHRFLIDVQKQDK--------ATREDAQSIINS---ASSLLHRNGLHLDAFFKYLFGD 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 299 ENSVLAHDTllIHQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIItHGFTM 378
Cdd:PLN02222   92 NNPPLALHE--VHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIDVL-HGMTL 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 379 TTDILFKEAIEAIAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDP----LENFplkpgiplPSPEDL 454
Cdd:PLN02222  169 TTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHL-TPDLQSKVAEMVTEIFGEILFTPPvgesLKEF--------PSPNSL 239


                  ....*....
gi 1907136685 455 RGKILIKNK 463
Cdd:PLN02222  240 KKRIIISTK 248

EF-hand_like

pfam09279

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

215-303

8.89e-10

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: 55.72 E-value: 8.89e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 215 LCPRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPRlnsllfppARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWF 294
Cdd:pfam09279   5 LTQREEIDEIFQEY-SGDGQKLSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKDGFLMY 75


                  ....*....
gi 1907136685 295 LCGPENSVL 303
Cdd:pfam09279  76 LCSPDGSIF 84

Name

Accession

Description

Interval

E-value

PI-PLCc_beta2

cd08624

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

311-585

1.33e-119

Pssm-ID: 176561 [Multi-domain] Cd Length: 261 Bit Score: 355.52 E-value: 1.33e-119

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08624     1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTEILFKDAIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 391 IAESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKKnqfsgp 470
Cdd:cd08624    81 IAESAFKTSPYPVILSFENHVDSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLKPGVPLPSPEDLRGKILIKNKK------ 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 471 aspskkpggvaegslpssvpveedtgwtaedrteveeeevveeeeeeesgnldeeeikkmqsdegtaglevtaYEEMSSL 550
Cdd:cd08624   155 -------------------------------------------------------------------------YEEMSSL 161

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1907136685 551 VNYIQPTKFISFEFSAR-----VQTRLFQLRAPAALSPSA 585
Cdd:cd08624   162 VNYIQPTKFVSFEFSAQknrsyVISSFTELKAYDLLSKAS 201

PI-PLCc_beta

cd08591

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

311-566

1.37e-117

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: 350.10 E-value: 1.37e-117

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGKGEDEEPIITHGKTMCTEILFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 391 IAESAFKTSPYPVILSFENHVDSPrQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKKnqfsgp 470
Cdd:cd08591    81 IAETAFKTSEYPVILSFENHCSSK-QQAKMAEYCREIFGDLLLTEPLEKYPLEPGVPLPSPNDLKRKILIKNKK------ 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 471 aspskkpggvaegslpssvpveedtgwtaedrteveeeevveeeeeeesgnldeeeikkmqsdegtaglevtayeeMSSL 550
Cdd:cd08591   154 ----------------------------------------------------------------------------LSSL 157

                         250
                  ....*....|....*.
gi 1907136685 551 VNYIQPTKFISFEFSA 566
Cdd:cd08591   158 VNYIQPVKFQGFEVAE 173

EFh_PI-PLCbeta2

cd16209

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

149-299

1.40e-102

Pssm-ID: 320039 Cd Length: 151 Bit Score: 307.58 E-value: 1.40e-102

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 149 DKILVKLKMQLNPEGKIPVKNFFQMFPADRKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSY 228
Cdd:cd16209     1 EKIYVKLKMQLNSEGKIPVKNFFQMFPADRKRVEAALSACHLPKGKNDAINPEDFPEAVFKTFLMQLCPRPEIDEIFTSY 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907136685 229 HSKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16209    81 HAKAKPYMTKEHLTKFINKKQRDSRLNEELFPPARPDQVQGLIEKYEPSGINAQRGQLSPEGMVWFLCGPE 151

PI-PLCc_beta3

cd08625

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

313-464

1.70e-99

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: 303.90 E-value: 1.70e-99

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 313 DMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEAIA 392
Cdd:cd08625     3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGRPPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907136685 393 ESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08625    83 ESAFKTSPYPVILSFENHVDSAKQQAKMAEYCRSIFGDALLIDPLDKYPLVPGVQLPSPQELMGKILVKNKK 154

PI-PLCc_eukaryota

cd08558

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

311-466

1.13e-97

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: 297.83 E-value: 1.13e-97

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08558     1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGHTLTSKILFKDVIEA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPlkpgIPLPSPEDLRGKILIKNKKNQ 466
Cdd:cd08558    79 IKEYAFVTSPYPVILSLENHC-SLEQQKKMAQILKEIFGDKLLTPPLDENP----VQLPSPEQLKGKILIKGKKYH 149

PI-PLCc_beta1

cd08623

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

312-464

5.74e-88

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: 273.88 E-value: 5.74e-88

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 312 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEAI 391
Cdd:cd08623     2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAEEEPVITHGFTMTTEISFKEVIEAI 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136685 392 AESAFKTSPYPVILSFENHVDSPRQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08623    82 AECAFKTSPFPILLSFENHVDSPKQQAKMAEYCRLIFGDALLMEPLEKYPLESGVPLPSPMDLMYKILVKNKK 154

PI-PLCc_beta4

cd08626

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

311-464

2.21e-85

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: 267.02 E-value: 2.21e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08626     1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGEDQEPIITHGKAMCTDILFKDVIQA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVDSPrQQAKMAEYCRSMFGETLLTDPLENFPLKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08626    81 IKDTAFVTSDYPVILSFENHCSKP-QQYKLAKYCEEIFGDLLLTKPLESHPLEPGVPLPSPNKLKRKILIKNKR 153

PI-PLC-X

pfam00388

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

314-462

2.05e-79

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: 247.42 E-value: 2.05e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 314 MTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAIAE 393
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDG--PDGEPVVYHGYTLTSKIPFRDVLEAIKD 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136685 394 SAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENfplkPGIPLPSPEDLRGKILIKN 462
Cdd:pfam00388  79 YAFVTSPYPVILSLENHC-SPEQQKKMAEILKEIFGDMLYTPPLDD----DLTELPSPEDLKGKILIKG 142

PI-PLCc_delta

cd08593

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

311-464

2.55e-74

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: 238.39 E-value: 2.55e-74

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08593     1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDG--PDGEPIIYHGHTLTSKILFKDVIQA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENfplkPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08593    79 IREYAFKVSPYPVILSLENHC-SVEQQKVMAQHLKSILGDKLLTQPLDG----VLTALPSPEELKGKILVKGKK 147

PI-PLCc

cd00137

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

311-482

2.05e-72

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: 234.08 E-value: 2.05e-72

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFS-----GLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTtDILFK 385
Cdd:cd00137     1 HHPDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDG--KPEEPIIYHGPTFL-DIFLK 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 386 EAIEAIAESAFKTSPYPVILSFENHVDS-PRQQAKMAEYCRSMFGETLLTdplenFPLKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd00137    78 EVIEAIAQFLKKNPPETIIMSLKNEVDSmDSFQAKMAEYCRTIFGDMLLT-----PPLKPTVPLPSLEDLRGKILLLNKK 152

                         170
                  ....*....|....*...
gi 1907136685 465 NQFSGPASPSKKPGGVAE 482
Cdd:cd00137   153 NGFSGPTGSSNDTGFVSF 170

PI-PLC1c_yeast

cd08598

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

312-466

7.19e-70

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: 225.59 E-value: 7.19e-70

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 312 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAI 391
Cdd:cd08598     2 EDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDG--DDGEPVVTHGYTLTSSVPFRDVCRAI 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907136685 392 AESAFKTSPYPVILSFENHVDsPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgipLPSPEDLRGKILIKNKKNQ 466
Cdd:cd08598    80 KKYAFVTSPYPLILSLEVHCD-AEQQERMVEIMKETFGDLLVTEPLDGLEDE----LPSPEELRGKILIKVKKES 149

EFh_PI-PLCbeta

cd16200

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

149-299

4.61e-68

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: 218.27 E-value: 4.61e-68

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 149 DKILVKLKMQLNPEGKIPVKNFFQMFPAD--RKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFT 226
Cdd:cd16200     1 KKLYTKLKLSVNITGKIPVKNIIKCFSSDkkRKRVLKALKALGLPDGKNDEIDPEDFTFEKFFKLYNKLCPRPDIDEIFK 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136685 227 SYHSKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16200    81 ELGGKRKPYLTLEQLVDFLNEEQRDPRLNEILFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSDE 153

PI-PLCc_PRIP_metazoa

cd08597

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

311-464

2.55e-67

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: 219.99 E-value: 2.55e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08597     1 CQDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDG--PNGEPVIYHGHTLTSKISFRSVIEA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPlenfPLKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08597    79 INEYAFVASEYPLILCIENHC-SEKQQLVMAQYLKEIFGDKLYTEP----PNEGESYLPSPHDLKGKIIIKGKK 147

PH_14

pfam17787

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

13-141

3.12e-67

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: 215.32 E-value: 3.12e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  13 VKAYLSQGERFIKWDDETSIASP-VILRVDPKGYYLYWTYQNQEMEFLDVTSIRDTRFGKFAKIPKSQKLREVFNMDFPD 91
Cdd:pfam17787   2 VPEKLQKGELFIKWDEESTVAEPnVLLKVDPKGFFLYWKSQGKEGEVLEITSIRDTRLGKFAKIPKDPKLREVLSMGGSD 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907136685  92 NHFLLKTLTVVSGPDMVDLTFYNFVSYKENVGKDWAEDVLALAKHPMTVN 141
Cdd:pfam17787  82 NSLEDKTLTVVSGTDMVNINFHNFVASNSEVAKNWAEGLRALAHNVLAAN 131

PLCXc

smart00148

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

314-463

2.49e-63

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 205.21 E-value: 2.49e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  314 MTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAIAE 393
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDG--PDGEPVIYHGHTFTLPIKLSEVLEAIKD 78

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  394 SAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgipLPSPEDLRGKILIKNK 463
Cdd:smart00148  79 FAFVTSPYPVILSLENHC-SPDQQAKMAQMFKEIFGDMLYTPPLTSSLEV----LPSPEQLRGKILLKVR 143

EFh_PI-PLCbeta1

cd16208

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

149-299

4.44e-63

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: 205.11 E-value: 4.44e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 149 DKILVKLKMQLNPEGKIPVKNFFQMFPADRKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSY 228
Cdd:cd16208     1 EKAYTKLKLQVNPEGRIPVKNIYRLFSADRKRVETALEACNLPSSRNDSIPQEDFTPEVYRVFLNNLCPRPEIDHIFSEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907136685 229 HSKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16208    81 GAKSKPYLSVDQMTEFINSKQRDPRLNEILYPPLKQEQVQQLIEKYEPNSTLAKKGQISVDGFMRYLSGEE 151

PI-PLCc_gamma

cd08592

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

312-464

1.33e-62

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: 206.51 E-value: 1.33e-62

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 312 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAI 391
Cdd:cd08592     2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPIIYHGHTLTSKIKFMDVLKTI 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136685 392 AESAFKTSPYPVILSFENHVDSPrQQAKMAEYCRSMFGETLLTDPLEnfplKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08592    80 KEHAFVTSEYPVILSIENHCSLP-QQRNMAQAFKEVFGDMLLTQPVD----RNADQLPSPNQLKRKIIIKHKK 147

PI-PLCc_delta3

cd08630

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

311-468

1.87e-61

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: 204.87 E-value: 1.87e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08630     1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEG--PGGEPVIYHGHTLTSKILFRDVIQA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgiPLPSPEDLRGKILIKNKKNQFS 468
Cdd:cd08630    79 VRQHAFTASPYPVILSLENHC-GLEQQAAMARHLQTILGDMLVTQPLDSLNPE---ELPSPEELKGRVLVKGKKLQIS 152

PI-PLCc_eta

cd08594

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

311-468

8.96e-61

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: 201.57 E-value: 8.96e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08594     1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKILFRDVIET 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLtdpLENFPLKPGIPLPSPEDLRGKILIKNKKNQFS 468
Cdd:cd08594    79 INKYAFIKNEYPVILSIENHC-SVQQQKKMAQYLKEILGDKLD---LSSVISGDSKQLPSPQSLKGKILIKGKKWQVS 152

PI-PLCc_epsilon

cd08596

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

312-466

8.14e-60

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: 200.08 E-value: 8.14e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 312 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMTTDILFKEAIEAI 391
Cdd:cd08596     2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGD--DGMPIIYHGHTLTTKIPFKDVVEAI 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907136685 392 AESAFKTSPYPVILSFENHVDSPrQQAKMAEYCRSMFGETLLTDPL--ENFPLKPGipLPSPEDLRGKILIKNKKNQ 466
Cdd:cd08596    80 NRSAFITSDYPVILSIENHCSLQ-QQRKMAEIFKTVFGEKLVTKFLfeSDFSDDPS--LPSPLQLKNKILLKNKKAP 153

PI-PLCc_delta1

cd08629

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

311-464

3.75e-59

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: 198.72 E-value: 3.75e-59

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08629     1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVLRA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgipLPSPEDLRGKILIKNKK 464
Cdd:cd08629    79 IRDYAFKASPYPVILSLENHC-SLEQQRVMARHLRAILGPILLDQPLDGVTTS----LPSPEQLKGKILLKGKK 147

PI-PLCc_zeta

cd08595

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

311-464

4.98e-58

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: 195.54 E-value: 4.98e-58

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08595     1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGA--DNEPVVYHGYTLTSKILFKEVITT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgiPLPSPEDLRGKILIKNKK 464
Cdd:cd08595    79 VEKYAFEKSDYPVVLSLENHC-STEQQEIMAHYLVSILGEKLLRAPIDDPATG---ELPSPEALKFKILVKNKK 148

PI-PLCc_eta2

cd08633

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

311-464

1.03e-55

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: 189.48 E-value: 1.03e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08633     1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVDSPrQQAKMAEYCRSMFGETLLTDPLENfplKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08633    79 INKYAFIKNEYPVILSIENHCSVP-QQKKMAQYLTEILGDKLDLSSVIS---NDCTRLPSPEILKGKILVKGKK 148

PI-PLCc_delta4

cd08631

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

311-464

2.13e-55

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: 188.62 E-value: 2.13e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08631     1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDG--PNGEPIVYHGHTFTSKILFKDVVAA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENfplKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08631    79 VAQYAFQVSDYPVILSLENHC-GVEQQQTMAQHLTEILGEKLLSTTLDG---VLPTQLPSPEELRGKILLKGKK 148

PH_PLC_beta

cd13361

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

17-144

2.01e-53

Pssm-ID: 270167 Cd Length: 127 Bit Score: 178.53 E-value: 2.01e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685  17 LSQGERFIKWDDETSIASPVILRVDPKGYYLYWTYQNQEMEFLDVTSIRDTRFGKFAKIPKSQKLREVfNMDFPDNHFLL 96
Cdd:cd13361     1 LLKGSKFDKWDEDSSLETPVTLKVDEYGFFLYWKSEGKETEVLDLSLIRDVRTGKYPKDPKDLKEREV-NVGGSDEDLED 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907136685  97 KTLTVVSGPDMVDLTFYNFVSYKENVGKDWAEDVLALAKHPMTVNAPR 144
Cdd:cd13361    80 RTLTIVSGTDLVNISFINFVAESEEVAKIWTEGLFKLAHNLLANNASP 127

EFh_PI-PLCbeta3

cd16210

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

150-299

8.21e-53

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: 177.80 E-value: 8.21e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 150 KILVKLKMQLNPEGKIPVKNFFQMFPADRKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSYH 229
Cdd:cd16210     2 KAYTKLKLQVNQDGRIPVKNILKMFSADKKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEIG 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 230 SKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16210    82 AKGKPYLTLEQLMDFINQKQRDPRLNEVLYPPLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYLGGEE 151

PI-PLCc_gamma2

cd08628

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

312-464

1.98e-51

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: 177.94 E-value: 1.98e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 312 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAI 391
Cdd:cd08628     2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDG--PDGKPIIYHGWTRTTKIKFDDVVQAI 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136685 392 AESAFKTSPYPVILSFENHVDSpRQQAKMAEYCRSMFGETLLTDPLEnfplKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08628    80 KDHAFVTSEYPVILSIEEHCSV-EQQRHMAKVFKEVFGDKLLMKPLE----ASADQLPSPTQLKEKIIIKHKK 147

EFh_PI-PLC21

cd16213

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

150-295

5.19e-51

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: 173.26 E-value: 5.19e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 150 KILVKLKMQLNPEGKIPVKNFFQMFPA---DRKRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFT 226
Cdd:cd16213     2 KAYTKLTLQTDKEGKIPVKNIVKMFAQhkdDRKRVEKALEAIGLPSGKNDAIDPKKFTFEDFFNFYRRLTGRQEVEKIFD 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136685 227 SYHSKAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFL 295
Cdd:cd16213    82 ELGAKKKPYLTTEQFVDFLNKTQRDPRLNEILYPYANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYL 150

PI-PLCc_gamma1

cd08627

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

312-464

7.12e-51

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: 175.60 E-value: 7.12e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 312 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEAI 391
Cdd:cd08627     2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDGMPVIYHGHTLTTKIKFSDVLHTI 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136685 392 AESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLEnfplKPGIPLPSPEDLRGKILIKNKK 464
Cdd:cd08627    80 KEHAFVTSEYPIILSIEDHC-SIVQQRNMAQHFKKVFGDMLLTKPVD----INADGLPSPNQLKRKILIKHKK 147

PI-PLCc_plant

cd08599

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

311-463

3.73e-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: 173.33 E-value: 3.73e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDeePIITHGFTMTTDILFKEAIEA 390
Cdd:cd08599     1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGD--ICVLHGGTLTKPVKFEDCIKA 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPlenfPLKPGIPLPSPEDLRGKILIKNK 463
Cdd:cd08599    79 IKENAFTASEYPVIITLENHL-SPELQAKAAQILRETLGDKLFYPD----SEDLPEEFPSPEELKGKILISDK 146

PI-PLCc_eta1

cd08632

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

311-464

4.49e-50

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: 174.06 E-value: 4.49e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTDILFKEAIEA 390
Cdd:cd08632     1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDG--PDGEPVVHHGYTLTSKITFRDVIET 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 391 IAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPLKpgiPLPSPEDLRGKILIKNKK 464
Cdd:cd08632    79 INKYAFVKNEFPVILSIENHC-SIQQQKKIAQYLKEIFGDKLDLSSVLTGDPK---QLPSPQLLKGKILVKGKK 148

PLN02222

phosphoinositide phospholipase C 2

219-463

1.02e-31

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 130.15 E-value: 1.02e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 219 PEIDEIFTSYHSKAkpYMTKEHLTKFINQKQRDPRlnsllfppARPEQVQVLIDKyepSGINVQRGQLSPEGMVWFLCGP 298
Cdd:PLN02222   25 REIKTIFEKYSENG--VMTVDHLHRFLIDVQKQDK--------ATREDAQSIINS---ASSLLHRNGLHLDAFFKYLFGD 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 299 ENSVLAHDTllIHQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDEEPIItHGFTM 378
Cdd:PLN02222   92 NNPPLALHE--VHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIDVL-HGMTL 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 379 TTDILFKEAIEAIAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDP----LENFplkpgiplPSPEDL 454
Cdd:PLN02222  169 TTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHL-TPDLQSKVAEMVTEIFGEILFTPPvgesLKEF--------PSPNSL 239


                  ....*....
gi 1907136685 455 RGKILIKNK 463
Cdd:PLN02222  240 KKRIIISTK 248

PLN02952

phosphoinositide phospholipase C

310-530

1.08e-31

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 130.12 E-value: 1.08e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 310 IHQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDeEPIITHGFTMTTDILFKEAIE 389
Cdd:PLN02952  121 VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKD-EILVLHGRTLTTPVPLIKCLK 199

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 390 AIAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLL---TDPLENFplkpgiplPSPEDLRGKILIKNKKN- 465
Cdd:PLN02952  200 SIRDYAFSSSPYPVIITLEDHL-TPDLQAKVAEMATQIFGQMLYypeSDSLVQF--------PSPESLKHRIIISTKPPk 270

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907136685 466 ---QFSGPASPSKKpGGVAEGSLPSSVPVEEDTGWTAEDRTEVEEEEVVEEEEEEESGNLDEEEIKKM 530
Cdd:PLN02952  271 eylESSGPIVIKKK-NNVSPSGRNSSEETEEAQTLESMLFEQEADSRSDSDQDDNKSGELQKPAYKRL 337

PLN02228

Phosphoinositide phospholipase C

217-463

3.23e-31

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 128.23 E-value: 3.23e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 217 PRPEIDEIFTSYHSKAKpyMTKEHLTKFINQKQRDPRlnsllfppARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLC 296
Cdd:PLN02228   22 PPVSIKRLFEAYSRNGK--MSFDELLRFVSEVQGERH--------AGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLF 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 297 GPENSVLAHdTLLIHQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKgKPPDEEPIITHGF 376
Cdd:PLN02228   92 SDTNSPLPM-SGQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWP-NPSGNAAEVRHGR 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 377 TMTTDILFKEAIEAIAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLL---TDPLENFplkpgiplPSPED 453
Cdd:PLN02228  170 TLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHL-PPNLQAQVAKMLTKTFRGMLFrctSESTKHF--------PSPEE 240

                         250
                  ....*....|
gi 1907136685 454 LRGKILIKNK 463
Cdd:PLN02228  241 LKNKILISTK 250

EFh_PI-PLCbeta4

cd16211

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

154-295

6.40e-31

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: 117.91 E-value: 6.40e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 154 KLKMQLNPEGKIPVKNFFQMFPADR--KRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSYHSK 231
Cdd:cd16211     6 RLCFLVNPNGKIPVRSITRTFASGKteKIVFQSLKELGLPSGKNDEIEPEAFTFEKFYELYHKICPRTDIEELFKKINGD 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907136685 232 AKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFL 295
Cdd:cd16211    86 KKDYLTVDQLISFLNEHQRDPRLNEILFPFYDRKRVMQIIETYEVDEEFKKKEQLSSDGFCRYL 149

EFh_NorpA_like

cd16212

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

153-299

2.24e-25

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: 102.24 E-value: 2.24e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 153 VKLKMQLNPEGKIPVKNFFQMFPADR--KRVEAALGACHLAKGKNDAINPEDFPESVYKSFLMSLCPRPEIDEIFTSYHS 230
Cdd:cd16212     5 MRLGFMVDSGGKIPVKHIARTFASGKteKLVYQCLAEMGLPSGKGDSIEKEDFTFEKFYALYHKICPRNDIEELFTSITK 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907136685 231 KAKPYMTKEHLTKFINQKQRDPRLNSLLFPPARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16212    85 GKGEHISLAQLINFMNDKQRDPRLNEILYPLYDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMSDE 153

PLN02230

phosphoinositide phospholipase C 4

217-463

1.57e-23

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 105.17 E-value: 1.57e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 217 PRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPRLNSLlfpparpEQVQVLIDKYEPSGINV---QRGQLSPEGMVW 293
Cdd:PLN02230   27 PVADVRDLFEKY-ADGDAHMSPEQLQKLMAEEGGGEGETSL-------EEAERIVDEVLRRKHHIakfTRRNLTLDDFNY 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 294 FLCGPENSVLAHDTllIHQDMTQPLNHYFINSSHNTYLTAGQFSGLSSAEMYRQVLLSGCRCVELDCWKGKPPDeePIIT 373
Cdd:PLN02230   99 YLFSTDLNPPIADQ--VHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDD--VCVK 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 374 HGFTMTTDILFKEAIEAIAESAFKTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLLTDPLENFPlkpgiPLPSPED 453
Cdd:PLN02230  175 HGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHL-TPKLQFKVAKMITQTFGDMLYYHDSEGCQ-----EFPSPEE 248

                         250
                  ....*....|
gi 1907136685 454 LRGKILIKNK 463
Cdd:PLN02230  249 LKEKILISTK 258

PI-PLCc_GDPD_SF

cd08555

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

324-464

1.96e-23

Pssm-ID: 176498 [Multi-domain] Cd Length: 179 Bit Score: 97.51 E-value: 1.96e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 324 NSSHNTYLTAGQfsgLSSAEMYRQVLLSGCRCVELDCWKGKppDEEPIITHGFTMT------TDILFKEAIEAIAESAFk 397
Cdd:cd08555     1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTK--DGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK- 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 398 TSPYPVILSFENHVDS---PRQQAKMAEYCRSMFGetlltdplenfplkpgiplpspEDLRGKILIKNKK 464
Cdd:cd08555    75 NPDYTIILSLEIKQDSpeyDEFLAKVLKELRVYFD----------------------YDLRGKVVLSSFN 122

PLN02223

phosphoinositide phospholipase C

311-463

6.49e-17

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 83.92 E-value: 6.49e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 311 HQDMTQPLNHYFINSSHNTYLTAGQ-FSGLSSAEMYRQVLLSGCRCVELDCWkgkPPDEEPI-ITHGFTMTTDILFKEAI 388
Cdd:PLN02223  105 HHDMHAPLSHYFIHTSLKSYFTGNNvFGKLYSIEPIIDALEQGVRVVELDLL---PDGKDGIcVRPKWNFEKPLELQECL 181

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 389 EAIAESAF-KTSPYPVILSFENHVdSPRQQAKMAEYCRSMFGETLL-TDP---LENFplkpgiplPSPEDLRGKILIKNK 463
Cdd:PLN02223  182 DAIKEHAFtKCRSYPLIITFKDGL-KPDLQSKATQMIDQTFGDMVYhEDPqhsLEEF--------PSPAELQNKILISRR 252

EFh_PI-PLCdelta

cd16202

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

195-299

5.85e-15

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: 72.26 E-value: 5.85e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 195 NDAINPEDFPEsvyksFLMSLCPRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPRLNsllfpparPEQVQVLIDKY 274
Cdd:cd16202    50 EDVLDEEEFVQ-----FYNRLTKRPEIEELFKKY-SGDDEALTVEELRRFLQEEQKVKDVT--------LEWAEQLIETY 115

                          90       100
                  ....*....|....*....|....*
gi 1907136685 275 EPSGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16202   116 EPSEDLKAQGLMSLDGFTLFLLSPD 140

EFh_PI-PLC

cd15898

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

155-299

2.12e-11

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: 61.91 E-value: 2.12e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 155 LKMQLNPEGKIPVKNFFQM-----FPADRKRVEAALGACHlaKGKNDAINPEDFpesvyKSFLMSLCPRPEIDEIFTSYH 229
Cdd:cd15898     7 IKADKDGDGKLSLKEIKKLlkrlnIRVSEKELKKLFKEVD--TNGDGTLTFDEF-----EELYKSLTERPELEPIFKKYA 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 230 SKAKPYMTKEHLTKFINQKQRDPRlnsllfppaRPEQVQVLIDKYEPsgiNVQRGQLSPEGMVWFLCGPE 299
Cdd:cd15898    80 GTNRDYMTLEEFIRFLREEQGENV---------SEEECEELIEKYEP---ERENRQLSFEGFTNFLLSPE 137

EF-hand_like

pfam09279

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

215-303

8.89e-10

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 55.72 E-value: 8.89e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 215 LCPRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPRlnsllfppARPEQVQVLIDKYEPSGINVQRGQLSPEGMVWF 294
Cdd:pfam09279   5 LTQREEIDEIFQEY-SGDGQKLSLDELVDFLREEQREED--------ASPALALSLIERYEPSETAKKQHAMTKDGFLMY 75


                  ....*....
gi 1907136685 295 LCGPENSVL 303
Cdd:pfam09279  76 LCSPDGSIF 84

EFh_PI-PLCdelta1

cd16217

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

209-299

1.44e-07

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: 50.89 E-value: 1.44e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 209 KSFLMSLCPRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPrlnsllfppARPEQVQVLIDKYEPSGINVQRGQLSP 288
Cdd:cd16217    59 EEFYKLLTKREEIDVIFGEY-AKSDGTMSRNNLLNFLQEEQREE---------VAPAYALSLIEKYEPDETAKAQRQMTK 128

                          90
                  ....*....|.
gi 1907136685 289 EGMVWFLCGPE 299
Cdd:cd16217   129 DGFLMYLLSPE 139

EFh_PI-PLCdelta4

cd16219

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

211-299

2.19e-06

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: 47.53 E-value: 2.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 211 FLMSLCPRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPRLNSllfpparpEQVQVLIDKYEPSGINVQRGQLSPEG 290
Cdd:cd16219    61 FYKALTQREDVLKIFQDF-SADGQKLTLLEFVDFLQQEQLERENTE--------ELAMELIDRYEPSDTAKKLHALSIDG 131


                  ....*....
gi 1907136685 291 MVWFLCGPE 299
Cdd:cd16219   132 FLMYLCSPE 140

PI-PLCc_bacteria_like

cd08557

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

317-460

4.96e-04

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: 42.46 E-value: 4.96e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 317 PLNHYFINSSHNTY-LTAGQFSGLSSA-----EMY-RQVLLSGCRCVELDCWKgKPPDEEPIITHGFTMTTDILFKEAIE 389
Cdd:cd08557     8 PLSQLSIPGTHNSYaYTIDGNSPIVSKwsktqDLSiTDQLDAGVRYLDLRVAY-DPDDGDLYVCHGLFLLNGQTLEDVLN 86

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907136685 390 AIAesAF-KTSPY-PVILSFENHVDSPRQQAKMAEycRSMFGETLLTDPLENFPLKPGIP-LpspEDLR-GKILI 460
Cdd:cd08557    87 EVK--DFlDAHPSeVVILDLEHEYGGDNGEDHDEL--DALLRDVLGDPLYRPPVRAGGWPtL---GELRaGKRVL 154

EFh_ScPlc1p_like

cd16207

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

202-295

1.39e-03

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: 39.54 E-value: 1.39e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 202 DFPEsvYKSFLMSLCPRPEIDEIFTSYHSKAKPYMTKEHLTKFINQKQRDPRlnsllfppaRPEQVQVLIDKYEPSGINV 281
Cdd:cd16207    56 NFEE--FQEFVKLLKRRKDIKAIFKQLTKPGSDGLTLEEFLKFLRDVQKEDV---------DRETWEKIFEKFARRIDDS 124

                          90
                  ....*....|....
gi 1907136685 282 QRGQLSPEGMVWFL 295
Cdd:cd16207   125 DSLTMTLEGFTSFL 138

EFh_PRIP

cd16206

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

197-299

6.35e-03

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: 37.58 E-value: 6.35e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907136685 197 AINPEDFPEsVYKSflmsLCPRPEIDEIFTSYhSKAKPYMTKEHLTKFINQKQRDPRLNsllfpparPEQVQVLIDKYEP 276
Cdd:cd16206    55 RVSSDEFVE-LFKE----LATRPEIYFLLVRY-ASNKDYLTVDDLMLFLEAEQGMTGVT--------KEKCLEIINKYEP 120

                          90       100
                  ....*....|....*....|...
gi 1907136685 277 SGINVQRGQLSPEGMVWFLCGPE 299
Cdd:cd16206   121 SEEGREKGQLGIDGFTRYLLSEE 143

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