NCBI Conserved Domain Search

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

334-491

2.58e-111

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: 348.65 E-value: 2.58e-111

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKE 413
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  414 HAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKlvegtLYEEVTS 491
Cdd:cd08592     82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKK-----LFYEMSS 154

EFh_PI-PLC super family

cl28895

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

173-320

1.03e-99

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.

The actual alignment was detected with superfamily member cd16216:

Pssm-ID: 333715 Cd Length: 150 Bit Score: 314.18 E-value: 1.03e-99

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  173 WLRKQFEVMDRNHEGSITVKDVKALLPQVNYRVPNMRFLKDKLQEVEARSDLSYPNFAQLYRTLMFDAQRSIIEQLELSF 252
Cdd:cd16216      1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFLRDKLVEVEARSELTFPHFIQFYKNLMFDAQKSIIEQLELSF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  253 PLRNVDRPELCQISLYDFQKFLQMDQKESWASDLSRVREFLMGYM--GGGPHPEPMLQLDEFLTFLFSKE 320
Cdd:cd16216     81 PLRNVDRPELCQISLYDFQKFLQHDQKESWASDVGRVRDYLCGYLkeSSNEAPEPSLQLDEFLTYLFSKE 150

PH_PLC_gamma

cd13362

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...

47-167

2.43e-66

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. 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.

Pssm-ID: 270168 Cd Length: 121 Bit Score: 219.46 E-value: 2.43e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   47 LEMGTVMTVFYQKKsqRPERRTFQIRQDARQIVWSRNPDK-IEGEIDIREIRELRLGKGSRDFERYPEEARKLDSAHCFI 125
Cdd:cd13362      1 LERGTVMTKFYQKK--RPERRTFQVKLETRQVVWSRGGGKrAEGAVDIREIKEIRPGKNSKDFERWPDEAKKLDPSCCFV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1469982874  126 VLYGLEFRLRTLSVAAFSEEEVNMWVTGLNWLMIDTQRAPAP 167
Cdd:cd13362     79 ILYGTEFRLKTLSVAATSEEECDMWIKGLRYLVEDTLSASYP 120

SH2_C-SH2_PLC_gamma_like

cd09932

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...

677-780

1.45e-62

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

Pssm-ID: 198186 Cd Length: 104 Bit Score: 207.89 E-value: 1.45e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  677 HESREWYHSSLSRVQAEHMLMRVPRDGAFLVRKRSE-HNSYAISFRAEGKIKHCRIQQEGRLFMLGSSaEFESLVDLVSY 755
Cdd:cd09932      1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETdPNSFAISFRAEGKIKHCRIKQEGRLFVIGTS-QFESLVELVSY 79

                           90       100
                   ....*....|....*....|....*
gi 1469982874  756 YEKHPLYRKMRLRYPINEDTLDRMG 780
Cdd:cd09932     80 YEKHPLYRKIKLRYPVNEELLEKYG 104

PLCYc

smart00149

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

971-1086

1.33e-55

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

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 188.22 E-value: 1.33e-55

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   971 SELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGS 1050
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLK-KSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 1469982874  1051 QLVALNFQTPDKPMQLNQALFMLGGGSGYVPQPDIM 1086
Cdd:smart00149   80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

SH2_N-SH2_PLC_gamma_like

cd10341

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...

560-663

2.48e-54

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

Pssm-ID: 199829 Cd Length: 99 Bit Score: 184.09 E-value: 2.48e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  560 HCAERWFHGKLGGGRDgrqVAEKLLQEYCEGGakDGTFLVRESETFVGDYTLSFWRSGRVQHCRIHSRQESGSTRFYLTD 639
Cdd:cd10341      1 HFTEPWFHGKLGDGRD---EAEKLLLEYCEGG--DGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLTD 75

                           90       100
                   ....*....|....*....|....
gi 1469982874  640 NLVFDSLYRLICHYRDTPLRCNEF 663
Cdd:cd10341     76 NLVFDSLYELIDYYRQNPLRCAEF 99

C2_PLC_like

cd00275

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

1103-1227

6.74e-52

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 178.12 E-value: 6.74e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1103 PITVQLQVLGARHLPKNG---RSIVCPFVEVEICGADY-DGCKCKTDVVADNGLNPVWvQNQFVFDIHNPTFSFLRFVVY 1178
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVW-NETFEFDVTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1469982874 1179 EEDMFSDpNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVHVEI 1227
Cdd:cd00275     80 DEDSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDI 127

SH3_PLCgamma1

cd11970

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...

806-864

5.84e-33

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212903 Cd Length: 60 Bit Score: 121.63 E-value: 5.84e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  806 TARCTVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVEEV 864
Cdd:cd11970      1 TFKCAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEI 59

PHsplit_PLC_gamma

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...

877-950

9.09e-31

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. 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.

Pssm-ID: 270054 Cd Length: 105 Bit Score: 117.18 E-value: 9.09e-31

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  877 TENSPLGTFLKGFIDVPTCHVVIHKDGKNSRPFVFTIHSQHLSSHPvqtLDVAADSLEDLSNWVSKIREAAQNA 950
Cdd:cd13234     35 TENSPLGSLLRGILDVPSCHVVKRPEGKNSRPFVFILSPKSLSDPP---LDVAADSQEELQDWVQKIREVAQTA 105

PH-like super family

cl17171

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...

502-536

7.60e-15

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

The actual alignment was detected with superfamily member cd13234:

Pssm-ID: 473070 Cd Length: 105 Bit Score: 71.73 E-value: 7.60e-15

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1469982874  502 SLKNGILYLEDPIDHTWTPHYFVLTSNKIYYSEET 536
Cdd:cd13234      1 SIKNGILYLEDPINHEWYPHFFVLTSNKIYYSEET 35

Name

Accession

Description

Interval

E-value

PI-PLCc_gamma

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

334-491

2.58e-111

Pssm-ID: 176534 [Multi-domain] Cd Length: 229 Bit Score: 348.65 E-value: 2.58e-111

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKE 413
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  414 HAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKlvegtLYEEVTS 491
Cdd:cd08592     82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKK-----LFYEMSS 154

EFh_PI-PLCgamma1_like

cd16216

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...

173-320

1.03e-99

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They 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. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. A second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker.

Pssm-ID: 320046 Cd Length: 150 Bit Score: 314.18 E-value: 1.03e-99

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  173 WLRKQFEVMDRNHEGSITVKDVKALLPQVNYRVPNMRFLKDKLQEVEARSDLSYPNFAQLYRTLMFDAQRSIIEQLELSF 252
Cdd:cd16216      1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFLRDKLVEVEARSELTFPHFIQFYKNLMFDAQKSIIEQLELSF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  253 PLRNVDRPELCQISLYDFQKFLQMDQKESWASDLSRVREFLMGYM--GGGPHPEPMLQLDEFLTFLFSKE 320
Cdd:cd16216     81 PLRNVDRPELCQISLYDFQKFLQHDQKESWASDVGRVRDYLCGYLkeSSNEAPEPSLQLDEFLTYLFSKE 150

PI-PLC-X

pfam00388

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

336-477

5.48e-84

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: 270.15 E-value: 5.48e-84

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  336 MKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEHA 415
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1469982874  416 FVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKH 477
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142

PLCXc

smart00148

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

336-478

3.15e-72

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: 236.79 E-value: 3.15e-72

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   336 MKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEHA 415
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1469982874   416 FVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHK 478
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143

PH_PLC_gamma

cd13362

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...

47-167

2.43e-66

Pssm-ID: 270168 Cd Length: 121 Bit Score: 219.46 E-value: 2.43e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   47 LEMGTVMTVFYQKKsqRPERRTFQIRQDARQIVWSRNPDK-IEGEIDIREIRELRLGKGSRDFERYPEEARKLDSAHCFI 125
Cdd:cd13362      1 LERGTVMTKFYQKK--RPERRTFQVKLETRQVVWSRGGGKrAEGAVDIREIKEIRPGKNSKDFERWPDEAKKLDPSCCFV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1469982874  126 VLYGLEFRLRTLSVAAFSEEEVNMWVTGLNWLMIDTQRAPAP 167
Cdd:cd13362     79 ILYGTEFRLKTLSVAATSEEECDMWIKGLRYLVEDTLSASYP 120

SH2_C-SH2_PLC_gamma_like

cd09932

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...

677-780

1.45e-62

Pssm-ID: 198186 Cd Length: 104 Bit Score: 207.89 E-value: 1.45e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  677 HESREWYHSSLSRVQAEHMLMRVPRDGAFLVRKRSE-HNSYAISFRAEGKIKHCRIQQEGRLFMLGSSaEFESLVDLVSY 755
Cdd:cd09932      1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETdPNSFAISFRAEGKIKHCRIKQEGRLFVIGTS-QFESLVELVSY 79

                           90       100
                   ....*....|....*....|....*
gi 1469982874  756 YEKHPLYRKMRLRYPINEDTLDRMG 780
Cdd:cd09932     80 YEKHPLYRKIKLRYPVNEELLEKYG 104

PLCYc

smart00149

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

971-1086

1.33e-55

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 188.22 E-value: 1.33e-55

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   971 SELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGS 1050
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLK-KSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 1469982874  1051 QLVALNFQTPDKPMQLNQALFMLGGGSGYVPQPDIM 1086
Cdd:smart00149   80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

SH2_N-SH2_PLC_gamma_like

cd10341

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...

560-663

2.48e-54

Pssm-ID: 199829 Cd Length: 99 Bit Score: 184.09 E-value: 2.48e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  560 HCAERWFHGKLGGGRDgrqVAEKLLQEYCEGGakDGTFLVRESETFVGDYTLSFWRSGRVQHCRIHSRQESGSTRFYLTD 639
Cdd:cd10341      1 HFTEPWFHGKLGDGRD---EAEKLLLEYCEGG--DGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLTD 75

                           90       100
                   ....*....|....*....|....
gi 1469982874  640 NLVFDSLYRLICHYRDTPLRCNEF 663
Cdd:cd10341     76 NLVFDSLYELIDYYRQNPLRCAEF 99

PI-PLC-Y

pfam00387

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

970-1084

3.54e-53

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 181.51 E-value: 3.54e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  970 LSELVVYCRPVPF-NEDKigTERACYRDMSSFPETKAEKFATHTRgKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLC 1048
Cdd:pfam00387    1 LSDLVVYTQSVKFkSFST--PESKTPNHIFSFSESKALKLIKSSS-AAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNC 77

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1469982874 1049 GSQLVALNFQTPDKPMQLNQALFMLGGGSGYVPQPD 1084
Cdd:pfam00387   78 GVQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPE 113

PI-PLCc_gamma1

cd08627

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

994-1074

3.98e-52

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: 182.92 E-value: 3.98e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  994 YRDMSSFPETKAEKFATHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFML 1073
Cdd:cd08627    149 YRDMSSFPETKAEKYVNRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFML 228


                   .
gi 1469982874 1074 G 1074
Cdd:cd08627    229 G 229

C2_PLC_like

cd00275

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

1103-1227

6.74e-52

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 178.12 E-value: 6.74e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1103 PITVQLQVLGARHLPKNG---RSIVCPFVEVEICGADY-DGCKCKTDVVADNGLNPVWvQNQFVFDIHNPTFSFLRFVVY 1178
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVW-NETFEFDVTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1469982874 1179 EEDMFSDpNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVHVEI 1227
Cdd:cd00275     80 DEDSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDI 127

PLN02228

Phosphoinositide phospholipase C

302-496

7.29e-37

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 147.88 E-value: 7.29e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  302 HPEPMLQLDEFLTFLFSKENSVCDprLSPVVHDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELD 381
Cdd:PLN02228    76 HHHGLVHLNAFYRYLFSDTNSPLP--MSGQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELD 153

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  382 CWDGPD-DLPIIYHGHTLTSKIKFLDVLHTIKEHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLtKPVDNNA 460
Cdd:PLN02228   154 LWPNPSgNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSEST 232

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1469982874  461 EELPSPYQLRRKILIKHK--------KLVEGTLYEEVTSASYSE 496
Cdd:PLN02228   233 KHFPSPEELKNKILISTKppkeylesKTVQTTRTPTVKETSWKR 276

SH3_PLCgamma1

cd11970

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...

806-864

5.84e-33

Pssm-ID: 212903 Cd Length: 60 Bit Score: 121.63 E-value: 5.84e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  806 TARCTVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVEEV 864
Cdd:cd11970      1 TFKCAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEI 59

PLN02952

phosphoinositide phospholipase C

999-1228

6.54e-32

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 133.20 E-value: 6.54e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  999 SFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFMLGGGSG 1078
Cdd:PLN02952   364 SLSEQELEKAAT-TNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCG 442

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1079 YVPQPDIM-----RDDIFDPfdKDTLhvePITVQLQV---------LGARHLPKNGRSIVCPFVEVEICGADYDGCKCKT 1144
Cdd:PLN02952   443 YLKKPDFLmkkgfHDEVFDP--KKKL---PVKKTLKVkvylgdgwrLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKKT 517

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1145 DVVADNgLNPVWVQnQFVFDIHNPTFSFLRFVVYEEDMFSDPNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVH 1224
Cdd:PLN02952   518 KIIEDN-WYPAWNE-EFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLMR 595


                   ....
gi 1469982874 1225 VEIV 1228
Cdd:PLN02952   596 FIFV 599

PHsplit_PLC_gamma

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...

877-950

9.09e-31

Pssm-ID: 270054 Cd Length: 105 Bit Score: 117.18 E-value: 9.09e-31

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  877 TENSPLGTFLKGFIDVPTCHVVIHKDGKNSRPFVFTIHSQHLSSHPvqtLDVAADSLEDLSNWVSKIREAAQNA 950
Cdd:cd13234     35 TENSPLGSLLRGILDVPSCHVVKRPEGKNSRPFVFILSPKSLSDPP---LDVAADSQEELQDWVQKIREVAQTA 105

SH2

SH2 domain;

565-653

1.38e-24

SH2 domain;

Pssm-ID: 425423 [Multi-domain] Cd Length: 77 Bit Score: 98.44 E-value: 1.38e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  565 WFHGKLGggrdgRQVAEKLLQEycegGAKDGTFLVRESETFVGDYTLSFWRSGRVQHCRIHSRQESGstrFYLTDNLVFD 644
Cdd:pfam00017    1 WYHGKIS-----RQEAERLLLN----GKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGG---YYISGGVKFS 68


                   ....*....
gi 1469982874  645 SLYRLICHY 653
Cdd:pfam00017   69 SLAELVEHY 77

SH2

SH2 domain;

682-756

2.28e-23

SH2 domain;

Pssm-ID: 425423 [Multi-domain] Cd Length: 77 Bit Score: 94.98 E-value: 2.28e-23

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1469982874  682 WYHSSLSRVQAEHMLMRVPRDGAFLVRKRSEH-NSYAISFRAEGKIKHCRIQQEGRL-FMLGSSAEFESLVDLVSYY 756
Cdd:pfam00017    1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTpGGYTLSVRDDGKVKHYKIQSTDNGgYYISGGVKFSSLAELVEHY 77

SH2

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...

563-659

2.00e-22

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.

Pssm-ID: 214585 [Multi-domain] Cd Length: 84 Bit Score: 92.29 E-value: 2.00e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   563 ERWFHGKLGggrdgRQVAEKLLQeycegGAKDGTFLVRESETFVGDYTLSFWRSGRVQHCRIhsrQESGSTRFYLTDNLV 642
Cdd:smart00252    1 QPWYHGFIS-----REEAEKLLK-----NEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRI---RRNEDGKFYLEGGRK 67

                            90
                    ....*....|....*..
gi 1469982874   643 FDSLYRLICHYRDTPLR 659
Cdd:smart00252   68 FPSLVELVEHYQKNSLG 84

SH2

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...

681-762

6.00e-22

Pssm-ID: 214585 [Multi-domain] Cd Length: 84 Bit Score: 91.14 E-value: 6.00e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   681 EWYHSSLSRVQAEHMLMRVPrDGAFLVRK-RSEHNSYAISFRAEGKIKHCRIQQ-EGRLFMLGSSAEFESLVDLVSYYEK 758
Cdd:smart00252    2 PWYHGFISREEAEKLLKNEG-DGDFLVRDsESSPGDYVLSVRVKGKVKHYRIRRnEDGKFYLEGGRKFPSLVELVEHYQK 80


                    ....
gi 1469982874   759 HPLY 762
Cdd:smart00252   81 NSLG 84

smart00239

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

1105-1208

7.40e-18

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

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 80.22 E-value: 7.40e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  1105 TVQLQVLGARHLP-KNGRSIVCPFVEVEICGADydGCKCKTDVVADNgLNPVWVQnQFVFDIHNPTFSFLRFVVYEEDMF 1183
Cdd:smart00239    1 TLTVKIISARNLPpKDKGGKSDPYVKVSLDGDP--KEKKKTKVVKNT-LNPVWNE-TFEFEVPPPELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 1469982874  1184 SDPNFLAQVTYPVRLLRTGYRSVPL 1208
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

1105-1204

2.22e-16

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 75.82 E-value: 2.22e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1105 TVQLQVLGARHLP-KNGRSIVCPFVEVEIcgaDYDGCKCKTDVVaDNGLNPVWVQnQFVFDIHNPTFSFLRFVVYEEDMF 1183
Cdd:pfam00168    2 RLTVTVIEAKNLPpKDGNGTSDPYVKVYL---LDGKQKKKTKVV-KNTLNPVWNE-TFTFSVPDPENAVLEIEVYDYDRF 76

                           90       100
                   ....*....|....*....|.
gi 1469982874 1184 SDPNFLAQVTYPVRLLRTGYR 1204
Cdd:pfam00168   77 GRDDFIGEVRIPLSELDSGEG 97

SH3

smart00326

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...

808-862

1.02e-15

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 72.57 E-value: 1.02e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874   808 RCTVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVE 862
Cdd:smart00326    2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56

PHsplit_PLC_gamma

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...

502-536

7.60e-15

Pssm-ID: 270054 Cd Length: 105 Bit Score: 71.73 E-value: 7.60e-15

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1469982874  502 SLKNGILYLEDPIDHTWTPHYFVLTSNKIYYSEET 536
Cdd:cd13234      1 SIKNGILYLEDPINHEWYPHFFVLTSNKIYYSEET 35

SH3_1

pfam00018

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...

812-858

1.30e-12

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

Pssm-ID: 394975 [Multi-domain] Cd Length: 47 Bit Score: 63.38 E-value: 1.30e-12

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1469982874  812 KALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPA 858
Cdd:pfam00018    1 VALYDYTAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47

smart00233

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...

872-948

1.39e-04

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 42.15 E-value: 1.39e-04

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874   872 LNEASTENSPLGTFLKGFIDVPTCHVVIHKDGKNS-RPFVFTIHSQHLsshpvQTLDVAADSLEDLSNWVSKIREAAQ 948
Cdd:smart00233   30 LLYYKSKKDKKSYKPKGSIDLSGCTVREAPDPDSSkKPHCFEIKTSDR-----KTLLLQAESEEEREKWVEALRKAIA 102

Name

Accession

Description

Interval

E-value

PI-PLCc_gamma

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

334-491

2.58e-111

Pssm-ID: 176534 [Multi-domain] Cd Length: 229 Bit Score: 348.65 E-value: 2.58e-111

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKE 413
Cdd:cd08592      2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  414 HAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKlvegtLYEEVTS 491
Cdd:cd08592     82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKK-----LFYEMSS 154

PI-PLCc_gamma1

cd08627

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

334-480

3.60e-103

Pssm-ID: 176564 [Multi-domain] Cd Length: 229 Bit Score: 326.60 E-value: 3.60e-103

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKE 413
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1469982874  414 HAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDINADGLPSPNQLKRKILIKHKKL 148

PI-PLCc_eukaryota

cd08558

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

333-487

1.58e-100

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: 319.40 E-value: 1.58e-100

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08558      1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKK-----LVEGTLYE 487
Cdd:cd08558     81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQLKGKILIKGKKyhmssFSETKALK 160

EFh_PI-PLCgamma1_like

cd16216

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...

173-320

1.03e-99

Pssm-ID: 320046 Cd Length: 150 Bit Score: 314.18 E-value: 1.03e-99

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  173 WLRKQFEVMDRNHEGSITVKDVKALLPQVNYRVPNMRFLKDKLQEVEARSDLSYPNFAQLYRTLMFDAQRSIIEQLELSF 252
Cdd:cd16216      1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFLRDKLVEVEARSELTFPHFIQFYKNLMFDAQKSIIEQLELSF 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  253 PLRNVDRPELCQISLYDFQKFLQMDQKESWASDLSRVREFLMGYM--GGGPHPEPMLQLDEFLTFLFSKE 320
Cdd:cd16216     81 PLRNVDRPELCQISLYDFQKFLQHDQKESWASDVGRVRDYLCGYLkeSSNEAPEPSLQLDEFLTYLFSKE 150

PI-PLC-X

pfam00388

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

336-477

5.48e-84

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: 270.15 E-value: 5.48e-84

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  336 MKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEHA 415
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1469982874  416 FVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKH 477
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142

PI-PLCc_gamma2

cd08628

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

335-489

3.16e-83

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: 272.70 E-value: 3.16e-83

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  335 DMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEH 414
Cdd:cd08628      3 DMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKDH 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874  415 AFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKLVEGTLYEEV 489
Cdd:cd08628     83 AFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQLKEKIIIKHKKLIAIELSDLV 157

PI-PLCc_delta

cd08593

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

333-480

2.29e-79

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: 261.89 E-value: 2.29e-79

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08593      1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08593     81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEELKGKILVKGKKL 148

PI-PLCc_PRIP_metazoa

cd08597

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

333-480

4.97e-73

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: 244.25 E-value: 4.97e-73

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08597      1 CQDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAIN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08597     81 EYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKGKIIIKGKKL 148

PLCXc

smart00148

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

336-478

3.15e-72

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 236.79 E-value: 3.15e-72

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   336 MKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEHA 415
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1469982874   416 FVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHK 478
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143

PI-PLC1c_yeast

cd08598

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

335-479

1.73e-71

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: 238.69 E-value: 1.73e-71

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  335 DMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEH 414
Cdd:cd08598      3 DLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKKY 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874  415 AFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKK 479
Cdd:cd08598     83 AFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDELPSPEELRGKILIKVKK 147

PI-PLCc_beta

cd08591

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

333-480

1.85e-70

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: 236.47 E-value: 1.85e-70

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDDLPIIYHGHTLTSKIKFLDVLHT 410
Cdd:cd08591      1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  411 IKEHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEE----LPSPYQLRRKILIKHKKL 480
Cdd:cd08591     81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPLEpgvpLPSPNDLKRKILIKNKKL 154

PI-PLCc_eta

cd08594

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

333-479

3.47e-67

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: 226.22 E-value: 3.47e-67

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08594      1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLL-LTKPVDNNAEELPSPYQLRRKILIKHKK 479
Cdd:cd08594     81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLdLSSVISGDSKQLPSPQSLKGKILIKGKK 148

PH_PLC_gamma

cd13362

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...

47-167

2.43e-66

Pssm-ID: 270168 Cd Length: 121 Bit Score: 219.46 E-value: 2.43e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   47 LEMGTVMTVFYQKKsqRPERRTFQIRQDARQIVWSRNPDK-IEGEIDIREIRELRLGKGSRDFERYPEEARKLDSAHCFI 125
Cdd:cd13362      1 LERGTVMTKFYQKK--RPERRTFQVKLETRQVVWSRGGGKrAEGAVDIREIKEIRPGKNSKDFERWPDEAKKLDPSCCFV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1469982874  126 VLYGLEFRLRTLSVAAFSEEEVNMWVTGLNWLMIDTQRAPAP 167
Cdd:cd13362     79 ILYGTEFRLKTLSVAATSEEECDMWIKGLRYLVEDTLSASYP 120

PI-PLCc_epsilon

cd08596

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

334-482

5.06e-65

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: 220.88 E-value: 5.06e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKE 413
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1469982874  414 HAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTK---PVDNNAE-ELPSPYQLRRKILIKHKKLVE 482
Cdd:cd08596     82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKflfESDFSDDpSLPSPLQLKNKILLKNKKAPE 154

PI-PLCc_delta3

cd08630

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

335-480

8.60e-65

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: 220.66 E-value: 8.60e-65

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  335 DMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIKEH 414
Cdd:cd08630      3 DMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQH 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1469982874  415 AFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDN-NAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08630     83 AFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSlNPEELPSPEELKGRVLVKGKKL 149

PI-PLCc_delta1

cd08629

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

333-480

1.48e-64

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: 219.91 E-value: 1.48e-64

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08629      1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08629     81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVTTSLPSPEQLKGKILLKGKKL 148

PI-PLCc_eta2

cd08633

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

333-480

1.32e-62

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: 214.13 E-value: 1.32e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLL-LTKPVDNNAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdLSSVISNDCTRLPSPEILKGKILVKGKKL 149

SH2_C-SH2_PLC_gamma_like

cd09932

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...

677-780

1.45e-62

Pssm-ID: 198186 Cd Length: 104 Bit Score: 207.89 E-value: 1.45e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  677 HESREWYHSSLSRVQAEHMLMRVPRDGAFLVRKRSE-HNSYAISFRAEGKIKHCRIQQEGRLFMLGSSaEFESLVDLVSY 755
Cdd:cd09932      1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETdPNSFAISFRAEGKIKHCRIKQEGRLFVIGTS-QFESLVELVSY 79

                           90       100
                   ....*....|....*....|....*
gi 1469982874  756 YEKHPLYRKMRLRYPINEDTLDRMG 780
Cdd:cd09932     80 YEKHPLYRKIKLRYPVNEELLEKYG 104

PI-PLCc_eta1

cd08632

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

333-480

1.38e-61

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: 211.04 E-value: 1.38e-61

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08632      1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDN-NAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08632     81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTgDPKQLPSPQLLKGKILVKGKKL 149

PI-PLCc_delta4

cd08631

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

333-480

2.08e-60

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: 207.88 E-value: 2.08e-60

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08631      1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAE-ELPSPYQLRRKILIKHKKL 480
Cdd:cd08631     81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPtQLPSPEELRGKILLKGKKI 149

PI-PLCc_beta4

cd08626

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

333-480

7.71e-60

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: 206.15 E-value: 7.71e-60

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGP--DDLPIIYHGHTLTSKIKFLDVLHT 410
Cdd:cd08626      1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  411 IKEHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEE----LPSPYQLRRKILIKHKKL 480
Cdd:cd08626     81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLEpgvpLPSPNKLKRKILIKNKRL 154

PI-PLCc_zeta

cd08595

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

333-479

2.67e-59

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: 204.79 E-value: 2.67e-59

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08595      1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNA-EELPSPYQLRRKILIKHKK 479
Cdd:cd08595     81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPAtGELPSPEALKFKILVKNKK 148

PLCYc

smart00149

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

971-1086

1.33e-55

Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 188.22 E-value: 1.33e-55

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   971 SELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGS 1050
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLK-KSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                            90       100       110
                    ....*....|....*....|....*....|....*.
gi 1469982874  1051 QLVALNFQTPDKPMQLNQALFMLGGGSGYVPQPDIM 1086
Cdd:smart00149   80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_beta2

cd08624

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

333-491

1.18e-54

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: 191.42 E-value: 1.18e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDDLPIIYHGHTLTSKIKFLDVLHT 410
Cdd:cd08624      1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  411 IKEHAFVTSEYPVILSIEDHC-SVVQQRNMATHFKKVFGDLLLTKPVD----NNAEELPSPYQLRRKILIKHKKlvegtl 485
Cdd:cd08624     81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEkyplKPGVPLPSPEDLRGKILIKNKK------ 154


                   ....*.
gi 1469982874  486 YEEVTS 491
Cdd:cd08624    155 YEEMSS 160

PI-PLCc_plant

cd08599

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

333-505

1.97e-54

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: 189.51 E-value: 1.97e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTSKIKFLDVLHTIK 412
Cdd:cd08599      1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  413 EHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPSPYQLRRKILIKHKKLVE-----GTLYE 487
Cdd:cd08599     81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLPEEFPSPEELKGKILISDKPPVIrnslsETQLK 160

                          170
                   ....*....|....*...
gi 1469982874  488 EVTSASYSENDISNSLKN 505
Cdd:cd08599    161 KVIEGEHPTDLIEFTQKN 178

SH2_N-SH2_PLC_gamma_like

cd10341

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...

560-663

2.48e-54

Pssm-ID: 199829 Cd Length: 99 Bit Score: 184.09 E-value: 2.48e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  560 HCAERWFHGKLGGGRDgrqVAEKLLQEYCEGGakDGTFLVRESETFVGDYTLSFWRSGRVQHCRIHSRQESGSTRFYLTD 639
Cdd:cd10341      1 HFTEPWFHGKLGDGRD---EAEKLLLEYCEGG--DGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLTD 75

                           90       100
                   ....*....|....*....|....
gi 1469982874  640 NLVFDSLYRLICHYRDTPLRCNEF 663
Cdd:cd10341     76 NLVFDSLYELIDYYRQNPLRCAEF 99

PI-PLC-Y

pfam00387

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

970-1084

3.54e-53

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 181.51 E-value: 3.54e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  970 LSELVVYCRPVPF-NEDKigTERACYRDMSSFPETKAEKFATHTRgKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLC 1048
Cdd:pfam00387    1 LSDLVVYTQSVKFkSFST--PESKTPNHIFSFSESKALKLIKSSS-AAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNC 77

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1469982874 1049 GSQLVALNFQTPDKPMQLNQALFMLGGGSGYVPQPD 1084
Cdd:pfam00387   78 GVQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPE 113

PI-PLCc_gamma1

cd08627

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

994-1074

3.98e-52

Pssm-ID: 176564 [Multi-domain] Cd Length: 229 Bit Score: 182.92 E-value: 3.98e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  994 YRDMSSFPETKAEKFATHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFML 1073
Cdd:cd08627    149 YRDMSSFPETKAEKYVNRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFML 228


                   .
gi 1469982874 1074 G 1074
Cdd:cd08627    229 G 229

C2_PLC_like

cd00275

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

1103-1227

6.74e-52

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 178.12 E-value: 6.74e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1103 PITVQLQVLGARHLPKNG---RSIVCPFVEVEICGADY-DGCKCKTDVVADNGLNPVWvQNQFVFDIHNPTFSFLRFVVY 1178
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVW-NETFEFDVTVPELAFLRFVVY 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1469982874 1179 EEDMFSDpNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVHVEI 1227
Cdd:cd00275     80 DEDSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDI 127

EFh_PI-PLCgamma1

cd16214

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, ...

173-320

2.37e-50

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, or PLC-148, or phospholipase C-II (PLC-II), or phospholipase C-gamma-1 (PLC-gamma-1), is abundantly expressed in embryonal cortical structures, neurons, oligodendrocytes and astrocytes, and is involved in various cellular events, including proliferation, differentiation, migration, survival, and cell death. It also associates with many diseases, including epilepsy, Huntington's disease (HD), depression, Alzheimer's disease (AD) and bipolar disorder. PI-PLC-gamma1 plays a critical role in cell migration and tumor cell invasiveness and metastasis. It can mediate the cell motility effects of growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), as well as adhesion receptors. Moreover, PI-PLC-gamma1 can modulate neurite outgrowth, neuronal cell migration and synaptic plasticity through the Trk receptor. PI-PLC-gamma1 contains 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. Besides, PI-PLC-gamma1 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma1 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain.

Pssm-ID: 320044 Cd Length: 146 Bit Score: 174.63 E-value: 2.37e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  173 WLRKQFEVMDRNHEGSITVKDVKALLPQVNYRVPNMRFLKDKLQEVEARS-DLSYPNFAQLYRTLMFDAQRSIieqlELS 251
Cdd:cd16214      1 WLRKQFYSVDRNREDRISVKDLKNMLSQVNYRVPNMKFLREKLTDLELRSgDITYGQFAQLYRSLMFDAQKTM----EVP 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1469982874  252 FPLRNVDRPElCQISLYDFQKFLQMDQKESWASDLSRVREFLMGYMGGGPHP--EPMLQLDEFLTFLFSKE 320
Cdd:cd16214     77 FLERFEEREE-CKISLEDFQKFLLDYQKELWATDTNQVQEFMFNFLRDPLREieEPYFSLDEFLTFLFSKE 146

PI-PLCc_gamma

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

994-1074

2.22e-49

Pssm-ID: 176534 [Multi-domain] Cd Length: 229 Bit Score: 175.31 E-value: 2.22e-49

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  994 YRDMSSFPETKAEKFATHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFML 1073
Cdd:cd08592    149 FYEMSSFPETKAEKYLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFML 228


                   .
gi 1469982874 1074 G 1074
Cdd:cd08592    229 N 229

PI-PLCc_beta3

cd08625

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

334-480

1.28e-48

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: 174.09 E-value: 1.28e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDDLPIIYHGHTLTSKIKFLDVLHTI 411
Cdd:cd08625      2 DDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAI 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  412 KEHAFVTSEYPVILSIEDHC-SVVQQRNMATHFKKVFGDLLLTKPVDN----NAEELPSPYQLRRKILIKHKKL 480
Cdd:cd08625     82 AESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKyplvPGVQLPSPQELMGKILVKNKKM 155

EFh_PI-PLCgamma

cd16201

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

173-320

4.11e-48

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma 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. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma 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. 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, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.

Pssm-ID: 320031 [Multi-domain] Cd Length: 145 Bit Score: 168.13 E-value: 4.11e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  173 WLRKQFEVMDRNHEGSITVKDVKALLPQVNYRVpNMRFLKDKLQEVEARS--DLSYPNFAQLYRTLMFDAqrSIIEQLEL 250
Cdd:cd16201      1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKI-STNKLREKFQEVDTRRrgELGFDDFAQLYHKLMFDQ--KIIEDFFK 77

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1469982874  251 SFPlrnvDRPELCQISLYDFQKFLQMDQKESWASDLSRVREFLMGYM---GGGPHpEPMLQLDEFLTFLFSKE 320
Cdd:cd16201     78 KYS----YSSDGQTVTLEDFQRFLLEEQKEPWANDPNAVREFMRDFLqdpLRDVQ-EPYFTLDEFLDYLFSKE 145

PI-PLCc

cd00137

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

333-480

7.91e-43

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: 157.81 E-value: 7.91e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  333 HDDMKRPLSQYWISSSHNTYLTGDQFSSE-----SSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLTsKIKFLDV 407
Cdd:cd00137      1 HHPDTQPLAHYSIPGTHDTYLTAGQFTIKqvwglTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874  408 LHTIKEHAFVTSEYPVILSIEDHCSVV--QQRNMATHFKKVFGDLLLTkPVDNNAEELPSPYQLRRKILIKHKKL 480
Cdd:cd00137     80 IEAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDMLLT-PPLKPTVPLPSLEDLRGKILLLNKKN 153

EFh_PI-PLCgamma2

cd16215

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed ...

173-320

4.02e-42

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, or phospholipase C-IV (PLC-IV), or phospholipase C-gamma-2 (PLC-gamma-2), is highly expressed in cells of hematopoietic origin. It has been implicated in cell motility important to invasion and dissemination of tumor cells. As an important component of the B cell receptor (BCR) signaling pathway, PI-PLC-gamma2 is required for efficient formation of germinal center (GC) and memory B cells. It works as a critical effector stimulating the increase of intracellular Ca2+ and activates various signaling pathways downstream of the BCR. Moreover, PI-PLC-gamma2 has been implicated in Fc receptor-mediated degranulation of mast cells, integrin signaling in platelets, as well as integrin and Fc receptor-mediated neutrophil functions. It also acts as a crucial signaling mediator modifying DC gene expression program to activate DC responses to beta-glucan-containing pathogens. PI-PLC-gamma2 contains 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. Besides, PI-PLC-gamma2 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma2 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.

Pssm-ID: 320045 Cd Length: 154 Bit Score: 151.54 E-value: 4.02e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  173 WLRKQFEVMDRNHEGSITVKDVKALLPQVNYRVPNMRFLKDKLQEVEA-RSDLSYPNFAQLYRTLMFDAQRSIIEQL--- 248
Cdd:cd16215      1 WLRKQIYSVDQTRRNSISVRELKTILPQVNFKVPSAKFLKDKFQEIGAkKDELTFEQFHLFYKKLMFEQQKSILDEFkkd 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  249 ELSFPLRNVDRPELCQISLYDFQKFLQMDQKESWASDLSRVREFLMGYMGGG--PHPEPMLQLDEFLTFLFSKE 320
Cdd:cd16215     81 SSVFILGNTDRPDASAVHLHDFQRFLVHEQKESWAQDLNKVRERMTKFIDDTmrETAEPFLFVDEFLTYLFSKE 154

PI-PLCc_beta1

cd08623

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

334-486

1.77e-41

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: 153.32 E-value: 1.77e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  334 DDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDG--PDDLPIIYHGHTLTSKIKFLDVLHTI 411
Cdd:cd08623      2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  412 KEHAFVTSEYPVILSIEDHC-SVVQQRNMATHFKKVFGDLLLTKPVDNNAEE----LPSPYQLRRKILIKHKKLVEGTLY 486
Cdd:cd08623     82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKYPLEsgvpLPSPMDLMYKILVKNKKMSNLVNY 161

PI-PLCc_gamma2

cd08628

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

952-1073

5.24e-40

Pssm-ID: 176565 [Multi-domain] Cd Length: 254 Bit Score: 149.05 E-value: 5.24e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  952 ARMQEEKQMERRKKIAVELSELVVYCRPVpfNEDKIGTERACYRDMSSFPETKAEKFATHtRGKRFLQYNRRQLSRVYPR 1031
Cdd:cd08628    135 TQLKEKIIIKHKKLIAIELSDLVVYCKPT--SKTKDNLENPDFKEIRSFVETKAPSIIRQ-KPVQLLKYNRKGLTRVYPK 211

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1469982874 1032 GQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFML 1073
Cdd:cd08628    212 GQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSL 253

PI-PLCc_eukaryota

cd08558

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

994-1072

2.43e-37

Pssm-ID: 176501 [Multi-domain] Cd Length: 226 Bit Score: 140.28 E-value: 2.43e-37

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  994 YRDMSSFPETKAEKFAtHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFM 1072
Cdd:cd08558    147 KYHMSSFSETKALKLL-KESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFE 224

PI-PLCc_beta

cd08591

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

960-1071

6.41e-37

Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 140.17 E-value: 6.41e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  960 MERRKKIAVE---LSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLD 1036
Cdd:cd08591    141 NDLKRKILIKnkkLSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLK-KSPIEFVNYNKRQLSRIYPKGTRVD 219

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1469982874 1037 SSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08591    220 SSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKF 254

PLN02228

Phosphoinositide phospholipase C

302-496

7.29e-37

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 147.88 E-value: 7.29e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  302 HPEPMLQLDEFLTFLFSKENSVCDprLSPVVHDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELD 381
Cdd:PLN02228    76 HHHGLVHLNAFYRYLFSDTNSPLP--MSGQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELD 153

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  382 CWDGPD-DLPIIYHGHTLTSKIKFLDVLHTIKEHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLtKPVDNNA 460
Cdd:PLN02228   154 LWPNPSgNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSEST 232

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1469982874  461 EELPSPYQLRRKILIKHK--------KLVEGTLYEEVTSASYSE 496
Cdd:PLN02228   233 KHFPSPEELKNKILISTKppkeylesKTVQTTRTPTVKETSWKR 276

PI-PLCc_delta

cd08593

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

965-1071

8.46e-37

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 139.78 E-value: 8.46e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  965 KIAVELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTrGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLP 1044
Cdd:cd08593    149 KLAKELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQES-GNEFVRHNKRQLSRIYPAGLRTDSSNYDPQE 227

                           90       100
                   ....*....|....*....|....*..
gi 1469982874 1045 MWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08593    228 MWNVGCQIVALNFQTPGEEMDLNDGLF 254

PLN02222

phosphoinositide phospholipase C 2

307-478

1.83e-36

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 147.10 E-value: 1.83e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  307 LQLDEFLTFLFSKENSvcdPRLSPVVHDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGP 386
Cdd:PLN02222    79 LHLDAFFKYLFGDNNP---PLALHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNS 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  387 DDLPI-IYHGHTLTSKIKFLDVLHTIKEHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEELPS 465
Cdd:PLN02222   156 DKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESLKEFPS 235

                          170
                   ....*....|...
gi 1469982874  466 PYQLRRKILIKHK 478
Cdd:PLN02222   236 PNSLKKRIIISTK 248

PLN02952

phosphoinositide phospholipase C

202-478

1.12e-35

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 144.76 E-value: 1.12e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  202 NYRVPNMRFLKDKLQEVEARSDLS--YPNFAQLYRTLMFDAQRSIIeqlelsfplrnVDRPELCQISLYDFQKFLQmdqk 279
Cdd:PLN02952    18 NYKMFNLFNRKFKITEAEPPDDVKdvFCKFSVGGGHMGADQLRRFL-----------VLHQDELDCTLAEAQRIVE---- 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  280 eswasDLSRVREFLMGYMGGGphpepmLQLDEFLTFLFSKEnsvCDPRLSPVVHDDMKRPLSQYWISSSHNTYLTGDQFS 359
Cdd:PLN02952    83 -----EVINRRHHVTRYTRHG------LNLDDFFHFLLYDD---LNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLS 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  360 SESSLEAYARCLRMGCRCIELDCWDGP--DDLpIIYHGHTLTSKIKFLDVLHTIKEHAFVTSEYPVILSIEDHCSVVQQR 437
Cdd:PLN02952   149 SDCSEVPIVKALQRGVRVIELDLWPGStkDEI-LVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQA 227

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1469982874  438 NMATHFKKVFGDLLLTkPVDNNAEELPSPYQLRRKILIKHK 478
Cdd:PLN02952   228 KVAEMATQIFGQMLYY-PESDSLVQFPSPESLKHRIIISTK 267

SH3_PLCgamma1

cd11970

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...

806-864

5.84e-33

Pssm-ID: 212903 Cd Length: 60 Bit Score: 121.63 E-value: 5.84e-33

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874  806 TARCTVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVEEV 864
Cdd:cd11970      1 TFKCAVKALFDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEI 59

PI-PLCc_delta1

cd08629

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

962-1071

8.97e-33

Pssm-ID: 176566 [Multi-domain] Cd Length: 258 Bit Score: 128.23 E-value: 8.97e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  962 RRKKIAVELSELVVYCRPVPFN--EDKIGTERACYrDMSSFPETKAEKFATHTrGKRFLQYNRRQLSRVYPRGQRLDSSN 1039
Cdd:cd08629    146 KKLKLVPELSDMIIYCKSVHFGgfSSPGTSGQAFY-EMASFSESRALRLLQES-GNGFVRHNVSCLSRIYPAGWRTDSSN 223

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1469982874 1040 YDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08629    224 YSPVEMWNGGCQIVALNFQTPGPEMDVYLGCF 255

PLN02230

phosphoinositide phospholipase C 4

307-478

1.32e-32

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 135.22 E-value: 1.32e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  307 LQLDEFLTFLFSKEnsvCDPRLSPVVHDDMKRPLSQYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWD-G 385
Cdd:PLN02230    91 LTLDDFNYYLFSTD---LNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPrG 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  386 PDDLpIIYHGHTLTSKIKFLDVLHTIKEHAFVTSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDnNAEELPS 465
Cdd:PLN02230   168 TDDV-CVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHDSE-GCQEFPS 245

                          170
                   ....*....|...
gi 1469982874  466 PYQLRRKILIKHK 478
Cdd:PLN02230   246 PEELKEKILISTK 258

SH3_PLCgamma

cd11825

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...

810-863

2.23e-32

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212759 [Multi-domain] Cd Length: 54 Bit Score: 119.74 E-value: 2.23e-32

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  810 TVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVEE 863
Cdd:cd11825      1 TVKALYDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKKQKWFPANYVEE 54

PLN02952

phosphoinositide phospholipase C

999-1228

6.54e-32

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 133.20 E-value: 6.54e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  999 SFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFMLGGGSG 1078
Cdd:PLN02952   364 SLSEQELEKAAT-TNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCG 442

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1079 YVPQPDIM-----RDDIFDPfdKDTLhvePITVQLQV---------LGARHLPKNGRSIVCPFVEVEICGADYDGCKCKT 1144
Cdd:PLN02952   443 YLKKPDFLmkkgfHDEVFDP--KKKL---PVKKTLKVkvylgdgwrLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKKT 517

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1145 DVVADNgLNPVWVQnQFVFDIHNPTFSFLRFVVYEEDMFSDPNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVH 1224
Cdd:PLN02952   518 KIIEDN-WYPAWNE-EFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLMR 595


                   ....
gi 1469982874 1225 VEIV 1228
Cdd:PLN02952   596 FIFV 599

PHsplit_PLC_gamma

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...

877-950

9.09e-31

Pssm-ID: 270054 Cd Length: 105 Bit Score: 117.18 E-value: 9.09e-31

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  877 TENSPLGTFLKGFIDVPTCHVVIHKDGKNSRPFVFTIHSQHLSSHPvqtLDVAADSLEDLSNWVSKIREAAQNA 950
Cdd:cd13234     35 TENSPLGSLLRGILDVPSCHVVKRPEGKNSRPFVFILSPKSLSDPP---LDVAADSQEELQDWVQKIREVAQTA 105

PLN02222

phosphoinositide phospholipase C 2

1002-1228

7.46e-30

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 126.68 E-value: 7.46e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1002 ETKAEKFAthtrgKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFMLGGGSGYVP 1081
Cdd:PLN02222   353 EKAAEKYA-----KQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIK 427

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1082 QPDIM-----RDDIFDPfdKDTLhvePITVQLQV---LGA------RHLPKNGRSIVCPFVEVEICGADYDGCKCKTDVV 1147
Cdd:PLN02222   428 KPDLLlksgsDSDIFDP--KATL---PVKTTLRVtiyMGEgwyfdfRHTHFDQYSPPDFYTRVGIAGVPGDTVMKKTKTL 502

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1148 ADNGLnPVWvQNQFVFDIHNPTFSFLRFVVYEEDMFSDPNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVHVEI 1227
Cdd:PLN02222   503 EDNWI-PAW-DEVFEFPLTVPELALLRLEVHEYDMSEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKVEF 580


                   .
gi 1469982874 1228 V 1228
Cdd:PLN02222   581 V 581

PLN02228

Phosphoinositide phospholipase C

1012-1223

1.65e-29

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 125.53 E-value: 1.65e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1012 TRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFMLGGGSGYVPQPDIMRDD-- 1089
Cdd:PLN02228   340 TRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEht 419

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1090 IFDPFD----KDTLHVEPITVQLQVLgarHLPKNGRSIVCP---FVEVEICGADYDGCKCKTDVVADNGLnPVWVQNQFV 1162
Cdd:PLN02228   420 LFDPCKrlpiKTTLKVKIYTGEGWDL---DFHLTHFDQYSPpdfFVKIGIAGVPRDTVSYRTETAVDQWF-PIWGNDEFL 495

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1469982874 1163 FDIHNPTFSFLRFVVYEEDMFSDPNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLV 1223
Cdd:PLN02228   496 FQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAGKAYKNTRLLV 556

PI-PLCc_beta4

cd08626

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

963-1071

1.90e-29

Pssm-ID: 176563 [Multi-domain] Cd Length: 257 Bit Score: 118.71 E-value: 1.90e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  963 RKKIAVE---LSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFAThTRGKRFLQYNRRQLSRVYPRGQRLDSSN 1039
Cdd:cd08626    144 KRKILIKnkrLSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLK-TSAIEFVNYNKRQMSRIYPKGTRVDSSN 222

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1469982874 1040 YDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08626    223 YMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKF 254

PI-PLCc_delta3

cd08630

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

962-1072

9.53e-29

Pssm-ID: 176567 [Multi-domain] Cd Length: 258 Bit Score: 116.66 E-value: 9.53e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  962 RRKKIAVELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTrGKRFLQYNRRQLSRVYPRGQRLDSSNYD 1041
Cdd:cd08630    147 KKLQISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREA-GNSFVRHNARQLTRVYPLGLRMNSANYS 225

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1469982874 1042 PLPMWLCGSQLVALNFQTPDKPMQLNQALFM 1072
Cdd:cd08630    226 PQEMWNSGCQLVALNFQTPGYEMDLNAGRFL 256

PI-PLCc_beta2

cd08624

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

969-1071

9.98e-28

Pssm-ID: 176561 [Multi-domain] Cd Length: 261 Bit Score: 114.00 E-value: 9.98e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  969 ELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTrGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLC 1048
Cdd:cd08624    157 EMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKA-SVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNV 235

                           90       100
                   ....*....|....*....|...
gi 1469982874 1049 GSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08624    236 GCQMVALNFQTMDLPMQQNMALF 258

PI-PLCc_delta4

cd08631

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

958-1071

2.65e-27

Pssm-ID: 176568 [Multi-domain] Cd Length: 258 Bit Score: 112.35 E-value: 2.65e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  958 KQMERRKKIAV--ELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTrGKRFLQYNRRQLSRVYPRGQRL 1035
Cdd:cd08631    141 KILLKGKKIRLspELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREA-GNEFVQHNTWQLSRVYPSGLRT 219

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1469982874 1036 DSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08631    220 DSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLF 255

PI-PLCc_beta3

cd08625

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

969-1071

1.78e-26

Pssm-ID: 176562 [Multi-domain] Cd Length: 258 Bit Score: 110.14 E-value: 1.78e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  969 ELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTRgKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLC 1048
Cdd:cd08625    154 KMSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSP-MEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNV 232

                           90       100
                   ....*....|....*....|...
gi 1469982874 1049 GSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08625    233 GCQMVALNFQTLDLAMQLNMGVF 255

PI-PLCc_eta1

cd08632

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

904-1073

1.78e-26

Pssm-ID: 176569 [Multi-domain] Cd Length: 253 Bit Score: 110.12 E-value: 1.78e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  904 KNSRPFVFTIHSqHLSSHPVQTL-----DVAADSLeDLSNWVSKirEAAQNADARMQEEKQMERRKKIAVELSELVVYCR 978
Cdd:cd08632     86 KNEFPVILSIEN-HCSIQQQKKIaqylkEIFGDKL-DLSSVLTG--DPKQLPSPQLLKGKILVKGKKLCRDLSDLVVYTN 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  979 PVPfNEDKIGTERACyrDMSSFPETKAEKfATHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQ 1058
Cdd:cd08632    162 SVA-AQDIVDDGSTG--NVLSFSETRAHQ-LVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQ 237

                          170
                   ....*....|....*
gi 1469982874 1059 TPDKPMQLNQALFML 1073
Cdd:cd08632    238 SEGRMMQLNRAKFMV 252

PI-PLCc_PRIP_metazoa

cd08597

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

962-1071

3.48e-26

Pssm-ID: 176539 [Multi-domain] Cd Length: 260 Bit Score: 109.43 E-value: 3.48e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  962 RRKKIAVELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTRGKrFLQYNRRQLSRVYPRGQRLDSSNYD 1041
Cdd:cd08597    149 KRRKLCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPED-FVNYNKKFLSRVYPSPMRVDSSNYN 227

                           90       100       110
                   ....*....|....*....|....*....|
gi 1469982874 1042 PLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08597    228 PQDFWNCGCQIVAMNYQTPGLMMDLNTGKF 257

PLN02230

phosphoinositide phospholipase C 4

999-1228

5.09e-25

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 111.72 E-value: 5.09e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  999 SFPETKAEKfATHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFMLGGGSG 1078
Cdd:PLN02230   363 SLSEQLLEK-AVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCG 441

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1079 YVPQPDIMRD-----DIFDPFD----KDTLHVEPITVQLQVLGARHLPKNGRSIVCPFVEVEICGADYDGCKCKTDVVAD 1149
Cdd:PLN02230   442 YVKKPDFLMDagpngQDFYPKDnscpKKTLKVKVCMGDGWLLDFKKTHFDSYSPPDFFVRVGIAGAPVDEVMEKTKIEYD 521

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1469982874 1150 NgLNPVWvQNQFVFDIHNPTFSFLRFVVYEEDMFSDPNFLAQVTYPVRLLRTGYRSVPLKNSYSEELELASLLVHVEIV 1228
Cdd:PLN02230   522 T-WTPIW-NKEFIFPLAVPELALLRVEVHEHDINEKDDFGGQTCLPVSEIRQGIHAVPLFNRKGVKYSSTRLLMRFEFV 598

SH2

SH2 domain;

565-653

1.38e-24

SH2 domain;

Pssm-ID: 425423 [Multi-domain] Cd Length: 77 Bit Score: 98.44 E-value: 1.38e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  565 WFHGKLGggrdgRQVAEKLLQEycegGAKDGTFLVRESETFVGDYTLSFWRSGRVQHCRIHSRQESGstrFYLTDNLVFD 644
Cdd:pfam00017    1 WYHGKIS-----RQEAERLLLN----GKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGG---YYISGGVKFS 68


                   ....*....
gi 1469982874  645 SLYRLICHY 653
Cdd:pfam00017   69 SLAELVEHY 77

PI-PLCc_eta

cd08594

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

996-1072

1.57e-24

Pssm-ID: 176536 [Multi-domain] Cd Length: 227 Bit Score: 103.34 E-value: 1.57e-24

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1469982874  996 DMSSFPETKAEKFaTHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALFM 1072
Cdd:cd08594    150 QVSSFSETRAHQI-VQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFR 225

PI-PLCc_zeta

cd08595

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

960-1072

2.41e-24

Pssm-ID: 176537 [Multi-domain] Cd Length: 257 Bit Score: 103.86 E-value: 2.41e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  960 MERRKKIAVELSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHtRGKRFLQYNRRQLSRVYPRGQRLDSSN 1039
Cdd:cd08595    144 VKNKKKIAKALSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKS-SGADFVGHTQRFITRIYPKGTRASSSN 222

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1469982874 1040 YDPLPMWLCGSQLVALNFQTPDKPMQLNQALFM 1072
Cdd:cd08595    223 YNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFL 255

PI-PLCc_epsilon

cd08596

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

945-1071

4.62e-24

Pssm-ID: 176538 [Multi-domain] Cd Length: 254 Bit Score: 103.01 E-value: 4.62e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  945 EAAQNADARMQEEKQMERR----KKIAVELSELVVYCRPVPFNedkiGTERA-CYRdMSSFPETKAEKFATHTRGKrFLQ 1019
Cdd:cd08596    126 ESDFSDDPSLPSPLQLKNKillkNKKAPELSDLVIYCQAVKFP----GLSTPkCYH-ISSLNENAAKRLCRRYPQK-LVQ 199

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1469982874 1020 YNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08596    200 HTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMF 251

SH3_PLCgamma2

cd11969

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...

810-864

8.71e-24

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212902 Cd Length: 55 Bit Score: 95.29 E-value: 8.71e-24

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874  810 TVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVEEV 864
Cdd:cd11969      1 TVKALYDYRAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQHYFPSNYVEDV 55

PI-PLCc_beta1

cd08623

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

960-1071

2.18e-23

Pssm-ID: 176560 [Multi-domain] Cd Length: 258 Bit Score: 100.93 E-value: 2.18e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  960 MERRKKIAVE---LSELVVYCRPVPFNEDKIGTERACYRDMSSFPETKAEKFATHTRGKrFLQYNRRQLSRVYPRGQRLD 1036
Cdd:cd08623    142 MDLMYKILVKnkkMSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVE-FVEYNKMQLSRIYPKGTRVD 220

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1469982874 1037 SSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08623    221 SSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMY 255

SH2

SH2 domain;

682-756

2.28e-23

SH2 domain;

Pssm-ID: 425423 [Multi-domain] Cd Length: 77 Bit Score: 94.98 E-value: 2.28e-23

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1469982874  682 WYHSSLSRVQAEHMLMRVPRDGAFLVRKRSEH-NSYAISFRAEGKIKHCRIQQEGRL-FMLGSSAEFESLVDLVSYY 756
Cdd:pfam00017    1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTpGGYTLSVRDDGKVKHYKIQSTDNGgYYISGGVKFSSLAELVEHY 77

PLN02223

phosphoinositide phospholipase C

307-518

3.14e-23

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 105.49 E-value: 3.14e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  307 LQLDEFLTFLFSKEnsvCDPRLS-PVVHDDMKRPLSQYWISSSHNTYLTGDQ-FSSESSLEAYARCLRMGCRCIELDCW- 383
Cdd:PLN02223    81 LELDHLNEFLFSTE---LNPPIGdQVRHHDMHAPLSHYFIHTSLKSYFTGNNvFGKLYSIEPIIDALEQGVRVVELDLLp 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  384 DGPDDLpIIYHGHTLTSKIKFLDVLHTIKEHAFV-TSEYPVILSIEDHCSVVQQRNMATHFKKVFGDLLLTKPVDNNAEE 462
Cdd:PLN02223   158 DGKDGI-CVRPKWNFEKPLELQECLDAIKEHAFTkCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSLEE 236

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1469982874  463 LPSPYQLRRKILIKHKKLVEgTLYeevtsASYSENDIsnSLKNGILYLEDPIDHTW 518
Cdd:PLN02223   237 FPSPAELQNKILISRRPPKE-LLY-----AKADDGGV--GVRNELEIQEGPADKNY 284

PI-PLCc_eta2

cd08633

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

904-1071

5.14e-23

Pssm-ID: 176570 [Multi-domain] Cd Length: 254 Bit Score: 99.73 E-value: 5.14e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  904 KNSRPFVFTIHSqHLSSHPVQTL-----DVAADSLeDLSNWVSKirEAAQNADARMQEEKQMERRKKIAVELSELVVYCR 978
Cdd:cd08633     86 KNEYPVILSIEN-HCSVPQQKKMaqyltEILGDKL-DLSSVISN--DCTRLPSPEILKGKILVKGKKLSRALSDLVKYTK 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  979 PVPFNEdkIGTERACYRDMSSFPETKAEKFaTHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQ 1058
Cdd:cd08633    162 SVRVHD--IETEATSSWQVSSFSETKAHQI-LQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQ 238

                          170
                   ....*....|...
gi 1469982874 1059 TPDKPMQLNQALF 1071
Cdd:cd08633    239 SEGRMLQLNRAKF 251

SH2

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...

563-659

2.00e-22

Pssm-ID: 214585 [Multi-domain] Cd Length: 84 Bit Score: 92.29 E-value: 2.00e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   563 ERWFHGKLGggrdgRQVAEKLLQeycegGAKDGTFLVRESETFVGDYTLSFWRSGRVQHCRIhsrQESGSTRFYLTDNLV 642
Cdd:smart00252    1 QPWYHGFIS-----REEAEKLLK-----NEGDGDFLVRDSESSPGDYVLSVRVKGKVKHYRI---RRNEDGKFYLEGGRK 67

                            90
                    ....*....|....*..
gi 1469982874   643 FDSLYRLICHYRDTPLR 659
Cdd:smart00252   68 FPSLVELVEHYQKNSLG 84

PI-PLC1c_yeast

cd08598

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

999-1071

3.61e-22

Pssm-ID: 176540 [Multi-domain] Cd Length: 231 Bit Score: 96.55 E-value: 3.61e-22

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1469982874  999 SFPETKAEKFATHTRgKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08598    157 SLSERSLLKLLKDKR-AALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228

SH2

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...

681-762

6.00e-22

Pssm-ID: 214585 [Multi-domain] Cd Length: 84 Bit Score: 91.14 E-value: 6.00e-22

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   681 EWYHSSLSRVQAEHMLMRVPrDGAFLVRK-RSEHNSYAISFRAEGKIKHCRIQQ-EGRLFMLGSSAEFESLVDLVSYYEK 758
Cdd:smart00252    2 PWYHGFISREEAEKLLKNEG-DGDFLVRDsESSPGDYVLSVRVKGKVKHYRIRRnEDGKFYLEGGRKFPSLVELVEHYQK 80


                    ....
gi 1469982874   759 HPLY 762
Cdd:smart00252   81 NSLG 84

PI-PLCc_GDPD_SF

cd08555

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

347-531

6.67e-22

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

Pssm-ID: 176498 [Multi-domain] Cd Length: 179 Bit Score: 94.42 E-value: 6.67e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  347 SSHNTYLTGDQfssESSLEAYARCLRMGCRCIELDCWDGPDDLPIIYHGHTLT------SKIKFLDVLHTIKEHAFvTSE 420
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  421 YPVILSIEDHCSVV----QQRNMATHFKKVFGdllltkpvdnnaeelpspYQLRRKILIKHKKLVEGTLYEEVTSASYSE 496
Cdd:cd08555     78 YTIILSLEIKQDSPeydeFLAKVLKELRVYFD------------------YDLRGKVVLSSFNALGVDYYNFSSKLIKDT 139

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1469982874  497 NDISNSLKNGILYledpidHTWTphyfVLTSNKIY 531
Cdd:cd08555    140 ELIASANKLGLLS------RIWT----VNDNNEII 164

PH_PLC_ELMO1

cd01248

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

47-158

1.23e-20

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

Pssm-ID: 269952 Cd Length: 108 Bit Score: 88.15 E-value: 1.23e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874   47 LEMGTVMTVFYQKKSqrPERRTFQIRQDARQIVWSRNPDK-IEGEIDIREIRELRLGKGSRDFERYPEEARKLDSaHCFI 125
Cdd:cd01248      1 LQQGTLLLKYREGSK--PKERTFYLDPDGTRITWESSKKKsEKKSIDISDIKEIRPGKDTDGFKRKKKSNKPKEE-RCFS 77

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1469982874  126 VLYGLEFRlrTLSVAAFSEEEVNMWVTGLNWLM 158
Cdd:cd01248     78 IIYGSNNK--TLDLVAPSEDEANLWVEGLRALL 108

SH2

cd00173

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...

681-756

4.79e-18

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.

Pssm-ID: 198173 [Multi-domain] Cd Length: 79 Bit Score: 79.81 E-value: 4.79e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  681 EWYHSSLSRVQAEHMLMRVPrDGAFLVRKR-SEHNSYAISFRAE-GKIKHCRIQQE--GRLFMLGSSAEFESLVDLVSYY 756
Cdd:cd00173      1 PWFHGSISREEAERLLRGKP-DGTFLVRESsSEPGDYVLSVRSGdGKVKHYLIERNegGYYLLGGSGRTFPSLPELVEHY 79

smart00239

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

1105-1208

7.40e-18

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 80.22 E-value: 7.40e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  1105 TVQLQVLGARHLP-KNGRSIVCPFVEVEICGADydGCKCKTDVVADNgLNPVWVQnQFVFDIHNPTFSFLRFVVYEEDMF 1183
Cdd:smart00239    1 TLTVKIISARNLPpKDKGGKSDPYVKVSLDGDP--KEKKKTKVVKNT-LNPVWNE-TFEFEVPPPELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 1469982874  1184 SDPNFLAQVTYPVRLLRTGYRSVPL 1208
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

SH2

cd00173

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...

564-653

2.90e-17

Pssm-ID: 198173 [Multi-domain] Cd Length: 79 Bit Score: 77.50 E-value: 2.90e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  564 RWFHGKLGggrdgRQVAEKLLQeycegGAKDGTFLVRESETFVGDYTLSFW-RSGRVQHCRIHSRqeSGSTRFYLTDNLV 642
Cdd:cd00173      1 PWFHGSIS-----REEAERLLR-----GKPDGTFLVRESSSEPGDYVLSVRsGDGKVKHYLIERN--EGGYYLLGGSGRT 68

                           90
                   ....*....|.
gi 1469982874  643 FDSLYRLICHY 653
Cdd:cd00173     69 FPSLPELVEHY 79

pfam00168

C2 domain;

1105-1204

2.22e-16

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 75.82 E-value: 2.22e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874 1105 TVQLQVLGARHLP-KNGRSIVCPFVEVEIcgaDYDGCKCKTDVVaDNGLNPVWVQnQFVFDIHNPTFSFLRFVVYEEDMF 1183
Cdd:pfam00168    2 RLTVTVIEAKNLPpKDGNGTSDPYVKVYL---LDGKQKKKTKVV-KNTLNPVWNE-TFTFSVPDPENAVLEIEVYDYDRF 76

                           90       100
                   ....*....|....*....|.
gi 1469982874 1184 SDPNFLAQVTYPVRLLRTGYR 1204
Cdd:pfam00168   77 GRDDFIGEVRIPLSELDSGEG 97

SH2_C-SH2_SHP_like

cd09931

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...

682-772

6.37e-16

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

Pssm-ID: 198185 Cd Length: 99 Bit Score: 74.62 E-value: 6.37e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  682 WYHSSLSRVQAEHMLMRVPRDGAFLVRK-RSEHNSYAISFRA-EGKIKHCRIQQEGRLFMLGSSAEFESLVDLVSYYEKH 759
Cdd:cd09931      2 WFHGHLSGKEAEKLLLEKGKPGSFLVREsQSKPGDFVLSVRTdDDKVTHIMIRCQGGKYDVGGGEEFDSLTDLVEHYKKN 81

                           90
                   ....*....|....*..
gi 1469982874  760 PLY----RKMRLRYPIN 772
Cdd:cd09931     82 PMVetsgTVVHLKQPLN 98

SH3

smart00326

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...

808-862

1.02e-15

Pssm-ID: 214620 [Multi-domain] Cd Length: 56 Bit Score: 72.57 E-value: 1.02e-15

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874   808 RCTVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQLWFPANYVE 862
Cdd:smart00326    2 GPQVRALYDYTAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56

PI-PLCc_plant

cd08599

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

997-1071

2.92e-15

Pssm-ID: 176541 [Multi-domain] Cd Length: 228 Bit Score: 76.64 E-value: 2.92e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1469982874  997 MSSFPETKAEKFATHTRGKRFLQYNRRQLSRVYPRGQRLDSSNYDPLPMWLCGSQLVALNFQTPDKPMQLNQALF 1071
Cdd:cd08599    151 RNSLSETQLKKVIEGEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKF 225

SH2_Vav_family

cd09940

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...

681-761

2.92e-15

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

Pssm-ID: 198193 Cd Length: 102 Bit Score: 72.71 E-value: 2.92e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1469982874  681 EWYHSSLSRVQAEHMLMRVPrDGAFLVRKRS-EHNSYAISFRAEGKIKHCRIQQE-GRLFMLGSSAEFESLVDLVSYYEK 758
Cdd:cd09940      6 LWFVGEMERDTAENRLENRP-DGTYLVRVRPqGETQYALSIKYNGDVKHMKIEQRsDGLYYLSESRHFKSLVELVNYYER 84


                   ...
gi 1469982874  759 HPL 761
Cdd:cd09940     85 NSL 87

SH3_PIX

cd11877

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...

810-863

6.65e-15

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

Pssm-ID: 212810 [Multi-domain] Cd Length: 53 Bit Score: 70.04 E-value: 6.65e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1469982874  810 TVKALYDYRAQREDELCFPKQALILNVDKQEGGWWRGDYGGKKQlWFPANYVEE 863
Cdd:cd11877      1 LVRAKFNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTG-WFPSNYVKE 53

PHsplit_PLC_gamma