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Conserved domains on  [gi|974005362|ref|NP_001305713|]
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inositol polyphosphate 5-phosphatase OCRL isoform c [Homo sapiens]

Protein Classification

Rho GTPase-activating protein( domain architecture ID 10194048)

Rho GTPase-activating protein for Rho/Rac/Cdc42-like small GTPases that act as molecular switches, active in their GTP-bound form but inactive when bound to GDP; contains a Pleckstrin homology (PH) domain

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 241-534 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


:

Pssm-ID: 197327  Cd Length: 292  Bit Score: 604.31  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 241 FRFFVGTWNVNGQSPDSGLEPWLNCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 320
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 321 VGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 400
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 401 VVPNQtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTYKY 480
Cdd:cd09093  161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005362 481 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 669-897 6.22e-87

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


:

Pssm-ID: 239845  Cd Length: 220  Bit Score: 276.53  E-value: 6.22e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 669 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 748
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 749 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDS-AYDPRICR 823
Cdd:cd04380   64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKR 143

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005362 824 QVIS-QLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLL 897
Cdd:cd04380  144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
 15-116 3.47e-59

oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL1 contains a PH domain and a Rho-GAP domain. Patients with Lowe syndrome suffer primarily from congenital cataracts, neonatal hypotonia, intellectual disability and Fanconi syndrome. Mutations in OCRL are also found in a subset of patients with type 2 Dent disease, who selectively suffer from renal proximal tubular dysfunction. 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: 270182  Cd Length: 105  Bit Score: 196.96  E-value: 3.47e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362  15 TVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRE 94
Cdd:cd13382    4 TVRGHEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDRTPE 83

                         90       100
                 ....*....|....*....|..
gi 974005362  95 RRFEIPDEEHCLKFLSAVLAAQ 116
Cdd:cd13382   84 RLFEIPDEEHCLSFLSHVLAAQ 105
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 241-534 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


Pssm-ID: 197327  Cd Length: 292  Bit Score: 604.31  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 241 FRFFVGTWNVNGQSPDSGLEPWLNCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 320
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 321 VGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 400
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 401 VVPNQtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTYKY 480
Cdd:cd09093  161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005362 481 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 239-537 3.17e-133

Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+)-sensitive enzymes.


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 400.96  E-value: 3.17e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   239 QTFRFFVGTWNVNGQS-PDSGLEPWLNC-----DPNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 311
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   312 YKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 391
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   392 KDICARMSFVVPnqtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGE 471
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   472 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-NYRSHMELKTSDHKPVSALFHIGVK 537
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 669-897 6.22e-87

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239845  Cd Length: 220  Bit Score: 276.53  E-value: 6.22e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 669 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 748
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 749 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDS-AYDPRICR 823
Cdd:cd04380   64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKR 143

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005362 824 QVIS-QLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLL 897
Cdd:cd04380  144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
224-541 2.47e-63

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 221.20  E-value: 2.47e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 224 IKHILAKREKEYVNIQTFRFFVGTWNVNGQSPDSGLEPWL---NCDPNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 298
Cdd:COG5411   13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 299 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 375
Cdd:COG5411   93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 376 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKD-LQRLLKFDQL 454
Cdd:COG5411  173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDDGrLDKLFEYDQL 246

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 455 NIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:COG5411  247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326


                 ....*..
gi 974005362 535 GVKVVDE 541
Cdd:COG5411  327 KIKVVDP 333
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
 15-116 3.47e-59

oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL1 contains a PH domain and a Rho-GAP domain. Patients with Lowe syndrome suffer primarily from congenital cataracts, neonatal hypotonia, intellectual disability and Fanconi syndrome. Mutations in OCRL are also found in a subset of patients with type 2 Dent disease, who selectively suffer from renal proximal tubular dysfunction. 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: 270182  Cd Length: 105  Bit Score: 196.96  E-value: 3.47e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362  15 TVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRE 94
Cdd:cd13382    4 TVRGHEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDRTPE 83

                         90       100
                 ....*....|....*....|..
gi 974005362  95 RRFEIPDEEHCLKFLSAVLAAQ 116
Cdd:cd13382   84 RLFEIPDEEHCLSFLSHVLAAQ 105
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
 19-119 6.66e-56

Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin binding domain found at the N-terminus of inositol polyphosphate 5-phosphatase OCRL. It has a PH domain-like fold.


Pssm-ID: 435540  Cd Length: 101  Bit Score: 187.61  E-value: 6.66e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   19 MEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRERRFE 98
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80

                          90       100
                  ....*....|....*....|.
gi 974005362   99 IPDEEHCLKFLSAVLAAQKAQ 119
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 295-546 1.72e-50

Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 188.58  E-value: 1.72e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 295 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 374
Cdd:PLN03191 347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 375 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHEVVIWLGDLNYRLCMPDAnEVKSLINKKDLQRLLKF 451
Cdd:PLN03191 427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 452 DQLNIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLNYRsHMELKTSDHK 526
Cdd:PLN03191 505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583

                        250       260
                 ....*....|....*....|
gi 974005362 527 PVSALFHIGVKVVDERRYRK 546
Cdd:PLN03191 584 PVSSMFLVEVEVFDHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 734-895 6.95e-41

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 148.18  E-value: 6.95e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   734 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 810
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   811 RCLDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMAR-QTPS 883
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161

                          170
                   ....*....|..
gi 974005362   884 DRQRAIQFLLGF 895
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 736-874 4.05e-35

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 130.74  E-value: 4.05e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362  736 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 812
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362  813 LDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 874
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 241-534 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


Pssm-ID: 197327  Cd Length: 292  Bit Score: 604.31  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 241 FRFFVGTWNVNGQSPDSGLEPWLNCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 320
Cdd:cd09093    1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 321 VGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 400
Cdd:cd09093   81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 401 VVPNQtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTYKY 480
Cdd:cd09093  161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 974005362 481 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09093  239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 239-537 3.17e-133

Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+)-sensitive enzymes.


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 400.96  E-value: 3.17e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   239 QTFRFFVGTWNVNGQS-PDSGLEPWLNC-----DPNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 311
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   312 YKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 391
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   392 KDICARMSFVVPnqtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGE 471
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   472 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-NYRSHMELKTSDHKPVSALFHIGVK 537
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 241-534 3.43e-117

Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate 5-phosphatases (5-phosphatases) are signal-modifying enzymes, which hydrolyze the 5-phosphate from the inositol ring of specific 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), such as PI(4,5)P2, PI(3,4,5)P3, PI(3,5)P2, I(1,4,5)P3, and I(1,3,4,5)P4. These enzymes are Mg2+-dependent, and belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In addition to this INPP5c domain, 5-phosphatases often contain additional domains and motifs, such as the SH2 domain, the Sac-1 domain, the proline-rich domain (PRD), CAAX, RhoGAP (RhoGTPase-activating protein), and SKICH [SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) carboxyl homology] domains, that are important for protein-protein interactions and/or for the subcellular localization of these enzymes. 5-phosphatases incorporate into large signaling complexes, and regulate diverse cellular processes including postsynaptic vesicular trafficking, insulin signaling, cell growth and survival, and endocytosis. Loss or gain of function of 5-phosphatases is implicated in certain human diseases. This family also contains a functionally unrelated nitric oxide transport protein, Cimex lectularius (bedbug) nitrophorin, which catalyzes a heme-assisted S-nitrosation of a proximal thiolate; the heme however binds at a site distinct from the active site of the 5-phosphatases.


Pssm-ID: 197308 [Multi-domain]  Cd Length: 299  Bit Score: 358.95  E-value: 3.43e-117
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 241 FRFFVGTWNVNGQ-SPDSGLEPWLNCDPN-PPDIYCIGFQELDLSTEAFFYFE-SVKEQEWSMAVERGLHSKAKYKKVQL 317
Cdd:cd09074    1 VKIFVVTWNVGGGiSPPENLENWLSPKGTeAPDIYAVGVQEVDMSVQGFVGNDdSAKAREWVDNIQEALNEKENYVLLGS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 318 VRLVGMMLLIFARKDQCRYIRDIATE--TVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 395
Cdd:cd09074   81 AQLVGIFLFVFVKKEHLPQIKDLEVEgvTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 396 ARMSFVVPNQtlPQLNIMKHEVVIWLGDLNYRLCMpDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFI 475
Cdd:cd09074  161 SKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDS-TDDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 974005362 476 PTYKYDSKTDRWDSSGKCRVPAWCDRILWR---GTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09074  238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 242-532 1.34e-90

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae Inp51p, Inp52p, and Inp53p, and related proteins; This subfamily contains the INPP5c domain of three Saccharomyces cerevisiae synaptojanin-like inositol polyphosphate 5-phosphatases (INP51, INP52, and INP53), Schizosaccharomyces pombe synaptojanin (SPsynaptojanin), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In addition to this INPP5c domain, these proteins have an N-terminal catalytic Sac1-like domain (found in other proteins including the phophoinositide phosphatase Sac1p), and a C-terminal proline-rich domain (PRD). The Sac1 domain allows Inp52p and Inp53p to recognize and dephosphorylate a wider range of substrates including PI3P, PI4P, and PI(3,5)P2. The Sac1 domain of Inp51p is non-functional. Disruption of any two of INP51, INP52, and INP53, in S. cerevisiae leads to abnormal vacuolar and plasma membrane morphology. During hyperosmotic stress, Inp52p and Inp53p localize at actin patches, where they may facilitate the hydrolysis of PI(4,5)P2, and consequently promote actin rearrangement to regulate cell growth. SPsynaptojanin is also active against a range of soluble and lipid inositol phosphates, including I(1,4,5)P3, I(1,3,4,5)P4, I(1,4,5,6)P4, PI(4,5)P2, and PIP3. Transformation of S. cerevisiae with a plasmid expressing the SPsynaptojanin 5-phosphatase domain rescues inp51/inp52/inp53 triple-mutant strains.


Pssm-ID: 197324  Cd Length: 291  Bit Score: 288.85  E-value: 1.34e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 242 RFFVGTWNVNGQSPDSGLEPWLnCDPN---PPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQL 317
Cdd:cd09090    2 NIFVGTFNVNGKSYKDDLSSWL-FPEEndeLPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLNGRGGEKYVLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 318 --VRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 395
Cdd:cd09090   81 rsEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 396 ARMSFVvPNQTLPQlnimkHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFI 475
Cdd:cd09090  161 RGLRFS-RGRTIKD-----HDHVIWLGDFNYRISLTN-EDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFP 233

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 974005362 476 PTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRShMELKTSDHKPVSALF 532
Cdd:cd09090  234 PTYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNS-APLRFSDHRPVYATF 289
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 242-534 1.95e-88

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This subfamily contains the INPP5c domains of two human synaptojanins, synaptojanin 1 (Synj1) and synaptojanin 2 (Synj2), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs). They belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, Synjs contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25 (a mitochondrial outer membrane protein). Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197323 [Multi-domain]  Cd Length: 328  Bit Score: 284.67  E-value: 1.95e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 242 RFFVGTWNVNGQS-------PDSGLEPWL--NC------------DPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWS 299
Cdd:cd09089    2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLldNPklagqcsndseeDEKPVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 300 MAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAA 379
Cdd:cd09089   82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 380 HVEDFERRNQDYKDICARMSFvvPNQTlpqlNIMKHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQRLLKFDQLNIQRT 459
Cdd:cd09089  162 GQSQVKERNEDFAEIARKLSF--PMGR----TLDSHDYVFWCGDFNYRIDLPN-DEVKELVRNGDWLKLLEFDQLTKQKA 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 460 QKKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------GTNVN-------QLNYRSHMEL 520
Cdd:cd09089  235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpsdkteesLVETNdptwnpgTLLYYGRAEL 314

                        330
                 ....*....|....
gi 974005362 521 KTSDHKPVSALFHI 534
Cdd:cd09089  315 KTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 669-897 6.22e-87

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239845  Cd Length: 220  Bit Score: 276.53  E-value: 6.22e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 669 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 748
Cdd:cd04380    1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 749 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDS-AYDPRICR 823
Cdd:cd04380   64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKR 143

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005362 824 QVIS-QLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLL 897
Cdd:cd04380  144 QVIRiSLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 241-534 1.26e-84

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate 5-phosphatase J and related proteins; INPP5c domain of Inositol polyphosphate-5-phosphatase J (INPP5J), also known as PIB5PA or PIPP, and related proteins. This subfamily belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5J hydrolyzes PI(4,5)P2, I(1,4,5)P3, and I(1,3,4,5)P4 at ruffling membranes. These proteins contain a C-terminal, SKIP carboxyl homology domain (SKICH), which may direct plasma membrane ruffle localization.


Pssm-ID: 197328  Cd Length: 300  Bit Score: 273.48  E-value: 1.26e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 241 FRFFVGTWNVNGQSPDSGLEPWLNCDPNP--PDIYCIGFQELDlSTEAFFYFESVKEQEWSMAVERGLhSKAKYKKVQLV 318
Cdd:cd09094    1 LRVYVVTWNVATAPPPIDVRSLLGLQSPEvaPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDIL-SPKGYVKVSSI 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 319 RLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARM 398
Cdd:cd09094   79 RLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQ 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 399 SFVVPNQTlpqlNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTY 478
Cdd:cd09094  159 VFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTY 234

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 974005362 479 KYDSKTDRWDSSGKCRVPAWCDRILWR----------GTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09094  235 KFDLGTDEYDTSGKKRKPAWTDRILWKvnpdasteekFLSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 242-534 1.74e-72

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This subfamily contains the INPP5c domains of human synaptojanin 2 (Synj2) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25, a mitochondrial outer membrane protein. Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197333  Cd Length: 336  Bit Score: 242.23  E-value: 1.74e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 242 RFFVGTWNVNG-------------------QSPD-SGLEPWLNCDPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 300
Cdd:cd09099    2 RVAMGTWNVNGgkqfrsnilgtseltdwllDSPKlSGTPDFQDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWGE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 301 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 380
Cdd:cd09099   82 QLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAG 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 381 VEDFERRNQDYKDICARMSFVVPNqtlpqlNIMKHEVVIWLGDLNYRLCMPdANEVKSLINKKDLQRLLKFDQLNIQRTQ 460
Cdd:cd09099  162 QNQVKERNEDYKEITQKLSFPMGR------NVFSHDYVFWCGDFNYRIDLT-YEEVFYFIKRQDWKKLLEFDQLQLQKSS 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 461 KKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILW----------------------RGTNVNQ------L 512
Cdd:cd09099  235 GKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWwrkkwpfektageinlldsdldFDTKIRHtwtpgaL 314

                        330       340
                 ....*....|....*....|..
gi 974005362 513 NYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09099  315 MYYGRAELQASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 242-534 6.93e-66

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This subfamily contains the INPP5c domains of human synaptojanin 1 (Synj1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro.


Pssm-ID: 197332  Cd Length: 336  Bit Score: 224.15  E-value: 6.93e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 242 RFFVGTWNVNGQSP-------DSGLEPWLNCDP-------------NPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 300
Cdd:cd09098    2 RVCVGTWNVNGGKQfrsiafkNQTLTDWLLDAPkkagipefqdvrsKPVDIFAIGFEEMvELNAGNIVSASTTNQKLWAA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 301 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 380
Cdd:cd09098   82 ELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAG 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 381 VEDFERRNQDYKDICARMSFvvPNQTLpqlnIMKHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQRLLKFDQLNIQRTQ 460
Cdd:cd09098  162 QSQVKERNEDFIEIARKLSF--PMGRM----LFSHDYVFWCGDFNYRIDIPN-EEVKELIRQQNWDSLIAGDQLINQKNA 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 461 KKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------------GTNVNQ----------L 512
Cdd:cd09098  235 GQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpfdrsaedldllnaSFPDNSkeqytwspgtL 314

                        330       340
                 ....*....|....*....|..
gi 974005362 513 NYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09098  315 LHYGRAELKTSDHRPVVALIDI 336
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
224-541 2.47e-63

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 221.20  E-value: 2.47e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 224 IKHILAKREKEYVNIQTFRFFVGTWNVNGQSPDSGLEPWL---NCDPNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 298
Cdd:COG5411   13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 299 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 375
Cdd:COG5411   93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 376 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKD-LQRLLKFDQL 454
Cdd:COG5411  173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDDGrLDKLFEYDQL 246

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 455 NIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:COG5411  247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326


                 ....*..
gi 974005362 535 GVKVVDE 541
Cdd:COG5411  327 KIKVVDP 333
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
 15-116 3.47e-59

oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL1 contains a PH domain and a Rho-GAP domain. Patients with Lowe syndrome suffer primarily from congenital cataracts, neonatal hypotonia, intellectual disability and Fanconi syndrome. Mutations in OCRL are also found in a subset of patients with type 2 Dent disease, who selectively suffer from renal proximal tubular dysfunction. 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: 270182  Cd Length: 105  Bit Score: 196.96  E-value: 3.47e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362  15 TVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRE 94
Cdd:cd13382    4 TVRGHEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDRTPE 83

                         90       100
                 ....*....|....*....|..
gi 974005362  95 RRFEIPDEEHCLKFLSAVLAAQ 116
Cdd:cd13382   84 RLFEIPDEEHCLSFLSHVLAAQ 105
PH_OCRL-like cd13320
oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has ...
 15-116 1.25e-56

oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has two members: OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) and OCRL2 ( also called IPNNB5, inositol polyphosphate-5-phosphatase, phosphoinositide 5-phosphatase, 5PTase, or type II inositol-1,4,5-trisphosphate 5-phosphatase). The OCRL proteins hydrolyze phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. They interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. All OCRL family members contain a PH domain and a Rho-GAP 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: 270130  Cd Length: 105  Bit Score: 190.03  E-value: 1.25e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362  15 TVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRE 94
Cdd:cd13320    4 AVQGVLCKGGSREPRLLSLAQRRGQYALIIQSHEREASLQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRLQGDETLE 83

                         90       100
                 ....*....|....*....|..
gi 974005362  95 RRFEIPDEEHCLKFLSAVLAAQ 116
Cdd:cd13320   84 RLFEIPDEEHCLTFLSEVLAAQ 105
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
 19-119 6.66e-56

Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin binding domain found at the N-terminus of inositol polyphosphate 5-phosphatase OCRL. It has a PH domain-like fold.


Pssm-ID: 435540  Cd Length: 101  Bit Score: 187.61  E-value: 6.66e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   19 MEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRERRFE 98
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80

                          90       100
                  ....*....|....*....|.
gi 974005362   99 IPDEEHCLKFLSAVLAAQKAQ 119
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 244-534 1.16e-54

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and -2, and related proteins; This subfamily contains the INPP5c domain of SHIP1 (SH2 domain containing inositol polyphosphate 5-phosphatase-1, also known as SHIP/INPP5D), and SHIP2 (also known as INPPL1). It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Both SHIP1 and -2 catalyze the dephosphorylation of the PI, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]. SHIP1 also converts inositol-1,3,4,5- polyphosphate [I(1,3,4,5)P4] to inositol-1,3,4-polyphosphate [I(1,3,4)P3]. SHIP1 and SHIP2 have little overlap in their in vivo functions. SHIP1 is a negative regulator of cell growth and plays a major part in mediating the inhibitory signaling in B cells; it is predominantly expressed in hematopoietic cells. SHIP2 is as an inhibitor of the insulin signaling pathway, and is implicated in actin structure remodeling, cell adhesion and cell spreading, receptor endocytosis and degradation, and in the JIP1-mediated JNK pathway. SHIP2 is widely expressed, most prominently in brain, heart and in skeletal muscle. In addition to this INPP5c domain, SHIP1 has an N-terminal SH2 domain, two NPXY motifs, and a C-terminal proline-rich region (PRD), while SHIP2 has an N-terminal SH2 domain, a C-terminal proline-rich domain (PRD), which includes a WW-domain binding motif (PPLP), an NPXY motif, and a sterile alpha motif (SAM) domain. The gene encoding SHIP2 is a candidate gene for conferring a predisposition for type 2 diabetes.


Pssm-ID: 197325  Cd Length: 307  Bit Score: 192.08  E-value: 1.16e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 244 FVGTWNVNGQSPDSGLEPWLNC-----------DPNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLH--SKA 310
Cdd:cd09091    4 FIGTWNMGSAPPPKNITSWFTSkgqgktrddvaDYIPHDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 311 KYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 390
Cdd:cd09091   73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 391 YKDICARMSfvVPNQTLPQLNI-MKHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQR---LLKFDQLNIQRTQKKAFVD 466
Cdd:cd09091  153 YLNILRFLS--LGDKKLSAFNItHRFTHLFWLGDLNYRLDLPI-QEAENIIQKIEQQQfepLLRHDQLNLEREEHKVFLR 229

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362 467 FNEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09091  230 FSEEEITFPPTYRYERGSrDTYaytkqKATGvKYNLPSWCDRILWKSypeTHIICQSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 244-534 3.47e-53

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and related proteins; This subfamily contains the INPP5c domain of SHIP1 (SH2 domain containing inositol polyphosphate 5-phosphatase-1, also known as SHIP/INPP5D) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. SHIP1's enzymic activity is restricted to phosphatidylinositol 3,4,5-trisphosphate [PI (3,4,5)P3] and inositol-1,3,4,5- polyphosphate [I(1,3,4,5)P4]. It converts these two phosphoinositides to phosphatidylinositol 3,4-bisphosphate [PI (3,4)P2] and inositol-1,3,4-polyphosphate [I(1,3,4)P3], respectively. SHIP1 is a negative regulator of cell growth and plays a major part in mediating the inhibitory signaling in B cells; it is predominantly expressed in hematopoietic cells. In addition to this INPP5c domain, SHIP1 has an N-terminal SH2 domain, two NPXY motifs, and a C-terminal proline-rich region (PRD). SHIP1's phosphorylated NPXY motifs interact with proteins with phosphotyrosine binding (PTB) domains, and facilitate the translocation of SHIP1 to the plasma membrane to hydrolyze PI(3,4,5)P3. SHIP1 generally acts to oppose the activity of phosphatidylinositol 3-kinase (PI3K). It acts as a negative signaling molecule, reducing the levels of PI(3,4,5)P3, thereby removing the latter as a membrane-targeting signal for PH domain-containing effector molecules. SHIP1 may also, in certain contexts, amplify PI3K signals. SHIP1 and SHIP2 have little overlap in their in vivo functions.


Pssm-ID: 197334  Cd Length: 307  Bit Score: 187.89  E-value: 3.47e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 244 FVGTWNVNGQSPDSGLEPWLNC-----------DPNPPDIYCIGFQELDLSteaffyfesvkEQEWSMAVERGLH--SKA 310
Cdd:cd09100    4 FIGTWNMGNAPPPKKITSWFQCkgqgktrddtaDYIPHDIYVIGTQEDPLG-----------EKEWLDTLKHSLReiTSI 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 311 KYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 390
Cdd:cd09100   73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 391 YKDIcarMSF-VVPNQTLPQLNIM-KHEVVIWLGDLNYRLCMP--DANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVD 466
Cdd:cd09100  153 YFNI---LRFlVLGDKKLSPFNIThRFTHLFWLGDLNYRVELPntEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQ 229

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362 467 FNEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09100  230 FEEEEITFAPTYRFERGTrERYaytkqKATGmKYNLPSWCDRVLWKSyplVHVVCQSYGCTDDITTSDHSPVFATFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 244-534 8.19e-53

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol 5-phosphatase-2 and related proteins; This subfamily contains the INPP5c domain of SHIP2 (SH2 domain containing inositol 5-phosphatase-2, also called INPPL1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. SHIP2 catalyzes the dephosphorylation of the PI, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]. SHIP2 is widely expressed, most prominently in brain, heart and in skeletal muscle. SHIP2 is an inhibitor of the insulin signaling pathway. It is implicated in actin structure remodeling, cell adhesion and cell spreading, receptor endocytosis and degradation, and in the JIP1-mediated JNK pathway. Its interacting partners include filamin/actin, p130Cas, Shc, Vinexin, Interesectin 1, and c-Jun NH2-terminal kinase (JNK)-interacting protein 1 (JIP1). A large variety of extracellular stimuli appear to lead to the tyrosine phosphorylation of SHIP2, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin, macrophage colony-stimulating factor (M-CSF) and hepatocyte growth factor (HGF). SHIP2 is localized to the cytosol in quiescent cells; following growth factor stimulation and /or cell adhesion, it relocalizes to membrane ruffles. In addition to this INPP5c domain, SHIP2 has an N-terminal SH2 domain, a C-terminal proline-rich domain (PRD), which includes a WW-domain binding motif (PPLP), an NPXY motif and a sterile alpha motif (SAM) domain. The gene encoding SHIP2 is a candidate for conferring a predisposition for type 2 diabetes; it has been suggested that suppression of SHIP2 may be of benefit in the treatment of obesity and thereby prevent type 2 diabetes. SHIP2 and SHIP1 have little overlap in their in vivo functions.


Pssm-ID: 197335  Cd Length: 304  Bit Score: 186.72  E-value: 8.19e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 244 FVGTWNVNGQSPDSGLEPWLNCD-----------PNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGL--HSKA 310
Cdd:cd09101    4 FIGTWNMGSVPPPKSLASWLTSRglgktldettvTIPHDIYVFGTQE-----------NSVGDREWVDFLRASLkeLTDI 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 311 KYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 390
Cdd:cd09101   73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 391 YKDICARMSfvVPNQTLPQLNI-MKHEVVIWLGDLNYRLCMpDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNE 469
Cdd:cd09101  153 YLDILRSLS--LGDKQLNAFDIsLRFTHLFWFGDLNYRLDM-DIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFRE 229

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005362 470 GEIKFIPTYKYDSKT------DRWDSSG-KCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALFHI 534
Cdd:cd09101  230 EEISFPPTYRYERGSrdtymwQKQKTTGmRTNVPSWCDRILWKSypeTHIVCNSYGCTDDIVTSDHSPVFGTFEV 304
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 295-546 1.72e-50

Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 188.58  E-value: 1.72e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 295 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 374
Cdd:PLN03191 347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 375 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHEVVIWLGDLNYRLCMPDAnEVKSLINKKDLQRLLKF 451
Cdd:PLN03191 427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 452 DQLNIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLNYRsHMELKTSDHK 526
Cdd:PLN03191 505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583

                        250       260
                 ....*....|....*....|
gi 974005362 527 PVSALFHIGVKVVDERRYRK 546
Cdd:PLN03191 584 PVSSMFLVEVEVFDHRKLQR 603
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 239-532 9.44e-48

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol polyphosphate-5-phosphatase E and related proteins; INPP5c domain of Inositol polyphosphate-5-phosphatase E (also called type IV or 72 kDa 5-phosphatase), rat pharbin, and related proteins. This subfamily belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5E hydrolyzes the 5-phosphate from PI(3,5)P2, PI(4,5)P2 and PI(3,4,5)P3, forming PI3P, PI4P, and PI(3,4)P2, respectively. It is a very potent PI(3,4,5)P3 5-phosphatase. Its intracellular localization is chiefly cytosolic, with pronounced perinuclear/Golgi localization. INPP5E also has an N-terminal proline rich domain (PRD) and a C-terminal CAAX motif. This protein is expressed in a variety of tissues, including the breast, brain, testis, and haemopoietic cells. It is differentially expressed in several cancers, for example, it is up-regulated in cervical cancer and down-regulated in stomach cancer. It is a candidate target for therapeutics of obesity and related disorders, as it is expressed in the hypothalamus, and following insulin stimulation, it undergoes tyrosine phosphorylation, associates with insulin receptor substrate-1, -2, and PI3-kinase, and become active as a 5-phosphatase. INPP5E may play a role, along with other 5-phosphatases SHIP2 and SKIP, in regulating glucose homoeostasis and energy metabolism. Mice deficient in INPPE5 develop a multi-organ disorder associated with structural defects of the primary cilium.


Pssm-ID: 197329  Cd Length: 298  Bit Score: 172.22  E-value: 9.44e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 239 QTFRFFVGTWNVNGQS--PDSGLEPWLNCDPN-PPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLhsKAKYKKV 315
Cdd:cd09095    3 RNVGIFVATWNMQGQKelPENLDDFLLPTSADfAQDIYVIGVQE-----------GCSDRREWEIRLQETL--GPSHVLL 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 316 QLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIc 395
Cdd:cd09095   70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKI- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 396 armsfvVPNQTLPQ---LNIMKHE---------VVIWLGDLNYRLCMPdANEVKSLINKK---DLQRLLKFDQLNIQRTQ 460
Cdd:cd09095  149 ------IQALNLPRnvpTNPYKSEsgdvttrfdEVFWFGDFNFRLSGP-RHLVDALINQGqevDVSALLQHDQLTREMSK 221

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 974005362 461 KKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALF 532
Cdd:cd09095  222 GSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSrqkGDVCCLKYNSCPSIKTSDHRPVFALF 296
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 734-895 6.95e-41

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.


Pssm-ID: 214618  Cd Length: 174  Bit Score: 148.18  E-value: 6.95e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   734 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 810
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362   811 RCLDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMAR-QTPS 883
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161

                          170
                   ....*....|..
gi 974005362   884 DRQRAIQFLLGF 895
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 736-874 4.05e-35

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.


Pssm-ID: 459875  Cd Length: 148  Bit Score: 130.74  E-value: 4.05e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362  736 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 812
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362  813 LDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 874
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
 736-893 3.87e-26

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.


Pssm-ID: 238090 [Multi-domain]  Cd Length: 169  Bit Score: 105.46  E-value: 3.87e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 736 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 813
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDrgEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 814 DSAYDPRI------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQ- 886
Cdd:cd00159   81 ELAKIEDEeerieaLKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKKLn 160


                 ....*..
gi 974005362 887 RAIQFLL 893
Cdd:cd00159  161 EIVEFLI 167
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 722-865 2.38e-14

RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of FAM13A1, isoform a-like proteins. The function of FAM13A1a is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by up several orders of magnitude.


Pssm-ID: 239858 [Multi-domain]  Cd Length: 189  Bit Score: 72.49  E-value: 2.38e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 722 VPLDE----GASERplQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETI--PGSNHSVAEALLIF 795
Cdd:cd04393    5 VPLQElqqaGQPEN--GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLskEADVCSAASLLRLF 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 974005362 796 LEALPEPVICYELYQRCLDSAYDPRI-------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLF 865
Cdd:cd04393   83 LQELPEGLIPASLQIRLMQLYQDYNGedefgrkLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVF 159
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 722-873 4.55e-14

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239851  Cd Length: 203  Bit Score: 71.72  E-value: 4.55e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 722 VPLDE--GASERPLQVPKEiwLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSN--HSVAEALLIF 795
Cdd:cd04386    7 TPLEEhlKRTGREIALPIE--ACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDagTFSLPLDEFYSdpHAVASALKSY 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 796 LEALPEPVICYELYQRCLDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLL 869
Cdd:cd04386   85 LRELPDPLLTYNLYEDWVQAANKPdederlQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNL 164


                 ....
gi 974005362 870 LRPP 873
Cdd:cd04386  165 LWAK 168
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 784-874 8.50e-11

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239843  Cd Length: 203  Bit Score: 62.44  E-value: 8.50e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 784 SNHSVAEALLIFLEALPEPVICYELY----------QRCLDSAYDPRIC----------RQVISQLPRCHRNVFRYLMAF 843
Cdd:cd04378   67 SPHDISSVLKLFLRQLPEPLILFRLYndfialakeiQRDTEEDKAPNTPievnriirklKDLLRQLPASNYNTLQHLIAH 146

                         90       100       110
                 ....*....|....*....|....*....|.
gi 974005362 844 LRELLKFSEYNSVNANMIATLFTSLLLRPPP 874
Cdd:cd04378  147 LYRVAEQFEENKMSPNNLGIVFGPTLIRPRP 177
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 753-873 5.99e-10

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239837 [Multi-domain]  Cd Length: 194  Bit Score: 59.84  E-value: 5.99e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 753 QEDLFQTPGMQEELQQIIDCLD-----TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSA----YDPRI-- 821
Cdd:cd04372   34 SEGLYRVSGFAEEIEDVKMAFDrdgekADISATVYPDINVITGALKLYFRDLPIPVITYDTYPKFIDAAkisnPDERLea 113

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005362 822 CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPP 873
Cdd:cd04372  114 VHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPP 165
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 733-871 7.38e-10

RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in KIAA1688-like proteins; KIAA1688 is a protein of unknown function that contains a RhoGAP domain and a myosin tail homology 4 (MyTH4) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239854  Cd Length: 187  Bit Score: 59.33  E-value: 7.38e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 733 LQVPKEIWLLVDHLFKYACHQ-EDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNHSVAEALLIFLEALPEPVICYELYQ 810
Cdd:cd04389   19 LKLPWILTFLSEKVLALGGFQtEGIFRVPGDIDEVNELKLRVDQwDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQ 98

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 974005362 811 RCLDSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFS--EYNSVNANMIATLFTSLLLR 871
Cdd:cd04389   99 QCISASEDPDKAVEIVQKLPIINRLVLCYLINFLQVFAQPEnvAHTKMDVSNLAMVFAPNILR 161
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 786-877 1.17e-09

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239869 [Multi-domain]  Cd Length: 195  Bit Score: 58.89  E-value: 1.17e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELYQRC-----LDSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANM 860
Cdd:cd04404   76 HLPAVILKTFLRELPEPLLTFDLYDDIvgflnVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSN 155

                         90
                 ....*....|....*..
gi 974005362 861 IATLFTSLLLRPPPNLM 877
Cdd:cd04404  156 LAVVFGPNLLWAKDASM 172
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 732-882 3.18e-09

RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP22, 24 and 25-like proteins; longer isoforms of these proteins contain an additional N-terminal pleckstrin homology (PH) domain. ARHGAP25 (KIA0053) has been identified as a GAP for Rac1 and Cdc42. Short isoforms (without the PH domain) of ARHGAP24, called RC-GAP72 and p73RhoGAP, and of ARHGAP22, called p68RacGAP, has been shown to be involved in angiogenesis and endothelial cell capillary formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239855 [Multi-domain]  Cd Length: 199  Bit Score: 57.45  E-value: 3.18e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 732 PLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN--HSVAEALLIFLEALPEPVICYELY 809
Cdd:cd04390   19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQY 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 810 QRCLDSAYDPRICRQV--------ISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRP----PPNLM 877
Cdd:cd04390   99 EDFLSCAQLLSKDEEKglgelmkqVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPkvedPATIM 178


                 ....*
gi 974005362 878 ARQTP 882
Cdd:cd04390  179 EGTPQ 183
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 245-528 5.04e-09

Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes the catalytic domain (exonuclease/endonuclease/phosphatase or EEP domain) of a diverse set of proteins including the ExoIII family of apurinic/apyrimidinic (AP) endonucleases, inositol polyphosphate 5-phosphatases (INPP5), neutral sphingomyelinases (nSMases), deadenylases (such as the vertebrate circadian-clock regulated nocturnin), bacterial cytolethal distending toxin B (CdtB), deoxyribonuclease 1 (DNase1), the endonuclease domain of the non-LTR retrotransposon LINE-1, and related domains. These diverse enzymes share a common catalytic mechanism of cleaving phosphodiester bonds; their substrates range from nucleic acids to phospholipids and perhaps proteins.


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 57.88  E-value: 5.04e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 245 VGTWNVNGQSPDSGLEPWL----NCDPnppDIYCIgfQELDLSTeAFFYFESVKEQEWSMAVERGLHSKAKYkkvqlvrl 320
Cdd:cd08372    1 VASYNVNGLNAATRASGIArwvrELDP---DIVCL--QEVKDSQ-YSAVALNQLLPEGYHQYQSGPSRKEGY-------- 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 321 VGMMLLIFARKdqcryiRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAhvedfERRNQDYKDICARMsF 400
Cdd:cd08372   67 EGVAILSKTPK------FKIVEKHQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQA-----GGTRADVRDAQLKE-V 134

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 401 VvpnQTLPQLNIMKHEVVIWLGDLNYRlcmpdanevKSLInkkDLQRLLKFDQLNIQRtqkkAFVDFNEgEIKFIPTYKY 480
Cdd:cd08372  135 L---EFLKRLRQPNSAPVVICGDFNVR---------PSEV---DSENPSSMLRLFVAL----NLVDSFE-TLPHAYTFDT 194

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 974005362 481 DSKtdrwdssgkcRVPAWCDRILWRGT---NV--NQLNYRSHMELKTSDHKPV 528
Cdd:cd08372  195 YMH----------NVKSRLDYIFVSKSllpSVksSKILSDAARARIPSDHYPI 237
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
 784-874 5.24e-09

RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239873  Cd Length: 200  Bit Score: 57.13  E-value: 5.24e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 784 SNHSVAEALLIFLEALPEPVICYELYQRCL--------DSAYDP----------RICRQVISQLPRCHRNVFRYLMAFLR 845
Cdd:cd04408   67 SPHDITSVLKHFLKELPEPVLPFQLYDDFIalakelqrDSEKAAespsiveniiRSLKELLGRLPVSNYNTLRHLMAHLY 146

                         90       100
                 ....*....|....*....|....*....
gi 974005362 846 ELLKFSEYNSVNANMIATLFTSLLLRPPP 874
Cdd:cd04408  147 RVAERFEDNKMSPNNLGIVFGPTLLRPLV 175
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 733-890 6.77e-09

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239841  Cd Length: 206  Bit Score: 56.68  E-value: 6.77e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 733 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI---IDC-LDTSIPETIpgSNHSVAEALLIFLEALPEPVICYEL 808
Cdd:cd04376    7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLreeFDRgIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPREL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 809 YQRCLDSA---YDPRI--CRQVISQLPRCHRNVFRYLMAFLRELLKFSEY-----------NSVNANMIATLFTslllrp 872
Cdd:cd04376   85 YTAFIGTAllePDEQLeaLQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFG------ 158

                        170
                 ....*....|....*...
gi 974005362 873 pPNLMARQTPSDRQRAIQ 890
Cdd:cd04376  159 -PNLLHKQKSGEREFVQA 175
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 737-875 4.99e-08

RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in srGAPs. srGAPs are components of the intracellular part of Slit-Robo signalling pathway that is important for axon guidance and cell migration. srGAPs contain an N-terminal FCH domain, a central RhoGAP domain and a C-terminal SH3 domain; this SH3 domain interacts with the intracellular proline-rich-tail of the Roundabout receptor (Robo). This interaction with Robo then activates the rhoGAP domain which in turn inhibits Cdc42 activity. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239848  Cd Length: 188  Bit Score: 53.96  E-value: 4.99e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 737 KEIWLLVDHLFKYAC----HQEDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNH---SVAEALLIFLEALPEPVICYEL 808
Cdd:cd04383   16 QAIPLVVESCIRFINlyglQHQGIFRVSGSQVEVNDIKNAFERgEDPLADDQNDHdinSVAGVLKLYFRGLENPLFPKER 95

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 974005362 809 YQRCLDSA-------YDPRIcRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPN 875
Cdd:cd04383   96 FEDLMSCVklenpteRVHQI-REILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEG 168
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 352-534 1.40e-07

Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I (INPP5A) hydrolyzes the 5-phosphate from inositol 1,3,4,5-tetrakisphosphate [I(1,3,4,5)P4] and inositol 1,4,5-trisphosphate [I(1,4,5)P3]. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. As the substrates of INPP5A mobilize intracellular calcium ions, INPP5A is a calcium signal-terminating enzyme. In platelets, phosphorylated pleckstrin binds and activates INPP5A in a 1:1 complex, and accelerates the degradation of the calcium ion-mobilizing I(1,4,5)P3.


Pssm-ID: 197326  Cd Length: 383  Bit Score: 54.78  E-value: 1.40e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 352 KMGNKGGVAVRFVFHNTTFCIVNSHL---AAHVEDFERRNQDYKDICAR-MSFV---VPNQTLPQLNImkhevvIWLGDL 424
Cdd:cd09092  151 KWSRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRaLGYVlerLTDERFEKVPF------FVFGDF 224

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 425 NYR---------LCM---------PDANEVKSLINKKD------LQRLLK-----FDQLNIQRTQKKAFVDFN------- 468
Cdd:cd09092  225 NFRldtksvvetLCAkatmqtvrkADSNIVVKLEFREKdndnkvVLQIEKkkfdyFNQDVFRDNNGKALLKFDkelevfk 304

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 469 ----EGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWrGTNVNQLN---------YRS-HMELKTSDHKPVSALFHI 534
Cdd:cd09092  305 dvlyELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILM-SHSARELKseneeksvtYDMiGPNVCMGDHKPVFLTFRI 383
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 722-884 1.54e-07

RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in class IX myosins. Class IX myosins contain a characteristic head domain, a neck domain, a tail domain which contains a C6H2-zinc binding motif and a RhoGAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239842  Cd Length: 186  Bit Score: 52.44  E-value: 1.54e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 722 VPLDEGASERPlQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGSN---HSVAEALLIFLEA 798
Cdd:cd04377    3 VSLSSLTSEDR-SVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTD-PDSVNLEDypiHVITSVLKQWLRE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 799 LPEPVICYELYQRCLDSAYDP----RIC--RQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRP 872
Cdd:cd04377   81 LPEPLMTFELYENFLRAMELEekqeRVRalYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160

                        170
                 ....*....|..
gi 974005362 873 PPNLMARQTPSD 884
Cdd:cd04377  161 PDTADPLQSLQD 172
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 735-893 1.79e-07

RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP20-like proteins. ArhGAP20, also known as KIAA1391 and RA-RhoGAP, contains a RhoGAP, a RA, and a PH domain, and ANXL repeats. ArhGAP20 is activated by Rap1 and induces inactivation of Rho, which in turn leads to neurite outgrowth. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239867  Cd Length: 192  Bit Score: 52.30  E-value: 1.79e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 735 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSI-PETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 813
Cdd:cd04402   15 LPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVeVDLKAEPVLLLASVLKDFLRNIPGSLLSSDLYEEWM 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 814 DSAYDPRI------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANmiatlftSLLLRPPPNLMARQTPSDRQR 887
Cdd:cd04402   95 SALDQENEeekiaeLQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAF-------NLAVCIAPSLLWPPASSELQN 167

                        170
                 ....*....|....
gi 974005362 888 A--------IQFLL 893
Cdd:cd04402  168 EdlkkvtslVQFLI 181
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 722-893 4.66e-07

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239863  Cd Length: 192  Bit Score: 51.25  E-value: 4.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 722 VPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-----HSVAEALLI 794
Cdd:cd04398    3 VPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKdpLNVLLISPEDyesdiHSVASLLKL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 795 FLEALPEPVICYELYQRCLDSAY--DPRICR----QVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSL 868
Cdd:cd04398   83 FFRELPEPLLTKALSREFIEAAKieDESRRRdalhGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPT 162

                        170       180
                 ....*....|....*....|....*...
gi 974005362 869 LLR-PPPNL--MARQTpsdrqRAIQFLL 893
Cdd:cd04398  163 LMNaAPDNAadMSFQS-----RVIETLL 185
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 722-872 6.77e-07

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239838  Cd Length: 185  Bit Score: 50.53  E-value: 6.77e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 722 VPL-DEGASERPlqVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI-----------IDCLDTSIpetipgsnHSVA 789
Cdd:cd04373    3 VPLaNVVTSEKP--IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLqkqfdqdhnldLVSKDFTV--------NAVA 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 790 EALLIFLEALPEPVICYELYQRCLDSAYDP-RICR-----QVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIAT 863
Cdd:cd04373   73 GALKSFFSELPDPLIPYSMHLELVEAAKINdREQRlhalkELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSI 152


                 ....*....
gi 974005362 864 LFTSLLLRP 872
Cdd:cd04373  153 CFWPTLMRP 161
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 735-884 3.00e-06

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239871  Cd Length: 186  Bit Score: 48.84  E-value: 3.00e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 735 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPET-IPGSN-HSVAEALLIFLEALPEPVICYELYQRC 812
Cdd:cd04406   15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVnLDDYNiHVIASVFKQWLRDLPNPLMTFELYEEF 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362 813 L------DSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSD 884
Cdd:cd04406   95 LramglqERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDTTDPLQSVQD 172
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 735-875 3.16e-06

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239872 [Multi-domain]  Cd Length: 186  Bit Score: 48.45  E-value: 3.16e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 735 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGSN---HSVAEALLIFLEALPEPVICYELYQR 811
Cdd:cd04407   15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQAD-PENVKLENypiHAITGLLKQWLRELPEPLMTFAQYND 93

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 812 CLDSAYDPRICRQ------VISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPN 875
Cdd:cd04407   94 FLRAVELPEKQEQlqaiyrVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDS 163
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 786-874 1.06e-05

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239849 [Multi-domain]  Cd Length: 195  Bit Score: 47.11  E-value: 1.06e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELYQRCLDS-AYDP-----RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 859
Cdd:cd04384   73 HSVSSLCKLYFRELPNPLLTYQLYEKFSEAvSAASdeerlEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAK 152

                         90
                 ....*....|....*
gi 974005362 860 MIATLFTSLLLRPPP 874
Cdd:cd04384  153 NLAIVWAPNLLRSKQ 167
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 784-874 3.21e-05

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239874  Cd Length: 211  Bit Score: 45.95  E-value: 3.21e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 784 SNHSVAEALLIFLEALPEPVICYELYQRCLDSAYD------------------PRIC----------RQVISQLPRCHRN 835
Cdd:cd04409   67 SPHDISNVLKLYLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwPNMCtelnrillksKDLLRQLPAPNYN 146

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 974005362 836 VFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 874
Cdd:cd04409  147 TLQFLIVHLHRVSEQAEENKMSASNLGIIFGPTLIRPRP 185
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
 786-877 3.48e-05

RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of fungal BEM3-like proteins. Bem3 is a GAP protein of Cdc42, and is specifically involved in the control of the initial assembly of the septin ring in yeast bud formation. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239865 [Multi-domain]  Cd Length: 190  Bit Score: 45.43  E-value: 3.48e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELY---QRCLDSAYDPR----ICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNA 858
Cdd:cd04400   79 HTVAGLLKLYLRELPTLILGGELHndfKRLVEENHDRSqralELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNL 158

                         90
                 ....*....|....*....
gi 974005362 859 NMIATLFTSLLLRPPPNLM 877
Cdd:cd04400  159 RNVCIVFSPTLNIPAGIFV 177
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
 734-896 3.54e-05

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239852 [Multi-domain]  Cd Length: 196  Bit Score: 45.69  E-value: 3.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 734 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN----HSVAEALLIFLEALPEPVICYELY 809
Cdd:cd04387   15 KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSemdvNAIAGTLKLYFRELPEPLFTDELY 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 810 QRCL------DSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRP-------PPNL 876
Cdd:cd04387   95 PNFAegialsDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPsekeskiPTNT 174

                        170       180
                 ....*....|....*....|
gi 974005362 877 MARQTPSDRQRAIQFLLGFL 896
Cdd:cd04387  175 MTDSWSLEVMSQVQVLLYFL 194
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 758-874 5.19e-05

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239853  Cd Length: 200  Bit Score: 45.25  E-value: 5.19e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 758 QTPGMQEELQQIIDClDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAYDP---RICRQVISQLPRC-- 832
Cdd:cd04388   40 QSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAPVYSEMISRAQEVqssDEYAQLLRKLIRSpn 118

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 974005362 833 ---HRNV-FRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 874
Cdd:cd04388  119 lphQYWLtLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 786-872 7.88e-05

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239850  Cd Length: 184  Bit Score: 44.22  E-value: 7.88e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELYQRCLDSAYDPRIC------RQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 859
Cdd:cd04385   70 HDVADVLKRFLRDLPDPLLTSELHAEWIEAAELENKDeriaryKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVH 149

                         90
                 ....*....|...
gi 974005362 860 MIATLFTSLLLRP 872
Cdd:cd04385  150 NLALVFGPTLFQT 162
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 786-878 1.42e-04

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239860  Cd Length: 196  Bit Score: 43.93  E-value: 1.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELYQRCLDS--AYDP----RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 859
Cdd:cd04395   74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEAnrIEDPverlKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153

                         90
                 ....*....|....*....
gi 974005362 860 MIATLFTSLLLRPPPNLMA 878
Cdd:cd04395  154 NLAIVFGPTLVRTSDDNME 172
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 778-872 3.08e-04

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239844  Cd Length: 207  Bit Score: 42.84  E-value: 3.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 778 PETIPGSNhSVAEALLIFLEALPEPVICYELYQRCLDSAY-----DP----RICRQVISQLPRCHRNVFRYLMAFLRELL 848
Cdd:cd04379   67 EELYPDIN-VITGVLKDYLRELPEPLITPQLYEMVLEALAvalpnDVqtntHLTLSIIDCLPLSAKATLLLLLDHLSLVL 145

                         90       100
                 ....*....|....*....|....
gi 974005362 849 KFSEYNSVNANMIATLFTSLLLRP 872
Cdd:cd04379  146 SNSERNKMTPQNLAVCFGPVLMFC 169
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 742-887 3.64e-04

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239859 [Multi-domain]  Cd Length: 202  Bit Score: 42.84  E-value: 3.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 742 LVDHLfkyacHQEDLFQTPG---MQEELQQIID----CLDTSIPEtipgsnhSVAEALLIFLEALPEPVICYELYQRCLD 814
Cdd:cd04394   31 LLDHL-----STEGLFRKSGsvvRQKELKAKLEggeaCLSSALPC-------DVAGLLKQFFRELPEPLLPYDLHEALLK 98

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005362 815 SAYDP----RICRQVISQ--LPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLrPPPNLMARQTPSDRQR 887
Cdd:cd04394   99 AQELPtdeeRKSATLLLTclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLF-QSEEGGEKMSSSTEKR 176
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 786-872 3.67e-04

RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ARHGAP27 (also called CAMGAP1), ARHGAP15, 12 and 9-like proteins; This subgroup of ARHGAPs are multidomain proteins that contain RhoGAP, PH, SH3 and WW domains. Most members that are studied show GAP activity towards Rac1, some additionally show activity towards Cdc42. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239868 [Multi-domain]  Cd Length: 187  Bit Score: 42.38  E-value: 3.67e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELYQ--RCLDSAYDPRIC----RQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 859
Cdd:cd04403   71 HVITGALKLFFRELPEPLFPYSLFNdfVAAIKLSDYEQRvsavKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQ 150

                         90
                 ....*....|...
gi 974005362 860 MIATLFTSLLLRP 872
Cdd:cd04403  151 NLAIVFGPTLLRP 163
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 733-875 4.26e-04

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239856  Cd Length: 216  Bit Score: 42.72  E-value: 4.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 733 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPE-TIPGSNHSVAEA---LLIFLEALPEPVICYEL 808
Cdd:cd04391   20 SKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEgTFLWDQVKQHDAaslLKLFIRELPQPLLTVEY 99

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362 809 YQRCLDSAYDPRICRQV------ISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIAT-----LFTSLLLRPPPN 875
Cdd:cd04391  100 LPAFYSVQGLPSKKDQLqalnllVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMimapnLFPPRGKHSKDN 177
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 725-875 6.78e-04

RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal LRG1-like proteins. Yeast Lrg1p is required for efficient cell fusion, and mother-daughter cell separation, possibly through acting as a RhoGAP specifically regulating 1,3-beta-glucan synthesis. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239862  Cd Length: 213  Bit Score: 41.97  E-value: 6.78e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 725 DEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIP--GSNHSVAEALLI--FLEALP 800
Cdd:cd04397   17 TLGVGPGKLRIPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKN-PTEVPdlSKENPVQLAALLkkFLRELP 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 801 EPVICYELYQRCLDSAY--DPRICRQVI----SQLPRCHRNVFRYLMAFLRELLKFSEY-----NSVNANMIATLFTSLL 869
Cdd:cd04397   96 DPLLTFKLYRLWISSQKieDEEERKRVLhlvyCLLPKYHRDTMEVLFSFLKWVSSFSHIdeetgSKMDIHNLATVITPNI 175


                 ....*.
gi 974005362 870 LRPPPN 875
Cdd:cd04397  176 LYSKTD 181
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 752-895 3.84e-03

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239847  Cd Length: 193  Bit Score: 39.58  E-value: 3.84e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 752 HQEDLFQTPGMQEELQQIIDCLDTSipETIPGSN----HSVAEALLIFLEALPEPVICYELYQRCLDSA--YDPRICR-- 823
Cdd:cd04382   34 TEEGLYRVSGSEREVKALKEKFLRG--KTVPNLSkvdiHVICGCLKDFLRSLKEPLITFALWKEFMEAAeiLDEDNSRaa 111

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 974005362 824 --QVISQLPRCHRNVFRYLMAFLRELLKfSEYNSVNANMIA-----TLFTSLLLRPPPNLMARQTPsDRQRAIQFLLGF 895
Cdd:cd04382  112 lyQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLArvfgpTIVGYSVPNPDPMTILQDTV-RQPRVVERLLEI 188
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 722-864 5.03e-03

RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in RalBP1 proteins, also known as RLIP, RLIP76 or cytocentrin. RalBP1 plays an important role in endocytosis during interphase. During mitosis, RalBP1 transiently associates with the centromere and has been shown to play an essential role in the proper assembly of the mitotic apparatus. RalBP1 is an effector of the Ral GTPase which itself is an effector of Ras. RalBP1 contains a RhoGAP domain, which shows weak activity towards Rac1 and Cdc42, but not towards Ral, and a Ral effector domain binding motif. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239846 [Multi-domain]  Cd Length: 182  Bit Score: 38.96  E-value: 5.03e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 722 VPLDEgASERP-----LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD----TSIPETIPgsnHSVAEAL 792
Cdd:cd04381    3 ASLSL-AVERSrchdgIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNrresPNLEEYEP---PTVASLL 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 974005362 793 LIFLEALPEPVICYELYQRCLDSAYDPRI------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATL 864
Cdd:cd04381   79 KQYLRELPEPLLTKELMPRFEEACGRPTEaereqeLQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIV 156
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 786-893 7.55e-03

RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal SAC7 and BAG7-like proteins. Both proteins are GTPase activating proteins of Rho1, but differ functionally in vivo: SAC7, but not BAG7, is involved in the control of Rho1-mediated activation of the PKC-MPK1 pathway. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.


Pssm-ID: 239861  Cd Length: 225  Bit Score: 38.93  E-value: 7.55e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 974005362 786 HSVAEALLIFLEALPEPVICYELY---------------------QRCLDSAYDPRI--CRQVISQLPRCHRNVFRYLMA 842
Cdd:cd04396   88 HDAASVLRRYLNNLPEPLVPLDLYeefrnplrkrprilqymkgriNEPLNTDIDQAIkeYRDLITRLPNLNRQLLLYLLD 167

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 974005362 843 FLRELLKFSEYNSVNANMIATLFT-SLLLRPPPNLMARQTPSDRQrAIQFLL 893
Cdd:cd04396  168 LLAVFARNSDKNLMTASNLAAIFQpGILSHPDHEMDPKEYKLSRL-VVEFLI 218
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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