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Conserved domains on  [gi|13325070|ref|NP_001578|]
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inositol polyphosphate 5-phosphatase OCRL isoform b [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 ...
240-533 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: 605.08  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 240 FRFFVGTWNVNGQSPDSGLEPWLNCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 319
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 320 VGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 399
Cdd:cd09093  81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 400 VVPNQtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTYKY 479
Cdd:cd09093 161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 13325070 480 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09093 239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
668-888 4.20e-88

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: 279.23  E-value: 4.20e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 668 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIdleksllqmVPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDL 747
Cdd:cd04380   1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLE---------LGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGL 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 748 FQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDS-AYDPRICRQVIS-QLP 821
Cdd:cd04380  72 FEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLP 151
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13325070 822 RCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLL 888
Cdd:cd04380 152 PVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
11-115 1.06e-60

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: 201.20  E-value: 1.06e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  11 PLATVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDW 90
Cdd:cd13382   1 CIATVRGHEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDR 80
                        90       100
                ....*....|....*....|....*
gi 13325070  91 IRERRFEIPDEEHCLKFLSAVLAAQ 115
Cdd:cd13382  81 TPERLFEIPDEEHCLSFLSHVLAAQ 105
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
240-533 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: 605.08  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 240 FRFFVGTWNVNGQSPDSGLEPWLNCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 319
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 320 VGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 399
Cdd:cd09093  81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 400 VVPNQtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTYKY 479
Cdd:cd09093 161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 13325070 480 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09093 239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
238-536 1.89e-133

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 401.35  E-value: 1.89e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    238 QTFRFFVGTWNVNGQS-PDSGLEPWLNC-----DPNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 310
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    311 YKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 390
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    391 KDICARMSFVVPnqtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGE 470
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    471 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-NYRSHMELKTSDHKPVSALFHIGVK 536
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
668-888 4.20e-88

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: 279.23  E-value: 4.20e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 668 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIdleksllqmVPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDL 747
Cdd:cd04380   1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLE---------LGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGL 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 748 FQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDS-AYDPRICRQVIS-QLP 821
Cdd:cd04380  72 FEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLP 151
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13325070 822 RCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLL 888
Cdd:cd04380 152 PVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
223-540 2.23e-63

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 221.20  E-value: 2.23e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 223 IKHILAKREKEYVNIQTFRFFVGTWNVNGQSPDSGLEPWL---NCDPNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 297
Cdd:COG5411  13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 298 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 374
Cdd:COG5411  93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 375 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKD-LQRLLKFDQL 453
Cdd:COG5411 173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDDGrLDKLFEYDQL 246
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 454 NIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:COG5411 247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326

                ....*..
gi 13325070 534 GVKVVDE 540
Cdd:COG5411 327 KIKVVDP 333
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
11-115 1.06e-60

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: 201.20  E-value: 1.06e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  11 PLATVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDW 90
Cdd:cd13382   1 CIATVRGHEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDR 80
                        90       100
                ....*....|....*....|....*
gi 13325070  91 IRERRFEIPDEEHCLKFLSAVLAAQ 115
Cdd:cd13382  81 TPERLFEIPDEEHCLSFLSHVLAAQ 105
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
18-118 4.89e-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: 187.99  E-value: 4.89e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    18 MEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRERRFE 97
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80
                          90       100
                  ....*....|....*....|.
gi 13325070    98 IPDEEHCLKFLSAVLAAQKAQ 118
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
294-545 1.33e-50

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 188.96  E-value: 1.33e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  294 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 373
Cdd:PLN03191 347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  374 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHEVVIWLGDLNYRLCMPDAnEVKSLINKKDLQRLLKF 450
Cdd:PLN03191 427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  451 DQLNIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLNYRsHMELKTSDHK 525
Cdd:PLN03191 505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583
                        250       260
                 ....*....|....*....|
gi 13325070  526 PVSALFHIGVKVVDERRYRK 545
Cdd:PLN03191 584 PVSSMFLVEVEVFDHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
725-886 6.15e-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: 6.15e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    725 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 801
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    802 RCLDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMAR-QTPS 874
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161
                          170
                   ....*....|..
gi 13325070    875 DRQRAIQFLLGF 886
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
727-865 3.74e-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: 3.74e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070   727 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 803
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070   804 LDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 865
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 ...
240-533 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: 605.08  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 240 FRFFVGTWNVNGQSPDSGLEPWLNCDPNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 319
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 320 VGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 399
Cdd:cd09093  81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 400 VVPNQtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTYKY 479
Cdd:cd09093 161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 13325070 480 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09093 239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
238-536 1.89e-133

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 401.35  E-value: 1.89e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    238 QTFRFFVGTWNVNGQS-PDSGLEPWLNC-----DPNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 310
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    311 YKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 390
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    391 KDICARMSFVVPnqtlPQLNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGE 470
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    471 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-NYRSHMELKTSDHKPVSALFHIGVK 536
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
240-533 2.23e-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: 359.34  E-value: 2.23e-117
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 240 FRFFVGTWNVNGQ-SPDSGLEPWLNCDPN-PPDIYCIGFQELDLSTEAFFYFE-SVKEQEWSMAVERGLHSKAKYKKVQL 316
Cdd:cd09074   1 VKIFVVTWNVGGGiSPPENLENWLSPKGTeAPDIYAVGVQEVDMSVQGFVGNDdSAKAREWVDNIQEALNEKENYVLLGS 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 317 VRLVGMMLLIFARKDQCRYIRDIATE--TVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 394
Cdd:cd09074  81 AQLVGIFLFVFVKKEHLPQIKDLEVEgvTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 395 ARMSFVVPNQtlPQLNIMKHEVVIWLGDLNYRLCMpDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFI 474
Cdd:cd09074 161 SKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDS-TDDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13325070 475 PTYKYDSKTDRWDSSGKCRVPAWCDRILWR---GTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09074 238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
241-531 1.15e-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: 1.15e-90
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 241 RFFVGTWNVNGQSPDSGLEPWLnCDPN---PPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQL 316
Cdd:cd09090   2 NIFVGTFNVNGKSYKDDLSSWL-FPEEndeLPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLNGRGGEKYVLL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 317 --VRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 394
Cdd:cd09090  81 rsEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 395 ARMSFVvPNQTLPQlnimkHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFI 474
Cdd:cd09090 161 RGLRFS-RGRTIKD-----HDHVIWLGDFNYRISLTN-EDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFP 233
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 13325070 475 PTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRShMELKTSDHKPVSALF 531
Cdd:cd09090 234 PTYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNS-APLRFSDHRPVYATF 289
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
241-533 1.68e-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: 1.68e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 241 RFFVGTWNVNGQS-------PDSGLEPWL--NC------------DPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWS 298
Cdd:cd09089   2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLldNPklagqcsndseeDEKPVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 299 MAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAA 378
Cdd:cd09089  82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 379 HVEDFERRNQDYKDICARMSFvvPNQTlpqlNIMKHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQRLLKFDQLNIQRT 458
Cdd:cd09089 162 GQSQVKERNEDFAEIARKLSF--PMGR----TLDSHDYVFWCGDFNYRIDLPN-DEVKELVRNGDWLKLLEFDQLTKQKA 234
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 459 QKKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------GTNVN-------QLNYRSHMEL 519
Cdd:cd09089 235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpsdkteesLVETNdptwnpgTLLYYGRAEL 314
                       330
                ....*....|....
gi 13325070 520 KTSDHKPVSALFHI 533
Cdd:cd09089 315 KTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
668-888 4.20e-88

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: 279.23  E-value: 4.20e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 668 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIdleksllqmVPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDL 747
Cdd:cd04380   1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLE---------LGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGL 71
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 748 FQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDS-AYDPRICRQVIS-QLP 821
Cdd:cd04380  72 FEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLP 151
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13325070 822 RCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQRAIQFLLGFLL 888
Cdd:cd04380 152 PVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGGKERRAERDRKRAFIEQFLL 218
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
240-533 8.41e-85

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: 273.86  E-value: 8.41e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 240 FRFFVGTWNVNGQSPDSGLEPWLNCDPNP--PDIYCIGFQELDlSTEAFFYFESVKEQEWSMAVERGLhSKAKYKKVQLV 317
Cdd:cd09094   1 LRVYVVTWNVATAPPPIDVRSLLGLQSPEvaPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDIL-SPKGYVKVSSI 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 318 RLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARM 397
Cdd:cd09094  79 RLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQ 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 398 SFVVPNQTlpqlNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNEGEIKFIPTY 477
Cdd:cd09094 159 VFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTY 234
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 13325070 478 KYDSKTDRWDSSGKCRVPAWCDRILWR----------GTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09094 235 KFDLGTDEYDTSGKKRKPAWTDRILWKvnpdasteekFLSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
241-533 1.55e-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: 1.55e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 241 RFFVGTWNVNG-------------------QSPD-SGLEPWLNCDPNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 299
Cdd:cd09099   2 RVAMGTWNVNGgkqfrsnilgtseltdwllDSPKlSGTPDFQDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWGE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 300 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 379
Cdd:cd09099  82 QLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 380 VEDFERRNQDYKDICARMSFVVPNqtlpqlNIMKHEVVIWLGDLNYRLCMPdANEVKSLINKKDLQRLLKFDQLNIQRTQ 459
Cdd:cd09099 162 QNQVKERNEDYKEITQKLSFPMGR------NVFSHDYVFWCGDFNYRIDLT-YEEVFYFIKRQDWKKLLEFDQLQLQKSS 234
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 460 KKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILW----------------------RGTNVNQ------L 511
Cdd:cd09099 235 GKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWwrkkwpfektageinlldsdldFDTKIRHtwtpgaL 314
                       330       340
                ....*....|....*....|..
gi 13325070 512 NYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09099 315 MYYGRAELQASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
241-533 6.31e-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: 6.31e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 241 RFFVGTWNVNGQSP-------DSGLEPWLNCDP-------------NPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 299
Cdd:cd09098   2 RVCVGTWNVNGGKQfrsiafkNQTLTDWLLDAPkkagipefqdvrsKPVDIFAIGFEEMvELNAGNIVSASTTNQKLWAA 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 300 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 379
Cdd:cd09098  82 ELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 380 VEDFERRNQDYKDICARMSFvvPNQTLpqlnIMKHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQRLLKFDQLNIQRTQ 459
Cdd:cd09098 162 QSQVKERNEDFIEIARKLSF--PMGRM----LFSHDYVFWCGDFNYRIDIPN-EEVKELIRQQNWDSLIAGDQLINQKNA 234
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 460 KKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------------GTNVNQ----------L 511
Cdd:cd09098 235 GQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpfdrsaedldllnaSFPDNSkeqytwspgtL 314
                       330       340
                ....*....|....*....|..
gi 13325070 512 NYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09098 315 LHYGRAELKTSDHRPVVALIDI 336
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
223-540 2.23e-63

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 221.20  E-value: 2.23e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 223 IKHILAKREKEYVNIQTFRFFVGTWNVNGQSPDSGLEPWL---NCDPNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 297
Cdd:COG5411  13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 298 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 374
Cdd:COG5411  93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 375 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHEVVIWLGDLNYRLCMPDANEVKSLINKKD-LQRLLKFDQL 453
Cdd:COG5411 173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDDGrLDKLFEYDQL 246
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 454 NIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:COG5411 247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326

                ....*..
gi 13325070 534 GVKVVDE 540
Cdd:COG5411 327 KIKVVDP 333
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
11-115 1.06e-60

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: 201.20  E-value: 1.06e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  11 PLATVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDW 90
Cdd:cd13382   1 CIATVRGHEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDR 80
                        90       100
                ....*....|....*....|....*
gi 13325070  91 IRERRFEIPDEEHCLKFLSAVLAAQ 115
Cdd:cd13382  81 TPERLFEIPDEEHCLSFLSHVLAAQ 105
PH_OCRL-like cd13320
oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has ...
11-115 6.95e-58

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: 193.11  E-value: 6.95e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  11 PLATVEGMEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDW 90
Cdd:cd13320   1 CVAAVQGVLCKGGSREPRLLSLAQRRGQYALIIQSHEREASLQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRLQGDE 80
                        90       100
                ....*....|....*....|....*
gi 13325070  91 IRERRFEIPDEEHCLKFLSAVLAAQ 115
Cdd:cd13320  81 TLERLFEIPDEEHCLTFLSEVLAAQ 105
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
18-118 4.89e-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: 187.99  E-value: 4.89e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    18 MEMKGPLREPCALTLAQRNGQYELIIQLHEKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRVQGDWIRERRFE 97
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80
                          90       100
                  ....*....|....*....|.
gi 13325070    98 IPDEEHCLKFLSAVLAAQKAQ 118
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
243-533 1.10e-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: 1.10e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 243 FVGTWNVNGQSPDSGLEPWLNC-----------DPNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLH--SKA 309
Cdd:cd09091   4 FIGTWNMGSAPPPKNITSWFTSkgqgktrddvaDYIPHDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 310 KYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 389
Cdd:cd09091  73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 390 YKDICARMSfvVPNQTLPQLNI-MKHEVVIWLGDLNYRLCMPDaNEVKSLINKKDLQR---LLKFDQLNIQRTQKKAFVD 465
Cdd:cd09091 153 YLNILRFLS--LGDKKLSAFNItHRFTHLFWLGDLNYRLDLPI-QEAENIIQKIEQQQfepLLRHDQLNLEREEHKVFLR 229
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070 466 FNEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09091 230 FSEEEITFPPTYRYERGSrDTYaytkqKATGvKYNLPSWCDRILWKSypeTHIICQSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
243-533 3.29e-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: 3.29e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 243 FVGTWNVNGQSPDSGLEPWLNC-----------DPNPPDIYCIGFQELDLSteaffyfesvkEQEWSMAVERGLH--SKA 309
Cdd:cd09100   4 FIGTWNMGNAPPPKKITSWFQCkgqgktrddtaDYIPHDIYVIGTQEDPLG-----------EKEWLDTLKHSLReiTSI 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 310 KYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 389
Cdd:cd09100  73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 390 YKDIcarMSF-VVPNQTLPQLNIM-KHEVVIWLGDLNYRLCMP--DANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVD 465
Cdd:cd09100 153 YFNI---LRFlVLGDKKLSPFNIThRFTHLFWLGDLNYRVELPntEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQ 229
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070 466 FNEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09100 230 FEEEEITFAPTYRFERGTrERYaytkqKATGmKYNLPSWCDRVLWKSyplVHVVCQSYGCTDDITTSDHSPVFATFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
243-533 7.80e-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: 7.80e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 243 FVGTWNVNGQSPDSGLEPWLNCD-----------PNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGL--HSKA 309
Cdd:cd09101   4 FIGTWNMGSVPPPKSLASWLTSRglgktldettvTIPHDIYVFGTQE-----------NSVGDREWVDFLRASLkeLTDI 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 310 KYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 389
Cdd:cd09101  73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 390 YKDICARMSfvVPNQTLPQLNI-MKHEVVIWLGDLNYRLCMpDANEVKSLINKKDLQRLLKFDQLNIQRTQKKAFVDFNE 468
Cdd:cd09101 153 YLDILRSLS--LGDKQLNAFDIsLRFTHLFWFGDLNYRLDM-DIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFRE 229
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13325070 469 GEIKFIPTYKYDSKT------DRWDSSG-KCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALFHI 533
Cdd:cd09101 230 EEISFPPTYRYERGSrdtymwQKQKTTGmRTNVPSWCDRILWKSypeTHIVCNSYGCTDDIVTSDHSPVFGTFEV 304
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
294-545 1.33e-50

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 188.96  E-value: 1.33e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  294 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 373
Cdd:PLN03191 347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  374 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHEVVIWLGDLNYRLCMPDAnEVKSLINKKDLQRLLKF 450
Cdd:PLN03191 427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070  451 DQLNIQRTQKKAFVDFNEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLNYRsHMELKTSDHK 525
Cdd:PLN03191 505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583
                        250       260
                 ....*....|....*....|
gi 13325070  526 PVSALFHIGVKVVDERRYRK 545
Cdd:PLN03191 584 PVSSMFLVEVEVFDHRKLQR 603
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
238-531 8.43e-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: 8.43e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 238 QTFRFFVGTWNVNGQS--PDSGLEPWLNCDPN-PPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLhsKAKYKKV 314
Cdd:cd09095   3 RNVGIFVATWNMQGQKelPENLDDFLLPTSADfAQDIYVIGVQE-----------GCSDRREWEIRLQETL--GPSHVLL 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 315 QLVRLVGMMLLIFARKDQCRYIRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIc 394
Cdd:cd09095  70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKI- 148
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 395 armsfvVPNQTLPQ---LNIMKHE---------VVIWLGDLNYRLCMPdANEVKSLINKK---DLQRLLKFDQLNIQRTQ 459
Cdd:cd09095 149 ------IQALNLPRnvpTNPYKSEsgdvttrfdEVFWFGDFNFRLSGP-RHLVDALINQGqevDVSALLQHDQLTREMSK 221
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13325070 460 KKAFVDFNEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRG---TNVNQLNYRSHMELKTSDHKPVSALF 531
Cdd:cd09095 222 GSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSrqkGDVCCLKYNSCPSIKTSDHRPVFALF 296
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
725-886 6.15e-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: 6.15e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    725 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 801
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070    802 RCLDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMAR-QTPS 874
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASlKDIR 161
                          170
                   ....*....|..
gi 13325070    875 DRQRAIQFLLGF 886
Cdd:smart00324 162 HQNTVIEFLIEN 173
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
727-865 3.74e-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: 3.74e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070   727 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 803
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070   804 LDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 865
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
727-884 3.44e-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: 105.85  E-value: 3.44e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 727 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 804
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDrgEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 805 DSAYDPRI------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSDRQ- 877
Cdd:cd00159  81 ELAKIEDEeerieaLKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKKLn 160

                ....*..
gi 13325070 878 RAIQFLL 884
Cdd:cd00159 161 EIVEFLI 167
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
713-856 2.13e-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: 2.13e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 713 VPLDE----GASERplQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETI--PGSNHSVAEALLIF 786
Cdd:cd04393   5 VPLQElqqaGQPEN--GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLskEADVCSAASLLRLF 82
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 13325070 787 LEALPEPVICYELYQRCLDSAYDPRI-------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLF 856
Cdd:cd04393  83 LQELPEGLIPASLQIRLMQLYQDYNGedefgrkLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVF 159
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
713-864 4.41e-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: 72.10  E-value: 4.41e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 713 VPLDE--GASERPLQVPKEiwLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSN--HSVAEALLIF 786
Cdd:cd04386   7 TPLEEhlKRTGREIALPIE--ACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDagTFSLPLDEFYSdpHAVASALKSY 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 787 LEALPEPVICYELYQRCLDSAYDP------RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLL 860
Cdd:cd04386  85 LRELPDPLLTYNLYEDWVQAANKPdederlQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNL 164

                ....
gi 13325070 861 LRPP 864
Cdd:cd04386 165 LWAK 168
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
775-865 7.86e-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: 7.86e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 775 SNHSVAEALLIFLEALPEPVICYELY----------QRCLDSAYDPRIC----------RQVISQLPRCHRNVFRYLMAF 834
Cdd:cd04378  67 SPHDISSVLKLFLRQLPEPLILFRLYndfialakeiQRDTEEDKAPNTPievnriirklKDLLRQLPASNYNTLQHLIAH 146
                        90       100       110
                ....*....|....*....|....*....|.
gi 13325070 835 LRELLKFSEYNSVNANMIATLFTSLLLRPPP 865
Cdd:cd04378 147 LYRVAEQFEENKMSPNNLGIVFGPTLIRPRP 177
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
744-864 5.65e-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: 5.65e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 744 QEDLFQTPGMQEELQQIIDCLD-----TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSA----YDPRI-- 812
Cdd:cd04372  34 SEGLYRVSGFAEEIEDVKMAFDrdgekADISATVYPDINVITGALKLYFRDLPIPVITYDTYPKFIDAAkisnPDERLea 113
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 13325070 813 CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPP 864
Cdd:cd04372 114 VHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPP 165
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
724-862 7.29e-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: 7.29e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 724 LQVPKEIWLLVDHLFKYACHQ-EDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNHSVAEALLIFLEALPEPVICYELYQ 801
Cdd:cd04389  19 LKLPWILTFLSEKVLALGGFQtEGIFRVPGDIDEVNELKLRVDQwDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQ 98
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 13325070 802 RCLDSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFS--EYNSVNANMIATLFTSLLLR 862
Cdd:cd04389  99 QCISASEDPDKAVEIVQKLPIINRLVLCYLINFLQVFAQPEnvAHTKMDVSNLAMVFAPNILR 161
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
777-868 1.15e-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: 1.15e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELYQRC-----LDSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANM 851
Cdd:cd04404  76 HLPAVILKTFLRELPEPLLTFDLYDDIvgflnVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSN 155
                        90
                ....*....|....*..
gi 13325070 852 IATLFTSLLLRPPPNLM 868
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 ...
723-873 3.11e-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: 57.84  E-value: 3.11e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 723 PLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN--HSVAEALLIFLEALPEPVICYELY 800
Cdd:cd04390  19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQY 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 801 QRCLDSAYDPRICRQV--------ISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRP----PPNLM 868
Cdd:cd04390  99 EDFLSCAQLLSKDEEKglgelmkqVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILRPkvedPATIM 178

                ....*
gi 13325070 869 ARQTP 873
Cdd:cd04390 179 EGTPQ 183
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
244-527 4.34e-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: 4.34e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 244 VGTWNVNGQSPDSGLEPWL----NCDPnppDIYCIgfQELDLSTeAFFYFESVKEQEWSMAVERGLHSKAKYkkvqlvrl 319
Cdd:cd08372   1 VASYNVNGLNAATRASGIArwvrELDP---DIVCL--QEVKDSQ-YSAVALNQLLPEGYHQYQSGPSRKEGY-------- 66
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 320 VGMMLLIFARKdqcryiRDIATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAhvedfERRNQDYKdicarmsf 399
Cdd:cd08372  67 EGVAILSKTPK------FKIVEKHQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQA-----GGTRADVR-------- 127
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 400 vvPNQTLPQLNIMK------HEVVIWLGDLNYRlcmpdanevKSLInkkDLQRLLKFDQLNIQRtqkkAFVDFNEgEIKF 473
Cdd:cd08372 128 --DAQLKEVLEFLKrlrqpnSAPVVICGDFNVR---------PSEV---DSENPSSMLRLFVAL----NLVDSFE-TLPH 188
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13325070 474 IPTYKYDSKtdrwdssgkcRVPAWCDRILWRGT---NV--NQLNYRSHMELKTSDHKPV 527
Cdd:cd08372 189 AYTFDTYMH----------NVKSRLDYIFVSKSllpSVksSKILSDAARARIPSDHYPI 237
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
775-865 4.76e-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: 4.76e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 775 SNHSVAEALLIFLEALPEPVICYELYQRCL--------DSAYDP----------RICRQVISQLPRCHRNVFRYLMAFLR 836
Cdd:cd04408  67 SPHDITSVLKHFLKELPEPVLPFQLYDDFIalakelqrDSEKAAespsiveniiRSLKELLGRLPVSNYNTLRHLMAHLY 146
                        90       100
                ....*....|....*....|....*....
gi 13325070 837 ELLKFSEYNSVNANMIATLFTSLLLRPPP 865
Cdd:cd04408 147 RVAERFEDNKMSPNNLGIVFGPTLLRPLV 175
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
724-881 6.32e-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: 57.07  E-value: 6.32e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 724 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI---IDC-LDTSIPETIpgSNHSVAEALLIFLEALPEPVICYEL 799
Cdd:cd04376   7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLreeFDRgIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPREL 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 800 YQRCLDSA---YDPRI--CRQVISQLPRCHRNVFRYLMAFLRELLKFSEY-----------NSVNANMIATLFTslllrp 863
Cdd:cd04376  85 YTAFIGTAllePDEQLeaLQLLIYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFG------ 158
                       170
                ....*....|....*...
gi 13325070 864 pPNLMARQTPSDRQRAIQ 881
Cdd:cd04376 159 -PNLLHKQKSGEREFVQA 175
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
728-866 4.84e-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: 4.84e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 728 KEIWLLVDHLFKYAC----HQEDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNH---SVAEALLIFLEALPEPVICYEL 799
Cdd:cd04383  16 QAIPLVVESCIRFINlyglQHQGIFRVSGSQVEVNDIKNAFERgEDPLADDQNDHdinSVAGVLKLYFRGLENPLFPKER 95
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13325070 800 YQRCLDSA-------YDPRIcRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPN 866
Cdd:cd04383  96 FEDLMSCVklenpteRVHQI-REILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEG 168
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
351-533 1.18e-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: 1.18e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 351 KMGNKGGVAVRFVFHNTTFCIVNSHL---AAHVEDFERRNQDYKDICAR-MSFV---VPNQTLPQLNImkhevvIWLGDL 423
Cdd:cd09092 151 KWSRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRaLGYVlerLTDERFEKVPF------FVFGDF 224
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 424 NYR---------LCM---------PDANEVKSLINKKD------LQRLLK-----FDQLNIQRTQKKAFVDFN------- 467
Cdd:cd09092 225 NFRldtksvvetLCAkatmqtvrkADSNIVVKLEFREKdndnkvVLQIEKkkfdyFNQDVFRDNNGKALLKFDkelevfk 304
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 468 ----EGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWrGTNVNQLN---------YRS-HMELKTSDHKPVSALFHI 533
Cdd:cd09092 305 dvlyELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILM-SHSARELKseneeksvtYDMiGPNVCMGDHKPVFLTFRI 383
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
713-875 1.48e-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: 1.48e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 713 VPLDEGASERPlQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGSN---HSVAEALLIFLEA 789
Cdd:cd04377   3 VSLSSLTSEDR-SVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTD-PDSVNLEDypiHVITSVLKQWLRE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 790 LPEPVICYELYQRCLDSAYDP----RIC--RQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRP 863
Cdd:cd04377  81 LPEPLMTFELYENFLRAMELEekqeRVRalYSVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRC 160
                       170
                ....*....|..
gi 13325070 864 PPNLMARQTPSD 875
Cdd:cd04377 161 PDTADPLQSLQD 172
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
726-884 1.55e-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: 52.69  E-value: 1.55e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 726 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSI-PETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 804
Cdd:cd04402  15 LPKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVeVDLKAEPVLLLASVLKDFLRNIPGSLLSSDLYEEWM 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 805 DSAYDPRI------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANmiatlftSLLLRPPPNLMARQTPSDRQR 878
Cdd:cd04402  95 SALDQENEeekiaeLQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAF-------NLAVCIAPSLLWPPASSELQN 167
                       170
                ....*....|....
gi 13325070 879 A--------IQFLL 884
Cdd:cd04402 168 EdlkkvtslVQFLI 181
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
713-884 4.52e-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: 4.52e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 713 VPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-----HSVAEALLI 785
Cdd:cd04398   3 VPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKdpLNVLLISPEDyesdiHSVASLLKL 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 786 FLEALPEPVICYELYQRCLDSAY--DPRICR----QVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSL 859
Cdd:cd04398  83 FFRELPEPLLTKALSREFIEAAKieDESRRRdalhGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAIIWGPT 162
                       170       180
                ....*....|....*....|....*...
gi 13325070 860 LLR-PPPNL--MARQTpsdrqRAIQFLL 884
Cdd:cd04398 163 LMNaAPDNAadMSFQS-----RVIETLL 185
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
713-863 5.76e-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: 5.76e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 713 VPL-DEGASERPlqVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI-----------IDCLDTSIpetipgsnHSVA 780
Cdd:cd04373   3 VPLaNVVTSEKP--IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLqkqfdqdhnldLVSKDFTV--------NAVA 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 781 EALLIFLEALPEPVICYELYQRCLDSAYDP-RICR-----QVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIAT 854
Cdd:cd04373  73 GALKSFFSELPDPLIPYSMHLELVEAAKINdREQRlhalkELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSI 152

                ....*....
gi 13325070 855 LFTSLLLRP 863
Cdd:cd04373 153 CFWPTLMRP 161
RhoGAP_myosin_IXA cd04406
RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
726-875 2.78e-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: 2.78e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 726 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPET-IPGSN-HSVAEALLIFLEALPEPVICYELYQRC 803
Cdd:cd04406  15 VPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVnLDDYNiHVIASVFKQWLRDLPNPLMTFELYEEF 94
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070 804 L------DSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPNLMARQTPSD 875
Cdd:cd04406  95 LramglqERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVFAPCILRCPDTTDPLQSVQD 172
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
726-866 3.10e-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: 3.10e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 726 VPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIPGSN---HSVAEALLIFLEALPEPVICYELYQR 802
Cdd:cd04407  15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQAD-PENVKLENypiHAITGLLKQWLRELPEPLMTFAQYND 93
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 803 CLDSAYDPRICRQ------VISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPPN 866
Cdd:cd04407  94 FLRAVELPEKQEQlqaiyrVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCPDS 163
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
777-865 1.02e-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: 1.02e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELYQRCLDS-AYDP-----RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 850
Cdd:cd04384  73 HSVSSLCKLYFRELPNPLLTYQLYEKFSEAvSAASdeerlEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAK 152
                        90
                ....*....|....*
gi 13325070 851 MIATLFTSLLLRPPP 865
Cdd:cd04384 153 NLAIVWAPNLLRSKQ 167
RhoGAP_PARG1 cd04409
RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
775-865 3.06e-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: 3.06e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 775 SNHSVAEALLIFLEALPEPVICYELYQRCLDSAYD------------------PRIC----------RQVISQLPRCHRN 826
Cdd:cd04409  67 SPHDISNVLKLYLRQLPEPLILFRLYNEFIGLAKEsqhvnetqeakknsdkkwPNMCtelnrillksKDLLRQLPAPNYN 146
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 13325070 827 VFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 865
Cdd:cd04409 147 TLQFLIVHLHRVSEQAEENKMSASNLGIIFGPTLIRPRP 185
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
725-887 3.34e-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: 3.34e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 725 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN----HSVAEALLIFLEALPEPVICYELY 800
Cdd:cd04387  15 KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSemdvNAIAGTLKLYFRELPEPLFTDELY 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 801 QRCL------DSAYDPRICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRP-------PPNL 867
Cdd:cd04387  95 PNFAegialsDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPsekeskiPTNT 174
                       170       180
                ....*....|....*....|
gi 13325070 868 MARQTPSDRQRAIQFLLGFL 887
Cdd:cd04387 175 MTDSWSLEVMSQVQVLLYFL 194
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
777-868 3.41e-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: 3.41e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELY---QRCLDSAYDPR----ICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNA 849
Cdd:cd04400  79 HTVAGLLKLYLRELPTLILGGELHndfKRLVEENHDRSqralELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNL 158
                        90
                ....*....|....*....
gi 13325070 850 NMIATLFTSLLLRPPPNLM 868
Cdd:cd04400 159 RNVCIVFSPTLNIPAGIFV 177
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
749-865 5.08e-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: 5.08e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 749 QTPGMQEELQQIIDClDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAYDP---RICRQVISQLPRC-- 823
Cdd:cd04388  40 QSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAPVYSEMISRAQEVqssDEYAQLLRKLIRSpn 118
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 13325070 824 ---HRNV-FRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLRPPP 865
Cdd:cd04388 119 lphQYWLtLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_ARAP cd04385
RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
777-863 7.58e-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: 44.61  E-value: 7.58e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELYQRCLDSAYDPRIC------RQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 850
Cdd:cd04385  70 HDVADVLKRFLRDLPDPLLTSELHAEWIEAAELENKDeriaryKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVH 149
                        90
                ....*....|...
gi 13325070 851 MIATLFTSLLLRP 863
Cdd:cd04385 150 NLALVFGPTLFQT 162
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
777-869 1.40e-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: 1.40e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELYQRCLDS--AYDP----RICRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 850
Cdd:cd04395  74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEAnrIEDPverlKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153
                        90
                ....*....|....*....
gi 13325070 851 MIATLFTSLLLRPPPNLMA 869
Cdd:cd04395 154 NLAIVFGPTLVRTSDDNME 172
RhoGAP_SYD1 cd04379
RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
769-863 3.04e-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: 3.04e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 769 PETIPGSNhSVAEALLIFLEALPEPVICYELYQRCLDSAY-----DP----RICRQVISQLPRCHRNVFRYLMAFLRELL 839
Cdd:cd04379  67 EELYPDIN-VITGVLKDYLRELPEPLITPQLYEMVLEALAvalpnDVqtntHLTLSIIDCLPLSAKATLLLLLDHLSLVL 145
                        90       100
                ....*....|....*....|....
gi 13325070 840 KFSEYNSVNANMIATLFTSLLLRP 863
Cdd:cd04379 146 SNSERNKMTPQNLAVCFGPVLMFC 169
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
777-863 3.50e-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: 3.50e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELYQ--RCLDSAYDPRIC----RQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNAN 850
Cdd:cd04403  71 HVITGALKLFFRELPEPLFPYSLFNdfVAAIKLSDYEQRvsavKDLIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQ 150
                        90
                ....*....|...
gi 13325070 851 MIATLFTSLLLRP 863
Cdd:cd04403 151 NLAIVFGPTLLRP 163
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
733-878 3.60e-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: 3.60e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 733 LVDHLfkyacHQEDLFQTPG---MQEELQQIID----CLDTSIPEtipgsnhSVAEALLIFLEALPEPVICYELYQRCLD 805
Cdd:cd04394  31 LLDHL-----STEGLFRKSGsvvRQKELKAKLEggeaCLSSALPC-------DVAGLLKQFFRELPEPLLPYDLHEALLK 98
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13325070 806 SAYDP----RICRQVISQ--LPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATLFTSLLLrPPPNLMARQTPSDRQR 878
Cdd:cd04394  99 AQELPtdeeRKSATLLLTclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLF-QSEEGGEKMSSSTEKR 176
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
724-866 4.18e-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: 4.18e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 724 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPE-TIPGSNHSVAEA---LLIFLEALPEPVICYEL 799
Cdd:cd04391  20 SKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEgTFLWDQVKQHDAaslLKLFIRELPQPLLTVEY 99
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070 800 YQRCLDSAYDPRICRQV------ISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIAT-----LFTSLLLRPPPN 866
Cdd:cd04391 100 LPAFYSVQGLPSKKDQLqalnllVLLLPEANRDTLKALLEFLQKVVDHEEKNKMNLWNVAMimapnLFPPRGKHSKDN 177
RhoGAP_fLRG1 cd04397
RhoGAP_fLRG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
716-866 6.52e-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: 6.52e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 716 DEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSiPETIP--GSNHSVAEALLI--FLEALP 791
Cdd:cd04397  17 TLGVGPGKLRIPALIDDIISAMRQMDMSVEGVFRKNGNIRRLKELTEEIDKN-PTEVPdlSKENPVQLAALLkkFLRELP 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 792 EPVICYELYQRCLDSAY--DPRICRQVI----SQLPRCHRNVFRYLMAFLRELLKFSEY-----NSVNANMIATLFTSLL 860
Cdd:cd04397  96 DPLLTFKLYRLWISSQKieDEEERKRVLhlvyCLLPKYHRDTMEVLFSFLKWVSSFSHIdeetgSKMDIHNLATVITPNI 175

                ....*.
gi 13325070 861 LRPPPN 866
Cdd:cd04397 176 LYSKTD 181
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
743-886 3.91e-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: 3.91e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 743 HQEDLFQTPGMQEELQQIIDCLDTSipETIPGSN----HSVAEALLIFLEALPEPVICYELYQRCLDSA--YDPRICR-- 814
Cdd:cd04382  34 TEEGLYRVSGSEREVKALKEKFLRG--KTVPNLSkvdiHVICGCLKDFLRSLKEPLITFALWKEFMEAAeiLDEDNSRaa 111
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13325070 815 --QVISQLPRCHRNVFRYLMAFLRELLKfSEYNSVNANMIA-----TLFTSLLLRPPPNLMARQTPsDRQRAIQFLLGF 886
Cdd:cd04382 112 lyQAISELPQPNRDTLAFLILHLQRVAQ-SPECKMDINNLArvfgpTIVGYSVPNPDPMTILQDTV-RQPRVVERLLEI 188
RhoGap_RalBP1 cd04381
RhoGap_RalBP1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
713-855 4.84e-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: 4.84e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 713 VPLDEgASERP-----LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD----TSIPETIPgsnHSVAEAL 783
Cdd:cd04381   3 ASLSL-AVERSrchdgIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNrresPNLEEYEP---PTVASLL 78
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13325070 784 LIFLEALPEPVICYELYQRCLDSAYDPRI------CRQVISQLPRCHRNVFRYLMAFLRELLKFSEYNSVNANMIATL 855
Cdd:cd04381  79 KQYLRELPEPLLTKELMPRFEEACGRPTEaereqeLQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNISIV 156
RhoGAP_fSAC7_BAG7 cd04396
RhoGAP_fSAC7_BAG7: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
777-884 7.33e-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: 7.33e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13325070 777 HSVAEALLIFLEALPEPVICYELY---------------------QRCLDSAYDPRI--CRQVISQLPRCHRNVFRYLMA 833
Cdd:cd04396  88 HDAASVLRRYLNNLPEPLVPLDLYeefrnplrkrprilqymkgriNEPLNTDIDQAIkeYRDLITRLPNLNRQLLLYLLD 167
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 13325070 834 FLRELLKFSEYNSVNANMIATLFT-SLLLRPPPNLMARQTPSDRQrAIQFLL 884
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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