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Conserved domains on  [gi|1475928938|ref|NP_001352749|]
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type II inositol 1,4,5-trisphosphate 5-phosphatase isoform 1 precursor [Homo sapiens]

Protein Classification

INPP5c_INPP5B and RhoGAP_OCRL1 domain-containing protein( domain architecture ID 11245537)

protein containing domains PH_OCRL2, INPP5c_INPP5B, and RhoGAP_OCRL1

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 ...
 265-558 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: 583.51  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 265 FRFFAGTYNVNGQSPKECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRL 344
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 345 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQF 424
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 425 CQPDPslPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKY 504
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1475928938 505 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 692-912 1.46e-86

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: 275.76  E-value: 1.46e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 692 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPLETIseltlmpvWTGDDGSQLDSPMEIPKELWMMVDYLYRNAVQQEDLF 771
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQL--------ELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 772 QQPGLRSE----FEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC-SGNYTASKQVIS-TLPI 845
Cdd:cd04380    73 EEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLPP 152

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 846 FHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQ-KLDMTEKKKAQEFIHQFLCNP 912
Cdd:cd04380   153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLLND 220
INPP5B_PH pfam16776
Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;
1-146 2.83e-71

Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;


:

Pssm-ID: 465268  Cd Length: 142  Bit Score: 231.44  E-value: 2.83e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938   1 MDQSVAIQETLAEGEYCVIAVQGVLCEGDSRQSRLLGLVRYrlehgGQEHALFLYTHRRMAITGDDVSLDQIVPVSRDFT 80
Cdd:pfam16776   1 MDQSAAIQETLAEGENCLAAVQGVLIQGDSTQSRLLGLVES-----NNEHALFLYTHRRMAITGEDLSLEDVVPIDEDFK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938  81 LEEVSPDGELYILGSDVTVQLDTAELSLVFQLPFGSQTRMFLHEVARACPG-FDSATRDPEFLWLSR 146
Cdd:pfam16776  76 CEEVSSPAELDVIGSDTTVRLSSRERELELELPFGSHTRLFLSEVNRAWSGvALKASPPPDFLWLSK 142
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 265-558 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: 583.51  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 265 FRFFAGTYNVNGQSPKECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRL 344
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 345 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQF 424
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 425 CQPDPslPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKY 504
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1475928938 505 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 263-560 2.20e-109

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 339.33  E-value: 2.20e-109
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  263 QNFRFFAGTYNVNGQS-PKECLRLWLSNGIQA-----PDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSEGLHPDAK 335
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQKIEVkqsekPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  336 YAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDY 415
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  416 KDICSRMQFcqpdPSLPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGE 495
Cdd:smart00128 161 KTILRALSF----PERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938  496 LTFQPTYKYDT-GSDDWDTSEKCRAPAWCDRILWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 560
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 692-912 1.46e-86

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: 275.76  E-value: 1.46e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 692 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPLETIseltlmpvWTGDDGSQLDSPMEIPKELWMMVDYLYRNAVQQEDLF 771
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQL--------ELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 772 QQPGLRSE----FEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC-SGNYTASKQVIS-TLPI 845
Cdd:cd04380    73 EEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLPP 152

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 846 FHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQ-KLDMTEKKKAQEFIHQFLCNP 912
Cdd:cd04380   153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLLND 220
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
252-566 1.42e-71

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 243.92  E-value: 1.42e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 252 LLQKEEDYTYIQNFRFFAGTYNVNGQSPKECLRLWLSNGIQA---PDVYCVGFQE-LDLSKEAFFFHDT-PKEEEWF-KA 325
Cdd:COG5411    17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEAtelADLYVVGLQEvVELTPGSILSADPyDRLRIWEsKV 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 326 VSE--GLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 403
Cdd:COG5411    97 LDClnGAQSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAA 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 404 HIEEYERRNQDYKDICSRMQFCQPdpslppLTISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKD--FQMLYAYDQLKIQ 481
Cdd:COG5411   177 GVNNIEERIFDYRSIASNICFSRG------LRIYDHDTIFWLGDLNYRVT-STNEEVRPEIASDDgrLDKLFEYDQLLWE 249

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 482 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVR 561
Cdd:COG5411   250 MEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIK 329


                  ....*
gi 1475928938 562 VVNDE 566
Cdd:COG5411   330 VVDPS 334
INPP5B_PH pfam16776
Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;
1-146 2.83e-71

Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;


Pssm-ID: 465268  Cd Length: 142  Bit Score: 231.44  E-value: 2.83e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938   1 MDQSVAIQETLAEGEYCVIAVQGVLCEGDSRQSRLLGLVRYrlehgGQEHALFLYTHRRMAITGDDVSLDQIVPVSRDFT 80
Cdd:pfam16776   1 MDQSAAIQETLAEGENCLAAVQGVLIQGDSTQSRLLGLVES-----NNEHALFLYTHRRMAITGEDLSLEDVVPIDEDFK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938  81 LEEVSPDGELYILGSDVTVQLDTAELSLVFQLPFGSQTRMFLHEVARACPG-FDSATRDPEFLWLSR 146
Cdd:pfam16776  76 CEEVSSPAELDVIGSDTTVRLSSRERELELELPFGSHTRLFLSEVNRAWSGvALKASPPPDFLWLSK 142
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 313-572 1.87e-56

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 205.91  E-value: 1.87e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 313 FHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNT 392
Cdd:PLN03191  341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 393 SICVVNSHLAA-HIEEYE-RRNQDYKDICSRMQFCQPDPSLPPLTISNHDVILWLGDLNYRIEELDVEkVKKLIEEKDFQ 470
Cdd:PLN03191  421 RLCFVCSHLTSgHKDGAEqRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWD 499

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 471 MLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRILWKGKNITQLSYQsHMALK 545
Cdd:PLN03191  500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578

                         250       260
                  ....*....|....*....|....*..
gi 1475928938 546 TSDHKPVSSVFDIGVRVVNDELYRKTL 572
Cdd:PLN03191  579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
PH_OCRL2 cd13383
oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called ...
 17-129 5.57e-51

oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called IPNNB5, inositol polyphosphate-5-phosphatase, phosphoinositide 5-phosphatase, 5PTase, or type II inositol-1,4,5-trisphosphate 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. OCRL2 contains 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: 270183  Cd Length: 108  Bit Score: 174.32  E-value: 5.57e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  17 CVIAVQGVLCEGDSRQSRLLGLVRYRlehggQEHALFLYTHRRMAITGDDVSLDQIVPVSRDFTLEEVSPDGELYILGSD 96
Cdd:cd13383     1 CEIAVQGSLIQGWSKASRLLGLVNKR-----TTHALVIYTHRRMAITYSDVTLERILPIDQDFKCEEVTDDSDLQQDGSD 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1475928938  97 VTVQLDTAELSLVFQLPFGSQTRMFLHEVARAC 129
Cdd:cd13383    76 VTVNVTSAKLHLVFEMRPGSVTSSLVSEIFRAI 108
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 748-912 4.85e-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: 148.57  E-value: 4.85e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  748 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNL---SASNHSVAEALLLFLESLPEPVICYSTYH 824
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLdlsEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  825 NCLECSGN------YTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKlDMTEK 898
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SLKDI 160

                          170
                   ....*....|....
gi 1475928938  899 KKAQEFIHQFLCNP 912
Cdd:smart00324 161 RHQNTVIEFLIENA 174
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 750-888 5.35e-34

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 127.28  E-value: 5.35e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 750 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG---MIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNC 826
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 827 LEC------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 888
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 ...
 265-558 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: 583.51  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 265 FRFFAGTYNVNGQSPKECLRLWLSNGIQAPDVYCVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRL 344
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 345 VGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQF 424
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 425 CQPDPslPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKY 504
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1475928938 505 DTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 265-558 2.38e-140

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: 419.43  E-value: 2.38e-140
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 265 FRFFAGTYNVNGQ-SPKECLRLWLS-NGIQAPDVYCVGFQELDLSKEAFF-FHDTPKEEEWFKAVSEGLHPDAKYAKVKL 341
Cdd:cd09074     1 VKIFVVTWNVGGGiSPPENLENWLSpKGTEAPDIYAVGVQEVDMSVQGFVgNDDSAKAREWVDNIQEALNEKENYVLLGS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 342 IRLVGIMLLLYVKQEHAAYIS--EVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDIC 419
Cdd:cd09074    81 AQLVGIFLFVFVKKEHLPQIKdlEVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 420 SRMQFCQPDPslPPLTISNHDVILWLGDLNYRIEELDVEkVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQ 499
Cdd:cd09074   161 SKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDSTDDE-VRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1475928938 500 PTYKYDTGSDDWDTSEKCRAPAWCDRILWK---GKNITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09074   238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 263-560 2.20e-109

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 339.33  E-value: 2.20e-109
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  263 QNFRFFAGTYNVNGQS-PKECLRLWLSNGIQA-----PDVYCVGFQELDLSKE-AFFFHDTPKEEEWFKAVSEGLHPDAK 335
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQKIEVkqsekPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  336 YAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDY 415
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  416 KDICSRMQFcqpdPSLPPLTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGE 495
Cdd:smart00128 161 KTILRALSF----PERALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938  496 LTFQPTYKYDT-GSDDWDTSEKCRAPAWCDRILWK--GKNITQLS-YQSHMALKTSDHKPVSSVFDIGV 560
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKV 305
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 266-556 1.14e-96

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: 305.03  E-value: 1.14e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 266 RFFAGTYNVNGQSPKECLRLWL--SNGIQAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWFKAVSEGL--HPDAKYAKVK 340
Cdd:cd09090     2 NIFVGTFNVNGKSYKDDLSSWLfpEENDELPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLngRGGEKYVLLR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 341 LIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICS 420
Cdd:cd09090    82 SEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIAR 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 421 RMQFCQPdpslppLTISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQP 500
Cdd:cd09090   162 GLRFSRG------RTIKDHDHVIWLGDFNYRIS-LTNEDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPP 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1475928938 501 TYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMaLKTSDHKPVSSVF 556
Cdd:cd09090   235 TYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNSAP-LRFSDHRPVYATF 289
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 265-558 1.42e-92

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: 294.66  E-value: 1.42e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 265 FRFFAGTYNVNGQSPKECLR---LWLSNGiQAPDVYCVGFQELDlSKEAFFFHDTPKEEEWFKAVSEGLHPDaKYAKVKL 341
Cdd:cd09094     1 LRVYVVTWNVATAPPPIDVRsllGLQSPE-VAPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDILSPK-GYVKVSS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 342 IRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSR 421
Cdd:cd09094    78 IRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILST 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 422 MQFCQPDPSlpplTISNHDVILWLGDLNYRIEELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGFTEGELTFQPT 501
Cdd:cd09094   158 QVFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPT 233

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 502 YKYDTGSDDWDTSEKCRAPAWCDRILWKGK----------NITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09094   234 YKFDLGTDEYDTSGKKRKPAWTDRILWKVNpdasteekflSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 266-558 1.37e-87

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: 282.36  E-value: 1.37e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 266 RFFAGTYNVNGQS-------PKECLRLWLSNGIQA--------------PDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 323
Cdd:cd09089     2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLLDNPKLagqcsndseedekpVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 324 KAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 403
Cdd:cd09089    82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 404 HIEEYERRNQDYKDICSRMQFcqpdpslpPL--TISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKDFQMLYAYDQLKIQ 481
Cdd:cd09089   162 GQSQVKERNEDFAEIARKLSF--------PMgrTLDSHDYVFWCGDFNYRID-LPNDEVKELVRNGDWLKLLEFDQLTKQ 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 482 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK-------------------NITQLSYQSHM 542
Cdd:cd09089   233 KAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpsdkteeslvetndptwNPGTLLYYGRA 312

                         330
                  ....*....|....*.
gi 1475928938 543 ALKTSDHKPVSSVFDI 558
Cdd:cd09089   313 ELKTSDHRPVVAIIDI 328
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 692-912 1.46e-86

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: 275.76  E-value: 1.46e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 692 FLSVSGNYLPSCFGSPIHTLCYMREPILDLPLETIseltlmpvWTGDDGSQLDSPMEIPKELWMMVDYLYRNAVQQEDLF 771
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQL--------ELGDNPDYSEVPLSIPKEIWRLVDYLYTRGLAQEGLF 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 772 QQPGLRSE----FEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLEC-SGNYTASKQVIS-TLPI 845
Cdd:cd04380    73 EEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAvANNEEDKRQVIRiSLPP 152

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 846 FHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQ-KLDMTEKKKAQEFIHQFLCNP 912
Cdd:cd04380   153 VHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAGgKERRAERDRKRAFIEQFLLND 220
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
252-566 1.42e-71

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 243.92  E-value: 1.42e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 252 LLQKEEDYTYIQNFRFFAGTYNVNGQSPKECLRLWLSNGIQA---PDVYCVGFQE-LDLSKEAFFFHDT-PKEEEWF-KA 325
Cdd:COG5411    17 LRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEAtelADLYVVGLQEvVELTPGSILSADPyDRLRIWEsKV 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 326 VSE--GLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 403
Cdd:COG5411    97 LDClnGAQSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAA 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 404 HIEEYERRNQDYKDICSRMQFCQPdpslppLTISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKD--FQMLYAYDQLKIQ 481
Cdd:COG5411   177 GVNNIEERIFDYRSIASNICFSRG------LRIYDHDTIFWLGDLNYRVT-STNEEVRPEIASDDgrLDKLFEYDQLLWE 249

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 482 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGKNITQLSYQSHMALKTSDHKPVSSVFDIGVR 561
Cdd:COG5411   250 MEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRAKIK 329


                  ....*
gi 1475928938 562 VVNDE 566
Cdd:COG5411   330 VVDPS 334
INPP5B_PH pfam16776
Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;
1-146 2.83e-71

Type II inositol 1,4,5-trisphosphate 5-phosphatase PH domain;


Pssm-ID: 465268  Cd Length: 142  Bit Score: 231.44  E-value: 2.83e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938   1 MDQSVAIQETLAEGEYCVIAVQGVLCEGDSRQSRLLGLVRYrlehgGQEHALFLYTHRRMAITGDDVSLDQIVPVSRDFT 80
Cdd:pfam16776   1 MDQSAAIQETLAEGENCLAAVQGVLIQGDSTQSRLLGLVES-----NNEHALFLYTHRRMAITGEDLSLEDVVPIDEDFK 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938  81 LEEVSPDGELYILGSDVTVQLDTAELSLVFQLPFGSQTRMFLHEVARACPG-FDSATRDPEFLWLSR 146
Cdd:pfam16776  76 CEEVSSPAELDVIGSDTTVRLSSRERELELELPFGSHTRLFLSEVNRAWSGvALKASPPPDFLWLSK 142
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 266-558 2.74e-67

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: 228.00  E-value: 2.74e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 266 RFFAGTYNVNGQSP-------KECLRLWLsngIQAP----------------DVYCVGFQEL-DLSKEAFFFHDTPKEEE 321
Cdd:cd09098     2 RVCVGTWNVNGGKQfrsiafkNQTLTDWL---LDAPkkagipefqdvrskpvDIFAIGFEEMvELNAGNIVSASTTNQKL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 322 WFKAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHL 401
Cdd:cd09098    79 WAAELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 402 AAHIEEYERRNQDYKDICSRMQFcqpdpslpPL--TISNHDVILWLGDLNYRIEeLDVEKVKKLIEEKDFQMLYAYDQLK 479
Cdd:cd09098   159 AAGQSQVKERNEDFIEIARKLSF--------PMgrMLFSHDYVFWCGDFNYRID-IPNEEVKELIRQQNWDSLIAGDQLI 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 480 IQVAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK---------------------------- 531
Cdd:cd09098   230 NQKNAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRkwpfdrsaedldllnasfpdnskeqytw 309

                         330       340
                  ....*....|....*....|....*..
gi 1475928938 532 NITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09098   310 SPGTLLHYGRAELKTSDHRPVVALIDI 336
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 266-558 3.47e-64

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: 219.51  E-value: 3.47e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 266 RFFAGTYNVNGQ--------SPKEcLRLWL-------------SNGIQAPDVYCVGFQEL-DLSKEAFFFHDTPKEEEWF 323
Cdd:cd09099     2 RVAMGTWNVNGGkqfrsnilGTSE-LTDWLldspklsgtpdfqDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 324 KAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAA 403
Cdd:cd09099    81 EQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 404 HIEEYERRNQDYKDICSRMQFcqpdpslpPL--TISNHDVILWLGDLNYRIeELDVEKVKKLIEEKDFQMLYAYDQLKIQ 481
Cdd:cd09099   161 GQNQVKERNEDYKEITQKLSF--------PMgrNVFSHDYVFWCGDFNYRI-DLTYEEVFYFIKRQDWKKLLEFDQLQLQ 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 482 VAAKTVFEGFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK----------------------NITQ---- 535
Cdd:cd09099   232 KSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKkwpfektageinlldsdldfdtKIRHtwtp 311

                         330       340
                  ....*....|....*....|....*
gi 1475928938 536 --LSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09099   312 gaLMYYGRAELQASDHRPVLAIVEV 336
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 313-572 1.87e-56

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 205.91  E-value: 1.87e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 313 FHDTPKEEEWFKAVSEGLHPDAKYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNT 392
Cdd:PLN03191  341 FKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQS 420

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 393 SICVVNSHLAA-HIEEYE-RRNQDYKDICSRMQFCQPDPSLPPLTISNHDVILWLGDLNYRIEELDVEkVKKLIEEKDFQ 470
Cdd:PLN03191  421 RLCFVCSHLTSgHKDGAEqRRNADVYEIIRRTRFSSVLDTDQPQTIPSHDQIFWFGDLNYRLNMLDTE-VRKLVAQKRWD 499

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 471 MLYAYDQLKIQVAAKTVFEGFTEGELTFQPTYKYDTGSDDW-----DTSEKCRAPAWCDRILWKGKNITQLSYQsHMALK 545
Cdd:PLN03191  500 ELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIR 578

                         250       260
                  ....*....|....*....|....*..
gi 1475928938 546 TSDHKPVSSVFDIGVRVVNDELYRKTL 572
Cdd:PLN03191  579 LSDHRPVSSMFLVEVEVFDHRKLQRAL 605
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 263-558 9.94e-54

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: 189.17  E-value: 9.94e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 263 QNFRFFAGTYNVNGQS--PKECLRLWLSNGIQ-APDVYCVGFQEldlskeafffhDTPKEEEWFKAVSEGLHPdaKYAKV 339
Cdd:cd09095     3 RNVGIFVATWNMQGQKelPENLDDFLLPTSADfAQDIYVIGVQE-----------GCSDRREWEIRLQETLGP--SHVLL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 340 KLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDIC 419
Cdd:cd09095    70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKII 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 420 SRMQFCQPDPSLP-------PLTisNHDVILWLGDLNYRIEElDVEKVKKLIE---EKDFQMLYAYDQLKIQVAAKTVFE 489
Cdd:cd09095   150 QALNLPRNVPTNPyksesgdVTT--RFDEVFWFGDFNFRLSG-PRHLVDALINqgqEVDVSALLQHDQLTREMSKGSIFK 226

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1475928938 490 GFTEGELTFQPTYKYDTGSDDWDTSEKCRAPAWCDRILWKGK---NITQLSYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09095   227 GFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRqkgDVCCLKYNSCPSIKTSDHRPVFALFRV 298
PH_OCRL2 cd13383
oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called ...
 17-129 5.57e-51

oculocerebrorenal syndrome of Lowe 2 Pleckstrin homology-like domain; OCRL2 ( also called IPNNB5, inositol polyphosphate-5-phosphatase, phosphoinositide 5-phosphatase, 5PTase, or type II inositol-1,4,5-trisphosphate 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. OCRL2 contains 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: 270183  Cd Length: 108  Bit Score: 174.32  E-value: 5.57e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  17 CVIAVQGVLCEGDSRQSRLLGLVRYRlehggQEHALFLYTHRRMAITGDDVSLDQIVPVSRDFTLEEVSPDGELYILGSD 96
Cdd:cd13383     1 CEIAVQGSLIQGWSKASRLLGLVNKR-----TTHALVIYTHRRMAITYSDVTLERILPIDQDFKCEEVTDDSDLQQDGSD 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1475928938  97 VTVQLDTAELSLVFQLPFGSQTRMFLHEVARAC 129
Cdd:cd13383    76 VTVNVTSAKLHLVFEMRPGSVTSSLVSEIFRAI 108
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 268-558 2.17e-49

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: 177.09  E-value: 2.17e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 268 FAGTYNVNGQSPKECLRLWL-SNGIQAP----------DVYCVGFQELDLSkeafffhdtpkEEEWFKAVSEGLHP--DA 334
Cdd:cd09101     4 FIGTWNMGSVPPPKSLASWLtSRGLGKTldettvtiphDIYVFGTQENSVG-----------DREWVDFLRASLKEltDI 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 335 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQD 414
Cdd:cd09101    73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 415 YKDICSRMQFcqPDPSLPPLTIS---NHdvILWLGDLNYRIeELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFEGF 491
Cdd:cd09101   153 YLDILRSLSL--GDKQLNAFDISlrfTH--LFWFGDLNYRL-DMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRF 227

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 492 TEGELTFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09101   228 REEEISFPPTYRYERGSRDtymWQkqktTGMRTNVPSWCDRILWKSYPETHIvcnSYGCTDDIVTSDHSPVFGTFEV 304
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 268-558 6.36e-49

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: 175.90  E-value: 6.36e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 268 FAGTYNVNGQSPKECLRLWLSNGIQAP-----------DVYCVGFQEldlskeafffhDTPKEEEWFKAVSEGLH--PDA 334
Cdd:cd09091     4 FIGTWNMGSAPPPKNITSWFTSKGQGKtrddvadyiphDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 335 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQD 414
Cdd:cd09091    73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 415 YKDICSRMQFcqPDPSLPPLTIS---NHdvILWLGDLNYRIE--ELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFE 489
Cdd:cd09091   153 YLNILRFLSL--GDKKLSAFNIThrfTH--LFWLGDLNYRLDlpIQEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVFL 228

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938 490 GFTEGELTFQPTYKYDTGSDD---WD----TSEKCRAPAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09091   229 RFSEEEITFPPTYRYERGSRDtyaYTkqkaTGVKYNLPSWCDRILWKSYPETHIicqSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 268-558 2.30e-48

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: 174.40  E-value: 2.30e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 268 FAGTYNVNGQSPKECLRLWLSNGIQAP-----------DVYCVGFQEldlskeafffhDTPKEEEWFKAVSEGLH--PDA 334
Cdd:cd09100     4 FIGTWNMGNAPPPKKITSWFQCKGQGKtrddtadyiphDIYVIGTQE-----------DPLGEKEWLDTLKHSLReiTSI 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 335 KYAKVKLIRLVGIMLLLYVKQEHAAYISEVEAETVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQD 414
Cdd:cd09100    73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 415 YKDICSRMQFcqPDPSLPPLTIS---NHdvILWLGDLNYRIE--ELDVEKVKKLIEEKDFQMLYAYDQLKIQVAAKTVFE 489
Cdd:cd09100   153 YFNILRFLVL--GDKKLSPFNIThrfTH--LFWLGDLNYRVElpNTEAENIIQKIKQQQYQELLPHDQLLIERKESKVFL 228

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938 490 GFTEGELTFQPTYKYDTGSDDWDTSEKCRA-------PAWCDRILWKGKNITQL---SYQSHMALKTSDHKPVSSVFDI 558
Cdd:cd09100   229 QFEEEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWKSYPLVHVvcqSYGCTDDITTSDHSPVFATFEV 307
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 748-912 4.85e-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: 148.57  E-value: 4.85e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  748 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNL---SASNHSVAEALLLFLESLPEPVICYSTYH 824
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLdlsEYDVHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  825 NCLECSGN------YTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKlDMTEK 898
Cdd:smart00324  82 EFIEAAKLedeterLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVA-SLKDI 160

                          170
                   ....*....|....
gi 1475928938  899 KKAQEFIHQFLCNP 912
Cdd:smart00324 161 RHQNTVIEFLIENA 174
PH_OCRL-like cd13320
oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has ...
 17-129 1.30e-35

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: 130.32  E-value: 1.30e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938  17 CVIAVQGVLCEGDSRQSRLLGLVRYRlehggQEHALFLYTHRRMAitgddvSLDQIVPVSRDFTLEEVSPDGEL--YILG 94
Cdd:cd13320     1 CVAAVQGVLCKGGSREPRLLSLAQRR-----GQYALIIQSHEREA------SLQDIIPINSHFRCVQEAEETLLidIASN 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1475928938  95 SDVTVQLDTAE-LSLVFQLPFGSQTRMFLHEVARAC 129
Cdd:cd13320    70 SGCKIRLQGDEtLERLFEIPDEEHCLTFLSEVLAAQ 105
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 750-888 5.35e-34

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 127.28  E-value: 5.35e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 750 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG---MIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNC 826
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGpdvDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 827 LEC------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 888
Cdd:pfam00620  81 IEAaklpdeEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
 750-911 9.25e-28

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: 110.47  E-value: 9.25e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 750 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGM-IDNLSASN-HSVAEALLLFLESLPEPVICYSTYHNCL 827
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEdIDDLEDYDvHDVASLLKLYLRELPEPLIPFELYDEFI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 828 ECSGNYTAS------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKlDMTEKKKA 901
Cdd:cd00159    81 ELAKIEDEEeriealKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDE-LLEDIKKL 159

                         170
                  ....*....|
gi 1475928938 902 QEFIHQFLCN 911
Cdd:cd00159   160 NEIVEFLIEN 169
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 748-880 1.76e-16

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: 78.66  E-value: 1.76e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 748 EIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLS--ASNHSVAEALLLFLESLPEPVICYSTYHN 825
Cdd:cd04393    19 GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSkeADVCSAASLLRLFLQELPEGLIPASLQIR 98

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1475928938 826 CLECSGNYTAS-------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFG 880
Cdd:cd04393    99 LMQLYQDYNGEdefgrklRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAVFG 160
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 757-885 3.36e-13

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: 69.39  E-value: 3.36e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 757 VDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN--HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYT 834
Cdd:cd04390    30 VDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQYEDFLSCAQLLS 109

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938 835 AS--------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLR 885
Cdd:cd04390   110 KDeekglgelMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATVFGPNILR 168
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 766-911 1.89e-12

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: 66.65  E-value: 1.89e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 766 QQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN-HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTASKQVISTLP 844
Cdd:cd04389    39 QTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLEDpHVPASLLKLWLRELEEPLIPDALYQQCISASEDPDKAVEIVQKLP 118

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938 845 IFHKNVFHYLMAFLRELLK--NSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQEFIHQFLCN 911
Cdd:cd04389   119 IINRLVLCYLINFLQVFAQpeNVAHTKMDVSNLAMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLIEH 187
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 270-552 9.09e-12

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: 65.97  E-value: 9.09e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 270 GTYNVNGQSPKECLRLWLSN-GIQAPDVycVGFQELDLSKEAFFFHDTPKEEEWFKAVSEGLHPDaKYAKVklirlvgim 348
Cdd:cd08372     2 ASYNVNGLNAATRASGIARWvRELDPDI--VCLQEVKDSQYSAVALNQLLPEGYHQYQSGPSRKE-GYEGV--------- 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 349 lLLYVKQEHAAyISEVeaeTVGTGIMGRMGNKGGVAIRFQFHNTSICVVNSHLAAHIEEYERRNQDYKDICSRMQFcqpd 428
Cdd:cd08372    70 -AILSKTPKFK-IVEK---HQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVLEFLKR---- 140

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 429 pslppLTISNHDVILWLGDLNYRIEELDVEKVKKLIEekdfqmlyaydqLKIQVAAKTVFEgftegELTFQPTykydtgs 508
Cdd:cd08372   141 -----LRQPNSAPVVICGDFNVRPSEVDSENPSSMLR------------LFVALNLVDSFE-----TLPHAYT------- 191

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1475928938 509 ddWDTSEKcRAPAWCDRILW--------KGKNITQLSYQSHMAlktSDHKPV 552
Cdd:cd08372   192 --FDTYMH-NVKSRLDYIFVsksllpsvKSSKILSDAARARIP---SDHYPI 237
RhoGAP_srGAP cd04383
RhoGAP_srGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 744-890 1.29e-11

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: 64.36  E-value: 1.29e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 744 DSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG---MIDNLSASN-HSVAEALLLFLESLPEPVIC 819
Cdd:cd04383    13 DSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGedpLADDQNDHDiNSVAGVLKLYFRGLENPLFP 92

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 820 YSTYHNCLEC------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGH 890
Cdd:cd04383    93 KERFEDLMSCvklenpTERVHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAICFGPTLMPVPEGQ 169
RhoGAP-p50rhoGAP cd04404
RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 749-887 1.88e-10

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: 61.20  E-value: 1.88e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 749 IPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASNHSVAEALLL--FLESLPEPVICYSTY--- 823
Cdd:cd04404    23 IPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILktFLRELPEPLLTFDLYddi 102

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 824 ---HNCLECSgNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNP 887
Cdd:cd04404   103 vgfLNVDKEE-RVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK 168
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 757-884 5.89e-09

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: 57.08  E-value: 5.89e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 757 VDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN----HSVAEALLLFLESLPEPVICYSTYHNCLECSG- 831
Cdd:cd04386    28 VMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGTFSLPLDEFysdpHAVASALKSYLRELPDPLLTYNLYEDWVQAANk 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 832 -----NYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLL 884
Cdd:cd04386   108 pdedeRLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIAIVLAPNLL 165
RhoGAP_chimaerin cd04372
RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 746-899 7.67e-09

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: 56.37  E-value: 7.67e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 746 PMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLD-TGMIDNLSASNHS----VAEALLLFLESLPEPVICY 820
Cdd:cd04372    13 NTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDrDGEKADISATVYPdinvITGALKLYFRDLPIPVITY 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 821 STYHNCLECS--GNY----TASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKL- 893
Cdd:cd04372    93 DTYPKFIDAAkiSNPderlEAVHEALMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSALTt 172


                  ....*...
gi 1475928938 894 --DMTEKK 899
Cdd:cd04372   173 lnDMRYQI 180
RhoGAP_ARHGAP20 cd04402
RhoGAP_ARHGAP20: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 750-909 3.63e-08

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: 54.23  E-value: 3.63e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 750 PKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN-HSVAEALLLFLESLPEPVICYSTYHNCLE 828
Cdd:cd04402    16 PKPILDMLSLLYQKGPSTEGIFRRSANAKACKELKEKLNSGVEVDLKAEPvLLLASVLKDFLRNIPGSLLSSDLYEEWMS 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 829 C------SGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGhQKLDMTEKKKAQ 902
Cdd:cd04402    96 AldqeneEEKIAELQRLLDKLPRPNVLLLKHLICVLHNISQNSETNKMDAFNLAVCIAPSLLWPPAS-SELQNEDLKKVT 174


                  ....*..
gi 1475928938 903 EFIhQFL 909
Cdd:cd04402   175 SLV-QFL 180
RhoGAP_GMIP_PARG1 cd04378
RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 737-896 6.15e-08

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: 53.97  E-value: 6.15e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 737 GDDGSQL--DSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGM--IDNLSASNHSVAEALLLFLES 812
Cdd:cd04378     2 GVDFSQVprDFPDEVPFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKdlVELSELSPHDISSVLKLFLRQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 813 LPEPVICYSTYHN--------------------CLECSGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDE 872
Cdd:cd04378    82 LPEPLILFRLYNDfialakeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSP 161

                         170       180
                  ....*....|....*....|....
gi 1475928938 873 NILASIFGSLLLRNPAGHQKLDMT 896
Cdd:cd04378   162 NNLGIVFGPTLIRPRPGDADVSLS 185
RhoGAP-ARHGAP11A cd04394
RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 765-904 1.02e-07

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: 53.24  E-value: 1.02e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 765 VQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTASKQVIST-- 842
Cdd:cd04394    35 LSTEGLFRKSGSVVRQKELKAKLEGGEACLSSALPCDVAGLLKQFFRELPEPLLPYDLHEALLKAQELPTDEERKSATll 114

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1475928938 843 ----LPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQEF 904
Cdd:cd04394   115 ltclLPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQSEEGGEKMSSSTEKRLRLQ 180
RhoGAP_GMIP cd04408
RhoGAP_GMIP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP ...
 737-889 6.78e-07

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: 50.97  E-value: 6.78e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 737 GDDGSQL--DSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG--MIDNLSASNHSVAEALLLFLES 812
Cdd:cd04408     2 GVDFSQLprDFPEEVPFVVVRCTAEIENRALGVQGIYRISGSKARVEKLCQAFENGrdLVDLSGHSPHDITSVLKHFLKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 813 LPEPVICYSTYHNCLECSGNYTAS------------------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENI 874
Cdd:cd04408    82 LPEPVLPFQLYDDFIALAKELQRDsekaaespsiveniirslKELLGRLPVSNYNTLRHLMAHLYRVAERFEDNKMSPNN 161

                         170
                  ....*....|....*
gi 1475928938 875 LASIFGSLLLRNPAG 889
Cdd:cd04408   162 LGIVFGPTLLRPLVG 176
RhoGAP_p85 cd04388
RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present ...
 745-888 7.02e-07

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: 50.64  E-value: 7.02e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 745 SPMEI-PKELWMMVDYLYRNAVQQEDLF--QQPGLRSEFEHIRDClDTGMIDNLSASNHSVAEALLLFLESLPEPVICYS 821
Cdd:cd04388    10 SPPDVaPPLLIKLVEAIEKKGLESSTLYrtQSSSSLTELRQILDC-DAASVDLEQFDVAALADALKRYLLDLPNPVIPAP 88

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1475928938 822 TYHNCLECSGNYTASKQVI---------STLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 888
Cdd:cd04388    89 VYSEMISRAQEVQSSDEYAqllrklirsPNLPHQYWLTLQYLLKHFFRLCQSSSKNLLSARALAEIFSPLLFRFQP 164
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 776-907 7.72e-07

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: 50.90  E-value: 7.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 776 LRSEFEHIrdcLDTGMIDNLSAsnHSVAEALLLFLESLPEPVIC---YSTYHNC--LECSGNYTASKQVISTLPIFHKNV 850
Cdd:cd04376    43 LREEFDRG---IDVVLDENHSV--HDVAALLKEFFRDMPDPLLPrelYTAFIGTalLEPDEQLEALQLLIYLLPPCNCDT 117

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 851 FHYLMAFLRELLKNSAKNH-----------LDENILASIFGSLLLRNPAGHQKLDMTEKKKAQEFIHQ 907
Cdd:cd04376   118 LHRLLKFLHTVAEHAADSIdedgqevsgnkMTSLNLATIFGPNLLHKQKSGEREFVQASLRIEESTAI 185
RhoGAP_p190 cd04373
RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 745-885 7.91e-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: 50.15  E-value: 7.91e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 745 SPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN---HSVAEALLLFLESLPEPVICYS 821
Cdd:cd04373    11 SEKPIPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSKDftvNAVAGALKSFFSELPDPLIPYS 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 822 TYHNCLECSG------NYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLR 885
Cdd:cd04373    91 MHLELVEAAKindreqRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR 160
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 776-905 1.04e-06

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: 50.09  E-value: 1.04e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 776 LRSEFEHIRDCLDTGMIDNLSASNHSVAEALLLFLESLPEPVICYSTYHNCLECsGNYT-------ASKQVISTLPIFHK 848
Cdd:cd04398    50 LKELFDKDPLNVLLISPEDYESDIHSVASLLKLFFRELPEPLLTKALSREFIEA-AKIEdesrrrdALHGLINDLPDANY 128

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 849 NVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLrNPAGHQKLDMTEKKKAQEFI 905
Cdd:cd04398   129 ATLRALMFHLARIKEHESVNRMSVNNLAIIWGPTLM-NAAPDNAADMSFQSRVIETL 184
RhoGAP_ARHGAP21 cd04395
RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 800-887 1.90e-06

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: 49.32  E-value: 1.90e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 800 HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTAS------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDEN 873
Cdd:cd04395    74 NVVSSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVerlkelRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPR 153

                          90
                  ....*....|....
gi 1475928938 874 ILASIFGSLLLRNP 887
Cdd:cd04395   154 NLAIVFGPTLVRTS 167
RhoGAP_DLC1 cd04375
RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 749-903 9.53e-06

RhoGAP_DLC1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of DLC1-like proteins. DLC1 shows in vitro GAP activity towards RhoA and CDC42. Beside its C-terminal GAP domain, DLC1 also contains a SAM (sterile alpha motif) and a START (StAR-related lipid transfer action) domain. DLC1 has tumor suppressor activity in cell culture. 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: 239840  Cd Length: 220  Bit Score: 47.80  E-value: 9.53e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 749 IPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCL----DTGMIDNLSAsnHSVAEALLLFLESLPEPVICY---S 821
Cdd:cd04375    20 LPRSIQQAMRWLRNNALDQVGLFRKSGVKSRIQKLRSMIesstDNVNYDGQQA--YDVADMLKQYFRDLPEPLLTNklsE 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 822 TYHNCLECSGNY---TASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILA-----SIFGSLLLR----NPAG 889
Cdd:cd04375    98 TFIAIFQYVPKEqrlEAVQCAILLLPDENREVLQTLLYFLSDVAANSQENQMTATNLAvclapSLFHLNTSRrensSPAR 177

                         170       180
                  ....*....|....*....|....
gi 1475928938 890 HQKL----------DMTEKKKAQE 903
Cdd:cd04375   178 RMQRkkslgkpdqkELSENKAAHQ 201
RhoGAP_myosin_IX cd04377
RhoGAP_myosin_IX: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 749-887 1.35e-05

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: 46.66  E-value: 1.35e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 749 IPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMiDNLSASN---HSVAEALLLFLESLPEPVICYSTYHN 825
Cdd:cd04377    15 VPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDP-DSVNLEDypiHVITSVLKQWLRELPEPLMTFELYEN 93

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 826 CLECSGNYTASKQ------VISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNP 887
Cdd:cd04377    94 FLRAMELEEKQERvralysVLEQLPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRCP 161
RhoGAP_ARHGAP19 cd04392
RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 752-884 1.71e-05

RhoGAP_ARHGAP19: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP19-like proteins. The function of ArhGAP19 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: 239857  Cd Length: 208  Bit Score: 46.69  E-value: 1.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 752 ELWMMVDYLYRNaVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSA---SNHSVAEALLLFLESLPEPVICYSTYHNCLE 828
Cdd:cd04392    12 QIYQLIEYLEKN-LRVEGLFRKPGNSARQQELRDLLNSGTDLDLESggfHAHDCATVLKGFLGELPEPLLTHAHYPAHLQ 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1475928938 829 CS--------GNYTASKQ----------VISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLL 884
Cdd:cd04392    91 IAdlcqfdekGNKTSAPDkerllealqlLLLLLPEENRNLLKLILDLLYQTAKHEDKNKMSADNLALLFTPHLI 164
RhoGAP_CdGAP cd04384
RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 770-888 2.83e-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: 45.96  E-value: 2.83e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 770 LFQQPGLRSEFEHIRDCLDTGMIDNLSASN-----HSVAEALLLFLESLPEPVICYSTYHNCLECSGNYTASKQ------ 838
Cdd:cd04384    38 IYRLSGIASNIQRLRHEFDSEQIPDLTKDVyiqdiHSVSSLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERlekihd 117

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1475928938 839 VISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPA 888
Cdd:cd04384   118 VIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLLRSKQ 167
RhoGAP_myosin_IXB cd04407
RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 740-887 3.61e-05

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: 45.37  E-value: 3.61e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 740 GSQLDSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMiDNLSASN---HSVAEALLLFLESLPEP 816
Cdd:cd04407     6 GSLTSNKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADP-ENVKLENypiHAITGLLKQWLRELPEP 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 817 VICYSTYHNCL------ECSGNYTASKQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNP 887
Cdd:cd04407    85 LMTFAQYNDFLravelpEKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRCP 161
RhoGAP_fBEM3 cd04400
RhoGAP_fBEM3: RhoGAP (GTPase-activator [GAP] protein for Rho-like small GTPases) domain of ...
 749-884 4.81e-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: 45.04  E-value: 4.81e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 749 IPKELWMMVDYLY-RNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN-----HSVAEALLLFLESLPEPVICYST 822
Cdd:cd04400    22 LPSVVYRCIEYLDkNRAIYEEGIFRLSGSASVIKQLKERFNTEYDVDLFSSSlypdvHTVAGLLKLYLRELPTLILGGEL 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 823 yHNCLECSGNYTAS--------KQVISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDE-----------NILASIFGSLL 883
Cdd:cd04400   102 -HNDFKRLVEENHDrsqralelKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLrnvcivfsptlNIPAGIFVLFL 180


                  .
gi 1475928938 884 L 884
Cdd:cd04400   181 T 181
RhoGAP_Bcr cd04387
RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr ...
 757-903 2.02e-04

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: 43.38  E-value: 2.02e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 757 VDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTGMIDNLSASN----HSVAEALLLFLESLPEPVIC---YSTYHNCLEC 829
Cdd:cd04387    24 VEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSemdvNAIAGTLKLYFRELPEPLFTdelYPNFAEGIAL 103

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1475928938 830 SGNYTASKQVIS---TLPIFHKNVFHYLMAFLRELLKNSAKNHLDENILASIFGSLLLRNPAGHQKLDMTEKKKAQE 903
Cdd:cd04387   104 SDPVAKESCMLNlllSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKESKIPTNTMTDSWS 180
RhoGAP_ARHGAP27_15_12_9 cd04403
RhoGAP_ARHGAP27_15_12_9: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 800-905 2.61e-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: 42.76  E-value: 2.61e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 800 HSVAEALLLFLESLPEPVICYS---TYHNCLECSGNYTASKQV---ISTLPIFHKNVFHYLMAFLRELLKNSAKNHLDEN 873
Cdd:cd04403    71 HVITGALKLFFRELPEPLFPYSlfnDFVAAIKLSDYEQRVSAVkdlIKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQ 150

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1475928938 874 ILASIFGSLLLRNP--AGHQKLDMTEKKKAQEFI 905
Cdd:cd04403   151 NLAIVFGPTLLRPEqeTGNIAVHMVYQNQIVELI 184
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 378-558 3.95e-04

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: 43.61  E-value: 3.95e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 378 GNKGGVAIRFQFHNTSICVVNSHL---AAHIEEYERRNQDYKDICSRMQfcqpDPSLPPLTISNHDVILWL--GDLNYRI 452
Cdd:cd09092   153 SRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRAL----GYVLERLTDERFEKVPFFvfGDFNFRL 228

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 453 EELDV-------------------EKVKKLIEEKDFQ---------MLYAY-DQ-----------LKIQVAAKTVFEGFT 492
Cdd:cd09092   229 DTKSVvetlcakatmqtvrkadsnIVVKLEFREKDNDnkvvlqiekKKFDYfNQdvfrdnngkalLKFDKELEVFKDVLY 308

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1475928938 493 EGELTFQPTYKYdtgSDDWDTSE---KCRAPAWCDRILWKgKNITQLSYQSH----------MALKTSDHKPVSSVFDI 558
Cdd:cd09092   309 ELDISFPPSYPY---SEDPEQGTqymNTRCPAWCDRILMS-HSARELKSENEeksvtydmigPNVCMGDHKPVFLTFRI 383
RhoGAP_ARHGAP18 cd04391
RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 741-868 3.16e-03

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: 40.02  E-value: 3.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 741 SQLDSPMEIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDT----GMIDNLSASNHSVAEALLLFLESLPEP 816
Cdd:cd04391    14 QKKVPGSKVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAkfyeGTFLWDQVKQHDAASLLKLFIRELPQP 93

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1475928938 817 VICYSTYHNCLECSGNYTASKQV------ISTLPIFHKNVFHYLMAFLRELLKNSAKN 868
Cdd:cd04391    94 LLTVEYLPAFYSVQGLPSKKDQLqalnllVLLLPEANRDTLKALLEFLQKVVDHEEKN 151
RhoGAP_MgcRacGAP cd04382
RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 745-880 9.10e-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: 38.43  E-value: 9.10e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475928938 745 SPMeIPKELWMMVDYLYRNAVQQEDLFQQPGLRSEFEHIRDCLDTG-MIDNLSASN-HSVAEALLLFLESLPEPVICYST 822
Cdd:cd04382    14 SPM-IPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGkTVPNLSKVDiHVICGCLKDFLRSLKEPLITFAL 92

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1475928938 823 YHNCLECSGNY------TASKQVISTLPIFHKNVFHYLMAFLRELLKNSAkNHLDENILASIFG 880
Cdd:cd04382    93 WKEFMEAAEILdednsrAALYQAISELPQPNRDTLAFLILHLQRVAQSPE-CKMDINNLARVFG 155
 
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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