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Conserved domains on  [gi|1603512665|emb|VFV37658|]
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inositol polyphosphate [Lynx pardinus]

Protein Classification

Rho GTPase-activating protein( domain architecture ID 11245245)

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

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 223-516 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: 603.92  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 223 FRFFVGTWNVNGQSPDSELEPWLNCDSNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 302
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 303 VGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 382
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 383 VVPNQtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTYKY 462
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1603512665 463 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
 1-101 4.70e-56

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


:

Pssm-ID: 435540  Cd Length: 101  Bit Score: 187.22  E-value: 4.70e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665   1 MEMKGALREPCFLTLAQRNGQYELIIQLREKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRIQGDWTRERRFE 80
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80

                          90       100
                  ....*....|....*....|.
gi 1603512665  81 IPDEEHCLKFLSEVLAAQEAQ 101
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 651-810 7.01e-54

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: 186.01  E-value: 7.01e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 651 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 730
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 731 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQNCR 805
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVAnNEEDKR 143


                  ....*
gi 1603512665 806 QLLSS 810
Cdd:cd04380   144 QVIRI 148
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 223-516 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: 603.92  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 223 FRFFVGTWNVNGQSPDSELEPWLNCDSNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 302
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 303 VGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 382
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 383 VVPNQtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTYKY 462
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1603512665 463 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 221-519 1.16e-130

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 391.72  E-value: 1.16e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  221 QNFRFFVGTWNVNGQS-PDSELEPWLNC-----DSNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 293
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  294 YKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 373
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  374 KDICARMSFVVPnqtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGE 453
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  454 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-HYRSHMELKTSDHKPVSALFHIGVK 519
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
206-523 1.17e-66

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 228.90  E-value: 1.17e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 206 IKHILAKREKEYVNIQNFRFFVGTWNVNGQSPDSELEPWL---NCDSNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 280
Cdd:COG5411    13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 281 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 357
Cdd:COG5411    93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 358 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHDVVIWLGDLNYRLCM-PDANEVKSLINKNDLQRLLKFDQL 436
Cdd:COG5411   173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTStNEEVRPEIASDDGRLDKLFEYDQL 246

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 437 NIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:COG5411   247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326


                  ....*..
gi 1603512665 517 GVKVVDE 523
Cdd:COG5411   327 KIKVVDP 333
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
 1-101 4.70e-56

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


Pssm-ID: 435540  Cd Length: 101  Bit Score: 187.22  E-value: 4.70e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665   1 MEMKGALREPCFLTLAQRNGQYELIIQLREKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRIQGDWTRERRFE 80
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80

                          90       100
                  ....*....|....*....|.
gi 1603512665  81 IPDEEHCLKFLSEVLAAQEAQ 101
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
 1-98 4.70e-56

oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL1 contains a PH domain and a Rho-GAP domain. Patients with Lowe syndrome suffer primarily from congenital cataracts, neonatal hypotonia, intellectual disability and Fanconi syndrome. Mutations in OCRL are also found in a subset of patients with type 2 Dent disease, who selectively suffer from renal proximal tubular dysfunction. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270182  Cd Length: 105  Bit Score: 187.33  E-value: 4.70e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665   1 MEMKGALREPCFLTLAQRNGQYELIIQLREKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRIQGDWTRERRFE 80
Cdd:cd13382     8 HEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDRTPERLFE 87

                          90
                  ....*....|....*...
gi 1603512665  81 IPDEEHCLKFLSEVLAAQ 98
Cdd:cd13382    88 IPDEEHCLSFLSHVLAAQ 105
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 651-810 7.01e-54

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: 186.01  E-value: 7.01e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 651 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 730
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 731 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQNCR 805
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVAnNEEDKR 143


                  ....*
gi 1603512665 806 QLLSS 810
Cdd:cd04380   144 QVIRI 148
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 277-528 1.64e-49

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 185.11  E-value: 1.64e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 277 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 356
Cdd:PLN03191  347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 357 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHDVVIWLGDLNYRLCMPDAnEVKSLINKNDLQRLLKF 433
Cdd:PLN03191  427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 434 DQLNIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLHYRsHMELKTSDHK 508
Cdd:PLN03191  505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583

                         250       260
                  ....*....|....*....|
gi 1603512665 509 PVSALFHIGVKVVDERRYRK 528
Cdd:PLN03191  584 PVSSMFLVEVEVFDHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 716-811 3.93e-19

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: 85.40  E-value: 3.93e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  716 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 792
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100
                   ....*....|....*....|....*
gi 1603512665  793 RCLDSAQDP------QNCRQLLSSL 811
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLL 106
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 718-811 9.45e-17

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 77.97  E-value: 9.45e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 718 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 794
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100
                  ....*....|....*....|...
gi 1603512665 795 LDSAQDP------QNCRQLLSSL 811
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKL 103
 
Name Accession Description Interval E-value
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 223-516 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: 603.92  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 223 FRFFVGTWNVNGQSPDSELEPWLNCDSNPPDIYCIGFQELDLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQLVRL 302
Cdd:cd09093     1 FRIFVGTWNVNGQSPDESLRPWLSCDEEPPDIYAIGFQELDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 303 VGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARMSF 382
Cdd:cd09093    81 VGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 383 VVPNQtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTYKY 462
Cdd:cd09093   161 EDPDG--PPLSISDHDVVFWLGDLNYRIQELPTEEVKELIEKNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1603512665 463 DSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09093   239 DPGTDNWDSSEKCRAPAWCDRILWRGTNIVQLSYRSHMELKTSDHKPVSALFDI 292
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 221-519 1.16e-130

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 391.72  E-value: 1.16e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  221 QNFRFFVGTWNVNGQS-PDSELEPWLNC-----DSNPPDIYCIGFQELDLSTE-AFFYFESVKEQEWSMAVERGLHSKAK 293
Cdd:smart00128   1 RDIKVLIGTWNVGGLEsPKVDVTSWLFQkievkQSEKPDIYVIGLQEVVGLAPgVILETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  294 YKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDY 373
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  374 KDICARMSFVVPnqtlPQLNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGE 453
Cdd:smart00128 161 KTILRALSFPER----ALLSQFDHDVVFWFGDLNFRLDSPSYEEVRRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGP 236

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  454 IKFIPTYKYDS-KTDRWDSSGKCRVPAWCDRILWR--GTNVNQL-HYRSHMELKTSDHKPVSALFHIGVK 519
Cdd:smart00128 237 ITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYRsnGPELIQLsEYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 223-516 3.45e-119

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: 362.03  E-value: 3.45e-119
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 223 FRFFVGTWNVNGQ-SPDSELEPWLNCD-SNPPDIYCIGFQELDLSTEAFFYFE-SVKEQEWSMAVERGLHSKAKYKKVQL 299
Cdd:cd09074     1 VKIFVVTWNVGGGiSPPENLENWLSPKgTEAPDIYAVGVQEVDMSVQGFVGNDdSAKAREWVDNIQEALNEKENYVLLGS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 300 VRLVGMMLLIFARKDQWQYIRD--VATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 377
Cdd:cd09074    81 AQLVGIFLFVFVKKEHLPQIKDleVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDIL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 378 ARMSFVVPNQtlPQLNIMKHDVVIWLGDLNYRLCMpDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFI 457
Cdd:cd09074   161 SKLKFYRGDP--AIDSIFDHDVVFWFGDLNYRIDS-TDDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1603512665 458 PTYKYDSKTDRWDSSGKCRVPAWCDRILWR---GTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09074   238 PTYKFDPGTDEYDTSDKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 224-514 3.80e-92

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: 291.17  E-value: 3.80e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 224 RFFVGTWNVNGQSPDSELEPWLNCDSN--PPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSMAVERGLHSKAKYKKVQL- 299
Cdd:cd09090     2 NIFVGTFNVNGKSYKDDLSSWLFPEENdeLPDIVVIGLQEVvELTAGQILNSDPSKSSFWEKKIKTTLNGRGGEKYVLLr 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 300 -VRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICA 378
Cdd:cd09090    82 sEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIAR 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 379 RMSFVvPNQTLPQlnimkHDVVIWLGDLNYRLCMPDaNEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIP 458
Cdd:cd09090   162 GLRFS-RGRTIKD-----HDHVIWLGDFNYRISLTN-EDVRRFILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPP 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1603512665 459 TYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRShMELKTSDHKPVSALF 514
Cdd:cd09090   235 TYKYDKGTDNYDTSEKQRIPAWTDRILYRGENLRQLSYNS-APLRFSDHRPVYATF 289
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 224-516 1.45e-89

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: 285.82  E-value: 1.45e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 224 RFFVGTWNVNGQS-------PDSELEPWL--NC------------DSNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWS 281
Cdd:cd09089     2 RVFVGTWNVNGGKhfrsiafKHQSMTDWLldNPklagqcsndseeDEKPVDIFAIGFEEMvDLNASNIVSASTTNQKEWG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 282 MAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAA 361
Cdd:cd09089    82 EELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFAA 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 362 HVEDFERRNQDYKDICARMSFvvPNQTlpqlNIMKHDVVIWLGDLNYRLCMPDaNEVKSLINKNDLQRLLKFDQLNIQRT 441
Cdd:cd09089   162 GQSQVKERNEDFAEIARKLSF--PMGR----TLDSHDYVFWCGDFNYRIDLPN-DEVKELVRNGDWLKLLEFDQLTKQKA 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 442 QKKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------GTNVNQ--------LHYRsHME 501
Cdd:cd09089   235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpsdkteesLVETNDptwnpgtlLYYG-RAE 313

                         330
                  ....*....|....*
gi 1603512665 502 LKTSDHKPVSALFHI 516
Cdd:cd09089   314 LKTSDHRPVVAIIDI 328
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 223-516 4.52e-86

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: 275.40  E-value: 4.52e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 223 FRFFVGTWNVNGQSPDSELEPWLNCDSNP--PDIYCIGFQELDlSTEAFFYFESVKEQEWSMAVERGLhSKAKYKKVQLV 300
Cdd:cd09094     1 LRVYVVTWNVATAPPPIDVRSLLGLQSPEvaPDIYIIGLQEVN-SKPVQFVSDLIFDDPWSDLFMDIL-SPKGYVKVSSI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 301 RLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDICARM 380
Cdd:cd09094    79 RLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQ 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 381 SFVVPNQTlpqlNIMKHDVVIWLGDLNYRLCMPDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTEGEIKFIPTY 460
Cdd:cd09094   159 VFNECNTP----SILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTY 234

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1603512665 461 KYDSKTDRWDSSGKCRVPAWCDRILWR----------GTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09094   235 KFDLGTDEYDTSGKKRKPAWTDRILWKvnpdasteekFLSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 224-516 2.86e-75

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: 248.01  E-value: 2.86e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 224 RFFVGTWNVNGQSP-------DSELEPWL-------------NCDSNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 282
Cdd:cd09099     2 RVAMGTWNVNGGKQfrsnilgTSELTDWLldspklsgtpdfqDDESNPPDIFAVGFEEMvELSAGNIVNASTTNRKMWGE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 283 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 362
Cdd:cd09099    82 QLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTAG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 363 VEDFERRNQDYKDICARMSFVVPNqtlpqlNIMKHDVVIWLGDLNYRLCMPdANEVKSLINKNDLQRLLKFDQLNIQRTQ 442
Cdd:cd09099   162 QNQVKERNEDYKEITQKLSFPMGR------NVFSHDYVFWCGDFNYRIDLT-YEEVFYFIKRQDWKKLLEFDQLQLQKSS 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 443 KKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILW----------------------RGTNVNQ------L 494
Cdd:cd09099   235 GKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWwrkkwpfektageinlldsdldFDTKIRHtwtpgaL 314

                         330       340
                  ....*....|....*....|..
gi 1603512665 495 HYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09099   315 MYYGRAELQASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 224-516 4.88e-68

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: 228.77  E-value: 4.88e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 224 RFFVGTWNVNGQSP-------DSELEPWL-------------NCDSNPPDIYCIGFQEL-DLSTEAFFYFESVKEQEWSM 282
Cdd:cd09098     2 RVCVGTWNVNGGKQfrsiafkNQTLTDWLldapkkagipefqDVRSKPVDIFAIGFEEMvELNAGNIVSASTTNQKLWAA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 283 AVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAH 362
Cdd:cd09098    82 ELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 363 VEDFERRNQDYKDICARMSFvvPNQTLpqlnIMKHDVVIWLGDLNYRLCMPDaNEVKSLINKNDLQRLLKFDQLNIQRTQ 442
Cdd:cd09098   162 QSQVKERNEDFIEIARKLSF--PMGRM----LFSHDYVFWCGDFNYRIDIPN-EEVKELIRQQNWDSLIAGDQLINQKNA 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 443 KKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWR------------------GTNVNQ----------- 493
Cdd:cd09098   235 GQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRrrkwpfdrsaedldllnaSFPDNSkeqytwspgtl 314

                         330       340
                  ....*....|....*....|...
gi 1603512665 494 LHYrSHMELKTSDHKPVSALFHI 516
Cdd:cd09098   315 LHY-GRAELKTSDHRPVVALIDI 336
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
206-523 1.17e-66

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 228.90  E-value: 1.17e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 206 IKHILAKREKEYVNIQNFRFFVGTWNVNGQSPDSELEPWL---NCDSNPPDIYCIGFQELDLSTEAFF--YFESVKEQEW 280
Cdd:COG5411    13 IVAVLRQRRSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLfpeIEATELADLYVVGLQEVVELTPGSIlsADPYDRLRIW 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 281 SMAVERGLHSKAKYKKVQLVR---LVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNS 357
Cdd:COG5411    93 ESKVLDCLNGAQSDEKYSLLRspqLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNS 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 358 HLAAHVEDFERRNQDYKDIcarMSFVVPNQTLpqlNIMKHDVVIWLGDLNYRLCM-PDANEVKSLINKNDLQRLLKFDQL 436
Cdd:COG5411   173 HLAAGVNNIEERIFDYRSI---ASNICFSRGL---RIYDHDTIFWLGDLNYRVTStNEEVRPEIASDDGRLDKLFEYDQL 246

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 437 NIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRGTNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:COG5411   247 LWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYKSEQLTPHSYSSIPHLMISDHRPVYATFRA 326


                  ....*..
gi 1603512665 517 GVKVVDE 523
Cdd:COG5411   327 KIKVVDP 333
OCRL_clath_bd pfam16726
Inositol polyphosphate 5-phosphatase clathrin binding domain; This domain is a clathrin ...
 1-101 4.70e-56

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


Pssm-ID: 435540  Cd Length: 101  Bit Score: 187.22  E-value: 4.70e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665   1 MEMKGALREPCFLTLAQRNGQYELIIQLREKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRIQGDWTRERRFE 80
Cdd:pfam16726   1 HELRAGQKEPCLLSLIERGGQYELIIQAVEKEPVSQDSIPINSHFKCVQEAEETLLIDIATNSGCKIRIQGDRAPERLFE 80

                          90       100
                  ....*....|....*....|.
gi 1603512665  81 IPDEEHCLKFLSEVLAAQEAQ 101
Cdd:pfam16726  81 IQDEERCQAFLSQVKSAQQQV 101
PH_OCRL1 cd13382
oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called ...
 1-98 4.70e-56

oculocerebrorenal syndrome of Lowe 1 Pleckstrin homology-like domain; OCRL1 (also called INPP5F, LOCR, NPHL2, or phosphatidylinositol polyphosphate 5-phosphatase) hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. It interact with APPL1, FAM109A and FAM109B and several Rab GTPases which might both target them to the specific membranes and as well as stimulating the phosphatase activity. OCRL1 contains a PH domain and a Rho-GAP domain. Patients with Lowe syndrome suffer primarily from congenital cataracts, neonatal hypotonia, intellectual disability and Fanconi syndrome. Mutations in OCRL are also found in a subset of patients with type 2 Dent disease, who selectively suffer from renal proximal tubular dysfunction. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270182  Cd Length: 105  Bit Score: 187.33  E-value: 4.70e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665   1 MEMKGALREPCFLTLAQRNGQYELIIQLREKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRIQGDWTRERRFE 80
Cdd:cd13382     8 HEIRSGQREPRALSLAQRSGQYKLIIQSNEKEPVSQDIIPINSHFRCVQEAEETLLIDIASNTGCKIRVQGDRTPERLFE 87

                          90
                  ....*....|....*...
gi 1603512665  81 IPDEEHCLKFLSEVLAAQ 98
Cdd:cd13382    88 IPDEEHCLSFLSHVLAAQ 105
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 226-516 2.49e-54

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


Pssm-ID: 197325  Cd Length: 307  Bit Score: 190.16  E-value: 2.49e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 226 FVGTWNVNGQSPDSELEPWLNC-----------DSNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLH--SKA 292
Cdd:cd09091     4 FIGTWNMGSAPPPKNITSWFTSkgqgktrddvaDYIPHDIYVIGTQE-----------DPLGEKEWLDLLRHSLKelTSL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 293 KYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 372
Cdd:cd09091    73 DYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 373 YKDICARMSfvVPNQTLPQLNI-MKHDVVIWLGDLNYRLCMP--DANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADF 449
Cdd:cd09091   153 YLNILRFLS--LGDKKLSAFNItHRFTHLFWLGDLNYRLDLPiqEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVFLRF 230

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1603512665 450 TEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRgtNVNQLH-----YRSHMELKTSDHKPVSALFHI 516
Cdd:cd09091   231 SEEEITFPPTYRYERGSrDTYaytkqKATGvKYNLPSWCDRILWK--SYPETHiicqsYGCTDDIVTSDHSPVFGTFEV 307
RhoGAP_OCRL1 cd04380
RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain ...
 651-810 7.01e-54

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: 186.01  E-value: 7.01e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 651 FLTISGNYLPSCFGTSLEALCRMKRPIREVPVTKLIDLEEDSflekeksllqmvpldegASERPLQVPKEIWLLVDHLFK 730
Cdd:cd04380     1 FITVTGVYLPSCFGSSLETLIRLPDPGIRNLIDQLELGDNPD-----------------YSEVPLSIPKEIWRLVDYLYT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 731 YACHQEDLFQTPGMQEE----LQQIIDCLDTSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCLDSAQ-DPQNCR 805
Cdd:cd04380    64 RGLAQEGLFEEPGLPSEpgelLAEIRDALDTGSPFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLEAVAnNEEDKR 143


                  ....*
gi 1603512665 806 QLLSS 810
Cdd:cd04380   144 QVIRI 148
PH_OCRL-like cd13320
oculocerebrorenal syndrome of Lowe family Pleckstrin homology-like domain; The OCRL family has ...
 1-98 1.83e-53

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: 180.40  E-value: 1.83e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665   1 MEMKGALREPCFLTLAQRNGQYELIIQLREKEQHVQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRIQGDWTRERRFE 80
Cdd:cd13320     8 VLCKGGSREPRLLSLAQRRGQYALIIQSHEREASLQDIIPINSHFRCVQEAEETLLIDIASNSGCKIRLQGDETLERLFE 87

                          90
                  ....*....|....*...
gi 1603512665  81 IPDEEHCLKFLSEVLAAQ 98
Cdd:cd13320    88 IPDEEHCLTFLSEVLAAQ 105
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 226-516 1.09e-52

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: 185.57  E-value: 1.09e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 226 FVGTWNVNGQSPDSELEPWLNC-----------DSNPPDIYCIGFQELDLSteaffyfesvkEQEWSMAVERGLH--SKA 292
Cdd:cd09100     4 FIGTWNMGNAPPPKKITSWFQCkgqgktrddtaDYIPHDIYVIGTQEDPLG-----------EKEWLDTLKHSLReiTSI 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 293 KYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 372
Cdd:cd09100    73 SFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 373 YKDIcarMSF-VVPNQTLPQLNIM-KHDVVIWLGDLNYRLCMP--DANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFAD 448
Cdd:cd09100   153 YFNI---LRFlVLGDKKLSPFNIThRFTHLFWLGDLNYRVELPntEAENIIQKIKQQQYQELLPHDQLLIERKESKVFLQ 229

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 449 FTEGEIKFIPTYKYDSKT-DRW-----DSSG-KCRVPAWCDRILWRgtNVNQLH-----YRSHMELKTSDHKPVSALFHI 516
Cdd:cd09100   230 FEEEEITFAPTYRFERGTrERYaytkqKATGmKYNLPSWCDRVLWK--SYPLVHvvcqsYGCTDDITTSDHSPVFATFEV 307
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 226-516 5.16e-52

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: 183.64  E-value: 5.16e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 226 FVGTWNVNGQSPDSELEPWLNCD-----------SNPPDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGL--HSKA 292
Cdd:cd09101     4 FIGTWNMGSVPPPKSLASWLTSRglgktldettvTIPHDIYVFGTQE-----------NSVGDREWVDFLRASLkeLTDI 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 293 KYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQD 372
Cdd:cd09101    73 DYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQN 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 373 YKDICARMSfvVPNQTLPQLNI-MKHDVVIWLGDLNYRLCMpDANEVKSLINKNDLQRLLKFDQLNIQRTQKKAFADFTE 451
Cdd:cd09101   153 YLDILRSLS--LGDKQLNAFDIsLRFTHLFWFGDLNYRLDM-DIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFRE 229

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1603512665 452 GEIKFIPTYKYDSKT------DRWDSSG-KCRVPAWCDRILWRG---TNVNQLHYRSHMELKTSDHKPVSALFHI 516
Cdd:cd09101   230 EEISFPPTYRYERGSrdtymwQKQKTTGmRTNVPSWCDRILWKSypeTHIVCNSYGCTDDIVTSDHSPVFGTFEV 304
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 221-514 3.34e-50

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: 178.39  E-value: 3.34e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 221 QNFRFFVGTWNVNGQ-SPDSELEPWLNCDSNP--PDIYCIGFQEldlsteaffyfESVKEQEWSMAVERGLhsKAKYKKV 297
Cdd:cd09095     3 RNVGIFVATWNMQGQkELPENLDDFLLPTSADfaQDIYVIGVQE-----------GCSDRREWEIRLQETL--GPSHVLL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 298 QLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAHVEDFERRNQDYKDIC 377
Cdd:cd09095    70 HSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKII 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 378 ARMSF--VVPNQTLPQLN---IMKHDVVIWLGDLNYRLCMPdANEVKSLINKN---DLQRLLKFDQLNIQRTQKKAFADF 449
Cdd:cd09095   150 QALNLprNVPTNPYKSESgdvTTRFDEVFWFGDFNFRLSGP-RHLVDALINQGqevDVSALLQHDQLTREMSKGSIFKGF 228

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1603512665 450 TEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWRG---TNVNQLHYRSHMELKTSDHKPVSALF 514
Cdd:cd09095   229 QEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSrqkGDVCCLKYNSCPSIKTSDHRPVFALF 296
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 277-528 1.64e-49

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 185.11  E-value: 1.64e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 277 EQEWSMAVERGLHSKAKYKKVQLVRLVGMMLLIFARKDQWQYIRDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVN 356
Cdd:PLN03191  347 YQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVC 426

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 357 SHLAAHVEDF--ERRNQDYKDICARMSFV-VPNQTLPQlNIMKHDVVIWLGDLNYRLCMPDAnEVKSLINKNDLQRLLKF 433
Cdd:PLN03191  427 SHLTSGHKDGaeQRRNADVYEIIRRTRFSsVLDTDQPQ-TIPSHDQIFWFGDLNYRLNMLDT-EVRKLVAQKRWDELINS 504

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 434 DQLNIQRTQKKAFADFTEGEIKFIPTYKYDSKTDRW-----DSSGKCRVPAWCDRILWRGTNVNQLHYRsHMELKTSDHK 508
Cdd:PLN03191  505 DQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGKGIKQLCYK-RSEIRLSDHR 583

                         250       260
                  ....*....|....*....|
gi 1603512665 509 PVSALFHIGVKVVDERRYRK 528
Cdd:PLN03191  584 PVSSMFLVEVEVFDHRKLQR 603
RhoGAP smart00324
GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac ...
 716-811 3.93e-19

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: 85.40  E-value: 3.93e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665  716 QVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN---HSVAEALLIFLEALPEPVICYELYQ 792
Cdd:smart00324   2 PIPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDLSEydvHDVAGLLKLFLRELPEPLITYELYE 81

                           90       100
                   ....*....|....*....|....*
gi 1603512665  793 RCLDSAQDP------QNCRQLLSSL 811
Cdd:smart00324  82 EFIEAAKLEdeterlRALRELLSLL 106
RhoGAP pfam00620
RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.
 718-811 9.45e-17

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


Pssm-ID: 459875  Cd Length: 148  Bit Score: 77.97  E-value: 9.45e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 718 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-HSVAEALLIFLEALPEPVICYELYQRC 794
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRgpDVDLDLEEEDvHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100
                  ....*....|....*....|...
gi 1603512665 795 LDSAQDP------QNCRQLLSSL 811
Cdd:pfam00620  81 IEAAKLPdeeerlEALRELLRKL 103
RhoGAP cd00159
RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like ...
 718-811 2.20e-11

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: 63.09  E-value: 2.20e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 718 PKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSNHSVAEALLIFLEALPEPVICYELYQRCL 795
Cdd:cd00159     1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDrgEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                          90       100
                  ....*....|....*....|..
gi 1603512665 796 DSAQDP------QNCRQLLSSL 811
Cdd:cd00159    81 ELAKIEdeeeriEALKELLKSL 102
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 227-510 3.50e-09

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


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 58.26  E-value: 3.50e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 227 VGTWNVNGQSPDSELEPWL-NCDSNPPDIYCIgfQELDLSTeAFFYFESVKEQEWSMAVERGLHSKAKYKKVqlvrlvgm 305
Cdd:cd08372     1 VASYNVNGLNAATRASGIArWVRELDPDIVCL--QEVKDSQ-YSAVALNQLLPEGYHQYQSGPSRKEGYEGV-------- 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 306 mlLIFARKDQWqyirDVATETVGTGIMGKMGNKGGVAVRFVFHNTTFCIVNSHLAAhvedfERRNQDYKDICARMsFVvp 385
Cdd:cd08372    70 --AILSKTPKF----KIVEKHQYKFGEGDSGERRAVVVKFDVHDKELCVVNAHLQA-----GGTRADVRDAQLKE-VL-- 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 386 nQTLPQLNIMKHDVVIWLGDLNYRlcmpdanevKSLInknDLQRLLKFDQLNIQRTQKKAFADFTegeikFIPTYKYDSK 465
Cdd:cd08372   136 -EFLKRLRQPNSAPVVICGDFNVR---------PSEV---DSENPSSMLRLFVALNLVDSFETLP-----HAYTFDTYMH 197

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1603512665 466 tdrwdssgkcRVPAWCDRILWRGT---NV--NQLHYRSHMELKTSDHKPV 510
Cdd:cd08372   198 ----------NVKSRLDYIFVSKSllpSVksSKILSDAARARIPSDHYPI 237
RhoGAP_FAM13A1a cd04393
RhoGAP_FAM13A1a: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 704-811 1.42e-08

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: 55.55  E-value: 1.42e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 704 VPLDE----GASERplQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETI--PGSNHSVAEALLIF 777
Cdd:cd04393     5 VPLQElqqaGQPEN--GVPAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLskEADVCSAASLLRLF 82

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1603512665 778 LEALPEPVICYELYQRCLDSAQDPQNCRQLLSSL 811
Cdd:cd04393    83 LQELPEGLIPASLQIRLMQLYQDYNGEDEFGRKL 116
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 334-516 6.36e-07

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


Pssm-ID: 197326  Cd Length: 383  Bit Score: 52.47  E-value: 6.36e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 334 KMGNKGGVAVRFVFHNTTFCIVNSHL---AAHVEDFERRNQDYKDICAR-MSFV---VPNQTLPQLNImkhdvvIWLGDL 406
Cdd:cd09092   151 KWSRKGFMRTRWKINNCVFDLVNIHLfhdASNLAACESSPSVYSQNRHRaLGYVlerLTDERFEKVPF------FVFGDF 224

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 407 NYR---------LCM---------PDANEVKSLIN---------------------------KNDLQRLLKFDQlniqrt 441
Cdd:cd09092   225 NFRldtksvvetLCAkatmqtvrkADSNIVVKLEFrekdndnkvvlqiekkkfdyfnqdvfrDNNGKALLKFDK------ 298

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 442 QKKAFAD-FTEGEIKFIPTYKYDSKTDRWDSSGKCRVPAWCDRILWrGTNVNQLH---------YRS-HMELKTSDHKPV 510
Cdd:cd09092   299 ELEVFKDvLYELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILM-SHSARELKseneeksvtYDMiGPNVCMGDHKPV 377


                  ....*.
gi 1603512665 511 SALFHI 516
Cdd:cd09092   378 FLTFRI 383
RhoGAP_nadrin cd04386
RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 704-807 3.55e-05

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: 45.53  E-value: 3.55e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 704 VPLDE--GASERPLQVPKEiwLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLD--TSIPETIPGSN--HSVAEALLIF 777
Cdd:cd04386     7 TPLEEhlKRTGREIALPIE--ACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDagTFSLPLDEFYSdpHAVASALKSY 84

                          90       100       110
                  ....*....|....*....|....*....|
gi 1603512665 778 LEALPEPVICYELYQRCLDSAQDPQNCRQL 807
Cdd:cd04386    85 LRELPDPLLTYNLYEDWVQAANKPDEDERL 114
RhoGAP_KIAA1688 cd04389
RhoGAP_KIAA1688: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 715-811 4.28e-04

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: 41.99  E-value: 4.28e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 715 LQVPKEIWLLVDHLFKYACHQ-EDLFQTPGMQEELQQIIDCLDT-SIPETIPGSNHSVAEALLIFLEALPEPVICYELYQ 792
Cdd:cd04389    19 LKLPWILTFLSEKVLALGGFQtEGIFRVPGDIDEVNELKLRVDQwDYPLSGLEDPHVPASLLKLWLRELEEPLIPDALYQ 98

                          90
                  ....*....|....*....
gi 1603512665 793 RCLDSAQDPQNCRQLLSSL 811
Cdd:cd04389    99 QCISASEDPDKAVEIVQKL 117
RhoGAP_ARHGAP22_24_25 cd04390
RhoGAP_ARHGAP22_24_25: GTPase-activator protein (GAP) domain for Rho-like GTPases found in ...
 714-799 4.59e-04

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: 42.04  E-value: 4.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 714 PLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDTSIPETIPGSN--HSVAEALLIFLEALPEPVICYELY 791
Cdd:cd04390    19 PRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTdvHTVASLLKLYLRELPEPVIPWAQY 98


                  ....*...
gi 1603512665 792 QRCLDSAQ 799
Cdd:cd04390    99 EDFLSCAQ 106
RhoGAP_fRGD1 cd04398
RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 704-814 2.40e-03

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: 40.08  E-value: 2.40e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 704 VPLDEGASERPLQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQIIDCLDT--SIPETIPGSN-----HSVAEALLI 776
Cdd:cd04398     3 VPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKdpLNVLLISPEDyesdiHSVASLLKL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1603512665 777 FLEALPEPVICYELYQRCLDSAQ--DPQNCRQLLSSLVFS 814
Cdd:cd04398    83 FFRELPEPLLTKALSREFIEAAKieDESRRRDALHGLIND 122
RhoGAP_ARHGAP6 cd04376
RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ...
 715-792 6.54e-03

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: 38.96  E-value: 6.54e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1603512665 715 LQVPKEIWLLVDHLFKYACHQEDLFQTPGMQEELQQI---IDC-LDTSIPETIpgSNHSVAEALLIFLEALPEPVICYEL 790
Cdd:cd04376     7 RQVPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLreeFDRgIDVVLDENH--SVHDVAALLKEFFRDMPDPLLPREL 84


                  ..
gi 1603512665 791 YQ 792
Cdd:cd04376    85 YT 86
 
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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