RHG35_RAT
ID RHG35_RAT Reviewed; 1499 AA.
AC P81128; A0A0G2KB46;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Rho GTPase-activating protein 35 {ECO:0000312|RGD:1308738};
DE AltName: Full=GAP-associated protein p190;
DE AltName: Full=Glucocorticoid receptor DNA-binding factor 1;
GN Name=Arhgap35 {ECO:0000312|RGD:1308738};
GN Synonyms=Grlf1, P190A {ECO:0000303|PubMed:9852136},
GN p190ARHOGAP {ECO:0000303|PubMed:9852136};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], PROTEIN SEQUENCE OF 379-391; 491-506 AND
RP 1304-1322, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=1581965; DOI=10.1016/0092-8674(92)90454-k;
RA Settleman J., Narasimhan V., Foster L.C., Weinberg R.A.;
RT "Molecular cloning of cDNAs encoding the GAP-associated protein p190:
RT implications for a signaling pathway from ras to the nucleus.";
RL Cell 69:539-549(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP FUNCTION, GTP-BINDING, AND MUTAGENESIS OF SER-36 AND ARG-1284.
RX PubMed=9852136; DOI=10.1074/jbc.273.51.34631;
RA Tatsis N., Lannigan D.A., Macara I.G.;
RT "The function of the p190 Rho GTPase-activating protein is controlled by
RT its N-terminal GTP binding domain.";
RL J. Biol. Chem. 273:34631-34638(1998).
RN [4]
RP FUNCTION, MUTAGENESIS OF SER-1451 AND 1476-SER--SER-1483, AND
RP PHOSPHORYLATION.
RX PubMed=20439493; DOI=10.1128/mcb.01178-09;
RA Pullikuth A.K., Catling A.D.;
RT "Extracellular signal-regulated kinase promotes Rho-dependent focal
RT adhesion formation by suppressing p190A RhoGAP.";
RL Mol. Cell. Biol. 30:3233-3248(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-975; SER-985;
RP SER-1134 AND SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Rho GTPase-activating protein (GAP). Binds several acidic
CC phospholipids which inhibits the Rho GAP activity to promote the Rac
CC GAP activity (PubMed:9852136, PubMed:20439493). This binding is
CC inhibited by phosphorylation by PRKCA (By similarity). Involved in cell
CC differentiation as well as cell adhesion and migration, plays an
CC important role in retinal tissue morphogenesis, neural tube fusion,
CC midline fusion of the cerebral hemispheres and mammary gland branching
CC morphogenesis (PubMed:9852136, PubMed:20439493). Transduces signals
CC from p21-ras to the nucleus, acting via the ras GTPase-activating
CC protein (GAP) (By similarity). Transduces SRC-dependent signals from
CC cell-surface adhesion molecules, such as laminin, to promote neurite
CC outgrowth. Regulates axon outgrowth, guidance and fasciculation (By
CC similarity). Modulates Rho GTPase-dependent F-actin polymerization,
CC organization and assembly, is involved in polarized cell migration and
CC in the positive regulation of ciliogenesis and cilia elongation (By
CC similarity). During mammary gland development, is required in both the
CC epithelial and stromal compartments for ductal outgrowth (By
CC similarity). Represses transcription of the glucocorticoid receptor by
CC binding to the cis-acting regulatory sequence 5'-
CC GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would
CC need additional experimental evidences (By similarity).
CC {ECO:0000250|UniProtKB:Q91YM2, ECO:0000250|UniProtKB:Q9NRY4,
CC ECO:0000269|PubMed:20439493, ECO:0000269|PubMed:9852136}.
CC -!- SUBUNIT: Interacts with RASA1 (By similarity). Interacts with the
CC general transcription factor GTF2I, the interaction sequesters GTF2I in
CC the cytoplasm (By similarity). {ECO:0000250|UniProtKB:Q91YM2,
CC ECO:0000250|UniProtKB:Q9NRY4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q91YM2}. Cytoplasm {ECO:0000269|PubMed:1581965}.
CC Nucleus {ECO:0000269|PubMed:1581965}. Cell membrane
CC {ECO:0000250|UniProtKB:Q91YM2}. Note=In response to integrins and SDC4
CC and upon phosphorylation by PKC, relocalizes from the cytoplasm to
CC regions of plasma membrane ruffling where it colocalizes with
CC polymerized actin. {ECO:0000250|UniProtKB:Q91YM2}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DOMAIN: N-terminal part (1-266) has GTPase activity. Required for
CC proper cellular localization. {ECO:0000250|UniProtKB:Q91YM2}.
CC -!- DOMAIN: The pG1 pseudoGTPase domain does not bind GTP.
CC {ECO:0000250|UniProtKB:Q6NU25}.
CC -!- PTM: Phosphorylation of Tyr-1105 by PTK6 promotes the association with
CC RASA1, inactivating RHOA while activating RAS. Phosphorylation at Tyr-
CC 308 by PDGFRA inhibits binding to GTF2I (By similarity). Phosphorylated
CC by PRKCA at Ser-1221 and Thr-1226, induces relocalization from the
CC cytoplasm to regions of plasma membrane ruffling and prevents the
CC binding and substrate specificity regulation by phospholipids (By
CC similarity). In brain, phosphorylated by FYN and SRC (By similarity).
CC During focal adhesion formation, phosphorylated by MAPK1 and MAPK3 at
CC the C-terminal region, probably at Ser-1451, Ser-1476, Thr-1480 and
CC Ser-1483. Phosphorylation by MAPK1 and MAPK3 inhibits GAP function and
CC localizes ARGHAP35 away from newly forming focal adhesions and stress
CC fibers in cells spreading on fibronectin (PubMed:20439493).
CC Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires priming by
CC MAPK and inhibits RhoGAP activity and modulates polarized cell
CC migration (By similarity). {ECO:0000250|UniProtKB:Q91YM2,
CC ECO:0000250|UniProtKB:Q9NRY4, ECO:0000269|PubMed:20439493}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M94721; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; AABR07002647; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07002648; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A38218; A38218.
DR RefSeq; NP_001258061.1; NM_001271132.1.
DR RefSeq; XP_006228474.1; XM_006228412.3.
DR RefSeq; XP_008757141.1; XM_008758919.1.
DR PDB; 5IRC; X-ray; 1.72 A; A/B=1242-1439.
DR PDB; 6D4G; X-ray; 2.80 A; A/B=1-266.
DR PDBsum; 5IRC; -.
DR PDBsum; 6D4G; -.
DR AlphaFoldDB; P81128; -.
DR BMRB; P81128; -.
DR SMR; P81128; -.
DR STRING; 10116.ENSRNOP00000021223; -.
DR iPTMnet; P81128; -.
DR PhosphoSitePlus; P81128; -.
DR jPOST; P81128; -.
DR PaxDb; P81128; -.
DR PRIDE; P81128; -.
DR Ensembl; ENSRNOT00000090519; ENSRNOP00000075649; ENSRNOG00000015852.
DR GeneID; 306400; -.
DR KEGG; rno:306400; -.
DR UCSC; RGD:1308738; rat.
DR CTD; 2909; -.
DR RGD; 1308738; Arhgap35.
DR eggNOG; KOG4271; Eukaryota.
DR GeneTree; ENSGT01030000234635; -.
DR InParanoid; P81128; -.
DR OrthoDB; 110157at2759; -.
DR Reactome; R-RNO-416550; Sema4D mediated inhibition of cell attachment and migration.
DR Reactome; R-RNO-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9696264; RND3 GTPase cycle.
DR Reactome; R-RNO-9696270; RND2 GTPase cycle.
DR Reactome; R-RNO-9696273; RND1 GTPase cycle.
DR PRO; PR:P81128; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000015852; Expressed in frontal cortex and 19 other tissues.
DR ExpressionAtlas; P81128; baseline and differential.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:RGD.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0032794; F:GTPase activating protein binding; IPI:RGD.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; ISS:UniProtKB.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISS:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0030879; P:mammary gland development; ISS:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISO:RGD.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:RGD.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0097485; P:neuron projection guidance; ISS:UniProtKB.
DR GO; GO:0045724; P:positive regulation of cilium assembly; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; ISS:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:0008361; P:regulation of cell size; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
DR Gene3D; 1.10.10.440; -; 2.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR002713; FF_domain.
DR InterPro; IPR036517; FF_domain_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039007; pG1.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR032835; RhoGAP-FF1.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR045786; RhoGAP_pG1_pG2.
DR InterPro; IPR039006; RhoGAP_pG2.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF01846; FF; 1.
DR Pfam; PF00071; Ras; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF16512; RhoGAP-FF1; 1.
DR Pfam; PF19518; RhoGAP_pG1_pG2; 1.
DR SMART; SM00441; FF; 4.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF81698; SSF81698; 1.
DR PROSITE; PS51676; FF; 4.
DR PROSITE; PS51852; PG1; 1.
DR PROSITE; PS51853; PG2; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; DNA-binding; GTP-binding; GTPase activation;
KW Lipid-binding; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..1499
FT /note="Rho GTPase-activating protein 35"
FT /id="PRO_0000056732"
FT DOMAIN 270..327
FT /note="FF 1"
FT DOMAIN 368..422
FT /note="FF 2"
FT DOMAIN 429..483
FT /note="FF 3"
FT DOMAIN 485..550
FT /note="FF 4"
FT DOMAIN 592..767
FT /note="pG1 pseudoGTPase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01199"
FT DOMAIN 783..947
FT /note="pG2 pseudoGTPase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01200"
FT DOMAIN 1249..1436
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 1..266
FT /note="Has GTPase activity, required for proper
FT localization"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT REGION 1124..1148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1177..1212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1213..1236
FT /note="Required for phospholipid binding and regulation of
FT the substrate preference"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT REGION 1446..1499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1124..1139
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1182..1196
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1470..1485
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 28
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT BINDING 33..37
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT BINDING 52
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT BINDING 56
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT BINDING 95..97
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT BINDING 201..203
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT BINDING 229..231
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 308
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 970
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 975
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1072
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1087
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1105
FT /note="Phosphotyrosine; by ABL2 and PTK6"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1179
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1221
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1226
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1236
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1472
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1480
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MUTAGEN 36
FT /note="S->N: Disrupts GTP-binding. No direct effect on GAP
FT activity 'in vitro' but affects the activity regulation 'in
FT vivo'."
FT /evidence="ECO:0000269|PubMed:9852136"
FT MUTAGEN 1284
FT /note="R->A: Abolishes GAP activity."
FT /evidence="ECO:0000269|PubMed:9852136"
FT MUTAGEN 1451
FT /note="S->A: Abolishes phosphorylation by MAPK, increases
FT functional activity and enhances retention in peripheral
FT membranes; when associated with 1476-A--A-1483."
FT /evidence="ECO:0000269|PubMed:20439493"
FT MUTAGEN 1476..1483
FT /note="SPPPTPQS->APPPAPQA: Abolishes phosphorylation by
FT MAPK, increases functional activity and enhances retention
FT in peripheral membranes; when associated with A-1451."
FT /evidence="ECO:0000269|PubMed:20439493"
FT STRAND 15..19
FT /evidence="ECO:0007829|PDB:6D4G"
FT TURN 25..30
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 35..43
FT /evidence="ECO:0007829|PDB:6D4G"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:6D4G"
FT TURN 66..70
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:6D4G"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 116..120
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:6D4G"
FT TURN 169..171
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 174..190
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 207..218
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:6D4G"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:6D4G"
FT HELIX 236..251
FT /evidence="ECO:0007829|PDB:6D4G"
FT STRAND 1245..1249
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1251..1254
FT /evidence="ECO:0007829|PDB:5IRC"
FT STRAND 1257..1259
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1263..1275
FT /evidence="ECO:0007829|PDB:5IRC"
FT TURN 1280..1284
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1289..1301
FT /evidence="ECO:0007829|PDB:5IRC"
FT TURN 1307..1309
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1314..1327
FT /evidence="ECO:0007829|PDB:5IRC"
FT STRAND 1328..1330
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1335..1345
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1350..1361
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1366..1383
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1386..1389
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1393..1398
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1401..1405
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1412..1416
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1419..1430
FT /evidence="ECO:0007829|PDB:5IRC"
FT HELIX 1432..1436
FT /evidence="ECO:0007829|PDB:5IRC"
SQ SEQUENCE 1499 AA; 170480 MW; B3AEBD920E98B310 CRC64;
MMMARKQDVR IPTYNISVVG LSGTEKEKGQ CGIGKSCLCN RFVRPSADEF HLDHTSVLST
SDFGGRVVNN DHFLYWGEVS RSLEDCVECK MHIVEQTEFI DDQTFQPHRS TALQPYIKRA
AATKLASAEK LMYFCTDQLG LEQDFEQKQM PDGKLLVDGF LLGIDVSRGM NRNFDDQLKF
VSNLYNQLAK TKKPIVIVLT KCDEGVERYI RDAHTFALSK KNLQVVETSA RSNVNVDLAF
STLVQLIDKS RGKTKIIPYF EALKQQSQQI ATAKDKYEWL VSRIVKSHNE NWLSVSRKMQ
ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA LIPNLDEVDH
LSCIKAKKLL ETKPEFLKWF VVLEETPWDE TSHIDNMENE RIPFDLMDTV PAEQLYETHL
EKLRNERKRA EMRRAFKENL ETSPFITPGK PWEEARSFIM NEDFYQWLEE SVYMDIYGKH
QKQIIDRAKE EFQELLLEYS ELFYELELDA KPSKEKMGVI QDVLGEEQRF KALQKLQAER
DALILKHIHF VYHPTKETCP SCPACVDAKI EHLISSRFIR PSDRNQKNSL SDPNIDRINL
VILGKDGLAR ELANEIRALC TNDDKYVIDG KMYELSLRPI EGNVRLPVNS FQTPTFQPHG
CLCLYNSKES LSYVVESIEK SRESTLGRRD NHLVHLPLTL ILVNKRGDTS GETLHSLIQQ
GQQIASKLQC VFLDPASAGI GYGRNINEKQ ISQVLKGLLD SKRNLNLVSS TASIKDLADV
DLRIVMCLMC GDPFSADDIL SPVLQSQTCK SSHCGSSNSV LLELPIGVHK KRIELSVLSY
HSSFSIRKSR LVHGYIVFYS AKRKASLAML RAFLCEVQDI IPIQLVALTD GAIDVLDNDL
SREQLTEGEE IAQEIDGRFT SIPCSQPQHK LELFHPFFKD VVEKKNIIEA THMYDNVAEA
CSTTEEVFNS PRAGSPLCNS NLQDSEEDVE PPSYHLFRED ATLPSLSKDH SKFSMELEGN
DGLSFIMSNF ESKLNNKVPP PVKPKPPVHF EITKDLSYLD QGHREGQRKS MSSSPWMPQD
GFDPSDYAEP MDAVVKPRNE EENIYSVPHD STQGKIITIR NINKAQSNGS GNGSDSEMDT
SSLERGRKVS AVSKPVLYRT RCTRLGRFAS YRTSFSVGSD DELGPIRKKE EDQASQGYKG
DNAVIPYETD EDPRRRNILR SLRRNTKKPK PKPRPSITKA TWESNYFGVP LTTVVTPEKP
IPIFIERCIE YIEATGLSTE GIYRVSGNKS EMESLQRQFD QDHNLDLAEK DFTVNTVAGA
MKSFFSELPD PLVPYSMQID LVEAHKINDR EQKLHALKEV LKKFPKENHE VFKYVISHLN
RVSHNNKVNL MTSENLSICF WPTLMRPDFS SMDALTATRS YQTIIELFIQ QCPFFFYNRP
ISEPPGAAPG SPSAMAPTVP FLTSTPATSQ PSPPQSPPPT PQSPMQPLLS SQLQAEHTL
