ID RHG35_MOUSE Reviewed; 1499 AA.
AC Q91YM2; Q3UGY1; Q69ZC4;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 24-JAN-2024, entry version 186.
DE RecName: Full=Rho GTPase-activating protein 35 {ECO:0000312|MGI:MGI:1929494};
DE AltName: Full=Glucocorticoid receptor DNA-binding factor 1;
GN Name=Arhgap35 {ECO:0000312|MGI:MGI:1929494};
GN Synonyms=Grlf1, Kiaa1722, P190A {ECO:0000303|PubMed:11044403},
GN p190ARHOGAP {ECO:0000303|PubMed:11044403};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 163-1499.
RC TISSUE=Brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY,
RP PHOSPHORYLATION BY PKC, AND DOMAIN.
RX PubMed=11044403; DOI=10.1242/dev.127.22.4891;
RA Brouns M.R., Matheson S.F., Hu K.Q., Delalle I., Caviness V.S., Silver J.,
RA Bronson R.T., Settleman J.;
RT "The adhesion signaling molecule p190 RhoGAP is required for morphogenetic
RT processes in neural development.";
RL Development 127:4891-4903(2000).
RN [4]
RP FUNCTION, PHOSPHORYLATION BY SRC AND FYN, AND DOMAIN.
RX PubMed=11283609; DOI=10.1038/35070042;
RA Brouns M.R., Matheson S.F., Settleman J.;
RT "p190 RhoGAP is the principal Src substrate in brain and regulates axon
RT outgrowth, guidance and fasciculation.";
RL Nat. Cell Biol. 3:361-367(2001).
RN [5]
RP PHOSPHORYLATION AT TYR-1105, INTERACTION WITH RASA1, AND FUNCTION.
RX PubMed=16971514; DOI=10.1091/mbc.e06-02-0132;
RA Bradley W.D., Hernandez S.E., Settleman J., Koleske A.J.;
RT "Integrin signaling through Arg activates p190RhoGAP by promoting its
RT binding to p120RasGAP and recruitment to the membrane.";
RL Mol. Biol. Cell 17:4827-4836(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP FUNCTION, PHOSPHORYLATION AT SER-1472; SER-1476; THR-1480 AND SER-1483, AND
RP MUTAGENESIS OF SER-1472; SER-1476; THR-1480 AND SER-1483.
RX PubMed=18502760; DOI=10.1074/jbc.m802588200;
RA Jiang W., Betson M., Mulloy R., Foster R., Levay M., Ligeti E.,
RA Settleman J.;
RT "p190A RhoGAP is a glycogen synthase kinase-3-beta substrate required for
RT polarized cell migration.";
RL J. Biol. Chem. 283:20978-20988(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-773; SER-970;
RP SER-975; SER-985; TYR-1087; TYR-1105; SER-1134; SER-1142 AND SER-1179, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20675588; DOI=10.4049/jimmunol.0904163;
RA Nemeth T., Futosi K., Hably C., Brouns M.R., Jakob S.M., Kovacs M.,
RA Kertesz Z., Walzog B., Settleman J., Mocsai A.;
RT "Neutrophil functions and autoimmune arthritis in the absence of
RT p190RhoGAP: generation and analysis of a novel null mutation in mice.";
RL J. Immunol. 185:3064-3075(2010).
RN [13]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=21945077; DOI=10.1016/j.ydbio.2011.09.006;
RA Heckman-Stoddard B.M., Vargo-Gogola T., Herrick M.P., Visbal A.P.,
RA Lewis M.T., Settleman J., Rosen J.M.;
RT "P190A RhoGAP is required for mammary gland development.";
RL Dev. Biol. 360:1-10(2011).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF LEU-1396.
RX PubMed=26859289; DOI=10.1371/journal.pgen.1005785;
RA Stewart K., Gaitan Y., Shafer M.E., Aoudjit L., Hu D., Sharma R.,
RA Tremblay M., Ishii H., Marcotte M., Stanga D., Tang Y.C., Boualia S.K.,
RA Nguyen A.H., Takano T., Lamarche-Vane N., Vidal S., Bouchard M.;
RT "A point mutation in p190A RhoGAP affects ciliogenesis and leads to
RT glomerulocystic kidney defects.";
RL PLoS Genet. 12:E1005785-E1005785(2016).
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:16971514). This binding is inhibited by
CC 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:11044403, PubMed:11283609, PubMed:18502760,
CC PubMed:21945077). Transduces signals from p21-ras to the nucleus,
CC acting via the ras GTPase-activating protein (GAP) (PubMed:16971514).
CC Transduces SRC-dependent signals from cell-surface adhesion molecules,
CC such as laminin, to promote neurite outgrowth. Regulates axon
CC outgrowth, guidance and fasciculation (PubMed:11283609). Modulates Rho
CC GTPase-dependent F-actin polymerization, organization and assembly, is
CC involved in polarized cell migration and in the positive regulation of
CC ciliogenesis and cilia elongation (PubMed:11044403, PubMed:26859289,
CC PubMed:18502760). During mammary gland development, is required in both
CC the epithelial and stromal compartments for ductal outgrowth
CC (PubMed:21945077). Represses transcription of the glucocorticoid
CC receptor by 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:Q9NRY4, ECO:0000269|PubMed:11044403,
CC ECO:0000269|PubMed:11283609, ECO:0000269|PubMed:16971514,
CC ECO:0000269|PubMed:18502760, ECO:0000269|PubMed:21945077,
CC ECO:0000269|PubMed:26859289}.
CC -!- SUBUNIT: Interacts with the general transcription factor GTF2I, the
CC interaction sequesters GTF2I in the cytoplasm (By similarity).
CC Interacts with RASA1 (PubMed:16971514). {ECO:0000250,
CC ECO:0000269|PubMed:16971514}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:26859289}. Cytoplasm {ECO:0000269|PubMed:11044403}.
CC Nucleus {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:11044403}.
CC Note=In response to integrins and SDC4 and upon phosphorylation by PKC,
CC relocalizes from the cytoplasm to regions of plasma membrane ruffling
CC where it colocalizes with polymerized actin.
CC {ECO:0000269|PubMed:11044403}.
CC -!- TISSUE SPECIFICITY: Expressed in the developing kidneys
CC (PubMed:26859289). Expressed in all regions of the mature nervous
CC system (at protein level) (PubMed:11044403). Detected in neutrophils
CC (at protein level) (PubMed:20675588). {ECO:0000269|PubMed:11044403,
CC ECO:0000269|PubMed:20675588, ECO:0000269|PubMed:26859289}.
CC -!- DEVELOPMENTAL STAGE: At 12.5 dpc, the highest level of expression is in
CC the spinal cord and lower expression levels are seen in the developing
CC brain. At 15.5 dpc, highly expressed in brain, spinal cord and eyes
CC (PubMed:11044403). In developing kidney, at 17.5 dpc, low expression is
CC observed in the glomerulus, while high expression levels are detected
CC in the proximal tubule (PubMed:26859289). At 14.5 dpc, is expressed
CC within the epithelial compartment of the embryonic mammary bud and at
CC lower level in the surrounding stroma and skin. Also expressed at
CC terminal end bunds (TEB) at comparable levels in body and cap cells as
CC well as in fibroblasts and stroma surrounding the TEB
CC (PubMed:21945077). {ECO:0000269|PubMed:11044403,
CC ECO:0000269|PubMed:21945077, ECO:0000269|PubMed:26859289}.
CC -!- DOMAIN: N-terminal part (1-266) has GTPase activity. Required for
CC proper cellular localization. Mutation of this region is a severely
CC defective loss of function. Mutants have defective morphogenesis of
CC neural retinal tissue, agenesis of the corpus callosum due to
CC defectuous midline fusion of the cerebral hemispheres
CC (PubMed:11044403). Mutants show defects in axon guidance and
CC fasciculation (PubMed:11283609). {ECO:0000269|PubMed:11044403,
CC ECO:0000269|PubMed:11283609}.
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
CC (PubMed:11044403). In brain, phosphorylated by FYN and SRC
CC (PubMed:11283609). During focal adhesion formation, phosphorylated by
CC MAPK1 and MAPK3 at the C-terminal region, probably at Ser-1451, Ser-
CC 1476, Thr-1480 and Ser-1483. Phosphorylation by MAPK1 and MAPK3
CC inhibits GAP function and localizes ARGHAP35 away from newly forming
CC focal adhesions and stress fibers in cells spreading on fibronectin (By
CC similarity). Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires
CC priming by MAPK and inhibits RhoGAP activity and modulates polarized
CC cell migration (PubMed:18502760). {ECO:0000250|UniProtKB:P81128,
CC ECO:0000250|UniProtKB:Q9NRY4, ECO:0000269|PubMed:11044403,
CC ECO:0000269|PubMed:11283609, ECO:0000269|PubMed:18502760}.
CC -!- DISRUPTION PHENOTYPE: Deficiency leads to perinatal lethality and
CC defective neural development. One third of the fetuses show exencephaly
CC and spina bifida as well as defective kidney development.
CC {ECO:0000269|PubMed:20675588}.
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DR EMBL; AK147326; BAE27848.1; -; mRNA.
DR EMBL; AK147688; BAE28076.1; -; mRNA.
DR EMBL; AK173242; BAD32520.1; -; Transcribed_RNA.
DR CCDS; CCDS20851.1; -.
DR RefSeq; NP_766327.3; NM_172739.4.
DR RefSeq; XP_006539872.1; XM_006539809.3.
DR RefSeq; XP_011248814.1; XM_011250512.2.
DR AlphaFoldDB; Q91YM2; -.
DR BMRB; Q91YM2; -.
DR SMR; Q91YM2; -.
DR BioGRID; 231317; 30.
DR CORUM; Q91YM2; -.
DR IntAct; Q91YM2; 1.
DR STRING; 10090.ENSMUSP00000075242; -.
DR ChEMBL; CHEMBL4879499; -.
DR iPTMnet; Q91YM2; -.
DR PhosphoSitePlus; Q91YM2; -.
DR SwissPalm; Q91YM2; -.
DR jPOST; Q91YM2; -.
DR MaxQB; Q91YM2; -.
DR PaxDb; 10090-ENSMUSP00000075242; -.
DR ProteomicsDB; 254968; -.
DR Pumba; Q91YM2; -.
DR Antibodypedia; 31509; 345 antibodies from 29 providers.
DR Ensembl; ENSMUST00000075845.11; ENSMUSP00000075242.5; ENSMUSG00000058230.13.
DR Ensembl; ENSMUST00000171937.2; ENSMUSP00000127379.2; ENSMUSG00000058230.13.
DR GeneID; 232906; -.
DR KEGG; mmu:232906; -.
DR UCSC; uc009fhw.1; mouse.
DR AGR; MGI:1929494; -.
DR CTD; 2909; -.
DR MGI; MGI:1929494; Arhgap35.
DR VEuPathDB; HostDB:ENSMUSG00000058230; -.
DR eggNOG; KOG4271; Eukaryota.
DR GeneTree; ENSGT01030000234635; -.
DR HOGENOM; CLU_004268_0_0_1; -.
DR InParanoid; Q91YM2; -.
DR OMA; IVMCLLC; -.
DR OrthoDB; 5405671at2759; -.
DR PhylomeDB; Q91YM2; -.
DR TreeFam; TF324451; -.
DR Reactome; R-MMU-416550; Sema4D mediated inhibition of cell attachment and migration.
DR Reactome; R-MMU-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-9696264; RND3 GTPase cycle.
DR Reactome; R-MMU-9696270; RND2 GTPase cycle.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR BioGRID-ORCS; 232906; 2 hits in 81 CRISPR screens.
DR ChiTaRS; Arhgap35; mouse.
DR PRO; PR:Q91YM2; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q91YM2; Protein.
DR Bgee; ENSMUSG00000058230; Expressed in saccule of membranous labyrinth and 260 other cell types or tissues.
DR ExpressionAtlas; Q91YM2; baseline and differential.
DR Genevisible; Q91YM2; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:MGI.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0007411; P:axon guidance; IDA:UniProtKB.
DR GO; GO:0007413; P:axonal fasciculation; IMP:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IMP:UniProtKB.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IMP:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:MGI.
DR GO; GO:0030879; P:mammary gland development; IMP:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IDA:MGI.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IMP:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0097485; P:neuron projection guidance; IMP:UniProtKB.
DR GO; GO:0045724; P:positive regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; IMP:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:MGI.
DR GO; GO:0008361; P:regulation of cell size; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IGI:MGI.
DR GO; GO:0044319; P:wound healing, spreading of cells; IMP:UniProtKB.
DR CDD; cd22221; pseudoGTPaseD_p190RhoGAP-A; 1.
DR CDD; cd04373; RhoGAP_p190; 1.
DR Gene3D; 1.10.10.440; FF domain; 2.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 1.10.555.10; Rho GTPase activation protein; 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 PANTHER; PTHR46005; RHO GTPASE-ACTIVATING PROTEIN 190; 1.
DR PANTHER; PTHR46005:SF1; RHO GTPASE-ACTIVATING PROTEIN 35; 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; SSF81698; FF domain; 1.
DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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 Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; DNA-binding;
KW GTP-binding; GTPase activation; Lipid-binding; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..1499
FT /note="Rho GTPase-activating protein 35"
FT /id="PRO_0000056731"
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:0000269|PubMed:11044403"
FT REGION 1124..1148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1177..1207
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:21183079"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 970
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 975
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1072
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRY4"
FT MOD_RES 1087
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1105
FT /note="Phosphotyrosine; by ABL2 and PTK6"
FT /evidence="ECO:0000269|PubMed:16971514,
FT ECO:0007744|PubMed:17947660, ECO:0007744|PubMed:18034455,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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:21183079"
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:0000269|PubMed:18502760"
FT MOD_RES 1476
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18502760"
FT MOD_RES 1480
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18502760"
FT MOD_RES 1483
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18502760"
FT MUTAGEN 1396
FT /note="L->Q: In ENU mutant Arhgap35-D34; mutant animals
FT show hypodysplastic kidneys and neural tube closure
FT defects; the number of ciliated cells and cilia average
FT length are drastically reduced in the proximal tubules.
FT Results in loss of activation of GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:26859289"
FT MUTAGEN 1472
FT /note="S->A: Reduces phosphorylation by GSK3B by 50%. No
FT effect on polarized cell migration."
FT /evidence="ECO:0000269|PubMed:18502760"
FT MUTAGEN 1476
FT /note="S->A: Abolishes phosphorylation by GSK3B. Reduces
FT phosphorylation by MAPK. Affects polarized cell migration.
FT Increases RhoGAP catalytic activity."
FT /evidence="ECO:0000269|PubMed:18502760"
FT MUTAGEN 1480
FT /note="T->A: Abolishes phosphorylation by GSK3B. Reduces
FT phosphorylation by MAPK. Affects polarized cell migration.
FT Increases RhoGAP catalytic activity."
FT /evidence="ECO:0000269|PubMed:18502760"
FT MUTAGEN 1483
FT /note="S->A: Abolishes phosphorylation by GSK3B. Reduces
FT phosphorylation by MAPK. No effect on polarized cell
FT migration."
FT /evidence="ECO:0000269|PubMed:18502760"
SQ SEQUENCE 1499 AA; 170393 MW; 7E13EC38257CE950 CRC64;
MMMARKQDVR IPTYNISVVG LSGTEKEKGQ CGIGKSCLCN RFVRPSADEF HLDHTSVLST
SDFGGRVVNN DHFLYWGEVS RSLEDCVECK MHIVEQTEFI DDQTFQPHRS TALQPYIKRA
AATKLASAEK LMYFCTDQLG LEQDFEQKQM PDGKLLVDGF LLGIDVSRGM NRNFDDQLKF
VSNLYNQLAK TKKPIVVVLT KCDEGVERYI RDAHTFALSK KNLQVVETSA RSNVNVDLAF
STLVQLIDKS RGKTKIIPYF EALKQQSQQI ATAKDKYEWL VSRIVKNHNE NWPSVSRKMQ
ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA LIPNLDEVDH
LSCIKAKKLL ETKPEFLKWF VVLEETPWDA TSHIDNMENE RIPFDLMDTV PAEQLYETHL
EKLRNERKRA EMRRAFKENL ETSPFITPGK PWEEARSFIM NEDFYQWLEE SVYMDIYGKH
QKQIIDRAKE EFQELLLEYS ELFYELELDA KPSKEKMGVI QDVLGEEQRF KALQKLQAER
DALILKHIHF VYHPTKETCP SCPACVDAKI EHLISSRFIR PSDRNQKNSL SDLNIDRINL
VILGKDGLAR ELANEIRALC TNDDKYVIDG KMYELSLRPI EGNVRLPVNS FQTPTFQPHG
CLCLYNSKES LSYVVESIEK SRESTLGRRD NHLVHLPLTL ILVNKRGDTS GETLHSLIQQ
GQQIASKLQC VFLDPASAGI GYGRNINEKQ ISQVLKGLLD SKRNLNLVSS TASIKDLADV
DLRIVMCLMC GDPFSADDVL SPVLQSQTCK SSHCGSSNSV LLELPIGLHK KRIELSVLSY
HSSFSIRKSR LVHGYIVFYS AKRKASLAML RAFLCEVQDI IPIQLVALTD GAIDVLDNDL
SREQLTEGEE IAQEIDGRFT SIPCSQPQHK LELFHPFFKD VVEKKNIIEA THMYDNVAEA
CSTTEEVFNS PRAGSPLCNS NLQDSEEDVE PPSYHLFRED ATLPSLSKDH SKFSMELEGN
DGLSFIMSNF ESKLNNKVPP PVKPKPPVHF DITKDLSYLD 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
KVSHNNKVNL MTSENLSICF WPTLMRPDFS SMDALTATRS YQTIIELFIQ QCPFFFYNRP
ISEPPGAAPG SPSAMAPTVP FLTSTPATSQ PSPPQSPPPT PQSPMQPLLS SQLQAEHTL
//
