ID RHG35_HUMAN Reviewed; 1499 AA. AC Q9NRY4; A7E2A4; Q14452; Q9C0E1; DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 3. DT 27-MAR-2024, entry version 218. DE RecName: Full=Rho GTPase-activating protein 35 {ECO:0000312|HGNC:HGNC:4591}; DE AltName: Full=Glucocorticoid receptor DNA-binding factor 1; DE AltName: Full=Glucocorticoid receptor repression factor 1; DE Short=GRF-1; DE AltName: Full=Rho GAP p190A; DE Short=p190-A {ECO:0000303|PubMed:11054565}; GN Name=ARHGAP35 {ECO:0000312|HGNC:HGNC:4591}; GN Synonyms=GRF1 {ECO:0000303|PubMed:1894621}, GRLF1 GN {ECO:0000303|PubMed:1894621}, KIAA1722, P190A GN {ECO:0000303|PubMed:19673492}, p190ARHOGAP GN {ECO:0000303|PubMed:19673492}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAF80386.1}; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=11214970; DOI=10.1093/dnares/7.6.347; RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:347-355(2000). RN [2] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1491. RC TISSUE=Mammary cancer; RX PubMed=11054565; DOI=10.1016/s0378-1119(00)00387-5; RA Tikoo A., Czekay S., Viars C., White S., Heath J.K., Arden K., Maruta H.; RT "p190-A, a human tumor suppressor gene, maps to the chromosomal region RT 19q13.3 that is reportedly deleted in some gliomas."; RL Gene 257:23-31(2000). RN [6] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] OF 377-1453, AND FUNCTION. RC TISSUE=Mammary cancer; RX PubMed=1894621; DOI=10.1016/s0021-9258(19)47378-x; RA LeClerc S., Palaniswami R., Xie B.X., Govindan M.V.; RT "Molecular cloning and characterization of a factor that binds the human RT glucocorticoid receptor gene and represses its expression."; RL J. Biol. Chem. 266:17333-17340(1991). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [9] RP PHOSPHORYLATION AT TYR-1105. RX PubMed=18829532; DOI=10.1158/0008-5472.can-08-0997; RA Shen C.H., Chen H.Y., Lin M.S., Li F.Y., Chang C.C., Kuo M.L., RA Settleman J., Chen R.H.; RT "Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and RT promote breast carcinoma growth, migration, and invasion."; RL Cancer Res. 68:7779-7787(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-970 AND SER-1179, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1179, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-970; SER-975; RP SER-1150 AND SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-1221; THR-1226 AND RP SER-1236, MUTAGENESIS OF SER-1221; THR-1226 AND SER-1236, AND BINDING TO RP PHOSPHOLIPIDS. RX PubMed=19673492; DOI=10.1021/bi900667y; RA Levay M., Settleman J., Ligeti E.; RT "Regulation of the substrate preference of p190RhoGAP by protein kinase C- RT mediated phosphorylation of a phospholipid binding site."; RL Biochemistry 48:8615-8623(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-773; SER-975; RP SER-1072; TYR-1087; TYR-1105; SER-1134 AND SER-1179, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [16] RP TISSUE SPECIFICITY. 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589 AND SER-1179, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-1134; SER-1150 AND RP SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-770; SER-773; RP SER-1134; SER-1150; SER-1176 AND SER-1179, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-1001; SER-1150 AND RP SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP FUNCTION, AND DOMAIN. RX PubMed=28894085; DOI=10.1038/s41467-017-00483-x; RA Stiegler A.L., Boggon T.J.; RT "p190RhoGAP proteins contain pseudoGTPase domains."; RL Nat. Commun. 8:506-506(2017). RN [23] {ECO:0007744|PDB:3C5H} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 13-249 IN COMPLEX WITH GTP RP ANALOG. RG Structural genomics consortium (SGC); RT "Crystal structure of the Ras homolog domain of human GRLF1 (p190RhoGAP)."; RL Submitted (JAN-2008) to the PDB data bank. RN [24] {ECO:0007744|PDB:3FK2} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1212-1439. RG Structural genomics consortium (SGC); RT "Crystal structure of the RhoGAP domain of human glucocorticoid receptor RT DNA-binding factor 1."; RL Submitted (DEC-2008) to the PDB data bank. RN [25] RP STRUCTURE BY NMR OF 267-331, PHOSPHORYLATION AT TYR-308, AND INTERACTION RP WITH GTF2I. RX PubMed=19393245; DOI=10.1016/j.jmb.2009.04.035; RA Bonet R., Ruiz L., Aragon E., Martin-Malpartida P., Macias M.J.; RT "NMR structural studies on human p190-A RhoGAPFF1 revealed that domain RT phosphorylation by the PDGF-receptor alpha requires its previous RT unfolding."; RL J. Mol. Biol. 389:230-237(2009). CC -!- FUNCTION: Rho GTPase-activating protein (GAP) (PubMed:19673492, CC PubMed:28894085). Binds several acidic phospholipids which inhibits the CC Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). CC This binding is inhibited by phosphorylation by PRKCA CC (PubMed:19673492). Involved in cell differentiation as well as cell CC adhesion and migration, plays an important role in retinal tissue CC morphogenesis, neural tube fusion, midline fusion of the cerebral CC hemispheres and mammary gland branching morphogenesis (By similarity). CC Transduces signals from p21-ras to the nucleus, acting via the ras CC GTPase-activating protein (GAP) (By similarity). Transduces SRC- CC dependent signals from cell-surface adhesion molecules, such as CC laminin, to promote neurite outgrowth. Regulates axon outgrowth, CC guidance and fasciculation (By similarity). Modulates Rho GTPase- CC 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 (By similarity). During mammary gland CC development, is required in both the epithelial and stromal CC compartments for ductal outgrowth (By similarity). Represses CC transcription of the glucocorticoid receptor by binding to the cis- CC acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function CC is however unclear and would need additional experimental evidences CC (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, CC ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, CC ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}. CC -!- ACTIVITY REGULATION: Binding of acidic phospholipids inhibits the Rho CC GAP activity and promotes the Rac GAP activity. CC {ECO:0000269|PubMed:19673492}. CC -!- SUBUNIT: Interacts with RASA1 (By similarity). Interacts with the CC general transcription factor GTF2I, the interaction sequesters GTF2I in CC the cytoplasm (PubMed:19393245). {ECO:0000250|UniProtKB:Q91YM2, CC ECO:0000269|PubMed:19393245}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body CC {ECO:0000250|UniProtKB:Q91YM2}. Cytoplasm CC {ECO:0000250|UniProtKB:Q91YM2}. Nucleus {ECO:0000305|PubMed:1894621}. CC Cell membrane {ECO:0000250|UniProtKB:Q91YM2}. Note=In response to CC integrins and SDC4 and upon phosphorylation by PKC, relocalizes from CC the cytoplasm to regions of plasma membrane ruffling where it CC colocalizes with polymerized actin. {ECO:0000250|UniProtKB:Q91YM2}. CC -!- TISSUE SPECIFICITY: Detected in neutrophils (at protein level). CC {ECO:0000269|PubMed:1894621}. 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:0000269|PubMed:28894085}. 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 (PubMed:18829532, CC PubMed:19393245). Phosphorylated by PRKCA at Ser-1221 and Thr-1226, CC induces relocalization from the cytoplasm to regions of plasma membrane CC ruffling and prevents the binding and substrate specificity regulation CC by phospholipids (PubMed:19673492). In brain, phosphorylated by FYN and CC SRC (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P81128, CC ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:18829532, CC ECO:0000269|PubMed:19393245, ECO:0000269|PubMed:19673492}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA58618.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAF80386.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAF80386.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305}; 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; AB051509; BAB21813.2; -; mRNA. DR EMBL; CH471126; EAW57450.1; -; Genomic_DNA. DR EMBL; BC150257; AAI50258.1; -; mRNA. DR EMBL; AF159851; AAF80386.1; ALT_SEQ; mRNA. DR EMBL; M73077; AAA58618.1; ALT_FRAME; mRNA. DR CCDS; CCDS46127.1; -. DR RefSeq; NP_004482.4; NM_004491.4. DR RefSeq; XP_016882203.1; XM_017026714.1. DR PDB; 2K85; NMR; -; A=267-331. DR PDB; 3C5H; X-ray; 1.80 A; A=13-249. DR PDB; 3FK2; X-ray; 2.80 A; A/B/C/D=1212-1439. DR PDB; 6PXC; X-ray; 1.60 A; U=1100-1112. DR PDB; 6WAY; X-ray; 1.50 A; V=1086-1093. DR PDB; 8DGQ; X-ray; 1.95 A; U/V=1083-1111. DR PDBsum; 2K85; -. DR PDBsum; 3C5H; -. DR PDBsum; 3FK2; -. DR PDBsum; 6PXC; -. DR PDBsum; 6WAY; -. DR PDBsum; 8DGQ; -. DR AlphaFoldDB; Q9NRY4; -. DR BMRB; Q9NRY4; -. DR SASBDB; Q9NRY4; -. DR SMR; Q9NRY4; -. DR BioGRID; 109166; 108. DR DIP; DIP-34578N; -. DR IntAct; Q9NRY4; 23. DR MINT; Q9NRY4; -. DR STRING; 9606.ENSP00000500409; -. DR BindingDB; Q9NRY4; -. DR ChEMBL; CHEMBL4523646; -. DR iPTMnet; Q9NRY4; -. DR PhosphoSitePlus; Q9NRY4; -. DR BioMuta; ARHGAP35; -. DR DMDM; 408360250; -. DR EPD; Q9NRY4; -. DR jPOST; Q9NRY4; -. DR MassIVE; Q9NRY4; -. DR MaxQB; Q9NRY4; -. DR PaxDb; 9606-ENSP00000385720; -. DR PeptideAtlas; Q9NRY4; -. DR ProteomicsDB; 82441; -. DR Pumba; Q9NRY4; -. DR Antibodypedia; 31509; 345 antibodies from 29 providers. DR DNASU; 2909; -. DR Ensembl; ENST00000672722.1; ENSP00000500409.1; ENSG00000160007.20. DR GeneID; 2909; -. DR KEGG; hsa:2909; -. DR MANE-Select; ENST00000672722.1; ENSP00000500409.1; NM_004491.5; NP_004482.4. DR UCSC; uc010ekv.4; human. DR AGR; HGNC:4591; -. DR CTD; 2909; -. DR DisGeNET; 2909; -. DR GeneCards; ARHGAP35; -. DR HGNC; HGNC:4591; ARHGAP35. DR HPA; ENSG00000160007; Low tissue specificity. DR MalaCards; ARHGAP35; -. DR MIM; 605277; gene. DR neXtProt; NX_Q9NRY4; -. DR OpenTargets; ENSG00000160007; -. DR PharmGKB; PA28988; -. DR VEuPathDB; HostDB:ENSG00000160007; -. DR eggNOG; KOG4271; Eukaryota. DR GeneTree; ENSGT01030000234635; -. DR HOGENOM; CLU_004268_0_0_1; -. DR InParanoid; Q9NRY4; -. DR OMA; IVMCLLC; -. DR OrthoDB; 5405671at2759; -. DR PhylomeDB; Q9NRY4; -. DR TreeFam; TF324451; -. DR PathwayCommons; Q9NRY4; -. DR Reactome; R-HSA-416550; Sema4D mediated inhibition of cell attachment and migration. DR Reactome; R-HSA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013026; RHOB GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9013405; RHOD GTPase cycle. DR Reactome; R-HSA-9013406; RHOQ GTPase cycle. DR Reactome; R-HSA-9013408; RHOG GTPase cycle. DR Reactome; R-HSA-9013409; RHOJ GTPase cycle. DR Reactome; R-HSA-9013423; RAC3 GTPase cycle. DR Reactome; R-HSA-9696264; RND3 GTPase cycle. DR Reactome; R-HSA-9696270; RND2 GTPase cycle. DR Reactome; R-HSA-9696273; RND1 GTPase cycle. DR SignaLink; Q9NRY4; -. DR SIGNOR; Q9NRY4; -. DR BioGRID-ORCS; 2909; 34 hits in 1171 CRISPR screens. DR ChiTaRS; ARHGAP35; human. DR EvolutionaryTrace; Q9NRY4; -. DR GeneWiki; GRLF1; -. DR GenomeRNAi; 2909; -. DR Pharos; Q9NRY4; Tbio. DR PRO; PR:Q9NRY4; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9NRY4; Protein. DR Bgee; ENSG00000160007; Expressed in Brodmann (1909) area 23 and 198 other cell types or tissues. DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl. DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB. 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; IEA:Ensembl. 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; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. 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; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:0030879; P:mammary gland development; ISS:UniProtKB. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISS:ARUK-UCL. DR GO; GO:0043116; P:negative regulation of vascular permeability; IEA:Ensembl. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. 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: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; IEA:Ensembl. DR GO; GO:0008361; P:regulation of cell size; IBA:GO_Central. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. 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 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. DR Genevisible; Q9NRY4; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; KW DNA-binding; 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_0000056730" 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 1058..1089 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1124..1146 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:0000269|PubMed:19673492" 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 1451..1469 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1470..1486 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:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT BINDING 33..37 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT BINDING 52 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT BINDING 56 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT BINDING 95..97 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT BINDING 201..203 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT BINDING 229..231 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H" FT MOD_RES 308 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:19393245" FT MOD_RES 589 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 770 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 773 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 970 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648" FT MOD_RES 975 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 985 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91YM2" FT MOD_RES 1001 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1072 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1087 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1105 FT /note="Phosphotyrosine; by ABL2 and PTK6" FT /evidence="ECO:0000269|PubMed:18829532, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1142 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91YM2" FT MOD_RES 1150 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1176 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1179 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1221 FT /note="Phosphoserine; by PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:19673492" FT MOD_RES 1226 FT /note="Phosphothreonine; by PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:19673492" FT MOD_RES 1236 FT /note="Phosphoserine; by PKC/PRKCA" FT /evidence="ECO:0000269|PubMed:19673492" 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 1221 FT /note="S->A: No effect on total phosphorylation levels. FT Abolishes inhibition of phospholipid binding by PRKCA FT phosphorylation. Decreases phosphorylation by PRKCA; when FT associated with A-1226. Abolishes phosphorylation by PRKCA; FT when associated with A-1126 and A-1236." FT /evidence="ECO:0000269|PubMed:19673492" FT MUTAGEN 1221 FT /note="S->D: Enhances Rac GAP activity." FT /evidence="ECO:0000269|PubMed:19673492" FT MUTAGEN 1226 FT /note="T->A: No effect on total phosphorylation levels. FT Abolishes inhibition of phospholipid binding by PRKCA FT phosphorylation. Decreases phosphorylation by PRKCA; when FT associated with A-1221. Abolishes phosphorylation by PRKCA; FT when associated with A-1121 and A-1236." FT /evidence="ECO:0000269|PubMed:19673492" FT MUTAGEN 1226 FT /note="T->D: Enhances Rac GAP activity." FT /evidence="ECO:0000269|PubMed:19673492" FT MUTAGEN 1236 FT /note="S->A: No effect on total phosphorylation levels. No FT effect on inhibition of phospholipid binding by PRKCA FT phosphorylation. Abolishes phosphorylation by PRKCA; when FT associated with A-1121 and A-1226." FT /evidence="ECO:0000269|PubMed:19673492" FT CONFLICT 251 FT /note="R -> P (in Ref. 5; AAF80386)" FT /evidence="ECO:0000305" FT CONFLICT 309 FT /note="V -> D (in Ref. 5; AAF80386)" FT /evidence="ECO:0000305" FT CONFLICT 362 FT /note="S -> G (in Ref. 5; AAF80386)" FT /evidence="ECO:0000305" FT CONFLICT 414 FT /note="Q -> A (in Ref. 5; AAF80386 and 6; AAA58618)" FT /evidence="ECO:0000305" FT CONFLICT 474 FT /note="M -> T (in Ref. 5; AAF80386 and 6; AAA58618)" FT /evidence="ECO:0000305" FT CONFLICT 978 FT /note="C -> S (in Ref. 5; AAF80386)" FT /evidence="ECO:0000305" FT CONFLICT 1292 FT /note="M -> I (in Ref. 5; AAF80386)" FT /evidence="ECO:0000305" FT CONFLICT 1452..1453 FT /note="PS -> RN (in Ref. 6; AAA58618)" FT /evidence="ECO:0000305" FT STRAND 14..21 FT /evidence="ECO:0007829|PDB:3C5H" FT TURN 25..30 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 35..43 FT /evidence="ECO:0007829|PDB:3C5H" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 60..63 FT /evidence="ECO:0007829|PDB:3C5H" FT TURN 66..70 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 72..79 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 91..96 FT /evidence="ECO:0007829|PDB:3C5H" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 116..120 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 123..126 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 136..138 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 151..153 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 159..165 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 174..190 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 195..200 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 207..218 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 220..222 FT /evidence="ECO:0007829|PDB:3C5H" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:3C5H" FT TURN 230..233 FT /evidence="ECO:0007829|PDB:3C5H" FT HELIX 236..248 FT /evidence="ECO:0007829|PDB:3C5H" FT TURN 268..271 FT /evidence="ECO:0007829|PDB:2K85" FT HELIX 272..284 FT /evidence="ECO:0007829|PDB:2K85" FT STRAND 286..288 FT /evidence="ECO:0007829|PDB:2K85" FT HELIX 292..299 FT /evidence="ECO:0007829|PDB:2K85" FT HELIX 303..311 FT /evidence="ECO:0007829|PDB:2K85" FT HELIX 314..330 FT /evidence="ECO:0007829|PDB:2K85" FT HELIX 1100..1102 FT /evidence="ECO:0007829|PDB:8DGQ" FT HELIX 1251..1254 FT /evidence="ECO:0007829|PDB:3FK2" FT STRAND 1257..1259 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1263..1275 FT /evidence="ECO:0007829|PDB:3FK2" FT TURN 1280..1284 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1289..1301 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1308..1310 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1314..1327 FT /evidence="ECO:0007829|PDB:3FK2" FT STRAND 1328..1330 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1335..1344 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1350..1362 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1366..1383 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1386..1389 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1393..1405 FT /evidence="ECO:0007829|PDB:3FK2" FT STRAND 1409..1412 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1414..1430 FT /evidence="ECO:0007829|PDB:3FK2" FT HELIX 1432..1436 FT /evidence="ECO:0007829|PDB:3FK2" SQ SEQUENCE 1499 AA; 170514 MW; 8CCB493414A7E3E6 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 NWLSVSRKMQ ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA LIPNLDEIDH LSCIKAKKLL ETKPEFLKWF VVLEETPWDA TSHIDNMENE RIPFDLMDTV PAEQLYEAHL EKLRNERKRV EMRRAFKENL ETSPFITPGK PWEEARSFIM NEDFYQWLEE SVYMDIYGKH QKQIIDKAKE 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 FPVLQSQTCK SSHCGSNNSV LLELPIGLHK KRIELSVLSY HSSFSIRKSR LVHGYIVFYS AKRKASLAML RAFLCEVQDI IPIQLVALTD GAVDVLDNDL SREQLTEGEE IAQEIDGRFT SIPCSQPQHK LEIFHPFFKD VVEKKNIIEA THMYDNAAEA CSTTEEVFNS PRAGSPLCNS NLQDSEEDIE PSYSLFREDT SLPSLSKDHS KLSMELEGND GLSFIMSNFE SKLNNKVPPP VKPKPPVHFE ITKGDLSYLD QGHRDGQRKS VSSSPWLPQD GFDPSDYAEP MDAVVKPRNE EENIYSVPHD STQGKIITIR NINKAQSNGS GNGSDSEMDT SSLERGRKVS IVSKPVLYRT RCTRLGRFAS YRTSFSVGSD DELGPIRKKE EDQASQGYKG DNAVIPYETD EDPRRRNILR SLRRNTKKPK PKPRPSITKA TWESNYFGVP LTTVVTPEKP IPIFIERCIE YIEATGLSTE GIYRVSGNKS EMESLQRQFD QDHNLDLAEK DFTVNTVAGA MKSFFSELPD PLVPYNMQID LVEAHKINDR EQKLHALKEV LKKFPKENHE VFKYVISHLN KVSHNNKVNL MTSENLSICF WPTLMRPDFS TMDALTATRT YQTIIELFIQ QCPFFFYNRP ITEPPGARPS SPSAVASTVP FLTSTPVTSQ PSPPQSPPPT PQSPMQPLLP SQLQAEHTL //