ID RASA1_HUMAN Reviewed; 1047 AA. AC P20936; B2R6W3; B4DTL2; Q68CU6; Q9UDI1; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 1. DT 27-MAR-2024, entry version 252. DE RecName: Full=Ras GTPase-activating protein 1; DE Short=GAP; DE Short=GTPase-activating protein; DE Short=RasGAP; DE AltName: Full=Ras p21 protein activator; DE AltName: Full=p120GAP; GN Name=RASA1; Synonyms=GAP, RASA; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Placenta; RX PubMed=3201259; DOI=10.1126/science.3201259; RA Trahey M., Wong G., Halenbeck R., Rubinfeld B., Martin G.A., Ladner M., RA Long C.M., Crosier W.J., Watt K., Koths K., McCormick F.; RT "Molecular cloning of two types of GAP complementary DNA from human RT placenta."; RL Science 242:1697-1700(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [6] RP PROTEIN SEQUENCE OF 294-303; 326-334; 392-398; 439-457; 458-466; 479-483; RP 777-790 AND 821-825, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Placenta; RX PubMed=8360177; DOI=10.1016/s0021-9258(17)46708-1; RA Zhang Y., Zhang G., Mollat P., Carles C., Riva M., Frobert Y., RA Malassine A., Rostene W., Thang D.C., Beltchev B., Tavitian A., Thane M.N.; RT "Purification, characterization, and cellular localization of the 100-kDa RT human placental GTPase-activating protein."; RL J. Biol. Chem. 268:18875-18881(1993). RN [7] RP PROTEIN SEQUENCE OF 1-7 (ISOFORM 2). RX PubMed=2123878; DOI=10.1016/s0021-9258(18)45826-7; RA Halenbeck R., Crosier W.J., Clark R., McCormick F., Koths K.; RT "Purification, characterization, and western blot analysis of human GTPase- RT activating protein from native and recombinant sources."; RL J. Biol. Chem. 265:21922-21928(1990). RN [8] RP PHOSPHORYLATION, AND FUNCTION. RX PubMed=11389730; DOI=10.1046/j.1432-1327.2001.02230.x; RA Giglione C., Gonfloni S., Parmeggiani A.; RT "Differential actions of p60c-Src and Lck kinases on the Ras regulators RT p120-GAP and GDP/GTP exchange factor CDC25Mm."; RL Eur. J. Biochem. 268:3275-3283(2001). RN [9] RP INTERACTION WITH PDGFRB. RX PubMed=1375321; DOI=10.1128/mcb.12.6.2534-2544.1992; RA Kazlauskas A., Kashishian A., Cooper J.A., Valius M.; RT "GTPase-activating protein and phosphatidylinositol 3-kinase bind to RT distinct regions of the platelet-derived growth factor receptor beta RT subunit."; RL Mol. Cell. Biol. 12:2534-2544(1992). RN [10] RP INTERACTION WITH SQSTM1. RX PubMed=8618896; DOI=10.1073/pnas.92.26.12338; RA Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.; RT "Phosphotyrosine-independent binding of a 62-kDa protein to the src RT homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of RT Ser-59 in the lck unique N-terminal region."; RL Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995). RN [11] RP INTERACTION WITH CAV2. RX PubMed=12091389; DOI=10.1074/jbc.m204367200; RA Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., Lisanti M.P.; RT "Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho- RT caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated RT with lipid rafts/caveolae, but no longer forms a high molecular mass RT hetero-oligomer with caveolin-1."; RL J. Biol. Chem. 277:34556-34567(2002). RN [12] RP INTERACTION WITH CAV2. RX PubMed=15504032; DOI=10.1021/bi049295+; RA Wang X.B., Lee H., Capozza F., Marmon S., Sotgia F., Brooks J.W., RA Campos-Gonzalez R., Lisanti M.P.; RT "Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the RT spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27)."; RL Biochemistry 43:13694-13706(2004). RN [13] RP INTERACTION WITH SPSB1. RX PubMed=15713673; DOI=10.1074/jbc.m413897200; RA Wang D., Li Z., Messing E.M., Wu G.; RT "The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET RT and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response RT element pathway."; RL J. Biol. Chem. 280:16393-16401(2005). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-615, AND IDENTIFICATION BY RP 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 [15] RP INTERACTION WITH PDPK1. RX PubMed=18024423; DOI=10.1074/jbc.m706361200; RA Yang K.J., Shin S., Piao L., Shin E., Li Y., Park K.A., Byun H.S., Won M., RA Hong J., Kweon G.R., Hur G.M., Seok J.H., Chun T., Brazil D.P., RA Hemmings B.A., Park J.; RT "Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src RT involves tyrosine phosphorylation of PDK1 and Src homology 2 domain RT binding."; RL J. Biol. Chem. 283:1480-1491(2008). RN [16] 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 [17] RP INTERACTION WITH NCK1. RX PubMed=21664272; DOI=10.1016/j.cellsig.2011.05.019; RA Ger M., Zitkus Z., Valius M.; RT "Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and RT regulates its activity."; RL Cell. Signal. 23:1651-1658(2011). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-831, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 INTERACTION WITH EPHB4. RX PubMed=30578106; DOI=10.1016/j.neuron.2018.11.041; RA Duran D., Zeng X., Jin S.C., Choi J., Nelson-Williams C., Yatsula B., RA Gaillard J., Furey C.G., Lu Q., Timberlake A.T., Dong W., Sorscher M.A., RA Loring E., Klein J., Allocco A., Hunt A., Conine S., Karimy J.K., RA Youngblood M.W., Zhang J., DiLuna M.L., Matouk C.C., Mane S., RA Tikhonova I.R., Castaldi C., Lopez-Giraldez F., Knight J., Haider S., RA Soban M., Alper S.L., Komiyama M., Ducruet A.F., Zabramski J.M., Dardik A., RA Walcott B.P., Stapleton C.J., Aagaard-Kienitz B., Rodesch G., Jackson E., RA Smith E.R., Orbach D.B., Berenstein A., Bilguvar K., Vikkula M., Gunel M., RA Lifton R.P., Kahle K.T.; RT "Mutations in chromatin modifier and ephrin signaling genes in vein of RT Galen malformation."; RL Neuron 101:429-443(2019). RN [22] RP STRUCTURE BY NMR OF 275-350. RX PubMed=8137811; DOI=10.1002/j.1460-2075.1994.tb06379.x; RA Yang Y.S., Garbay C., Duschesne M., Cornille F., Jullian N., Fromage N., RA Tocque B., Roques B.P.; RT "Solution structure of GAP SH3 domain by 1H NMR and spatial arrangement of RT essential Ras signaling-involved sequence."; RL EMBO J. 13:1270-1279(1994). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 714-1047. RX PubMed=8955277; DOI=10.1038/384591a0; RA Scheffzek K., Lautwein A., Kabsch W., Reza Ahmadian M., Wittinghofer A.; RT "Crystal structure of the GTPase-activating domain of human p120GAP and RT implications for the interaction with Ras."; RL Nature 384:591-596(1996). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 714-1047 IN COMPLEX WITH RAS. RX PubMed=9219684; DOI=10.1126/science.277.5324.333; RA Scheffzek K., Ahmadian M.R., Kabsch W., Wiesmuller L., Lautwein A., RA Schmitz F., Wittinghofer A.; RT "The Ras-RasGAP complex: structural basis for GTPase activation and its RT loss in oncogenic Ras mutants."; RL Science 277:333-338(1997). RN [25] RP STRUCTURE BY NMR OF 282-446. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH3 domain and of the second SH2 domain of human RT RAS GTPase-activating protein 1."; RL Submitted (MAY-2007) to the PDB data bank. RN [26] RP VARIANTS LEU-398; GLU-400 AND VAL-401. RX PubMed=8275088; DOI=10.1038/ng1193-242; RA Friedman E., Gejman P.V., Martin G.A., McCormick F.; RT "Nonsense mutations in the C-terminal SH2 region of the GTPase activating RT protein (GAP) gene in human tumours."; RL Nat. Genet. 5:242-247(1993). RN [27] RP VARIANT CMAVM1 TYR-540. RX PubMed=14639529; DOI=10.1086/379793; RA Eerola I., Boon L.M., Mulliken J.B., Burrows P.E., Dompmartin A., RA Watanabe S., Vanwijck R., Vikkula M.; RT "Capillary malformation-arteriovenous malformation, a new clinical and RT genetic disorder caused by RASA1 mutations."; RL Am. J. Hum. Genet. 73:1240-1249(2003). RN [28] RP VARIANTS CMAVM1 CYS-528; ASP-530; GLU-626 AND VAL-763. RX PubMed=24038909; DOI=10.1002/humu.22431; RA Revencu N., Boon L.M., Mendola A., Cordisco M.R., Dubois J., Clapuyt P., RA Hammer F., Amor D.J., Irvine A.D., Baselga E., Dompmartin A., Syed S., RA Martin-Santiago A., Ades L., Collins F., Smith J., Sandaradura S., RA Barrio V.R., Burrows P.E., Blei F., Cozzolino M., Brunetti-Pierri N., RA Vicente A., Abramowicz M., Desir J., Vilain C., Chung W.K., Wilson A., RA Gardiner C.A., Dwight Y., Lord D.J., Fishman L., Cytrynbaum C., Chamlin S., RA Ghali F., Gilaberte Y., Joss S., Boente Mdel C., Leaute-Labreze C., RA Delrue M.A., Bayliss S., Martorell L., Gonzalez-Ensenat M.A., RA Mazereeuw-Hautier J., O'Donnell B., Bessis D., Pyeritz R.E., Salhi A., RA Tan O.T., Wargon O., Mulliken J.B., Vikkula M.; RT "RASA1 mutations and associated phenotypes in 68 families with capillary RT malformation-arteriovenous malformation."; RL Hum. Mutat. 34:1632-1641(2013). CC -!- FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. CC Stimulates the GTPase of normal but not oncogenic Ras p21; this CC stimulation may be further increased in the presence of NCK1. CC {ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:8360177}. CC -!- SUBUNIT: Interacts with SQSTM1. Interacts with SPSB1; the interaction CC does not promote degradation. Interacts with CAV2 (tyrosine CC phosphorylated form). Directly interacts with NCK1. Interacts with CC PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the CC 'Tyr-9' phosphorylated form of PDPK1. Interacts with tyrosine- CC phosphorylated EPHB4 (PubMed:8955277). {ECO:0000269|PubMed:12091389, CC ECO:0000269|PubMed:1375321, ECO:0000269|PubMed:15504032, CC ECO:0000269|PubMed:15713673, ECO:0000269|PubMed:18024423, CC ECO:0000269|PubMed:21664272, ECO:0000269|PubMed:8618896, CC ECO:0000269|PubMed:8955277, ECO:0000269|PubMed:9219684}. CC -!- INTERACTION: CC P20936; Q8IZP0: ABI1; NbExp=2; IntAct=EBI-1026476, EBI-375446; CC P20936; P10275: AR; NbExp=16; IntAct=EBI-1026476, EBI-608057; CC P20936; P04632: CAPNS1; NbExp=3; IntAct=EBI-1026476, EBI-711828; CC P20936; Q03135: CAV1; NbExp=2; IntAct=EBI-1026476, EBI-603614; CC P20936; Q96QB1: DLC1; NbExp=7; IntAct=EBI-1026476, EBI-2608428; CC P20936; P00533: EGFR; NbExp=7; IntAct=EBI-1026476, EBI-297353; CC P20936; P04626: ERBB2; NbExp=8; IntAct=EBI-1026476, EBI-641062; CC P20936; P21860: ERBB3; NbExp=6; IntAct=EBI-1026476, EBI-720706; CC P20936; P36888: FLT3; NbExp=2; IntAct=EBI-1026476, EBI-3946257; CC P20936; Q13480: GAB1; NbExp=25; IntAct=EBI-1026476, EBI-517684; CC P20936; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-1026476, EBI-2548508; CC P20936; P42858: HTT; NbExp=3; IntAct=EBI-1026476, EBI-466029; CC P20936; P10721: KIT; NbExp=16; IntAct=EBI-1026476, EBI-1379503; CC P20936; P08581: MET; NbExp=15; IntAct=EBI-1026476, EBI-1039152; CC P20936; P16333: NCK1; NbExp=6; IntAct=EBI-1026476, EBI-389883; CC P20936; P09619: PDGFRB; NbExp=3; IntAct=EBI-1026476, EBI-641237; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8360177}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Long; CC IsoId=P20936-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P20936-2; Sequence=VSP_001625, VSP_001626; CC Name=3; CC IsoId=P20936-3; Sequence=VSP_057434, VSP_057435; CC Name=4; CC IsoId=P20936-4; Sequence=VSP_057432, VSP_057433; CC -!- TISSUE SPECIFICITY: In placental villi, detected only in the CC trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not CC detected in stromal, endothelial or Hofbauer cells (at protein level). CC {ECO:0000269|PubMed:8360177}. CC -!- PTM: The N-terminus is blocked. CC -!- PTM: Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits CC its ability to stimulate the Ras-GTPase activity, whereas CC phosphorylation by LCK does not display any effect on stimulation CC activity. {ECO:0000269|PubMed:11389730}. CC -!- DISEASE: Note=Mutations in the SH2 domain of RASA seem to be oncogenic CC and cause basal cell carcinomas. CC -!- DISEASE: Capillary malformation-arteriovenous malformation 1 (CMAVM1) CC [MIM:608354]: A disorder characterized by atypical capillary CC malformations that are multiple, small, round to oval in shape and CC pinkish red in color. These capillary malformations are associated with CC either arteriovenous malformation, arteriovenous fistula, or Parkes CC Weber syndrome. CMAVM1 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:14639529, ECO:0000269|PubMed:24038909}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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; M23379; AAA52517.1; -; mRNA. DR EMBL; M23612; AAA35865.1; -; mRNA. DR EMBL; AK300263; BAG62024.1; -; mRNA. DR EMBL; AK312739; BAG35610.1; -; mRNA. DR EMBL; CR749722; CAH18488.2; -; mRNA. DR EMBL; AC010410; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018754; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC035142; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC126776; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC033015; AAH33015.1; -; mRNA. DR CCDS; CCDS34200.1; -. [P20936-1] DR CCDS; CCDS47243.1; -. [P20936-2] DR PIR; A40121; A40121. DR PIR; B40121; B40121. DR RefSeq; NP_002881.1; NM_002890.2. [P20936-1] DR RefSeq; NP_072179.1; NM_022650.2. [P20936-2] DR PDB; 1WER; X-ray; 1.60 A; A=714-1047. DR PDB; 1WQ1; X-ray; 2.50 A; G=714-1047. DR PDB; 2GQI; NMR; -; A=282-339. DR PDB; 2GSB; NMR; -; A=341-446. DR PDB; 2J05; X-ray; 1.50 A; A/B=281-341. DR PDB; 2J06; X-ray; 1.80 A; A/B=281-341. DR PDB; 2M51; NMR; -; A=281-341. DR PDB; 4FSS; X-ray; 2.25 A; A/B/C=281-341. DR PDB; 6PXB; X-ray; 1.75 A; A/B/C/D/E/F=174-280. DR PDB; 6PXC; X-ray; 1.60 A; A=174-280. DR PDB; 6WAX; X-ray; 1.50 A; A/B=340-444. DR PDB; 6WAY; X-ray; 1.50 A; A=340-444. DR PDB; 8BOS; X-ray; 2.10 A; G=713-1042. DR PDB; 8DGQ; X-ray; 1.95 A; A/B=174-444. DR PDBsum; 1WER; -. DR PDBsum; 1WQ1; -. DR PDBsum; 2GQI; -. DR PDBsum; 2GSB; -. DR PDBsum; 2J05; -. DR PDBsum; 2J06; -. DR PDBsum; 2M51; -. DR PDBsum; 4FSS; -. DR PDBsum; 6PXB; -. DR PDBsum; 6PXC; -. DR PDBsum; 6WAX; -. DR PDBsum; 6WAY; -. DR PDBsum; 8BOS; -. DR PDBsum; 8DGQ; -. DR AlphaFoldDB; P20936; -. DR BMRB; P20936; -. DR SASBDB; P20936; -. DR SMR; P20936; -. DR BioGRID; 111856; 141. DR CORUM; P20936; -. DR DIP; DIP-144N; -. DR IntAct; P20936; 136. DR MINT; P20936; -. DR STRING; 9606.ENSP00000274376; -. DR iPTMnet; P20936; -. DR MetOSite; P20936; -. DR PhosphoSitePlus; P20936; -. DR SwissPalm; P20936; -. DR BioMuta; RASA1; -. DR DMDM; 121743; -. DR CPTAC; CPTAC-1548; -. DR EPD; P20936; -. DR jPOST; P20936; -. DR MassIVE; P20936; -. DR MaxQB; P20936; -. DR PaxDb; 9606-ENSP00000274376; -. DR PeptideAtlas; P20936; -. DR ProteomicsDB; 5112; -. DR ProteomicsDB; 53828; -. [P20936-1] DR ProteomicsDB; 53829; -. [P20936-2] DR ProteomicsDB; 66031; -. DR Pumba; P20936; -. DR ABCD; P20936; 9 sequenced antibodies. DR Antibodypedia; 24766; 597 antibodies from 36 providers. DR DNASU; 5921; -. DR Ensembl; ENST00000274376.11; ENSP00000274376.6; ENSG00000145715.15. [P20936-1] DR Ensembl; ENST00000456692.6; ENSP00000411221.2; ENSG00000145715.15. [P20936-2] DR Ensembl; ENST00000512763.5; ENSP00000422008.1; ENSG00000145715.15. [P20936-4] DR Ensembl; ENST00000515800.6; ENSP00000423395.2; ENSG00000145715.15. [P20936-3] DR GeneID; 5921; -. DR KEGG; hsa:5921; -. DR MANE-Select; ENST00000274376.11; ENSP00000274376.6; NM_002890.3; NP_002881.1. DR UCSC; uc003kiw.4; human. [P20936-1] DR UCSC; uc011ctv.3; human. DR UCSC; uc063fdq.1; human. DR AGR; HGNC:9871; -. DR CTD; 5921; -. DR DisGeNET; 5921; -. DR GeneCards; RASA1; -. DR GeneReviews; RASA1; -. DR HGNC; HGNC:9871; RASA1. DR HPA; ENSG00000145715; Tissue enhanced (placenta). DR MalaCards; RASA1; -. DR MIM; 139150; gene. DR MIM; 608354; phenotype. DR neXtProt; NX_P20936; -. DR OpenTargets; ENSG00000145715; -. DR Orphanet; 137667; Capillary malformation-arteriovenous malformation. DR Orphanet; 90307; Parkes Weber syndrome. DR PharmGKB; PA34232; -. DR VEuPathDB; HostDB:ENSG00000145715; -. DR eggNOG; KOG3508; Eukaryota. DR GeneTree; ENSGT00940000155846; -. DR HOGENOM; CLU_500517_0_0_1; -. DR InParanoid; P20936; -. DR OMA; ICGCLQR; -. DR OrthoDB; 22721at2759; -. DR PhylomeDB; P20936; -. DR TreeFam; TF105301; -. DR PathwayCommons; P20936; -. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs. DR Reactome; R-HSA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases. DR SignaLink; P20936; -. DR SIGNOR; P20936; -. DR BioGRID-ORCS; 5921; 12 hits in 1168 CRISPR screens. DR ChiTaRS; RASA1; human. DR EvolutionaryTrace; P20936; -. DR GeneWiki; RAS_p21_protein_activator_1; -. DR GenomeRNAi; 5921; -. DR Pharos; P20936; Tbio. DR PRO; PR:P20936; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P20936; Protein. DR Bgee; ENSG00000145715; Expressed in endothelial cell and 213 other cell types or tissues. DR ExpressionAtlas; P20936; baseline and differential. DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0001726; C:ruffle; IEA:Ensembl. DR GO; GO:0005096; F:GTPase activator activity; EXP:Reactome. DR GO; GO:0003924; F:GTPase activity; TAS:Reactome. DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. DR GO; GO:0019870; F:potassium channel inhibitor activity; NAS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:UniProtKB. DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome. DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IDA:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0030833; P:regulation of actin filament polymerization; IDA:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; NAS:UniProtKB. DR GO; GO:0051252; P:regulation of RNA metabolic process; NAS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB. DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB. DR CDD; cd08400; C2_Ras_p21A1; 1. DR CDD; cd13260; PH_RASA1; 1. DR CDD; cd05391; RasGAP_p120GAP; 1. DR CDD; cd10354; SH2_Cterm_RasGAP; 1. DR CDD; cd10353; SH2_Nterm_RasGAP; 1. DR CDD; cd11788; SH3_RasGAP; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR039360; Ras_GTPase. DR InterPro; IPR035842; RasGAP_C_SH2. DR InterPro; IPR023152; RasGAP_CS. DR InterPro; IPR001936; RasGAP_dom. DR InterPro; IPR035841; RasGAP_N_SH2. DR InterPro; IPR035652; RasGAP_SH3. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR10194:SF146; RAS GTPASE-ACTIVATING PROTEIN 1; 1. DR PANTHER; PTHR10194; RAS GTPASE-ACTIVATING PROTEINS; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00616; RasGAP; 1. DR Pfam; PF00017; SH2; 2. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00323; RasGAP; 1. DR SMART; SM00252; SH2; 2. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF55550; SH2 domain; 2. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1. DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1. DR PROSITE; PS50001; SH2; 2. DR PROSITE; PS50002; SH3; 1. DR Genevisible; P20936; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Disease variant; GTPase activation; KW Phosphoprotein; Reference proteome; Repeat; SH2 domain; SH3 domain; KW Tumor suppressor. FT CHAIN 1..1047 FT /note="Ras GTPase-activating protein 1" FT /id="PRO_0000056636" FT DOMAIN 181..272 FT /note="SH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 279..341 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 351..441 FT /note="SH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 474..577 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 577..690 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 748..942 FT /note="Ras-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 615 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 831 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..177 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:3201259" FT /id="VSP_001625" FT VAR_SEQ 1..13 FT /note="MMAAEAGSEEGGP -> MRTGYSSVPSKLR (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057432" FT VAR_SEQ 14..180 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057433" FT VAR_SEQ 178..180 FT /note="TNQ -> MKG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:3201259" FT /id="VSP_001626" FT VAR_SEQ 538..539 FT /note="PN -> CS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_057434" FT VAR_SEQ 540..1047 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_057435" FT VARIANT 398 FT /note="R -> L (in basal cell carcinomas; FT dbSNP:rs137853214)" FT /evidence="ECO:0000269|PubMed:8275088" FT /id="VAR_002650" FT VARIANT 400 FT /note="K -> E (in basal cell carcinomas; FT dbSNP:rs137853215)" FT /evidence="ECO:0000269|PubMed:8275088" FT /id="VAR_002651" FT VARIANT 401 FT /note="I -> V (in basal cell carcinomas; FT dbSNP:rs137853216)" FT /evidence="ECO:0000269|PubMed:8275088" FT /id="VAR_002652" FT VARIANT 528 FT /note="Y -> C (in CMAVM1; uncertain significance; FT dbSNP:rs145752649)" FT /evidence="ECO:0000269|PubMed:24038909" FT /id="VAR_072088" FT VARIANT 530 FT /note="V -> D (in CMAVM1)" FT /evidence="ECO:0000269|PubMed:24038909" FT /id="VAR_072089" FT VARIANT 540 FT /note="C -> Y (in CMAVM1; dbSNP:rs137853217)" FT /evidence="ECO:0000269|PubMed:14639529" FT /id="VAR_017744" FT VARIANT 626 FT /note="A -> E (in CMAVM1; dbSNP:rs745690594)" FT /evidence="ECO:0000269|PubMed:24038909" FT /id="VAR_072090" FT VARIANT 763 FT /note="E -> V (in CMAVM1; uncertain significance; FT dbSNP:rs373098580)" FT /evidence="ECO:0000269|PubMed:24038909" FT /id="VAR_072091" FT CONFLICT 789 FT /note="R -> A (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 178..180 FT /evidence="ECO:0007829|PDB:6PXC" FT STRAND 182..186 FT /evidence="ECO:0007829|PDB:6PXC" FT HELIX 188..198 FT /evidence="ECO:0007829|PDB:6PXC" FT STRAND 203..212 FT /evidence="ECO:0007829|PDB:6PXC" FT STRAND 216..221 FT /evidence="ECO:0007829|PDB:6PXC" FT HELIX 223..225 FT /evidence="ECO:0007829|PDB:6PXB" FT STRAND 227..235 FT /evidence="ECO:0007829|PDB:6PXC" FT STRAND 238..241 FT /evidence="ECO:0007829|PDB:6PXC" FT STRAND 244..248 FT /evidence="ECO:0007829|PDB:6PXC" FT HELIX 249..258 FT /evidence="ECO:0007829|PDB:6PXC" FT STRAND 283..288 FT /evidence="ECO:0007829|PDB:2J05" FT STRAND 296..298 FT /evidence="ECO:0007829|PDB:2J05" FT STRAND 306..312 FT /evidence="ECO:0007829|PDB:2J05" FT STRAND 316..322 FT /evidence="ECO:0007829|PDB:2J05" FT TURN 323..325 FT /evidence="ECO:0007829|PDB:2J05" FT STRAND 328..332 FT /evidence="ECO:0007829|PDB:2J05" FT HELIX 333..335 FT /evidence="ECO:0007829|PDB:2J05" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:2J05" FT TURN 345..348 FT /evidence="ECO:0007829|PDB:6WAX" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:2GSB" FT HELIX 358..367 FT /evidence="ECO:0007829|PDB:6WAX" FT STRAND 374..378 FT /evidence="ECO:0007829|PDB:6WAX" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:6WAX" FT STRAND 386..391 FT /evidence="ECO:0007829|PDB:6WAX" FT STRAND 396..403 FT /evidence="ECO:0007829|PDB:6WAX" FT TURN 405..407 FT /evidence="ECO:0007829|PDB:2GSB" FT STRAND 409..411 FT /evidence="ECO:0007829|PDB:6WAX" FT STRAND 414..417 FT /evidence="ECO:0007829|PDB:6WAX" FT HELIX 419..428 FT /evidence="ECO:0007829|PDB:6WAX" FT HELIX 720..723 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 724..730 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 736..744 FT /evidence="ECO:0007829|PDB:1WER" FT STRAND 746..748 FT /evidence="ECO:0007829|PDB:1WQ1" FT HELIX 749..762 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 766..780 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 784..786 FT /evidence="ECO:0007829|PDB:1WER" FT TURN 787..789 FT /evidence="ECO:0007829|PDB:1WQ1" FT HELIX 793..805 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 807..823 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 832..834 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 841..860 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 861..865 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 868..884 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 891..900 FT /evidence="ECO:0007829|PDB:1WER" FT TURN 901..904 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 905..910 FT /evidence="ECO:0007829|PDB:1WER" FT TURN 912..916 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 924..941 FT /evidence="ECO:0007829|PDB:1WER" FT STRAND 946..949 FT /evidence="ECO:0007829|PDB:1WQ1" FT HELIX 951..956 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 957..974 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 992..1004 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 1006..1013 FT /evidence="ECO:0007829|PDB:1WER" FT HELIX 1020..1038 FT /evidence="ECO:0007829|PDB:1WER" SQ SEQUENCE 1047 AA; 116403 MW; C35B6567F5BC5370 CRC64; MMAAEAGSEE GGPVTAGAGG GGAAAGSSAY PAVCRVKIPA ALPVAAAPYP GLVETGVAGT LGGGAALGSE FLGAGSVAGA LGGAGLTGGG TAAGVAGAAA GVAGAAVAGP SGDMALTKLP TSLLAETLGP GGGFPPLPPP PYLPPLGAGL GTVDEGDSLD GPEYEEEEVA IPLTAPPTNQ WYHGKLDRTI AEERLRQAGK SGSYLIRESD RRPGSFVLSF LSQMNVVNHF RIIAMCGDYY IGGRRFSSLS DLIGYYSHVS CLLKGEKLLY PVAPPEPVED RRRVRAILPY TKVPDTDEIS FLKGDMFIVH NELEDGWMWV TNLRTDEQGL IVEDLVEEVG REEDPHEGKI WFHGKISKQE AYNLLMTVGQ VCSFLVRPSD NTPGDYSLYF RTNENIQRFK ICPTPNNQFM MGGRYYNSIG DIIDHYRKEQ IVEGYYLKEP VPMQDQEQVL NDTVDGKEIY NTIRRKTKDA FYKNIVKKGY LLKKGKGKRW KNLYFILEGS DAQLIYFESE KRATKPKGLI DLSVCSVYVV HDSLFGRPNC FQIVVQHFSE EHYIFYFAGE TPEQAEDWMK GLQAFCNLRK SSPGTSNKRL RQVSSLVLHI EEAHKLPVKH FTNPYCNIYL NSVQVAKTHA REGQNPVWSE EFVFDDLPPD INRFEITLSN KTKKSKDPDI LFMRCQLSRL QKGHATDEWF LLSSHIPLKG IEPGSLRVRA RYSMEKIMPE EEYSEFKELI LQKELHVVYA LSHVCGQDRT LLASILLRIF LHEKLESLLL CTLNDREISM EDEATTLFRA TTLASTLMEQ YMKATATQFV HHALKDSILK IMESKQSCEL SPSKLEKNED VNTNLTHLLN ILSELVEKIF MASEILPPTL RYIYGCLQKS VQHKWPTNTT MRTRVVSGFV FLRLICPAIL NPRMFNIISD SPSPIAARTL ILVAKSVQNL ANLVEFGAKE PYMEGVNPFI KSNKHRMIMF LDELGNVPEL PDTTEHSRTD LSRDLAALHE ICVAHSDELR TLSNERGAQQ HVLKKLLAIT ELLQQKQNQY TKTNDVR //