RASA1_HUMAN
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 03-AUG-2022, entry version 243.
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.
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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 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 AlphaFoldDB; P20936; -.
DR BMRB; P20936; -.
DR SMR; P20936; -.
DR BioGRID; 111856; 135.
DR CORUM; P20936; -.
DR DIP; DIP-144N; -.
DR IntAct; P20936; 137.
DR MINT; P20936; -.
DR STRING; 9606.ENSP00000274376; -.
DR iPTMnet; P20936; -.
DR MetOSite; P20936; -.
DR PhosphoSitePlus; 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; P20936; -.
DR PeptideAtlas; P20936; -.
DR PRIDE; P20936; -.
DR ProteomicsDB; 5112; -.
DR ProteomicsDB; 53828; -. [P20936-1]
DR ProteomicsDB; 53829; -. [P20936-2]
DR ProteomicsDB; 66031; -.
DR ABCD; P20936; 9 sequenced antibodies.
DR Antibodypedia; 24766; 537 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 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; KEPYMEV; -.
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; 11 hits in 1082 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 211 other tissues.
DR ExpressionAtlas; P20936; baseline and differential.
DR Genevisible; P20936; HS.
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:0046580; P:negative regulation of Ras protein signal transduction; IEA:InterPro.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
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; cd10354; SH2_Cterm_RasGAP; 1.
DR CDD; cd10353; SH2_Nterm_RasGAP; 1.
DR CDD; cd11788; SH3_RasGAP; 1.
DR Gene3D; 1.10.506.10; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR028554; p120-RasGAP.
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; PTHR10194; 2.
DR PANTHER; PTHR10194:SF19; PTHR10194:SF19; 2.
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; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
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.
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; unknown pathological
FT significance; 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; unknown pathological
FT significance; 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
