RAP2A_HUMAN
ID RAP2A_HUMAN Reviewed; 183 AA.
AC P10114; B2RCJ1; Q5JSC1; Q5JSC2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Ras-related protein Rap-2a;
DE EC=3.6.5.2 {ECO:0000269|PubMed:1900290};
DE AltName: Full=RbBP-30;
DE Flags: Precursor;
GN Name=RAP2A;
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].
RX PubMed=3045729;
RA Pizon V., Chardin P., Lerosey I., Olofsson B., Tavitian A.;
RT "Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode
RT proteins closely related to ras in the 'effector' region.";
RL Oncogene 3:201-204(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymph node;
RA Fan Z.S., Ao S.Z.;
RT "A novel new gene associated with pRb.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [8]
RP CATALYTIC ACTIVITY, GTP-BINDING, AND MUTAGENESIS OF GLY-12; SER-17; THR-35
RP AND THR-145.
RX PubMed=1900290; DOI=10.1016/s0021-9258(20)64324-1;
RA Lerosey I., Chardin P., de Gunzburg J., Tavitian A.;
RT "The product of the rap2 gene, member of the ras superfamily. Biochemical
RT characterization and site-directed mutagenesis.";
RL J. Biol. Chem. 266:4315-4321(1991).
RN [9]
RP ISOPRENYLATION AT CYS-180, AND METHYLATION AT CYS-180.
RX PubMed=8424780; DOI=10.1042/bj2890349;
RA Farrell F.X., Yamamoto K., Lapetina E.G.;
RT "Prenyl group identification of rap2 proteins: a ras superfamily member
RT other than ras that is farnesylated.";
RL Biochem. J. 289:349-355(1993).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=8391995; DOI=10.1016/0014-5793(93)81792-x;
RA Mollinedo F., Perez-Sala D., Gajate C., Jimenez B., Rodriguez P.,
RA Lacal J.C.;
RT "Localization of rap1 and rap2 proteins in the gelatinase-containing
RT granules of human neutrophils.";
RL FEBS Lett. 326:209-214(1993).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=7962206; DOI=10.1242/jcs.107.6.1661;
RA Pizon V., Desjardins M., Bucci C., Parton R.G., Zerial M.;
RT "Association of Rap1a and Rap1b proteins with late endocytic/phagocytic
RT compartments and Rap2a with the Golgi complex.";
RL J. Cell Sci. 107:1661-1670(1994).
RN [12]
RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION).
RX PubMed=8626586; DOI=10.1074/jbc.271.17.10217;
RA Popoff M.R., Chaves-Olarte E., Lemichez E., von Eichel-Streiber C.,
RA Thelestam M., Chardin P., Cussac D., Antonny B., Chavrier P., Flatau G.,
RA Giry M., de Gunzburg J., Boquet P.;
RT "Ras, Rap, and Rac small GTP-binding proteins are targets for Clostridium
RT sordellii lethal toxin glucosylation.";
RL J. Biol. Chem. 271:10217-10224(1996).
RN [13]
RP INTERACTION WITH ACTIN.
RX PubMed=10572250;
RX DOI=10.1002/(sici)1097-4644(19991215)75:4<675::aid-jcb13>3.0.co;2-m;
RA Torti M., Bertoni A., Canobbio I., Sinigaglia F., Lapetina E.G.,
RA Balduini C.;
RT "Interaction of the low-molecular-weight GTP-binding protein rap2 with the
RT platelet cytoskeleton is mediated by direct binding to the actin
RT filaments.";
RL J. Cell. Biochem. 75:675-685(1999).
RN [14]
RP ACTIVATION BY RAPGEF3; RAPGEF4 AND RAPGEF5.
RX PubMed=10777494; DOI=10.1074/jbc.m001113200;
RA de Rooij J., Rehmann H., van Triest M., Cool R.H., Wittinghofer A.,
RA Bos J.L.;
RT "Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs.";
RL J. Biol. Chem. 275:20829-20836(2000).
RN [15]
RP INTERACTION WITH PLCE1.
RX PubMed=12444546; DOI=10.1038/sj.onc.1206003;
RA Song C., Satoh T., Edamatsu H., Wu D., Tadano M., Gao X., Kataoka T.;
RT "Differential roles of Ras and Rap1 in growth factor-dependent activation
RT of phospholipase C epsilon.";
RL Oncogene 21:8105-8113(2002).
RN [16]
RP FUNCTION, AND INTERACTION WITH MAP4K4.
RX PubMed=14966141; DOI=10.1074/jbc.c300542200;
RA Machida N., Umikawa M., Takei K., Sakima N., Myagmar B.E., Taira K.,
RA Uezato H., Ogawa Y., Kariya K.;
RT "Mitogen-activated protein kinase kinase kinase kinase 4 as a putative
RT effector of Rap2 to activate the c-Jun N-terminal kinase.";
RL J. Biol. Chem. 279:15711-15714(2004).
RN [17]
RP FUNCTION, INTERACTION WITH TNIK, AND MUTAGENESIS OF GLY-12; SER-17 AND
RP PHE-39.
RX PubMed=15342639; DOI=10.1074/jbc.m406370200;
RA Taira K., Umikawa M., Takei K., Myagmar B.-E., Shinzato M., Machida N.,
RA Uezato H., Nonaka S., Kariya K.;
RT "The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to
RT regulate actin cytoskeleton.";
RL J. Biol. Chem. 279:49488-49496(2004).
RN [18]
RP INTERACTION WITH ARHGAP29.
RX PubMed=15752761; DOI=10.1016/j.bbrc.2005.02.069;
RA Myagmar B.-E., Umikawa M., Asato T., Taira K., Oshiro M., Hino A.,
RA Takei K., Uezato H., Kariya K.;
RT "PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative
RT Rap2 effector.";
RL Biochem. Biophys. Res. Commun. 329:1046-1052(2005).
RN [19]
RP FUNCTION.
RX PubMed=16246175; DOI=10.1042/bj20051086;
RA Mittal V., Linder M.E.;
RT "Biochemical characterization of RGS14: RGS14 activity towards G-protein
RT alpha subunits is independent of its binding to Rap2A.";
RL Biochem. J. 394:309-315(2006).
RN [20]
RP FUNCTION.
RX PubMed=16540189; DOI=10.1016/j.bbamcr.2006.02.001;
RA Greco F., Ciana A., Pietra D., Balduini C., Minetti G., Torti M.;
RT "Rap2, but not Rap1 GTPase is expressed in human red blood cells and is
RT involved in vesiculation.";
RL Biochim. Biophys. Acta 1763:330-335(2006).
RN [21]
RP INTERACTION WITH SGSM1; SGSM2 AND SGSM3.
RX PubMed=17509819; DOI=10.1016/j.ygeno.2007.03.013;
RA Yang H., Sasaki T., Minoshima S., Shimizu N.;
RT "Identification of three novel proteins (SGSM1, 2, 3) which modulate small
RT G protein (RAP and RAB)-mediated signaling pathway.";
RL Genomics 90:249-260(2007).
RN [22]
RP FUNCTION, AND INTERACTION WITH MINK1.
RX PubMed=18930710; DOI=10.1016/j.bbrc.2008.10.038;
RA Nonaka H., Takei K., Umikawa M., Oshiro M., Kuninaka K., Bayarjargal M.,
RA Asato T., Yamashiro Y., Uechi Y., Endo S., Suzuki T., Kariya K.;
RT "MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold
RT protein TANC1.";
RL Biochem. Biophys. Res. Commun. 377:573-578(2008).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=19061864; DOI=10.1016/j.bbrc.2008.11.107;
RA Uechi Y., Bayarjargal M., Umikawa M., Oshiro M., Takei K., Yamashiro Y.,
RA Asato T., Endo S., Misaki R., Taguchi T., Kariya K.;
RT "Rap2 function requires palmitoylation and recycling endosome
RT localization.";
RL Biochem. Biophys. Res. Commun. 378:732-737(2009).
RN [24]
RP MUTAGENESIS OF PHE-39, AND ACTIVATION BY RASGEF1A AND RASGEF1B.
RX PubMed=19645719; DOI=10.1111/j.1742-4658.2009.07166.x;
RA Yaman E., Gasper R., Koerner C., Wittinghofer A., Tazebay U.H.;
RT "RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that
RT discriminate between Rap GTP-binding proteins and mediate Rap2-specific
RT nucleotide exchange.";
RL FEBS J. 276:4607-4616(2009).
RN [25]
RP FUNCTION, INTERACTION WITH NEDD4 AND TNIK, UBIQUITINATION BY NEDD4, AND
RP MUTAGENESIS OF LYS-5; PHE-39; LYS-94; LYS-148 AND LYS-150.
RX PubMed=20159449; DOI=10.1016/j.neuron.2010.01.007;
RA Kawabe H., Neeb A., Dimova K., Young S.M. Jr., Takeda M.,
RA Katsurabayashi S., Mitkovski M., Malakhova O.A., Zhang D.E., Umikawa M.,
RA Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O., Rhee J.,
RA Brose N.;
RT "Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite
RT development.";
RL Neuron 65:358-372(2010).
RN [26]
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 [27]
RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION).
RX PubMed=22267739; DOI=10.1074/jbc.m111.298414;
RA Pruitt R.N., Chumbler N.M., Rutherford S.A., Farrow M.A., Friedman D.B.,
RA Spiller B., Lacy D.B.;
RT "Structural determinants of Clostridium difficile toxin A
RT glucosyltransferase activity.";
RL J. Biol. Chem. 287:8013-8020(2012).
RN [28]
RP SUBCELLULAR LOCATION, AND ACTIVITY REGULATION BY RASGEF1B.
RX PubMed=23894443; DOI=10.1371/journal.pone.0069289;
RA Telkoparan P., Erkek S., Yaman E., Alotaibi H., Bayik D., Tazebay U.H.;
RT "Coiled-coil domain containing protein 124 is a novel centrosome and
RT midbody protein that interacts with the ras-guanine nucleotide exchange
RT factor 1B and is involved in cytokinesis.";
RL PLoS ONE 8:E69289-E69289(2013).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=9312017; DOI=10.1093/emboj/16.18.5582;
RA Cherfils J., Menetrey J., Le Bras G., Janoueix-Lerosey I., de Gunzburg J.,
RA Garel J.-R., Auzat I.;
RT "Crystal structures of the small G protein Rap2A in complex with its
RT substrate GTP, with GDP and with GTPgammaS.";
RL EMBO J. 16:5582-5591(1997).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=10591105;
RX DOI=10.1002/(sici)1097-0134(19991115)37:3<465::aid-prot13>3.0.co;2-o;
RA Menetrey J., Cherfils J.;
RT "Structure of the small G protein Rap2 in a non-catalytic complex with
RT GTP.";
RL Proteins 37:465-473(1999).
CC -!- FUNCTION: Small GTP-binding protein which cycles between a GDP-bound
CC inactive and a GTP-bound active form. In its active form interacts with
CC and regulates several effectors including MAP4K4, MINK1 and TNIK. Part
CC of a signaling complex composed of NEDD4, RAP2A and TNIK which
CC regulates neuronal dendrite extension and arborization during
CC development. More generally, it is part of several signaling cascades
CC and may regulate cytoskeletal rearrangements, cell migration, cell
CC adhesion and cell spreading. {ECO:0000269|PubMed:14966141,
CC ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:16246175,
CC ECO:0000269|PubMed:16540189, ECO:0000269|PubMed:18930710,
CC ECO:0000269|PubMed:20159449}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000269|PubMed:1900290};
CC -!- ACTIVITY REGULATION: Activated by the guanine nucleotide-exchange
CC factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide
CC exchange is also specifically stimulated by RAPGEF5, RASGEF1A and
CC RASGEF1B. {ECO:0000269|PubMed:23894443}.
CC -!- SUBUNIT: Interacts (GTP-bound form) with RUNDC3A. Interacts with RGS14;
CC the interaction is GTP-dependent (By similarity). Interacts with PLCE1.
CC Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3. Interacts (GTP-bound
CC form preferentially) with TNIK (via the CNH domain); the interaction is
CC direct and recruits RAP2A to the E3 ubiquitin ligase NEDD4. Interacts
CC with MINK1. Interacts (GTP-bound form preferentially) with MAP4K4.
CC Interacts with cytoskeletal actin. {ECO:0000250,
CC ECO:0000269|PubMed:10572250, ECO:0000269|PubMed:12444546,
CC ECO:0000269|PubMed:14966141, ECO:0000269|PubMed:15342639,
CC ECO:0000269|PubMed:15752761, ECO:0000269|PubMed:17509819,
CC ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:20159449}.
CC -!- INTERACTION:
CC P10114; P54852: EMP3; NbExp=3; IntAct=EBI-602366, EBI-3907816;
CC P10114; Q9NZL6-2: RGL1; NbExp=3; IntAct=EBI-602366, EBI-23868346;
CC P10114; Q59EK9-3: RUNDC3A; NbExp=3; IntAct=EBI-602366, EBI-11957366;
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane; Lipid-anchor;
CC Cytoplasmic side. Midbody. Note=May also localize to the Golgi
CC (PubMed:7962206) and the gelatinase-containing granules of neutrophils
CC (PubMed:8391995). Colocalizes with RASGEF1B to midbody at telophase
CC (PubMed:23894443). {ECO:0000269|PubMed:23894443,
CC ECO:0000269|PubMed:7962206, ECO:0000269|PubMed:8391995}.
CC -!- DOMAIN: The effector domain mediates the interaction with RUNDC3A.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-63' monoubiquitination and
CC diubiquitination by NEDD4. Multiple lysine residues are probably
CC modified. Ubiquitination requires TNIK, prevents interaction with
CC effectors and inactivates RAP2A. {ECO:0000269|PubMed:20159449}.
CC -!- PTM: Palmitoylated. Palmitoylation is required for association with
CC recycling endosome membranes and activation of TNIK.
CC {ECO:0000250|UniProtKB:Q80ZJ1}.
CC -!- PTM: (Microbial infection) Glucosylated at Thr-35 by C.difficile toxin
CC TcdA in the colonic epithelium, and by P.sordellii toxin TcsL in the
CC vascular endothelium. {ECO:0000269|PubMed:22267739,
CC ECO:0000269|PubMed:8626586}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RAP2AID274.html";
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DR EMBL; X12534; CAA31052.1; -; mRNA.
DR EMBL; AF205602; AAN71845.1; -; mRNA.
DR EMBL; AF493914; AAM12628.1; -; mRNA.
DR EMBL; AK315139; BAG37588.1; -; mRNA.
DR EMBL; AL442067; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471085; EAX08974.1; -; Genomic_DNA.
DR EMBL; BC041333; AAH41333.1; -; mRNA.
DR EMBL; BC070031; AAH70031.1; -; mRNA.
DR CCDS; CCDS9485.1; -.
DR PIR; S03180; S03180.
DR RefSeq; NP_066361.1; NM_021033.6.
DR PDB; 1KAO; X-ray; 1.70 A; A=1-167.
DR PDB; 2RAP; X-ray; 2.60 A; A=1-167.
DR PDB; 3RAP; X-ray; 2.20 A; R/S=1-167.
DR PDBsum; 1KAO; -.
DR PDBsum; 2RAP; -.
DR PDBsum; 3RAP; -.
DR AlphaFoldDB; P10114; -.
DR SMR; P10114; -.
DR BioGRID; 111846; 88.
DR IntAct; P10114; 25.
DR MINT; P10114; -.
DR STRING; 9606.ENSP00000245304; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR DrugBank; DB04137; Guanosine-5'-Triphosphate.
DR iPTMnet; P10114; -.
DR PhosphoSitePlus; P10114; -.
DR SwissPalm; P10114; -.
DR BioMuta; RAP2A; -.
DR DMDM; 131852; -.
DR EPD; P10114; -.
DR jPOST; P10114; -.
DR MassIVE; P10114; -.
DR MaxQB; P10114; -.
DR PaxDb; P10114; -.
DR PeptideAtlas; P10114; -.
DR PRIDE; P10114; -.
DR ProteomicsDB; 52567; -.
DR Antibodypedia; 10676; 147 antibodies from 28 providers.
DR DNASU; 5911; -.
DR Ensembl; ENST00000245304.5; ENSP00000245304.3; ENSG00000125249.7.
DR GeneID; 5911; -.
DR KEGG; hsa:5911; -.
DR MANE-Select; ENST00000245304.5; ENSP00000245304.3; NM_021033.7; NP_066361.1.
DR UCSC; uc001vnd.4; human.
DR CTD; 5911; -.
DR DisGeNET; 5911; -.
DR GeneCards; RAP2A; -.
DR HGNC; HGNC:9861; RAP2A.
DR HPA; ENSG00000125249; Low tissue specificity.
DR MIM; 179540; gene.
DR neXtProt; NX_P10114; -.
DR OpenTargets; ENSG00000125249; -.
DR PharmGKB; PA34222; -.
DR VEuPathDB; HostDB:ENSG00000125249; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000160594; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P10114; -.
DR OMA; EYSPTIE; -.
DR OrthoDB; 1353024at2759; -.
DR PhylomeDB; P10114; -.
DR TreeFam; TF313014; -.
DR PathwayCommons; P10114; -.
DR SignaLink; P10114; -.
DR BioGRID-ORCS; 5911; 15 hits in 1076 CRISPR screens.
DR ChiTaRS; RAP2A; human.
DR EvolutionaryTrace; P10114; -.
DR GeneWiki; RAP2A; -.
DR GenomeRNAi; 5911; -.
DR Pharos; P10114; Tbio.
DR PRO; PR:P10114; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P10114; protein.
DR Bgee; ENSG00000125249; Expressed in pons and 216 other tissues.
DR ExpressionAtlas; P10114; baseline and differential.
DR Genevisible; P10114; HS.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IMP:CAFA.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IMP:CAFA.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0045184; P:establishment of protein localization; IDA:MGI.
DR GO; GO:0030033; P:microvillus assembly; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IBA:GO_Central.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IDA:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0032486; P:Rap protein signal transduction; ISS:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IDA:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR CDD; cd04176; Rap2; 1.
DR DisProt; DP00167; -.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041840; Rap2.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endosome; Glycoprotein; GTP-binding; Hydrolase; Lipoprotein;
KW Membrane; Methylation; Nucleotide-binding; Palmitate; Prenylation;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..180
FT /note="Ras-related protein Rap-2a"
FT /id="PRO_0000082687"
FT PROPEP 181..183
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:8424780"
FT /id="PRO_0000281336"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000305"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 57..61
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 180
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305|PubMed:8424780"
FT LIPID 176
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q80ZJ1"
FT LIPID 177
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q80ZJ1"
FT LIPID 180
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:8424780"
FT CARBOHYD 35
FT /note="(Microbial infection) O-linked (Glc) threonine; by
FT C.difficile toxin TcdA, and by P.sordellii toxin TcsL"
FT /evidence="ECO:0000269|PubMed:22267739,
FT ECO:0000269|PubMed:8626586"
FT MUTAGEN 5
FT /note="K->R: Reduced NEDD4-dependent ubiquitination; when
FT associated with R-94; R-148 and R-150."
FT /evidence="ECO:0000269|PubMed:20159449"
FT MUTAGEN 12
FT /note="G->V: Dominant active. 2-fold decrease in GDP
FT dissociation rate constant and GTPase activity. No change
FT in interaction with TNIK."
FT /evidence="ECO:0000269|PubMed:15342639,
FT ECO:0000269|PubMed:1900290"
FT MUTAGEN 17
FT /note="S->N: Dominant negative. Severely impairs GTP-
FT binding and partial loss of interaction with MAP4K4, MINK1
FT and TNIK."
FT /evidence="ECO:0000269|PubMed:15342639,
FT ECO:0000269|PubMed:1900290"
FT MUTAGEN 35
FT /note="T->A: Decreases affinity for GTP and 3-fold
FT reduction of GTPase activity."
FT /evidence="ECO:0000269|PubMed:1900290"
FT MUTAGEN 39
FT /note="F->S: Loss of RASGEF1A- and RASGEF1B-mediated GDP to
FT GTP exchange. Complete loss of interaction with MAP4K4,
FT MINK1 and TNIK, and loss of ubiquitination by NEDD4."
FT /evidence="ECO:0000269|PubMed:15342639,
FT ECO:0000269|PubMed:19645719, ECO:0000269|PubMed:20159449"
FT MUTAGEN 94
FT /note="K->R: Reduced NEDD4-dependent ubiquitination; when
FT associated with R-5; R-148 and R-150."
FT /evidence="ECO:0000269|PubMed:20159449"
FT MUTAGEN 145
FT /note="T->I: Imperfect binding of guanyl nucleotides."
FT /evidence="ECO:0000269|PubMed:1900290"
FT MUTAGEN 148
FT /note="K->R: Reduced NEDD4-dependent ubiquitination; when
FT associated with R-5; R-94 and R-150."
FT /evidence="ECO:0000269|PubMed:20159449"
FT MUTAGEN 150
FT /note="K->R: Reduced NEDD4-dependent ubiquitination; when
FT associated with R-5; R-94 and R-148."
FT /evidence="ECO:0000269|PubMed:20159449"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:1KAO"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:1KAO"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:1KAO"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:1KAO"
FT HELIX 65..74
FT /evidence="ECO:0007829|PDB:1KAO"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:1KAO"
FT HELIX 87..103
FT /evidence="ECO:0007829|PDB:1KAO"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:1KAO"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:1KAO"
FT HELIX 118..123
FT /evidence="ECO:0007829|PDB:1KAO"
FT HELIX 128..138
FT /evidence="ECO:0007829|PDB:1KAO"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:1KAO"
FT HELIX 150..166
FT /evidence="ECO:0007829|PDB:1KAO"
SQ SEQUENCE 183 AA; 20615 MW; 047D49762765F0B7 CRC64;
MREYKVVVLG SGGVGKSALT VQFVTGTFIE KYDPTIEDFY RKEIEVDSSP SVLEILDTAG
TEQFASMRDL YIKNGQGFIL VYSLVNQQSF QDIKPMRDQI IRVKRYEKVP VILVGNKVDL
ESEREVSSSE GRALAEEWGC PFMETSAKSK TMVDELFAEI VRQMNYAAQP DKDDPCCSAC
NIQ
