RBCC

Full text data of RAP2A

RAP2A [Confidence: high (present in two of the MS resources)]
Ras-related protein Rap-2a (RbBP-30; Flags: Precursor)

UniProt P10114
ID RAP2A_HUMAN Reviewed; 183 AA.
AC P10114; B2RCJ1; Q5JSC1; Q5JSC2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Ras-related protein Rap-2a;
DE AltName: Full=RbBP-30;
DE Flags: Precursor;
GN Name=RAP2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT encode 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
RT sequenced by 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA 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.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA 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.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP GTPASE ACTIVITY, GTP-BINDING, AND MUTAGENESIS OF GLY-12; SER-17;
RP THR-35 AND THR-145.
RX PubMed=1900290;
RA Lerosey I., Chardin P., de Gunzburg J., Tavitian A.;
RT "The product of the rap2 gene, member of the ras superfamily.
RT Biochemical characterization and site-directed mutagenesis.";
RL J. Biol. Chem. 266:4315-4321(1991).
RN [9]
RP ISOPRENYLATION AT CYS-180.
RX PubMed=8424780;
RA Farrell F.X., Yamamoto K., Lapetina E.G.;
RT "Prenyl group identification of rap2 proteins: a ras superfamily
RT member 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;
RA Pizon V., Desjardins M., Bucci C., Parton R.G., Zerial M.;
RT "Association of Rap1a and Rap1b proteins with late
RT endocytic/phagocytic compartments and Rap2a with the Golgi complex.";
RL J. Cell Sci. 107:1661-1670(1994).
RN [12]
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
RT the platelet cytoskeleton is mediated by direct binding to the actin
RT filaments.";
RL J. Cell. Biochem. 75:675-685(1999).
RN [13]
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
RT RapGEFs.";
RL J. Biol. Chem. 275:20829-20836(2000).
RN [14]
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
RT activation of phospholipase C epsilon.";
RL Oncogene 21:8105-8113(2002).
RN [15]
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 [16]
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.,
RA Machida N., Uezato H., Nonaka S., Kariya K.;
RT "The Traf2- and Nck-interacting kinase as a putative effector of Rap2
RT to regulate actin cytoskeleton.";
RL J. Biol. Chem. 279:49488-49496(2004).
RN [17]
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
RT putative Rap2 effector.";
RL Biochem. Biophys. Res. Commun. 329:1046-1052(2005).
RN [18]
RP FUNCTION.
RX PubMed=16246175; DOI=10.1042/BJ20051086;
RA Mittal V., Linder M.E.;
RT "Biochemical characterization of RGS14: RGS14 activity towards G-
RT protein alpha subunits is independent of its binding to Rap2A.";
RL Biochem. J. 394:309-315(2006).
RN [19]
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
RT is involved in vesiculation.";
RL Biochim. Biophys. Acta 1763:330-335(2006).
RN [20]
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
RT small G protein (RAP and RAB)-mediated signaling pathway.";
RL Genomics 90:249-260(2007).
RN [21]
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.,
RA Bayarjargal M., Asato T., Yamashiro Y., Uechi Y., Endo S., Suzuki T.,
RA Kariya K.;
RT "MINK is a Rap2 effector for phosphorylation of the postsynaptic
RT scaffold protein TANC1.";
RL Biochem. Biophys. Res. Commun. 377:573-578(2008).
RN [22]
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.,
RA Yamashiro Y., 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 [23]
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-
RT specific nucleotide exchange.";
RL FEBS J. 276:4607-4616(2009).
RN [24]
RP FUNCTION, INTERACTION WITH NEDD4 AND TNIK, UBIQUITINATION BY NEDD4,
RP AND 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.,
RA Umikawa M., Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O.,
RA Rhee J., Brose N.;
RT "Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite
RT development.";
RL Neuron 65:358-372(2010).
RN [25]
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.,
RA Buerckstuemmer T., 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 [26]
RP SUBCELLULAR LOCATION, AND ENZYME REGULATION BY RASGEF1B.
RX PubMed=23894443; DOI=10.1371/journal.pone.0069289;
RA Telkoparan P., Erkek S., Yaman E., Alotaibi H., Bayik D.,
RA 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
RT exchange factor 1B and is involved in cytokinesis.";
RL PLoS ONE 8:E69289-E69289(2013).
RN [27]
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.,
RA de Gunzburg J., 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 [28]
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-
CC bound inactive and a GTP-bound active form. In its active form
CC interacts with and regulates several effectors including MAP4K4,
CC MINK1 and TNIK. Part of a signaling complex composed of NEDD4,
CC RAP2A and TNIK which regulates neuronal dendrite extension and
CC arborization during development. More generally, it is part of
CC several signaling cascades and may regulate cytoskeletal
CC rearrangements, cell migration, cell adhesion and cell spreading.
CC -!- ENZYME 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.
CC -!- SUBUNIT: Interacts (GTP-bound form) with RUNDC3A. Interacts with
CC RGS14; the interaction is GTP-dependent (By similarity). Interacts
CC with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3.
CC Interacts (GTP-bound form preferentially) with TNIK (via the CNH
CC domain); the interaction is direct and recruits RAP2A to the E3
CC ubiquitin ligase NEDD4. Interacts with MINK1. Interacts (GTP-bound
CC form preferentially) with MAP4K4. Interacts with cytoskeletal
CC actin.
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
CC neutrophils (PubMed:8391995). Colocalizes with RASGEF1B to midbody
CC at telophase (PubMed:23894443).
CC -!- DOMAIN: The effector domain mediates the interaction with RUNDC3A
CC (By similarity).
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.
CC -!- PTM: Palmitoylated. Palmitoylation is required for association
CC with recycling endosome membranes and activation of TNIK (By
CC similarity).
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and 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; CAI39499.1; -; Genomic_DNA.
DR EMBL; CH471085; EAX08974.1; -; Genomic_DNA.
DR EMBL; BC041333; AAH41333.1; -; mRNA.
DR EMBL; BC070031; AAH70031.1; -; mRNA.
DR PIR; S03180; S03180.
DR RefSeq; NP_066361.1; NM_021033.6.
DR UniGene; Hs.508480; -.
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 DisProt; DP00167; -.
DR ProteinModelPortal; P10114; -.
DR SMR; P10114; 1-167.
DR IntAct; P10114; 13.
DR MINT; MINT-1172095; -.
DR STRING; 9606.ENSP00000245304; -.
DR PhosphoSite; P10114; -.
DR DMDM; 131852; -.
DR PaxDb; P10114; -.
DR PRIDE; P10114; -.
DR DNASU; 5911; -.
DR Ensembl; ENST00000245304; ENSP00000245304; ENSG00000125249.
DR GeneID; 5911; -.
DR KEGG; hsa:5911; -.
DR UCSC; uc001vnd.3; human.
DR CTD; 5911; -.
DR GeneCards; GC13P098086; -.
DR HGNC; HGNC:9861; RAP2A.
DR HPA; CAB018552; -.
DR MIM; 179540; gene.
DR neXtProt; NX_P10114; -.
DR PharmGKB; PA34222; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233973; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; P10114; -.
DR KO; K07837; -.
DR OMA; FRQSMLR; -.
DR OrthoDB; EOG7QVM41; -.
DR PhylomeDB; P10114; -.
DR SignaLink; P10114; -.
DR ChiTaRS; RAP2A; human.
DR EvolutionaryTrace; P10114; -.
DR GeneWiki; RAP2A; -.
DR GenomeRNAi; 5911; -.
DR NextBio; 23004; -.
DR PRO; PR:P10114; -.
DR ArrayExpress; P10114; -.
DR Bgee; P10114; -.
DR CleanEx; HS_RAP2A; -.
DR Genevestigator; P10114; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IEA:UniProtKB-SubCell.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB.
DR GO; GO:0034613; P:cellular protein localization; IDA:UniProtKB.
DR GO; GO:0045184; P:establishment of protein localization; IDA:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; IEA:Ensembl.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IDA: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 InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00173; RAS; 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; Complete proteome; Endosome; GTP-binding; Lipoprotein;
KW Membrane; Methylation; Nucleotide-binding; Palmitate; Prenylation;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1 180 Ras-related protein Rap-2a.
FT /FTId=PRO_0000082687.
FT PROPEP 181 183 Removed in mature form (By similarity).
FT /FTId=PRO_0000281336.
FT NP_BIND 10 17 GTP (By similarity).
FT NP_BIND 57 61 GTP (By similarity).
FT NP_BIND 116 119 GTP (By similarity).
FT MOTIF 32 40 Effector region (Probable).
FT MOD_RES 180 180 Cysteine methyl ester (Probable).
FT LIPID 180 180 S-farnesyl cysteine.
FT MUTAGEN 5 5 K->R: Reduced NEDD4-dependent
FT ubiquitination; when associated with R-
FT 94; R-148 and R-150.
FT MUTAGEN 12 12 G->V: Dominant active. 2-fold decrease in
FT GDP dissociation rate constant and GTPase
FT activity. No change in interaction with
FT TNIK.
FT MUTAGEN 17 17 S->N: Dominant negative. Severely impairs
FT GTP-binding and partial loss of
FT interaction with MAP4K4, MINK1 and TNIK.
FT MUTAGEN 35 35 T->A: Decreases affinity for GTP and 3-
FT fold reduction of GTPase activity.
FT MUTAGEN 39 39 F->S: Loss of RASGEF1A- and RASGEF1B-
FT mediated GDP to GTP exchange. Complete
FT loss of interaction with MAP4K4, MINK1
FT and TNIK, and loss of ubiquitination by
FT NEDD4.
FT MUTAGEN 94 94 K->R: Reduced NEDD4-dependent
FT ubiquitination; when associated with R-5;
FT R-148 and R-150.
FT MUTAGEN 145 145 T->I: Imperfect binding of guanyl
FT nucleotides.
FT MUTAGEN 148 148 K->R: Reduced NEDD4-dependent
FT ubiquitination; when associated with R-5;
FT R-94 and R-150.
FT MUTAGEN 150 150 K->R: Reduced NEDD4-dependent
FT ubiquitination; when associated with R-5;
FT R-94 and R-148.
FT STRAND 3 9
FT HELIX 16 25
FT STRAND 38 46
FT STRAND 49 57
FT HELIX 65 74
FT STRAND 76 83
FT HELIX 87 103
FT TURN 104 106
FT STRAND 111 116
FT HELIX 118 123
FT HELIX 128 138
FT STRAND 142 145
FT HELIX 150 166
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
//

MIM 179540
*RECORD*
*FIELD* NO
179540
*FIELD* TI
*179540 RAS-RELATED PROTEIN 2A; RAP2A
;;RAP2;;
KREV
*FIELD* TX

CLONING

By screening a Raji Burkitt lymphoma cell line cDNA library with
read moreDrosophila Dras3 cDNA, Pizon et al. (1988) cloned RAP1A (179520) and
RAP2A. The deduced 183-amino acid protein has a calculated molecular
mass of 20.7 kD. It contains domains required for GTP binding and a Ras
(see 190020)-like C-terminal motif for posttranslational lipid binding
and subsequent anchoring to the plasma membrane. Northern blot analysis
of lymphocyte mRNA detected transcripts of 2.2, 2.5, and 4.6 kb.

GENE FUNCTION

Lerosey et al. (1991) demonstrated that purified recombinant RAP2A bound
GTP and exhibited a low intrinsic GTPase activity in the presence of
Mg(2+). By site-directed mutagenesis, they showed that gly12 and thr35
were involved in the GTPase activity, thr145 was involved in guanyl
nucleotide binding, and ser17 coordinated the Mg(2+) required for GTP
binding.

Zhu et al. (2005) stated that Rap2a and Jnk (see MAPK8, 601158), as well
as their regulators, are expressed at excitatory synapses in rodent
brain, and they identified a functional Rap2a signaling pathway in
cultured mouse hippocampal CA1 neurons. Synaptic activity and activation
of NR2A (GRIN2A; 138253)-containing NMDA receptor complexes activated
Rap2a, which stimulated Jnk activity. Activation of Rap2a and Jnk led to
the removal of Glur1 (GRIA1; 138248)- and Glur2 (GRIA2;
138247)-containing AMPA receptor complexes, and was essential for
depolarization. In the bidirectional control of synaptic strength, Rap2a
activity appeared to complement the long-term depression due to Rap1
(see 179520) signaling and oppose the long-term potentiation due to Ras
signaling.

By affinity chromatography of rat brain synaptosome extracts, Kawabe et
al. (2010) identified Tnik (610005) among 15 proteins that interacted
with immobilized Nedd4 (602278), an E3 ubiquitin ligase. Rap2a
coimmunoprecipitated with Nedd4 and Tnik, but only following protein
crosslinking. In vitro ubiquitination experiments revealed that Nedd4
monoubiquitinated Rap2a, but not Tnik or any other Ras-related small
GTPase examined. Tnik was required for Nedd4 ubiquitination of Rap2a,
and Rap2a monoubiquitination blocked Rap2a/Tnik signaling. Nedd4 -/-
mouse cortical neurons showed underdeveloped dendrite extensions and
arborizations, and expression of dominant-negative Rap2a or Tnik mutants
rescued dendrite morphology in Nedd4 -/- embryos. Kawabe et al. (2010)
concluded that NEDD4 positively regulates dendrite extension by blocking
RAP2A/TNIK signaling.

MAPPING

Rousseau-Merck et al. (1990) used cDNA probes to assign 3 RAP genes by
in situ hybridization; RAP1A, RAP1B (179530), and RAP2A were assigned to
1p13-p12, 12q14, and 13q34, respectively, without cross-hybridization or
any secondary signal.

*FIELD* RF
1. Kawabe, H.; Neeb, A.; Dimova, K.; Young, S. M., Jr.; Takeda, M.;
Katsurabayashi, S.; Mitkovski, M.; Malakhova, O. A.; Zhang, D.-E.;
Umikawa, M.; Kariya, K.; Goebbels, S.; Nave, K.-A.; Rosenmund, C.;
Jahn, O.; Rhee, J.; Brose, N.: Regulation of Rap2A by the ubiquitin
ligase Nedd4-1 controls neurite development. Neuron 65: 358-372,
2010.

2. Lerosey, I.; Chardin, P.; de Gunzburg, J.; Tavitian, A.: The product
of the rap2 gene, member of the ras superfamily: biochemical characterization
and site-directed mutagenesis. J. Biol. Chem. 266: 4315-4321, 1991.

3. Pizon, V.; Chardin, P.; Lerosey, I.; Olofsson, B.; Tavitian, A.
: Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3
encode proteins closely related to ras in the 'effector' region. Oncogene 3:
201-204, 1988.

4. Rousseau-Merck, M. F.; Pizon, V.; Tavitian, A.; Berger, R.: Chromosome
mapping of the human RAS-related RAP1A, RAP1B, and RAP2 genes to chromosomes
1p12-p13, 12q14, and 13q34, respectively. Cytogenet. Cell Genet. 53:
2-4, 1990.

5. Zhu, Y.; Pak, D.; Qin, Y.; McCormack, S. G.; Kim, M. J.; Baumgart,
J. P.; Velamoor, V.; Auberson, Y. P.; Osten, P.; van Aelst, L.; Sheng,
M.; Zhu, J. J.: Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron 46:
905-916, 2005. Note: Erratum: Neuron 47: 321 only, 2005.

*FIELD* CN
Patricia A. Hartz - updated: 10/14/2011
Patricia A. Hartz - updated: 10/12/2006
Mark H. Paalman - updated: 1/10/1997

*FIELD* CD
Victor A. McKusick: 9/6/1989

*FIELD* ED
mgross: 10/14/2011
carol: 10/13/2006
terry: 10/12/2006
mark: 1/10/1997
supermim: 3/16/1992
carol: 10/16/1990
supermim: 3/20/1990
ddp: 10/27/1989
root: 9/6/1989

RBCC Red Blood Cell Collection

Full text data of RAP2A