Ras-related protein Rap-2a

Details

Name
Ras-related protein Rap-2a
Synonyms
  • RbBP-30
Gene Name
RAP2A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011322|Ras-related protein Rap-2a
MREYKVVVLGSGGVGKSALTVQFVTGTFIEKYDPTIEDFYRKEIEVDSSPSVLEILDTAG
TEQFASMRDLYIKNGQGFILVYSLVNQQSFQDIKPMRDQIIRVKRYEKVPVILVGNKVDL
ESEREVSSSEGRALAEEWGCPFMETSAKSKTMVDELFAEIVRQMNYAAQPDKDDPCCSAC
NIQ
Number of residues
183
Molecular Weight
20615.3
Theoretical pI
4.45
GO Classification
Functions
GTP binding / GTPase activity
Processes
actin cytoskeleton reorganization / cellular protein localization / cellular response to drug / establishment of protein localization / microvillus assembly / negative regulation of cell migration / positive regulation of protein autophosphorylation / positive regulation of protein phosphorylation / protein localization to plasma membrane / Rap protein signal transduction / regulation of dendrite morphogenesis / regulation of JNK cascade
Components
cytosol / extracellular exosome / midbody / plasma membrane / recycling endosome / recycling endosome membrane
General Function
Gtpase activity
Specific Function
Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Recycling endosome membrane
Gene sequence
>lcl|BSEQ0011323|Ras-related protein Rap-2a (RAP2A)
ATGCGCGAGTACAAAGTGGTGGTGCTGGGCTCGGGCGGGGTAGGCAAATCCGCCCTGACC
GTGCAGTTCGTGACCGGCACCTTCATCGAGAAATACGACCCCACCATCGAGGACTTCTAC
CGCAAGGAGATCGAGGTGGATTCGTCGCCGTCGGTGCTGGAGATCCTGGACACGGCGGGC
ACCGAGCAGTTCGCGTCCATGCGGGACCTGTACATCAAGAACGGCCAGGGCTTCATCCTC
GTCTACAGCCTCGTCAACCAGCAGAGCTTCCAGGACATCAAGCCCATGCGGGACCAGATC
ATCCGCGTGAAGCGGTATGAGAAAGTGCCAGTCATCTTGGTTGGGAACAAAGTGGACCTG
GAAAGTGAGAGAGAAGTATCGTCCAGCGAAGGCAGAGCCCTTGCTGAAGAGTGGGGCTGC
CCCTTTATGGAAACTTCCGCTAAGAGTAAAACAATGGTGGACGAACTCTTTGCAGAAATT
GTGAGGCAGATGAACTATGCTGCTCAGCCTGACAAAGATGACCCATGCTGTTCTGCATGT
AACATACAATAG
Chromosome Location
13
Locus
13q34
External Identifiers
ResourceLink
UniProtKB IDP10114
UniProtKB Entry NameRAP2A_HUMAN
GenBank Protein ID35861
GenBank Gene IDX12534
GenAtlas IDRAP2A
HGNC IDHGNC:9861
General References
  1. 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. 1988 Aug;3(2):201-4. [PubMed:3045729]
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  5. 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. 1991 Mar 5;266(7):4315-21. [PubMed:1900290]
  6. Farrell FX, Yamamoto K, Lapetina EG: Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated. Biochem J. 1993 Jan 15;289 ( Pt 2):349-55. [PubMed:8424780]
  7. Mollinedo F, Perez-Sala D, Gajate C, Jimenez B, Rodriguez P, Lacal JC: Localization of rap1 and rap2 proteins in the gelatinase-containing granules of human neutrophils. FEBS Lett. 1993 Jul 12;326(1-3):209-14. [PubMed:8391995]
  8. Pizon V, Desjardins M, Bucci C, Parton RG, Zerial M: Association of Rap1a and Rap1b proteins with late endocytic/phagocytic compartments and Rap2a with the Golgi complex. J Cell Sci. 1994 Jun;107 ( Pt 6):1661-70. [PubMed:7962206]
  9. Torti M, Bertoni A, Canobbio I, Sinigaglia F, Lapetina EG, Balduini C: Interaction of the low-molecular-weight GTP-binding protein rap2 with the platelet cytoskeleton is mediated by direct binding to the actin filaments. J Cell Biochem. 1999 Dec 15;75(4):675-85. [PubMed:10572250]
  10. de Rooij J, Rehmann H, van Triest M, Cool RH, Wittinghofer A, Bos JL: Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J Biol Chem. 2000 Jul 7;275(27):20829-36. [PubMed:10777494]
  11. Song C, Satoh T, Edamatsu H, Wu D, Tadano M, Gao X, Kataoka T: Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase C epsilon. Oncogene. 2002 Nov 21;21(53):8105-13. [PubMed:12444546]
  12. Machida N, Umikawa M, Takei K, Sakima N, Myagmar BE, Taira K, Uezato H, Ogawa Y, Kariya K: Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase. J Biol Chem. 2004 Apr 16;279(16):15711-4. Epub 2004 Feb 13. [PubMed:14966141]
  13. Taira K, Umikawa M, Takei K, Myagmar BE, Shinzato M, Machida N, Uezato H, Nonaka S, Kariya K: The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J Biol Chem. 2004 Nov 19;279(47):49488-96. Epub 2004 Sep 1. [PubMed:15342639]
  14. Myagmar BE, Umikawa M, Asato T, Taira K, Oshiro M, Hino A, Takei K, Uezato H, Kariya K: PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector. Biochem Biophys Res Commun. 2005 Apr 15;329(3):1046-52. [PubMed:15752761]
  15. Mittal V, Linder ME: Biochemical characterization of RGS14: RGS14 activity towards G-protein alpha subunits is independent of its binding to Rap2A. Biochem J. 2006 Feb 15;394(Pt 1):309-15. [PubMed:16246175]
  16. Greco F, Ciana A, Pietra D, Balduini C, Minetti G, Torti M: Rap2, but not Rap1 GTPase is expressed in human red blood cells and is involved in vesiculation. Biochim Biophys Acta. 2006 Mar;1763(3):330-5. Epub 2006 Feb 28. [PubMed:16540189]
  17. Yang H, Sasaki T, Minoshima S, Shimizu N: Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway. Genomics. 2007 Aug;90(2):249-60. Epub 2007 May 23. [PubMed:17509819]
  18. Nonaka H, Takei K, Umikawa M, Oshiro M, Kuninaka K, Bayarjargal M, Asato T, Yamashiro Y, Uechi Y, Endo S, Suzuki T, Kariya K: MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1. Biochem Biophys Res Commun. 2008 Dec 12;377(2):573-8. doi: 10.1016/j.bbrc.2008.10.038. Epub 2008 Oct 18. [PubMed:18930710]
  19. Uechi Y, Bayarjargal M, Umikawa M, Oshiro M, Takei K, Yamashiro Y, Asato T, Endo S, Misaki R, Taguchi T, Kariya K: Rap2 function requires palmitoylation and recycling endosome localization. Biochem Biophys Res Commun. 2009 Jan 23;378(4):732-7. doi: 10.1016/j.bbrc.2008.11.107. Epub 2008 Dec 4. [PubMed:19061864]
  20. Yaman E, Gasper R, Koerner C, Wittinghofer A, Tazebay UH: RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that discriminate between Rap GTP-binding proteins and mediate Rap2-specific nucleotide exchange. FEBS J. 2009 Aug;276(16):4607-16. doi: 10.1111/j.1742-4658.2009.07166.x. Epub 2009 Jul 23. [PubMed:19645719]
  21. Kawabe H, Neeb A, Dimova K, Young SM Jr, Takeda M, Katsurabayashi S, Mitkovski M, Malakhova OA, Zhang DE, Umikawa M, Kariya K, Goebbels S, Nave KA, Rosenmund C, Jahn O, Rhee J, Brose N: Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007. [PubMed:20159449]
  22. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  23. Telkoparan P, Erkek S, Yaman E, Alotaibi H, Bayik D, Tazebay UH: Coiled-coil domain containing protein 124 is a novel centrosome and midbody protein that interacts with the Ras-guanine nucleotide exchange factor 1B and is involved in cytokinesis. PLoS One. 2013 Jul 19;8(7):e69289. doi: 10.1371/journal.pone.0069289. Print 2013. [PubMed:23894443]
  24. Cherfils J, Menetrey J, Le Bras G, Janoueix-Lerosey I, de Gunzburg J, Garel JR, Auzat I: Crystal structures of the small G protein Rap2A in complex with its substrate GTP, with GDP and with GTPgammaS. EMBO J. 1997 Sep 15;16(18):5582-91. [PubMed:9312017]
  25. Menetrey J, Cherfils J: Structure of the small G protein Rap2 in a non-catalytic complex with GTP. Proteins. 1999 Nov 15;37(3):465-73. [PubMed:10591105]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04137Guanosine-5'-TriphosphateexperimentalunknownDetails
DB04315Guanosine-5'-DiphosphateexperimentalunknownDetails