| Structural highlights
Function
[RAP2A_HUMAN] 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.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The small G protein Rap2A has been crystallized in complex with GDP, GTP and GTPgammaS. The Rap2A-GTP complex is the first structure of a small G protein with its natural ligand GTP. It shows that the hydroxyl group of Tyr32 forms a hydrogen bond with the gamma-phosphate of GTP and with Gly13. This interaction does not exist in the Rap2A-GTPgammaS complex. Tyr32 is conserved in many small G proteins, which probably also form this hydrogen bond with GTP. In addition, Tyr32 is structurally equivalent to a conserved arginine that binds GTP in trimeric G proteins. The actual participation of Tyr32 in GTP hydrolysis is not yet clear, but several possible roles are discussed. The conformational changes between the GDP and GTP complexes are located essentially in the switch I and II regions as described for the related oncoprotein H-Ras. However, the mobile segments vary in length and in the amplitude of movement. This suggests that even though similar regions might be involved in the GDP-GTP cycle of small G proteins, the details of the changes will be different for each G protein and will ensure the specificity of its interaction with a given set of cellular proteins.
Crystal structures of the small G protein Rap2A in complex with its substrate GTP, with GDP and with GTPgammaS.,Cherfils J, Menetrey J, Le Bras G, Janoueix-Lerosey I, de Gunzburg J, Garel JR, Auzat I EMBO J. 1997 Sep 15;16(18):5582-91. PMID:9312017[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. PMID:14966141 doi:10.1074/jbc.C300542200
- ↑ 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. PMID:15342639 doi:10.1074/jbc.M406370200
- ↑ 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. PMID:16246175 doi:10.1042/BJ20051086
- ↑ 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. PMID:16540189 doi:10.1016/j.bbamcr.2006.02.001
- ↑ 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. PMID:18930710 doi:10.1016/j.bbrc.2008.10.038
- ↑ 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. PMID:20159449 doi:10.1016/j.neuron.2010.01.007
- ↑ 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. PMID:9312017 doi:10.1093/emboj/16.18.5582
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