RAP1A

RAP1A, member of RAS oncogene family
PDB rendering based on 1c1y.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1C1Y​, 1GUA​, 3KUC​, 4KVG​
Identifiers
Symbols	RAP1A ; C21KG; G-22K; KREV-1; KREV1; RAP1; SMGP21
External IDs	OMIM: 179520 MGI: 97852 HomoloGene: 2162 ChEMBL: 1255139 GeneCards: RAP1A Gene
Gene ontology Molecular function • GTPase activity • protein binding • GTP binding • protein transporter activity • Ras GTPase binding • Rap guanyl-nucleotide exchange factor activity • protein complex binding Cellular component • cytoplasm • early endosome • late endosome • cytosol • plasma membrane • cell junction • guanyl-nucleotide exchange factor complex • neuron projection • myelin sheath • perinuclear region of cytoplasm • extracellular exosome Biological process • activation of MAPKK activity • energy reserve metabolic process • signal transduction • blood coagulation • positive regulation of neuron projection development • protein transport • microvillus assembly • platelet activation • Rap protein signal transduction • nerve growth factor signaling pathway • positive regulation of GTPase activity • small molecule metabolic process • positive regulation of protein kinase activity • neurotrophin TRK receptor signaling pathway • regulation of insulin secretion • establishment of endothelial barrier • positive regulation of ERK1 and ERK2 cascade • cellular response to cAMP • regulation of cell junction assembly • cellular response to nerve growth factor stimulus • negative regulation of synaptic vesicle exocytosis • positive regulation of vasculogenesis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5906	109905
Ensembl	ENSG00000116473	ENSMUSG00000068798
UniProt	P62834	P62835
RefSeq (mRNA)	NM_001010935	NM_145541
RefSeq (protein)	NP_001010935	NP_663516
Location (UCSC)	Chr 1: 111.54 – 111.72 Mb	Chr 3: 105.73 – 105.8 Mb
PubMed search

Ras-related protein Rap-1A is a protein that in humans is encoded by the RAP1A gene.^[1]

Function

The product of this gene belongs to the family of Ras-related proteins. These proteins share approximately 50% amino acid identity with the classical RAS proteins and have numerous structural features in common. The most striking difference between RAP proteins and RAS proteins resides in their 61st amino acid: glutamine in RAS is replaced by threonine in RAP proteins. The product of this gene counteracts the mitogenic function of RAS because it can interact with RAS GAPs and RAF in a competitive manner. Two transcript variants encoding the same protein have been identified for this gene.^[2]

Interactions

RAP1A has been shown to interact with:

• C-Raf,^[3][4][5][6]
• MLLT4,^[7]
• PDE6D,^[8][9]
• RALGDS,^[7][10]
• RAPGEF2,^[11] and
• TSC2.^[12][13]

References

1. Kawata M, Matsui Y, Kondo J, Hishida T, Teranishi Y, Takai Y (Dec 1988). "A novel small molecular weight GTP-binding protein with the same putative effector domain as the ras proteins in bovine brain membranes. Purification, determination of primary structure, and characterization". The Journal of Biological Chemistry 263 (35): 18965–71. PMID 3143720.
2. "Entrez Gene: RAP1A RAP1A, member of RAS oncogene family".
3. Han L, Colicelli J (Mar 1995). "A human protein selected for interference with Ras function interacts directly with Ras and competes with Raf1". Molecular and Cellular Biology 15 (3): 1318–23. doi:10.1128/mcb.15.3.1318. PMC 230355. PMID 7862125.
4. Nassar N, Horn G, Herrmann C, Scherer A, McCormick F, Wittinghofer A (Jun 1995). "The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue". Nature 375 (6532): 554–60. doi:10.1038/375554a0. PMID 7791872.
5. Hu CD, Kariya K, Okada T, Qi X, Song C, Kataoka T (Jan 1999). "Effect of phosphorylation on activities of Rap1A to interact with Raf-1 and to suppress Ras-dependent Raf-1 activation". The Journal of Biological Chemistry 274 (1): 48–51. doi:10.1074/jbc.274.1.48. PMID 9867809.
6. Okada T, Hu CD, Jin TG, Kariya K, Yamawaki-Kataoka Y, Kataoka T (Sep 1999). "The strength of interaction at the Raf cysteine-rich domain is a critical determinant of response of Raf to Ras family small GTPases". Molecular and Cellular Biology 19 (9): 6057–64. doi:10.1128/mcb.19.9.6057. PMC 84512. PMID 10454553.
7. Boettner B, Govek EE, Cross J, Van Aelst L (Aug 2000). "The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin". Proceedings of the National Academy of Sciences of the United States of America 97 (16): 9064–9. doi:10.1073/pnas.97.16.9064. PMC 16822. PMID 10922060.
8. Nancy V, Callebaut I, El Marjou A, de Gunzburg J (Apr 2002). "The delta subunit of retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases". The Journal of Biological Chemistry 277 (17): 15076–84. doi:10.1074/jbc.M109983200. PMID 11786539.
9. Hanzal-Bayer M, Renault L, Roversi P, Wittinghofer A, Hillig RC (May 2002). "The complex of Arl2-GTP and PDE delta: from structure to function". The EMBO Journal 21 (9): 2095–106. doi:10.1093/emboj/21.9.2095. PMC 125981. PMID 11980706.
10. Nancy V, Wolthuis RM, de Tand MF, Janoueix-Lerosey I, Bos JL, de Gunzburg J (Mar 1999). "Identification and characterization of potential effector molecules of the Ras-related GTPase Rap2". The Journal of Biological Chemistry 274 (13): 8737–45. doi:10.1074/jbc.274.13.8737. PMID 10085114.
11. Rebhun JF, Castro AF, Quilliam LA (Nov 2000). "Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction". The Journal of Biological Chemistry 275 (45): 34901–8. doi:10.1074/jbc.M005327200. PMID 10934204.
12. Castro AF, Rebhun JF, Clark GJ, Quilliam LA (Aug 2003). "Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner". The Journal of Biological Chemistry 278 (35): 32493–6. doi:10.1074/jbc.C300226200. PMID 12842888.
13. Yamamoto Y, Jones KA, Mak BC, Muehlenbachs A, Yeung RS (Aug 2002). "Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin". Archives of Biochemistry and Biophysics 404 (2): 210–7. doi:10.1016/s0003-9861(02)00300-4. PMID 12147258.