RAP1A

Ras-related protein Rap-1A is a protein that in humans is encoded by the RAP1A gene.[5]

RAP1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1C1Y, 1GUA, 3KUC, 4KVG
Identifiers
Aliases	RAP1A, C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21, member of RAS oncogene family
External IDs	OMIM: 179520 MGI: 97852 HomoloGene: 2162 GeneCards: RAP1A
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p13.2 Start 111,542,218 bp[1] End 111,716,691 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F2.2|3 46.45 cM Start 105,727,267 bp[2] End 105,801,336 bp[2]
Gene ontology Molecular function • nucleotide binding • GO:0032403 macromolecular complex binding • GTP binding • Ras GTPase binding • GO:0001948 protein binding • Rap guanyl-nucleotide exchange factor activity • GTPase activity • GDP binding Cellular component • cytosol • endosome • membrane • myelin • cell membrane • guanyl-nucleotide exchange factor complex • neuron projection • extracellular exosome • early endosome • late endosome • cytoplasm • cell junction • perinuclear region of cytoplasm • specific granule membrane • phagocytic vesicle • glutamatergic synapse Biological process • establishment of endothelial barrier • positive regulation of glucose import • microvillus assembly • regulation of cell junction assembly • activation of MAPKK activity • regulation of insulin secretion • small GTPase mediated signal transduction • Rap protein signal transduction • cellular response to organic cyclic compound • nervous system development • negative regulation of synaptic vesicle exocytosis • cellular response to drug • liver regeneration • protein transport • response to antineoplastic agent • response to carbohydrate • negative regulation of collagen biosynthetic process • cellular response to glucose stimulus • signal transduction • cellular response to nerve growth factor stimulus • nerve growth factor signaling pathway • positive regulation of ERK1 and ERK2 cascade • positive regulation of protein kinase activity • positive regulation of vasculogenesis • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • cellular response to cAMP • positive regulation of neuron projection development • neutrophil degranulation • positive regulation of Fc-gamma receptor signaling pathway involved in phagocytosis • regulation of neurotransmitter receptor localization to postsynaptic specialization membrane • protein localization to plasma membrane Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5906	109905
Ensembl	ENSG00000116473	ENSMUSG00000068798
UniProt	P62834	P62835
RefSeq (mRNA)	NM_001010935 NM_001291896 NM_002884 NM_001370216 NM_001370217	NM_145541
RefSeq (protein)	NP_001010935 NP_001278825 NP_002875 NP_001357145 NP_001357146	NP_663516
Location (UCSC)	Chr 1: 111.54 – 111.72 Mb	Chr 3: 105.73 – 105.8 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

Interactions

RAP1A has been shown to interact with:

• C-Raf,[7][8][9][10]
• MLLT4,[11]
• PDE6D,[12][13]
• RALGDS,[11][14]
• RAPGEF2,[15] and
• TSC2.[16][17]

References

1. GRCh38: Ensembl release 89: ENSG00000116473 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000068798 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: RAP1A RAP1A, member of RAS oncogene family".
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.