Repulsive guidance molecule A

Repulsive guidance molecule family member a
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4UHY​
Identifiers
Symbols	RGMA ; RGM
External IDs	OMIM: 607362 MGI: 2679262 HomoloGene: 10626 GeneCards: RGMA Gene
Gene ontology Molecular function • glycoprotein binding • coreceptor activity • transferrin receptor binding Cellular component • endoplasmic reticulum • plasma membrane • anchored component of membrane • extracellular exosome Biological process • axon guidance • BMP signaling pathway Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	56963	244058
Ensembl	ENSG00000182175	ENSMUSG00000070509
UniProt	Q96B86	Q6PCX7
RefSeq (mRNA)	NM_001166283	NM_177740
RefSeq (protein)	NP_001159755	NP_808408
Location (UCSC)	Chr 15: 93.04 – 93.09 Mb	Chr 7: 73.38 – 73.42 Mb
PubMed search

Repulsive guidance molecule A (RGMa) is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. Together with BMPR1A and BMPR1B, as well as ACVR2A and BMPR2, it binds BMPs thereby activating the intracellular SMAD1/5/8 signalling pathway.^[1] In humans this protein is encoded by the RGMA gene.^[2]

Function

RGMa is a repulsive guidance molecule for retinal axons.^[3] Furthermore neogenin functions as a receptor for RGM.^[4] Neogenin overexpression and RGM downexpression in the developing embryonic neural tube induces apoptosis. The apoptotic activity of neogenin in the neural tube is associated with cleavage of its cytoplasmic domain by caspases.^[5]

RGMA belongs to a family of repulsive guidance molecules that are (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins. The three proteins, RGMa (this protein), RGMb and RGMc are 40-50% identical to each other, and share similarities in predicted protein domains and overall structure. All three RGM proteins appear capable of binding selected BMPs (bone morphogenetic proteins).^[6]

RGMs may play inhibitory roles in prostate cancer by suppressing cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent and Smad-independent signalling of BMPs in prostate cancer and breast cancer cells.^[7][8]

References

1. Corradini, Elena; Babitt, Jodie L.; Lin, Herbert Y. (October 2009). "The RGM/DRAGON family of BMP co-receptors". Cytokine & Growth Factor Reviews 20 (5-6): 389–398. doi:10.1016/j.cytogfr.2009.10.008.
2. "Entrez Gene: RGMA RGM domain family, member A".
3. Monnier PP, Sierra A, Macchi P, Deitinghoff L, Andersen JS, Mann M, Flad M, Hornberger MR, Stahl B, Bonhoeffer F, Mueller BK (September 2002). "RGM is a repulsive guidance molecule for retinal axons". Nature 419 (6905): 392–5. doi:10.1038/nature01041. PMID 12353034.
4. Rajagopalan S, Deitinghoff L, Davis D, Conrad S, Skutella T, Chedotal A, Mueller BK, Strittmatter SM (August 2004). "Neogenin mediates the action of repulsive guidance molecule". Nat. Cell Biol. 6 (8): 756–62. doi:10.1038/ncb1156. PMID 15258590.
5. Matsunaga E, Tauszig-Delamasure S, Monnier PP, Mueller BK, Strittmatter SM, Mehlen P, Chédotal A (August 2004). "RGM and its receptor neogenin regulate neuronal survival". Nat. Cell Biol. 6 (8): 749–55. doi:10.1038/ncb1157. PMID 15258591.
6. Severyn CJ, Shinde U, Rotwein P (September 2009). "Molecular biology, genetics and biochemistry of the repulsive guidance molecule family". Biochem. J. 422 (3): 393–403. doi:10.1042/BJ20090978. PMID 19698085.
7. Li J, Ye L, Sanders AJ, Jiang WG (March 2012). "Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling". J Cell Biochem 113 (7): 2523–31. doi:10.1002/jcb.24128. PMID 22415859.
8. Li J, Ye L, Kynaston HG, Jiang WG (February 2012). "Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells". Int. J. Oncol. 40 (2): 544–50. doi:10.3892/ijo.2011.1251. PMID 22076499.

Further reading

• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to Biology: A Functional Genomics Pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Schwab JM, Monnier PP, Schluesener HJ, et al. (2005). "Central nervous system injury-induced repulsive guidance molecule expression in the adult human brain". Arch. Neurol. 62 (10): 1561–8. doi:10.1001/archneur.62.10.1561. PMID 16216939.
• Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Xia Y, Yu PB, Sidis Y, et al. (2007). "Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4". J. Biol. Chem. 282 (25): 18129–40. doi:10.1074/jbc.M701679200. PMID 17472960.
• Feys T, Poppe B, De Preter K, et al. (2007). "A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines". Haematologica 92 (7): 913–20. doi:10.3324/haematol.11073. PMID 17606441.