Repulsive guidance molecule A

For the Philippine radio network, see RGMA Network, Inc.

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.^[5] In humans this protein is encoded by the RGMA gene.^[6]

RGMA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4UHY
Identifiers
Aliases	RGMA, RGM, repulsive guidance molecule family member a, repulsive guidance molecule BMP co-receptor a
External IDs	OMIM: 607362; MGI: 2679262; HomoloGene: 10626; GeneCards: RGMA; OMA:RGMA - orthologs
Gene ___location (Human) Chr. Chromosome 15 (human)[1] Band 15q26.1 Start 93,035,271 bp[1] End 93,089,211 bp[1]
Gene ___location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 D1 Start 73,025,257 bp[2] End 73,069,647 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle ventricular zone tibialis anterior muscle muscle of thigh muscle layer of sigmoid colon canal of the cervix gastric mucosa left uterine tube hypothalamus apex of heart Top expressed in ventricular zone medial habenular nucleus lip interpeduncular nucleus paraventricular nucleus of thalamus layer of dentate gyrus enteric plexus molecular layer of neocortex lumbar subsegment of spinal cord superior frontal gyrus More reference expression data BioGPS n/a
Gene ontology Molecular function transferrin receptor binding protein binding coreceptor activity Cellular component anchored component of membrane plasma membrane endoplasmic reticulum membrane Biological process positive regulation of transcription by RNA polymerase II BMP signaling pathway negative regulation of axon regeneration regulation of neuron projection development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 56963 244058 Ensembl ENSG00000182175 ENSMUSG00000070509 UniProt Q96B86 Q6PCX7 RefSeq (mRNA) NM_020211 NM_001166283 NM_001166286 NM_001166287 NM_001166288 NM_001166289 NM_177740 RefSeq (protein) NP_001159755 NP_001159758 NP_001159759 NP_001159760 NP_001159761 NP_064596 NP_808408 Location (UCSC) Chr 15: 93.04 – 93.09 Mb Chr 7: 73.03 – 73.07 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

RGMa is a repulsive guidance molecule for retinal axons.^[7] Furthermore, neogenin functions as a receptor for RGM.^[8] 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.^[9]

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).^[10]

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.^[11][12] RGMa is also pointed as a component of the mechanisms that determine skeletal cell fusion via neogenin receptor.^[13][14][15]

References

1. GRCh38: Ensembl release 89: ENSG00000182175 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000070509 – 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. Corradini E, Babitt JL, Lin HY (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. PMC 3715994. PMID 19897400.
6. "Entrez Gene: RGMA RGM ___domain family, member A".
7. 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. Bibcode:2002Natur.419..392M. doi:10.1038/nature01041. PMID 12353034. S2CID 3234138.
8. 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. S2CID 23448687.
9. 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. S2CID 15433313.
10. 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. PMC 4242795. PMID 19698085.
11. 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. S2CID 35629616.
12. 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.
13. Do Carmo Costa A, Copola AG, Carvalho e Souza C, Nogueira JM, Silva GA, Jorge EC (2021). "RGMa can induce skeletal muscle cell hyperplasia via association with neogenin signalling pathway". In Vitro Cellular & Developmental Biology - Animal. 57 (4): 415–427. doi:10.1007/s11626-021-00555-9. PMID 33748906. S2CID 232311370.
14. Martins AF, Xavier Neto J, Azambuja A, Sereno ML, Figueira A, Campos-Junior PH, Rosário MF, Toledo CB, Silva GA, Kitten GT, Coutinho LL, Dietrich S, Jorge EC (2014). "Repulsive Guidance Molecules a, b and c Are Skeletal Muscle Proteins, and Repulsive Guidance Molecule a Promotes Cellular Hypertrophy and is Necessary for Myotube Fusion". Cells Tissues Organs. 200 (5): 326–338. doi:10.1159/000433491. PMID 26397945. S2CID 9469435.
15. Jorge EC, Ahmed MU, Bothe I, Coutinho LL, Dietrich S (2012). "RGMaandRGMbexpression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis". Developmental Dynamics. 241 (12): 1886–1900. doi:10.1002/dvdy.23889. PMID 23073896. S2CID 16006086.

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. Bibcode:2002PNAS...9916899M. 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. hdl:1854/LU-376639. PMID 17606441.