Repulsive guidance molecule A

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RGMA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRGMA, RGM, repulsive guidance molecule family member a, repulsive guidance molecule BMP co-receptor a
External IDsOMIM: 607362 MGI: 2679262 HomoloGene: 10626 GeneCards: RGMA
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_177740

RefSeq (protein)

NP_808408

Location (UCSC)Chr 15: 93.04 – 93.09 MbChr 7: 73.03 – 73.07 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000182175Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000070509Ensembl, 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