repulsive guidance molecule family member a

Target id: 2911

Nomenclature: repulsive guidance molecule family member a

Family: Repulsive guidance molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     repulsive guidance molecule family member a has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 458 15q26.1 RGMA repulsive guidance molecule family member a
Mouse - 454 7 D1 Rgma repulsive guidance molecule family member A 7
Rat - 449 1q31 Rgma repulsive guidance molecule family member A
Gene and Protein Information Comments
Multiple transcript variants are reported in human, as the result of alternate splicing. We show the longest transcript in the table.
Database Links
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
elezanumab Hs Binding - - 5
[5]
Immunopharmacology Comments
RGMA has been validated as a novel target for pharmacological intervention in neurodegenerative and neuroinflammatory diseases such as multiple sclerosis (MS), as well as for spinal cord injury [3]. Inhibition of RGMA is expected to promote regeneration and neuroprotection in MS [1], acting to concurrently block autoimmune demyelination and axon injury. A clinical candidate monoclonal anti-RGMA antibody, elezanumab (ABT-555), is in Phase 1 development for MS.
Physiological Functions
Inhibits neuronal regeneration and functional recovery in rat spinal cord injury model.
Species:  Rat
Tissue: 
References:  2,4
Causes CNS demyelination via enhanced CD4(+) T cell activation in mouse experimental autoimmune encephalomyelitis (EAE), EAE being a mouse model of MS.
Species:  Mouse
Tissue: 
References:  3
Clinically-Relevant Mutations and Pathophysiology
Disease:  Multiple Sclerosis
Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
References:  6
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  An RGMA SNP associated with MS in male subjects
SNP accession: 
References:  6
General Comments
RGMA is a member of a family of related proteins with functions in the developing and adult nervous systems. Structurally, RGMA is a glycosylphosphatidylinositol-anchored glycoprotein that can also be detected as a soluble form. It inhibits neurite growth [8] which can result in axon and neuron degeneration. The neuronal receptor for RGMA is neogenin (NEO1; Q92859), an immunoglobulin family membrane protein.

References

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1. Demicheva E, Cui YF, Bardwell P, Barghorn S, Kron M, Meyer AH, Schmidt M, Gerlach B, Leddy M, Barlow E et al.. (2015) Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis. Cell Rep10 (11): 1887-98. [PMID:25801027]

2. Hata K, Fujitani M, Yasuda Y, Doya H, Saito T, Yamagishi S, Mueller BK, Yamashita T. (2006) RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J. Cell Biol.173 (1): 47-58. [PMID:16585268]

3. Kubo T, Tokita S, Yamashita T. (2012) Repulsive guidance molecule-a and demyelination: implications for multiple sclerosis. J Neuroimmune Pharmacol7 (3): 524-8. [PMID:22183806]

4. Kyoto A, Hata K, Yamashita T. (2007) Synapse formation of the cortico-spinal axons is enhanced by RGMa inhibition after spinal cord injury. Brain Res.1186: 74-86. [PMID:17996222]

5. Mueller B, Huang L, Bardwell PD, Kutsova Y, Memmot J. (2013) Composition and method for diagnosis and treatment of diseases associated with neurite degeneration. Patent number: WO2013112922 A1. Assignee: AbbVie Deutschland GmbH & Co. KG, Abbvie Inc.. Priority date: 27/01/2012. Publication date: 01/08/2013.

6. Nohra R, Beyeen AD, Guo JP, Khademi M, Sundqvist E, Hedreul MT, Sellebjerg F, Smestad C, Oturai AB, Harbo HF et al.. (2010) RGMA and IL21R show association with experimental inflammation and multiple sclerosis. Genes Immun.11 (4): 279-93. [PMID:20072140]

7. Schmidtmer J, Engelkamp D. (2004) Isolation and expression pattern of three mouse homologues of chick Rgm. Gene Expr. Patterns4 (1): 105-10. [PMID:14678836]

8. Tassew NG, Charish J, Seidah NG, Monnier PP. (2012) SKI-1 and Furin generate multiple RGMa fragments that regulate axonal growth. Dev. Cell22 (2): 391-402. [PMID:22340500]

How to cite this page

Repulsive guidance molecules: repulsive guidance molecule family member a. Last modified on 08/05/2017. Accessed on 22/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2911.