GM2A

GM2 ganglioside activator also known as GM2A is a protein which in humans is encoded by the GM2A gene.[5][6]

GM2A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGM2A, GM2-AP, SAP-3, GM2 ganglioside activator
External IDsOMIM: 613109 MGI: 95762 HomoloGene: 349 GeneCards: GM2A
Gene location (Human)
Chr.Chromosome 5 (human)[1]
Band5q33.1Start151,212,150 bp[1]
End151,270,440 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

2760

14667

Ensembl

ENSG00000196743

ENSMUSG00000000594

UniProt

P17900

Q60648

RefSeq (mRNA)

NM_001167607
NM_000405

NM_010299

RefSeq (protein)

NP_000396
NP_001161079

NP_034429

Location (UCSC)Chr 5: 151.21 – 151.27 MbChr 11: 55.1 – 55.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

The protein encoded by this gene is a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme β-hexosaminidase A. β-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines.

GM2A is a lipid transfer protein that stimulates the enzymatic processing of gangliosides, and also T-cell activation through lipid presentation. This protein binds molecules of ganglioside GM2, extracts them from membranes, and presents them to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3.

It was identified as a member of ML domain family of proteins involved in innate immunity and lipid metabolism in the SMART database. .

Regulation

In melanocytic cells GM2A gene expression may be regulated by MITF.[7]

Clinical significance

Mutations in this gene, inherited in an autosomal recessive pattern, result in GM2-gangliosidosis, AB variant, a rare GM2 gangliosidosis that has symptoms and pathology identical with Tay–Sachs disease and Sandhoff disease.[8]

GM2A mutations are rarely reported, and the cases that are observed often occur with consanguineous parents or in genetically isolated populations.[9]

Because AB variant is so rarely diagnosed, even in infants, it is likely that most mutations of GM2A are fatal in the fetus in homozygotes and genetic compounds, and thus are never observed clinically.

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000196743 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000000594 - 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. Li SC, Nakamura T, Ogamo A, Li YT (November 1979). "Evidence for the presence of two separate protein activators for the enzymic hydrolysis of GM1 and GM2 gangliosides". J. Biol. Chem. 254 (21): 10592–5. PMID 115863.
  6. Klima H, Tanaka A, Schnabel D, Nakano T, Schröder M, Suzuki K, Sandhoff K (September 1991). "Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein". FEBS Lett. 289 (2): 260–4. doi:10.1016/0014-5793(91)81084-L. PMID 1915857. S2CID 40408626.
  7. Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
  8. Mahuran DJ (1999-10-08). "Biochemical consequences of mutations causing the GM2 gangliosidoses". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1455 (2–3): 105–138. doi:10.1016/S0925-4439(99)00074-5. PMID 10571007.
  9. "Online Mendelian Inheritance in Man". United States National Institute of Health. Retrieved 2009-04-21.

Further reading


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