GM2A

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GM2 ganglioside activator
Protein GM2A PDB 1g13.png
PDB rendering based on 1g13.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GM2A ; GM2-AP; SAP-3
External IDs OMIM613109 MGI95762 HomoloGene349 GeneCards: GM2A Gene
RNA expression pattern
PBB GE GM2A 212737 at tn.png
PBB GE GM2A 33646 g at tn.png
PBB GE GM2A 35820 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2760 14667
Ensembl ENSG00000196743 ENSMUSG00000000594
UniProt P17900 Q60648
RefSeq (mRNA) NM_000405 NM_010299
RefSeq (protein) NP_000396 NP_034429
Location (UCSC) Chr 5:
150.59 – 150.65 Mb
Chr 11:
55.1 – 55.11 Mb
PubMed search [1] [2]

GM2 ganglioside activator also known as GM2A is a protein which in humans is encoded by the GM2A gene.[1][2]

Function[edit]

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. [3].

Regulation[edit]

In melanocytic cells GM2A gene expression may be regulated by MITF.[3]

Clinical significance[edit]

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.[4]

GM2A mutations are rarely reported, and the cases that are observed often occur with consanguineous parents or in genetically isolated populations.[5]

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[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Mahuran DJ (1999-10-08). "Biochemical consequences of mutations causing the GM2 gangliosidoses". Biochimica Biophysica Acta 1455 (2–3): 105–138. doi:10.1016/S0925-4439(99)00074-5. PMID 10571007. 
  5. ^ "Online Mendelian Inheritance in Man". United States National Institute of Health. Retrieved 2009-04-21. 

Further reading[edit]