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词条 GM2A
释义

  1. Function

  2. Regulation

  3. Clinical significance

  4. See also

  5. References

  6. Further reading

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

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.[3]

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.[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

  • Gangliosidosis
  • Sandhoff disease
  • Tay–Sachs disease
  • Hexosaminidase
  • GM1

References

1. ^{{cite journal |vauthors=Li SC, Nakamura T, Ogamo A, Li YT | title = Evidence for the presence of two separate protein activators for the enzymic hydrolysis of GM1 and GM2 gangliosides | journal = J. Biol. Chem. | volume = 254 | issue = 21 | pages = 10592–5 |date=November 1979 | pmid = 115863 | doi = | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=115863 | issn = }}
2. ^{{cite journal |vauthors=Klima H, Tanaka A, Schnabel D, Nakano T, Schröder M, Suzuki K, Sandhoff K | title = Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein | journal = FEBS Lett. | volume = 289 | issue = 2 | pages = 260–4 |date=September 1991 | pmid = 1915857 | doi = 10.1016/0014-5793(91)81084-L| url = http://linkinghub.elsevier.com/retrieve/pii/0014-5793(91)81084-L }}
3. ^{{cite journal |vauthors=Hoek KS, Schlegel NC, Eichhoff OM | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–76 | year = 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x |display-authors=etal}}
4. ^{{cite journal |author=Mahuran DJ |title=Biochemical consequences of mutations causing the GM2 gangliosidoses |journal=Biochimica et Biophysica Acta |pages=105–138 |date=1999-10-08 |pmid=10571007 |volume=1455 |issue=2–3 |doi=10.1016/S0925-4439(99)00074-5}}
5. ^{{cite web| publisher= United States National Institute of Health | title= Online Mendelian Inheritance in Man | url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=272750 | accessdate=2009-04-21 }}

Further reading

{{refbegin | 2}}
  • {{cite journal |vauthors=Li SC, Nakamura T, Ogamo A, Li YT |title=Evidence for the presence of two separate protein activators for the enzymic hydrolysis of GM1 and GM2 gangliosides |journal=J. Biol. Chem. |volume=254 |issue= 21 |pages= 10592–5 |year= 1980 |pmid= 115863 |doi= }}
  • {{cite journal |vauthors=Xie B, Kennedy JL, McInnes B |title=Identification of a processed pseudogene related to the functional gene encoding the GM2 activator protein: localization of the pseudogene to human chromosome 3 and the functional gene to human chromosome 5 |journal=Genomics |volume=14 |issue= 3 |pages= 796–8 |year= 1992 |pmid= 1427911 |doi=10.1016/S0888-7543(05)80190-9 |display-authors=etal}}
  • {{cite journal |vauthors=Nagarajan S, Chen HC, Li SC |title=Evidence for two cDNA clones encoding human GM2-activator protein |journal=Biochem. J. |volume=282 |issue= 3|pages= 807–13 |year= 1992 |pmid= 1554364 |doi= | pmc=1130859 |display-authors=etal}}
  • {{cite journal |vauthors=Klima H, Tanaka A, Schnabel D |title=Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein |journal=FEBS Lett. |volume=289 |issue= 2 |pages= 260–4 |year= 1991 |pmid= 1915857 |doi=10.1016/0014-5793(91)81084-L |display-authors=etal}}
  • {{cite journal |vauthors=Schröder M, Schnabel D, Suzuki K, Sandhoff K |title=A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB |journal=FEBS Lett. |volume=290 |issue= 1–2 |pages= 1–3 |year= 1991 |pmid= 1915858 |doi=10.1016/0014-5793(91)81211-P }}
  • {{cite journal |vauthors=Xie B, McInnes B, Neote K |title=Isolation and expression of a full-length cDNA encoding the human GM2 activator protein |journal=Biochem. Biophys. Res. Commun. |volume=177 |issue= 3 |pages= 1217–23 |year= 1991 |pmid= 2059210 |doi=10.1016/0006-291X(91)90671-S |display-authors=etal}}
  • {{cite journal |vauthors=Fürst W, Schubert J, Machleidt W |title=The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein |journal=Eur. J. Biochem. |volume=192 |issue= 3 |pages= 709–14 |year= 1990 |pmid= 2209618 |doi=10.1111/j.1432-1033.1990.tb19280.x |display-authors=etal}}
  • {{cite journal |vauthors=Schröder M, Klima H, Nakano T |title=Isolation of a cDNA encoding the human GM2 activator protein |journal=FEBS Lett. |volume=251 |issue= 1–2 |pages= 197–200 |year= 1989 |pmid= 2753159 |doi=10.1016/0014-5793(89)81454-1 |display-authors=etal}}
  • {{cite journal |vauthors=Burg J, Banerjee A, Sandhoff K |title=Molecular forms of GM2-activator protein. A study on its biosynthesis in human skin fibroblasts |journal=Biol. Chem. Hoppe-Seyler |volume=366 |issue= 9 |pages= 887–91 |year= 1986 |pmid= 3935131 |doi= 10.1515/bchm3.1985.366.2.887}}
  • {{cite journal |vauthors=Banerjee A, Burg J, Conzelmann E |title=Enzyme-linked immunosorbent assay for the ganglioside GM2-activator protein. Screening of normal human tissues and body fluids, of tissues of GM2 gangliosidosis, and for its subcellular localization |journal=Hoppe-Seyler's Z. Physiol. Chem. |volume=365 |issue= 3 |pages= 347–56 |year= 1984 |pmid= 6724528 |doi= 10.1515/bchm2.1984.365.1.347|display-authors=etal}}
  • {{cite journal |vauthors=Hirabayashi Y, Li YT, Li SC |title=The protein activator specific for the enzymic hydrolysis of GM2 ganglioside in normal human brain and brains of three types of GM2 gangliosidosis |journal=J. Neurochem. |volume=40 |issue= 1 |pages= 168–75 |year= 1983 |pmid= 6848657 |doi=10.1111/j.1471-4159.1983.tb12667.x }}
  • {{cite journal |vauthors=Schröder M, Schnabel D, Hurwitz R |title=Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells |journal=Hum. Genet. |volume=92 |issue= 5 |pages= 437–40 |year= 1994 |pmid= 8244332 |doi=10.1007/BF00216446 |display-authors=etal}}
  • {{cite journal |vauthors=Heng HH, Xie B, Shi XM |title=Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus |journal=Genomics |volume=18 |issue= 2 |pages= 429–31 |year= 1994 |pmid= 8288250 |doi= 10.1006/geno.1993.1491 |display-authors=etal}}
  • {{cite journal |vauthors=Klima H, Klein A, van Echten G |title=Over-expression of a functionally active human GM2-activator protein in Escherichia coli |journal=Biochem. J. |volume=292 |issue= 2|pages= 571–6 |year= 1993 |pmid= 8503891 |doi= | pmc=1134248 |display-authors=etal}}
  • {{cite journal |vauthors=Schepers U, Glombitza G, Lemm T |title=Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant |journal=Am. J. Hum. Genet. |volume=59 |issue= 5 |pages= 1048–56 |year= 1996 |pmid= 8900233 |doi= | pmc=1914821 |display-authors=etal}}
  • {{cite journal |vauthors=Rigat B, Wang W, Leung A, Mahuran DJ |title=Two mechanisms for the recapture of extracellular GM2 activator protein: evidence for a major secretory form of the protein |journal=Biochemistry |volume=36 |issue= 27 |pages= 8325–31 |year= 1997 |pmid= 9204879 |doi= 10.1021/bi970571c }}
  • {{cite journal |vauthors=Yadao F, Hechtman P, Kaplan F |title=Formation of a ternary complex between GM2 activator protein, GM2 ganglioside and hexosaminidase A |journal=Biochim. Biophys. Acta |volume=1340 |issue= 1 |pages= 45–52 |year= 1997 |pmid= 9217013 |doi= 10.1016/S0167-4838(97)00027-7}}
  • {{cite journal |vauthors=Schütte CG, Lemm T, Glombitza GJ, Sandhoff K |title=Complete localization of disulfide bonds in GM2 activator protein |journal=Protein Sci. |volume=7 |issue= 4 |pages= 1039–45 |year= 1998 |pmid= 9568910 |doi=10.1002/pro.5560070421 | pmc=2143992 }}
  • {{cite journal |vauthors=Chen B, Rigat B, Curry C, Mahuran DJ |title=Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2 |journal=Am. J. Hum. Genet. |volume=65 |issue= 1 |pages= 77–87 |year= 1999 |pmid= 10364519 |doi=10.1086/302463 | pmc=1378077 }}
  • {{cite journal |vauthors=Jinnai H, Nakamura S |title=Characterization of phospholipase D activation by GM2 activator in a cell-free system |journal=Kobe Journal of Medical Sciences |volume=45 |issue= 3–4 |pages= 181–90 |year= 2000 |pmid= 10752311 |doi= }}
{{refend}}{{PDB Gallery|geneid=2760}}{{Glycolipid/sphingolipid metabolism enzymes}}{{DEFAULTSORT:Gm2a}}{{gene-5-stub}}

3 : Cell signaling|Peripheral membrane proteins|Water-soluble transporters
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