View source for GM2A

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox_gene}}
'''GM2 ganglioside activator''' also known as '''GM2A''' is a [[protein]] which in humans is encoded by the ''GM2A'' [[gene]].<ref name="pmid115863">{{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 | doi = 10.1016/S0021-9258(19)86559-6 | pmid = 115863 | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=115863 | doi-access = free }}</ref><ref name="pmid1915857">{{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| s2cid = 40408626 | doi-access = free }}</ref>
== Function ==
The protein encoded by this gene is a small glycolipid transport protein which acts as a substrate specific co-factor for the [[lysosome|lysosomal]] enzyme [[HEXA|β-hexosaminidase A]]. β-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the [[GM2 (ganglioside)|ganglioside GM2]], and other molecules containing terminal N-acetyl [[hexosamine]]s.
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)|SMART database]].
[http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=ML&BLAST=DUMMY].
== Regulation ==
In melanocytic cells GM2A gene expression may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{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 | s2cid = 24698373 |display-authors=etal| doi-access = free }}</ref>
== Clinical significance ==
Mutations in this gene, inherited in an [[autosomal recessive]] pattern, result in [[GM2-gangliosidosis, AB variant]], a rare [[GM2 gangliosidoses|GM2 gangliosidosis]] that has symptoms and pathology identical with [[Tay–Sachs disease]] and [[Sandhoff disease]].<ref name="mahuran">{{cite journal |author=Mahuran DJ |title=Biochemical consequences of mutations causing the GM2 gangliosidoses |journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease |pages=105–138 |date=1999-10-08 |pmid=10571007 |volume=1455 |issue=2–3 |doi=10.1016/S0925-4439(99)00074-5|doi-access= }}</ref>
GM2A mutations are rarely reported, and the cases that are observed often occur with [[consanguineous]] parents or in genetically isolated populations.<ref name="omim">{{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 | access-date=2009-04-21 }}</ref>
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==
{{reflist}}
==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 |doi=10.1016/S0021-9258(19)86559-6 |pmid= 115863 |doi-access=free }}
*{{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=  10.1042/bj2820807| 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  |s2cid=40408626 |display-authors=etal|doi-access=free }}
*{{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  |s2cid=26669859 }}
*{{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  |s2cid=22615177 |display-authors=etal|doi-access=free }}
*{{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  |s2cid=33699881 }}
*{{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  |s2cid=21839371 |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=  10.1042/bj2920571| 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 | 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 }}
{{refend}}
{{PDB Gallery|geneid=2760}}
{{Glycolipid/sphingolipid metabolism enzymes}}
{{DEFAULTSORT:Gm2a}}
[[Category:Cell signaling]]
[[Category:Peripheral membrane proteins]]
[[Category:Water-soluble transporters]]
{{gene-5-stub}}