GM2A

GM2A
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1G13, 1PU5, 1PUB, 1TJJ, 2AF9, 2AG2, 2AG4, 2AG9
Identifikatori
Aliasi	GM2A
Vanjski ID-jevi	OMIM: 613109 MGI: 95762 HomoloGene: 349 GeneCards: GM2A
Lokacija gena (čovjek) Hrom. Hromosom 5 (čovjek) Bend 5q33.1 Početak 151,212,150 bp Kraj 151,270,440 bp
Lokacija gena (miš) Hrom. Hromosom 11 (miš) Bend 11 B1.3|11 32.13 cM Početak 54,988,941 bp Kraj 55,003,855 bp
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • lipid transporter activity • phospholipase activator activity • beta-N-acetylgalactosaminidase activity • beta-N-acetylhexosaminidase activity • GO:0010577 enzyme activator activity • hydrolase activity • sphingolipid activator protein activity Ćelijska komponenta • citoplazma • apical cortex • lysosomal lumen • mitohondrija • potassium:proton exchanging ATPase complex • cytoplasmic side of plasma membrane • Lizozom • Egzosom • extracellular region • azurophil granule lumen • basolateral plasma membrane • apical plasma membrane Biološki proces • positive regulation of hydrolase activity • lipid transport • glycosphingolipid metabolic process • neuromuscular process controlling balance • lipid metabolism • lipid storage • nervous system process • learning or memory • oligosaccharide catabolic process • ganglioside metabolic process • ganglioside catabolic process • sphingolipid metabolic process • neutrophil degranulation • GO:0048554 positive regulation of catalytic activity Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	2760	14667
Ensembl	ENSG00000196743	ENSMUSG00000000594
UniProt	P17900	Q60648
RefSeq (mRNK)	NM_001167607 NM_000405	NM_010299
RefSeq (bjelančevina)	NP_000396 NP_001161079	NP_034429
Lokacija (UCSC)	Chr 5: 151.21 – 151.27 Mb	Chr 11: 54.99 – 55 Mb
PubMed pretraga
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Gangliozidni aktivator GM2 znan i kaoGM2A jest protein koji je kod ljudi kodiran genom GM2A sa hromosoma 5.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 193 aminokiseline, а molekulska težina Da. 20 838

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MQSLMQAPLL		IALGLLLAAP		AQAHLKKPSQ		LSSFSWDNCD		EGKDPAVIRS
LTLEPDPIIV		PGNVTLSVMG		STSVPLSSPL		KVDLVLEKEV		AGLWIKIPCT
DYIGSCTFEH		FCDVLDMLIP		TGEPCPEPLR		TYGLPCHCPF		KEGTYSLPKS
EFVVPDLELP		SWLTTGNYRI		ESVLSSSGKR		LGCIKIAASL		KGI

Funkcija

Protein kodiran ovim genom je mali transportni glikolipidni protein koji djeluje kao supstratni specifični kofaktor za lizosomski enzim β-heksozaminidazu A. β-heksozaminidaza A, zajedno s GM2 aktivatorom gangliozida, katalizira razgradnju gangliozida GM2 i drugih molekula koje sadrže terminalne N-acetil heksozamine.

GM2A je protein za prijenos lipida, koji stimulira enzimsku obradu gangliozida, a također i aktivaciju -ćelija putem prezentacije lipida. Ovaj protein veže molekule gangliozida GM2, ekstrahira ih iz membrana i prezentira ih beta-heksozaminidazi A radi cijepanja N-acetil-D-galaktozamina i pretvaranja u GM3.

Identificiran je kao član porodice proteina ML-domena uključenih u urođenu imunost i metabolizam lipida u bazi podataka SMART. [1].

Regulacija

U melanocitnim ćelijama ekspresija gena GM2A može se regulirati trankripcijskim faktorom MITF.

Klinički značaj

Mutacije u ovom genu, naslijeđene po autosomno recesivnom obrascu, rezultiraju GM2-gangliosidozom varijanta AB, rijetkom GM2 gangliosidozom koja ima simptome i patološke promjene identične kao što ima Tay-Sachsova bolest i Sandhoffova bolest.

GM2A mutacije se rijetko prijavljuju, a zabilježeni slučajevi često se javljaju kod srodnih roditelja ili u genetički izoliranim populacijama.

Budući da se varijanta AB tako rijetko dijagnosticira, čak i kod dojenčadi, vjerovatno je da je većina mutacija GM2A fatalna za fetus u homozigotima i genetički vezanim slučajevima, pa se stoga nikada klinički ne promatraju.

Također pogledajte

• Gangliozidoza
• Sandhoffova bolest
• Tay-Sachsova bolest
• Heksozaminidaza
• GM1

Dopunska literatura

• Li SC, Nakamura T, Ogamo A, Li YT (1980). "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.
• Xie B, Kennedy JL, McInnes B, et al. (1992). "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". Genomics. 14 (3): 796–8. doi:10.1016/S0888-7543(05)80190-9. PMID 1427911.
• Nagarajan S, Chen HC, Li SC, et al. (1992). "Evidence for two cDNA clones encoding human GM2-activator protein". Biochem. J. 282 (3): 807–13. doi:10.1042/bj2820807. PMC 1130859. PMID 1554364.
• Klima H, Tanaka A, Schnabel D, et al. (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.
• Schröder M, Schnabel D, Suzuki K, Sandhoff K (1991). "A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB". FEBS Lett. 290 (1–2): 1–3. doi:10.1016/0014-5793(91)81211-P. PMID 1915858. S2CID 26669859.
• Xie B, McInnes B, Neote K, et al. (1991). "Isolation and expression of a full-length cDNA encoding the human GM2 activator protein". Biochem. Biophys. Res. Commun. 177 (3): 1217–23. doi:10.1016/0006-291X(91)90671-S. PMID 2059210.
• Fürst W, Schubert J, Machleidt W, et al. (1990). "The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein". Eur. J. Biochem. 192 (3): 709–14. doi:10.1111/j.1432-1033.1990.tb19280.x. PMID 2209618.
• Schröder M, Klima H, Nakano T, et al. (1989). "Isolation of a cDNA encoding the human GM2 activator protein". FEBS Lett. 251 (1–2): 197–200. doi:10.1016/0014-5793(89)81454-1. PMID 2753159. S2CID 22615177.
• Burg J, Banerjee A, Sandhoff K (1986). "Molecular forms of GM2-activator protein. A study on its biosynthesis in human skin fibroblasts". Biol. Chem. Hoppe-Seyler. 366 (9): 887–91. doi:10.1515/bchm3.1985.366.2.887. PMID 3935131.
• Banerjee A, Burg J, Conzelmann E, et al. (1984). "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". Hoppe-Seyler's Z. Physiol. Chem. 365 (3): 347–56. doi:10.1515/bchm2.1984.365.1.347. PMID 6724528.
• Hirabayashi Y, Li YT, Li SC (1983). "The protein activator specific for the enzymic hydrolysis of GM2 ganglioside in normal human brain and brains of three types of GM2 gangliosidosis". J. Neurochem. 40 (1): 168–75. doi:10.1111/j.1471-4159.1983.tb12667.x. PMID 6848657. S2CID 33699881.
• Schröder M, Schnabel D, Hurwitz R, et al. (1994). "Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells". Hum. Genet. 92 (5): 437–40. doi:10.1007/BF00216446. PMID 8244332. S2CID 21839371.
• Heng HH, Xie B, Shi XM, et al. (1994). "Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus". Genomics. 18 (2): 429–31. doi:10.1006/geno.1993.1491. PMID 8288250.
• Klima H, Klein A, van Echten G, et al. (1993). "Over-expression of a functionally active human GM2-activator protein in Escherichia coli". Biochem. J. 292 (2): 571–6. doi:10.1042/bj2920571. PMC 1134248. PMID 8503891.
• Schepers U, Glombitza G, Lemm T, et al. (1996). "Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant". Am. J. Hum. Genet. 59 (5): 1048–56. PMC 1914821. PMID 8900233.
• Rigat B, Wang W, Leung A, Mahuran DJ (1997). "Two mechanisms for the recapture of extracellular GM2 activator protein: evidence for a major secretory form of the protein". Biochemistry. 36 (27): 8325–31. doi:10.1021/bi970571c. PMID 9204879.
• Yadao F, Hechtman P, Kaplan F (1997). "Formation of a ternary complex between GM2 activator protein, GM2 ganglioside and hexosaminidase A". Biochim. Biophys. Acta. 1340 (1): 45–52. doi:10.1016/S0167-4838(97)00027-7. PMID 9217013.
• Schütte CG, Lemm T, Glombitza GJ, Sandhoff K (1998). "Complete localization of disulfide bonds in GM2 activator protein". Protein Sci. 7 (4): 1039–45. doi:10.1002/pro.5560070421. PMC 2143992. PMID 9568910.
• Chen B, Rigat B, Curry C, Mahuran DJ (1999). "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". Am. J. Hum. Genet. 65 (1): 77–87. doi:10.1086/302463. PMC 1378077. PMID 10364519.
• Jinnai H, Nakamura S (2000). "Characterization of phospholipase D activation by GM2 activator in a cell-free system". Kobe Journal of Medical Sciences. 45 (3–4): 181–90. PMID 10752311.