GM2A
Gangliozidni aktivator GM2 znan i kaoGM2A jest protein koji je kod ljudi kodiran genom GM2A sa hromosoma 5.[5][6]
Aminokiselinska sekvenca
Dužina polipeptidnog lanca je 193 aminokiseline, а molekulska težina Da. 20 838[7]
| 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.[8]
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.[9]
GM2A mutacije se rijetko prijavljuju, a zabilježeni slučajevi često se javljaju kod srodnih roditelja ili u genetički izoliranim populacijama.[10]
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
Reference
Dopunska literatura
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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