Showing Protein Beta-hexosaminidase subunit alpha (HMDBP00872)

• 6154

1. Beta-N-acetylhexosaminidase subunit alpha
2. Hexosaminidase subunit A
3. N-acetyl-beta-glucosaminidase subunit alpha

• Amino sugar and nucleotide sugar metabolism
• Amino Sugar Metabolism
• G(M2)-Gangliosidosis: Variant B, Tay-sachs disease
• Glycosaminoglycan degradation
• Glycosphingolipid biosynthesis - ganglio series
• Glycosphingolipid biosynthesis - globo and isoglobo series
• Lysosome
• Other glycan degradation
• Salla Disease/Infantile Sialic Acid Storage Disease
• Sialuria or French Type Sialuria
• Tay-Sachs Disease

1. Lysosome

>1590 bp
ATGACAAGCTCCAGGCTTTGGTTTTCGCTGCTGCTGGCGGCAGCGTTCGCAGGACGGGCG
ACGGCCCTCTGGCCCTGGCCTCAGAACTTCCAAACCTCCGACCAGCGCTACGTCCTTTAC
CCGAACAACTTTCAATTCCAGTACGATGTCAGCTCGGCCGCGCAGCCCGGCTGCTCAGTC
CTCGACGAGGCCTTCCAGCGCTATCGTGACCTGCTTTTCGGTTCCGGGTCTTGGCCCCGT
CCTTACCTCACAGGGAAACGGCATACACTGGAGAAGAATGTGTTGGTTGTCTCTGTAGTC
ACACCTGGATGTAACCAGCTTCCTACTTTGGAGTCAGTGGAGAATTATACCCTGACCATA
AATGATGACCAGTGTTTACTCCTCTCTGAGACTGTCTGGGGAGCTCTCCGAGGTCTGGAG
ACTTTTAGCCAGCTTGTTTGGAAATCTGCTGAGGGCACATTCTTTATCAACAAGACTGAG
ATTGAGGACTTTCCCCGCTTTCCTCACCGGGGCTTGCTGTTGGATACATCTCGCCATTAC
CTGCCACTCTCTAGCATCCTGGACACTCTGGATGTCATGGCGTACAATAAATTGAACGTG
TTCCACTGGCATCTGGTAGATGATCCTTCCTTCCCATATGAGAGCTTCACTTTTCCAGAG
CTCATGAGAAAGGGGTCCTACAACCCTGTCACCCACATCTACACAGCACAGGATGTGAAG
GAGGTCATTGAATACGCACGGCTCCGGGGTATCCGTGTGCTTGCAGAGTTTGACACTCCT
GGCCACACTTTGTCCTGGGGACCAGGTATCCCTGGATTACTGACTCCTTGCTACTCTGGG
TCTGAGCCCTCTGGCACCTTTGGACCAGTGAATCCCAGTCTCAATAATACCTATGAGTTC
ATGAGCACATTCTTCTTAGAAGTCAGCTCTGTCTTCCCAGATTTTTATCTTCATCTTGGA
GGAGATGAGGTTGATTTCACCTGCTGGAAGCCCAACCCAGAGATCCAGGACTTTATGAGG
AAGAAAGGCTTCGGTGAGGACTTCAAGCAGCTGGAGTCCTTCTACATCCAGACGCTGCTG
GACATCGTCTCTTCTTATGGCAAGGGCTATGTGGTGTGGCAGGAGGTGTTTGATAATAAA
GTAAAGATTCAGCCAGACACAATCATACAGGTGTGGCGAGAGGATATTCCAGTGAACTAT
ATGAAGGAGCTGGAACTGGTCACCAAGGCCGGCTTCCGGGCCCTTCTCTCTGCCCCCTGG
TACCTGAACCGTATATCCTACGGCCCTGACTGGAAGGATTTCTACGTAGTGGAACCCCTG
GCATTTGAAGGTACCCCTGAGCAGAAGGCTCTGGTGATTGGTGGAGAGGCTTGTATGTGG
GGAGAATATGTGGACAACACAAACCTGGTCCCCAGGCTCTGGCCCAGAGCAGGGGCTGTT
GCCGAAAGGCTGTGGAGCAACAAGTTGACATCTGACCTGACATTTGCCTATGAACGTTTG
TCACACTTCCGCTGTGAGTTGCTGAGGCGAGGTGTCCAGGCCCAACCCCTCAATGTAGGC
TTCTGTGAGCAGGAGTTTGAACAGACCTGA

• Glyco_hydro_20 (PF00728 )
• Glyco_hydro_20b (PF02838 )

>Beta-hexosaminidase subunit alpha
MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSV
LDEAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTI
NDDQCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHY
LPLSSILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVK
EVIEYARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEF
MSTFFLEVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLL
DIVSSYGKGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPW
YLNRISYGPDWKDFYVVEPLAFEGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPRAGAV
AERLWSNKLTSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT

• 1QBC
• 2GJX
• 2GK1

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7. Tews I, Perrakis A, Oppenheim A, Dauter Z, Wilson KS, Vorgias CE: Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease. Nat Struct Biol. 1996 Jul;3(7):638-48. [PubMed:8673609 ]
8. Mahuran DJ: The biochemistry of HEXA and HEXB gene mutations causing GM2 gangliosidosis. Biochim Biophys Acta. 1991 Feb 22;1096(2):87-94. [PubMed:1825792 ]
9. Myerowitz R, Piekarz R, Neufeld EF, Shows TB, Suzuki K: Human beta-hexosaminidase alpha chain: coding sequence and homology with the beta chain. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7830-4. [PubMed:2933746 ]
10. Proia RL, Soravia E: Organization of the gene encoding the human beta-hexosaminidase alpha-chain. J Biol Chem. 1987 Apr 25;262(12):5677-81. [PubMed:2952641 ]
11. Triggs-Raine BL, Akerman BR, Clarke JT, Gravel RA: Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease. Am J Hum Genet. 1991 Nov;49(5):1041-54. [PubMed:1833974 ]
12. Weitz G, Proia RL: Analysis of the glycosylation and phosphorylation of the alpha-subunit of the lysosomal enzyme, beta-hexosaminidase A, by site-directed mutagenesis. J Biol Chem. 1992 May 15;267(14):10039-44. [PubMed:1533633 ]
13. Tse R, Vavougios G, Hou Y, Mahuran DJ: Identification of an active acidic residue in the catalytic site of beta-hexosaminidase. Biochemistry. 1996 Jun 11;35(23):7599-607. [PubMed:8652542 ]
14. Myerowitz R: Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene. Hum Mutat. 1997;9(3):195-208. [PubMed:9090523 ]
15. Nakano T, Muscillo M, Ohno K, Hoffman AJ, Suzuki K: A point mutation in the coding sequence of the beta-hexosaminidase alpha gene results in defective processing of the enzyme protein in an unusual GM2-gangliosidosis variant. J Neurochem. 1988 Sep;51(3):984-7. [PubMed:2970528 ]
16. Navon R, Proia RL: The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult form of Tay-Sachs disease. Science. 1989 Mar 17;243(4897):1471-4. [PubMed:2522679 ]
17. Tanaka A, Punnett HH, Suzuki K: A new point mutation in the beta-hexosaminidase alpha subunit gene responsible for infantile Tay-Sachs disease in a non-Jewish Caucasian patient (a Kpn mutant). Am J Hum Genet. 1990 Sep;47(3):568-74. [PubMed:2144098 ]
18. Akli S, Chelly J, Lacorte JM, Poenaru L, Kahn A: Seven novel Tay-Sachs mutations detected by chemical mismatch cleavage of PCR-amplified cDNA fragments. Genomics. 1991 Sep;11(1):124-34. [PubMed:1837283 ]
19. Mules EH, Hayflick S, Miller CS, Reynolds LW, Thomas GH: Six novel deleterious and three neutral mutations in the gene encoding the alpha-subunit of hexosaminidase A in non-Jewish individuals. Am J Hum Genet. 1992 Apr;50(4):834-41. [PubMed:1532289 ]
20. Triggs-Raine BL, Mules EH, Kaback MM, Lim-Steele JS, Dowling CE, Akerman BR, Natowicz MR, Grebner EE, Navon R, Welch JP, et al.: A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: implications for carrier screening. Am J Hum Genet. 1992 Oct;51(4):793-801. [PubMed:1384323 ]
21. Fernandes M, Kaplan F, Natowicz M, Prence E, Kolodny E, Kaback M, Hechtman P: A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes each with a second novel mutation. Hum Mol Genet. 1992 Dec;1(9):759-61. [PubMed:1302612 ]
22. Trop I, Kaplan F, Brown C, Mahuran D, Hechtman P: A glycine250--> aspartate substitution in the alpha-subunit of hexosaminidase A causes juvenile-onset Tay-Sachs disease in a Lebanese-Canadian family. Hum Mutat. 1992;1(1):35-9. [PubMed:1301189 ]
23. Akalin N, Shi HP, Vavougios G, Hechtman P, Lo W, Scriver CR, Mahuran D, Kaplan F: Novel Tay-Sachs disease mutations from China. Hum Mutat. 1992;1(1):40-6. [PubMed:1301190 ]
24. Cao Z, Natowicz MR, Kaback MM, Lim-Steele JS, Prence EM, Brown D, Chabot T, Triggs-Raine BL: A second mutation associated with apparent beta-hexosaminidase A pseudodeficiency: identification and frequency estimation. Am J Hum Genet. 1993 Dec;53(6):1198-205. [PubMed:7902672 ]
25. Akli S, Chomel JC, Lacorte JM, Bachner L, Kahn A, Poenaru L: Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients. Hum Mol Genet. 1993 Jan;2(1):61-7. [PubMed:8490625 ]
26. Harmon DL, Gardner-Medwin D, Stirling JL: Two new mutations in a late infantile Tay-Sachs patient are both in exon 1 of the beta-hexosaminidase alpha subunit gene. J Med Genet. 1993 Feb;30(2):123-8. [PubMed:8445615 ]
27. Tomczak J, Grebner EE: Three novel beta-hexosaminidase A mutations in obligate carriers of Tay-Sachs disease. Hum Mutat. 1994;4(1):71-2. [PubMed:7951261 ]
28. Tanaka A, Sakazaki H, Murakami H, Isshiki G, Suzuki K: Molecular genetics of Tay-Sachs disease in Japan. J Inherit Metab Dis. 1994;17(5):593-600. [PubMed:7837766 ]
29. Triggs-Raine B, Richard M, Wasel N, Prence EM, Natowicz MR: Mutational analyses of Tay-Sachs disease: studies on Tay-Sachs carriers of French Canadian background living in New England. Am J Hum Genet. 1995 Apr;56(4):870-9. [PubMed:7717398 ]
30. Peleg L, Meltzer F, Karpati M, Goldman B: GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A. Biochem Mol Med. 1995 Apr;54(2):126-32. [PubMed:8581357 ]
31. Navon R, Khosravi R, Korczyn T, Masson M, Sonnino S, Fardeau M, Eymard B, Lefevre M, Turpin JC, Rondot P, et al.: A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype. Neurology. 1995 Mar;45(3 Pt 1):539-43. [PubMed:7898712 ]
32. De Gasperi R, Gama Sosa MA, Battistini S, Yeretsian J, Raghavan S, Zelnik N, Leshinsky E, Kolodny EH: Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene. Neurology. 1996 Aug;47(2):547-52. [PubMed:8757036 ]
33. Akerman BR, Natowicz MR, Kaback MM, Loyer M, Campeau E, Gravel RA: Novel mutations and DNA-based screening in non-Jewish carriers of Tay-Sachs disease. Am J Hum Genet. 1997 May;60(5):1099-106. [PubMed:9150157 ]
34. Kaufman M, Grinshpun-Cohen J, Karpati M, Peleg L, Goldman B, Akstein E, Adam A, Navon R: Tay-Sachs disease and HEXA mutations among Moroccan Jews. Hum Mutat. 1997;10(4):295-300. [PubMed:9338583 ]
35. Gil Ribeiro M, Pinto RA, Suzuki K, Sa Miranda MC: Two novel (1334delC and 1363G to A, G455R) mutations in exon 12 of the beta-hexosaminidase alpha-chain gene in two Portuguese patients. Hum Mutat. 1997;10(5):359-60. [PubMed:9375850 ]
36. Drucker L, Hemli JA, Navon R: Two mutated HEXA alleles in a Druze patient with late-infantile Tay-Sachs disease. Hum Mutat. 1997;10(6):451-7. [PubMed:9401008 ]
37. Petroulakis E, Cao Z, Clarke JT, Mahuran DJ, Lee G, Triggs-Raine B: W474C amino acid substitution affects early processing of the alpha-subunit of beta-hexosaminidase A and is associated with subacute G(M2) gangliosidosis. Hum Mutat. 1998;11(6):432-42. [PubMed:9603435 ]
38. Tanaka A, Hoang LT, Nishi Y, Maniwa S, Oka M, Yamano T: Different attenuated phenotypes of GM2 gangliosidosis variant B in Japanese patients with HEXA mutations at codon 499, and five novel mutations responsible for infantile acute form. J Hum Genet. 2003;48(11):571-4. Epub 2003 Oct 18. [PubMed:14566483 ]