Beta-hexosaminidase subunit beta

Details

Name
Beta-hexosaminidase subunit beta
Synonyms
  • 3.2.1.52
  • Beta-N-acetylhexosaminidase subunit beta
  • Cervical cancer proto-oncogene 7 protein
  • HCC-7
  • Hexosaminidase subunit B
  • N-acetyl-beta-glucosaminidase subunit beta
Gene Name
HEXB
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002293|Beta-hexosaminidase subunit beta
MELCGLGLPRPPMLLALLLATLLAAMLALLTQVALVVQVAEAARAPSVSAKPGPALWPLP
LSVKMTPNLLHLAPENFYISHSPNSTAGPSCTLLEEAFRRYHGYIFGFYKWHHEPAEFQA
KTQVQQLLVSITLQSECDAFPNISSDESYTLLVKEPVAVLKANRVWGALRGLETFSQLVY
QDSYGTFTINESTIIDSPRFSHRGILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHIVD
DQSFPYQSITFPELSNKGSYSLSHVYTPNDVRMVIEYARLRGIRVLPEFDTPGHTLSWGK
GQKDLLTPCYSRQNKLDSFGPINPTLNTTYSFLTTFFKEISEVFPDQFIHLGGDEVEFKC
WESNPKIQDFMRQKGFGTDFKKLESFYIQKVLDIIATINKGSIVWQEVFDDKAKLAPGTI
VEVWKDSAYPEELSRVTASGFPVILSAPWYLDLISYGQDWRKYYKVEPLDFGGTQKQKQL
FIGGEACLWGEYVDATNLTPRLWPRASAVGERLWSSKDVRDMDDAYDRLTRHRCRMVERG
IAAQPLYAGYCNHENM
Number of residues
556
Molecular Weight
63110.745
Theoretical pI
6.75
GO Classification
Functions
acetylglucosaminyltransferase activity / beta-N-acetylhexosaminidase activity / protein heterodimerization activity / protein homodimerization activity
Processes
astrocyte cell migration / carbohydrate metabolic process / cellular calcium ion homeostasis / cellular protein metabolic process / chondroitin sulfate catabolic process / chondroitin sulfate metabolic process / ganglioside catabolic process / glycosaminoglycan metabolic process / glycosphingolipid metabolic process / hyaluronan catabolic process / hyaluronan metabolic process / keratan sulfate catabolic process / keratan sulfate metabolic process / lipid storage / locomotory behavior / lysosome organization / male courtship behavior / myelination / neuromuscular process controlling balance / oligosaccharide catabolic process / oogenesis / penetration of zona pellucida / phospholipid biosynthetic process / positive regulation of transcription from RNA polymerase II promoter / regulation of cell shape / sensory perception of sound / skeletal system development / small molecule metabolic process / sphingolipid metabolic process
Components
acrosomal vesicle / azurophil granule / extracellular exosome / lysosomal lumen / membrane
General Function
Protein homodimerization activity
Specific Function
Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Lysosome
Gene sequence
>lcl|BSEQ0016330|Beta-hexosaminidase subunit beta (HEXB)
ATGGAGCTGTGCGGGCTGGGGCTGCCCCGGCCGCCCATGCTGCTGGCGCTGCTGTTGGCG
ACACTGCTGGCGGCGATGTTGGCGCTGCTGACTCAGGTGGCGCTGGTGGTGCAGGTGGCG
GAGGCGGCTCGGGCCCCGAGCGTCTCGGCCAAGCCGGGGCCGGCGCTGTGGCCCCTGCCG
CTCTCGGTGAAGATGACCCCGAACCTGCTGCATCTCGCCCCGGAGAACTTCTACATCAGC
CACAGCCCCAATTCCACGGCGGGCCCCTCCTGCACCCTGCTGGAGGAAGCGTTTCGACGA
TATCATGGCTATATTTTTGGTTTCTACAAGTGGCATCATGAACCTGCTGAATTCCAGGCT
AAAACCCAGGTTCAGCAACTTCTTGTCTCAATCACCCTTCAGTCAGAGTGTGATGCTTTC
CCCAACATATCTTCAGATGAGTCTTATACTTTACTTGTGAAAGAACCAGTGGCTGTCCTT
AAGGCCAACAGAGTTTGGGGAGCATTACGAGGTTTAGAGACCTTTAGCCAGTTAGTTTAT
CAAGATTCTTATGGAACTTTCACCATCAATGAATCCACCATTATTGATTCTCCAAGGTTT
TCTCACAGAGGAATTTTGATTGATACATCCAGACATTATCTGCCAGTTAAGATTATTCTT
AAAACTCTGGATGCCATGGCTTTTAATAAGTTTAATGTTCTTCACTGGCACATAGTTGAT
GACCAGTCTTTCCCATATCAGAGCATCACTTTTCCTGAGTTAAGCAATAAAGGAAGCTAT
TCTTTGTCTCATGTTTATACACCAAATGATGTCCGTATGGTGATTGAATATGCCAGATTA
CGAGGAATTCGAGTCCTGCCAGAATTTGATACCCCTGGGCATACACTATCTTGGGGAAAA
GGTCAGAAAGACCTCCTGACTCCATGTTACAGTAGACAAAACAAGTTGGACTCTTTTGGA
CCTATAAACCCTACTCTGAATACAACATACAGCTTCCTTACTACATTTTTCAAAGAAATT
AGTGAGGTGTTTCCAGATCAATTCATTCATTTGGGAGGAGATGAAGTGGAATTTAAATGT
TGGGAATCAAATCCAAAAATTCAAGATTTCATGAGGCAAAAAGGCTTTGGCACAGATTTT
AAGAAACTAGAATCTTTCTACATTCAAAAGGTTTTGGATATTATTGCAACCATAAACAAG
GGATCCATTGTCTGGCAGGAGGTTTTTGATGATAAAGCAAAGCTTGCGCCGGGCACAATA
GTTGAAGTATGGAAAGACAGCGCATATCCTGAGGAACTCAGTAGAGTCACAGCATCTGGC
TTCCCTGTAATCCTTTCTGCTCCTTGGTACTTAGATTTGATTAGCTATGGACAAGATTGG
AGGAAATACTATAAAGTGGAACCTCTTGATTTTGGCGGTACTCAGAAACAGAAACAACTT
TTCATTGGTGGAGAAGCTTGTCTATGGGGAGAATATGTGGATGCAACTAACCTCACTCCA
AGATTATGGCCTCGGGCAAGTGCTGTTGGTGAGAGACTCTGGAGTTCCAAAGATGTCAGA
GATATGGATGACGCCTATGACAGACTGACAAGGCACCGCTGCAGGATGGTCGAACGTGGA
ATAGCTGCACAACCTCTTTATGCTGGATATTGTAACCATGAGAACATGTAA
Chromosome Location
5
Locus
5q13
External Identifiers
ResourceLink
UniProtKB IDP07686
UniProtKB Entry NameHEXB_HUMAN
GenBank Protein ID179462
GenBank Gene IDM13519
GenAtlas IDHEXB
HGNC IDHGNC:4879
General References
  1. Korneluk RG, Mahuran DJ, Neote K, Klavins MH, O'Dowd BF, Tropak M, Willard HF, Anderson MJ, Lowden JA, Gravel RA: Isolation of cDNA clones coding for the alpha-subunit of human beta-hexosaminidase. Extensive homology between the alpha- and beta-subunits and studies on Tay-Sachs disease. J Biol Chem. 1986 Jun 25;261(18):8407-13. [PubMed:3013851]
  2. Neote K, Bapat B, Dumbrille-Ross A, Troxel C, Schuster SM, Mahuran DJ, Gravel RA: Characterization of the human HEXB gene encoding lysosomal beta-hexosaminidase. Genomics. 1988 Nov;3(4):279-86. [PubMed:2977375]
  3. Proia RL: Gene encoding the human beta-hexosaminidase beta chain: extensive homology of intron placement in the alpha- and beta-chain genes. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1883-7. [PubMed:2964638]
  4. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [PubMed:15372022]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Sonderfeld-Fresko S, Proia RL: Synthesis and assembly of a catalytically active lysosomal enzyme, beta-hexosaminidase B, in a cell-free system. J Biol Chem. 1988 Sep 15;263(26):13463-9. [PubMed:2971039]
  7. Neote K, Brown CA, Mahuran DJ, Gravel RA: Translation initiation in the HEXB gene encoding the beta-subunit of human beta-hexosaminidase. J Biol Chem. 1990 Dec 5;265(34):20799-806. [PubMed:2147427]
  8. Stirling J, Leung A, Gravel RA, Mahuran D: Localization of the pro-sequence within the total deduced primary structure of human beta-hexosaminidase B. FEBS Lett. 1988 Apr 11;231(1):47-50. [PubMed:2966076]
  9. Mahuran DJ: Characterization of human placental beta-hexosaminidase I2. Proteolytic processing intermediates of hexosaminidase A. J Biol Chem. 1990 Apr 25;265(12):6794-9. [PubMed:2139028]
  10. Hubbes M, Callahan J, Gravel R, Mahuran D: The amino-terminal sequences in the pro-alpha and -beta polypeptides of human lysosomal beta-hexosaminidase A and B are retained in the mature isozymes. FEBS Lett. 1989 Jun 5;249(2):316-20. [PubMed:2525487]
  11. Mahuran DJ, Neote K, Klavins MH, Leung A, Gravel RA: Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits. J Biol Chem. 1988 Apr 5;263(10):4612-8. [PubMed:2965147]
  12. O'Dowd BF, Quan F, Willard HF, Lamhonwah AM, Korneluk RG, Lowden JA, Gravel RA, Mahuran DJ: Isolation of cDNA clones coding for the beta subunit of human beta-hexosaminidase. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1184-8. [PubMed:2579389]
  13. O'Dowd BF, Cumming DA, Gravel RA, Mahuran D: Oligosaccharide structure and amino acid sequence of the major glycopeptides of mature human beta-hexosaminidase. Biochemistry. 1988 Jul 12;27(14):5216-26. [PubMed:2971395]
  14. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed:12754519]
  15. Schuette CG, Weisgerber J, Sandhoff K: Complete analysis of the glycosylation and disulfide bond pattern of human beta-hexosaminidase B by MALDI-MS. Glycobiology. 2001 Jul;11(7):549-56. [PubMed:11447134]
  16. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  17. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  18. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  19. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712]
  20. 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]
  21. Mark BL, Mahuran DJ, Cherney MM, Zhao D, Knapp S, James MN: Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease. J Mol Biol. 2003 Apr 11;327(5):1093-109. [PubMed:12662933]
  22. Maier T, Strater N, Schuette CG, Klingenstein R, Sandhoff K, Saenger W: The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease. J Mol Biol. 2003 May 2;328(3):669-81. [PubMed:12706724]
  23. 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]
  24. Banerjee P, Siciliano L, Oliveri D, McCabe NR, Boyers MJ, Horwitz AL, Li SC, Dawson G: Molecular basis of an adult form of beta-hexosaminidase B deficiency with motor neuron disease. Biochem Biophys Res Commun. 1991 Nov 27;181(1):108-15. [PubMed:1720305]
  25. Wakamatsu N, Kobayashi H, Miyatake T, Tsuji S: A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3' splice site selection. J Biol Chem. 1992 Feb 5;267(4):2406-13. [PubMed:1531140]
  26. Bolhuis PA, Ponne NJ, Bikker H, Baas F, Vianney de Jong JM: Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme. Biochim Biophys Acta. 1993 Sep 8;1182(2):142-6. [PubMed:8357844]
  27. Kuroki Y, Itoh K, Nadaoka Y, Tanaka T, Sakuraba H: A novel missense mutation (C522Y) is present in the beta-hexosaminidase beta-subunit gene of a Japanese patient with infantile Sandhoff disease. Biochem Biophys Res Commun. 1995 Jul 17;212(2):564-71. [PubMed:7626071]
  28. Gomez-Lira M, Sangalli A, Mottes M, Perusi C, Pignatti PF, Rizzuto N, Salviati A: A common beta hexosaminidase gene mutation in adult Sandhoff disease patients. Hum Genet. 1995 Oct;96(4):417-22. [PubMed:7557963]
  29. Zhang ZX, Wakamatsu N, Akerman BR, Mules EH, Thomas GH, Gravel RA: A second, large deletion in the HEXB gene in a patient with infantile Sandhoff disease. Hum Mol Genet. 1995 Apr;4(4):777-80. [PubMed:7633435]
  30. Redonnet-Vernhet I, Mahuran DJ, Salvayre R, Dubas F, Levade T: Significance of two point mutations present in each HEXB allele of patients with adult GM2 gangliosidosis (Sandhoff disease) homozygosity for the Ile207-->Val substitution is not associated with a clinical or biochemical phenotype. Biochim Biophys Acta. 1996 Nov 15;1317(2):127-33. [PubMed:8950198]
  31. Narkis G, Adam A, Jaber L, Pennybacker M, Proia RL, Navon R: Molecular basis of heat labile hexosaminidase B among Jews and Arabs. Hum Mutat. 1997;10(6):424-9. [PubMed:9401004]
  32. Fujimaru M, Tanaka A, Choeh K, Wakamatsu N, Sakuraba H, Isshiki G: Two mutations remote from an exon/intron junction in the beta-hexosaminidase beta-subunit gene affect 3'-splice site selection and cause Sandhoff disease. Hum Genet. 1998 Oct;103(4):462-9. [PubMed:9856491]
  33. Hou Y, McInnes B, Hinek A, Karpati G, Mahuran D: A Pro504 --> Ser substitution in the beta-subunit of beta-hexosaminidase A inhibits alpha-subunit hydrolysis of GM2 ganglioside, resulting in chronic Sandhoff disease. J Biol Chem. 1998 Aug 14;273(33):21386-92. [PubMed:9694901]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB028132-Acetamido-2-Deoxy-D-Glucono-1,5-LactoneexperimentalunknownDetails
DB03747N-Acetyl-glucosamine thiazolineexperimentalunknownDetails
DB03861(2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidineexperimentalunknownDetails
DB00205Pyrimethamineapproved, investigational, vet_approvedunknownDetails
DB09301Chondroitin sulfateapproved, investigational, nutraceuticalnosubstrateDetails