Beta-glucuronidase

Details

Name
Beta-glucuronidase
Synonyms
  • 3.2.1.31
  • Beta-G1
Gene Name
GUSB
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001935|Beta-glucuronidase
MARGSAVAWAALGPLLWGCALGLQGGMLYPQESPSRECKELDGLWSFRADFSDNRRRGFE
EQWYRRPLWESGPTVDMPVPSSFNDISQDWRLRHFVGWVWYEREVILPERWTQDLRTRVV
LRIGSAHSYAIVWVNGVDTLEHEGGYLPFEADISNLVQVGPLPSRLRITIAINNTLTPTT
LPPGTIQYLTDTSKYPKGYFVQNTYFDFFNYAGLQRSVLLYTTPTTYIDDITVTTSVEQD
SGLVNYQISVKGSNLFKLEVRLLDAENKVVANGTGTQGQLKVPGVSLWWPYLMHERPAYL
YSLEVQLTAQTSLGPVSDFYTLPVGIRTVAVTKSQFLINGKPFYFHGVNKHEDADIRGKG
FDWPLLVKDFNLLRWLGANAFRTSHYPYAEEVMQMCDRYGIVVIDECPGVGLALPQFFNN
VSLHHHMQVMEEVVRRDKNHPAVVMWSVANEPASHLESAGYYLKMVIAHTKSLDPSRPVT
FVSNSNYAADKGAPYVDVICLNSYYSWYHDYGHLELIQLQLATQFENWYKKYQKPIIQSE
YGAETIAGFHQDPPLMFTEEYQKSLLEQYHLGLDQKRRKYVVGELIWNFADFMTEQSPTR
VLGNKKGIFTRQRQPKSAAFLLRERYWKIANETRYPHSVAKSQCLENSLFT
Number of residues
651
Molecular Weight
74731.46
Theoretical pI
7.02
GO Classification
Functions
beta-glucuronidase activity / protein domain specific binding / receptor binding
Processes
carbohydrate metabolic process / glycosaminoglycan catabolic process / glycosaminoglycan metabolic process / hyaluronan catabolic process / hyaluronan metabolic process / small molecule metabolic process
Components
extracellular exosome / extracellular space / intracellular membrane-bounded organelle / lysosomal lumen / membrane
General Function
Receptor binding
Specific Function
Plays an important role in the degradation of dermatan and keratan sulfates.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Lysosome
Gene sequence
>lcl|BSEQ0010681|Beta-glucuronidase (GUSB)
ATGGCCCGGGGGTCGGCGGTTGCCTGGGCGGCGCTCGGGCCGTTGTTGTGGGGCTGCGCG
CTGGGGCTGCAGGGCGGGATGCTGTACCCCCAGGAGAGCCCGTCGCGGGAGTGCAAGGAG
CTGGACGGCCTCTGGAGCTTCCGCGCCGACTTCTCTGACAACCGACGCCGGGGCTTCGAG
GAGCAGTGGTACCGGCGGCCGCTGTGGGAGTCAGGCCCCACCGTGGACATGCCAGTTCCC
TCCAGCTTCAATGACATCAGCCAGGACTGGCGTCTGCGGCATTTTGTCGGCTGGGTGTGG
TACGAACGGGAGGTGATCCTGCCGGAGCGATGGACCCAGGACCTGCGCACAAGAGTGGTG
CTGAGGATTGGCAGTGCCCATTCCTATGCCATCGTGTGGGTGAATGGGGTCGACACGCTA
GAGCATGAGGGGGGCTACCTCCCCTTCGAGGCCGACATCAGCAACCTGGTCCAGGTGGGG
CCCCTGCCCTCCCGGCTCCGAATCACTATCGCCATCAACAACACACTCACCCCCACCACC
CTGCCACCAGGGACCATCCAATACCTGACTGACACCTCCAAGTATCCCAAGGGTTACTTT
GTCCAGAACACATATTTTGACTTTTTCAACTACGCTGGACTGCAGCGGTCTGTACTTCTG
TACACGACACCCACCACCTACATCGATGACATCACCGTCACCACCAGCGTGGAGCAAGAC
AGTGGGCTGGTGAATTACCAGATCTCTGTCAAGGGCAGTAACCTGTTCAAGTTGGAAGTG
CGTCTTTTGGATGCAGAAAACAAAGTCGTGGCGAATGGGACTGGGACCCAGGGCCAACTT
AAGGTGCCAGGTGTCAGCCTCTGGTGGCCGTACCTGATGCACGAACGCCCTGCCTATCTG
TATTCATTGGAGGTGCAGCTGACTGCACAGACGTCACTGGGGCCTGTGTCTGACTTCTAC
ACACTCCCTGTGGGGATCCGCACTGTGGCTGTCACCAAGAGCCAGTTCCTCATCAATGGG
AAACCTTTCTATTTCCACGGTGTCAACAAGCATGAGGATGCGGACATCCGAGGGAAGGGC
TTCGACTGGCCGCTGCTGGTGAAGGACTTCAACCTGCTTCGCTGGCTTGGTGCCAACGCT
TTCCGTACCAGCCACTACCCCTATGCAGAGGAAGTGATGCAGATGTGTGACCGCTATGGG
ATTGTGGTCATCGATGAGTGTCCCGGCGTGGGCCTGGCGCTGCCGCAGTTCTTCAACAAC
GTTTCTCTGCATCACCACATGCAGGTGATGGAAGAAGTGGTGCGTAGGGACAAGAACCAC
CCCGCGGTCGTGATGTGGTCTGTGGCCAACGAGCCTGCGTCCCACCTAGAATCTGCTGGC
TACTACTTGAAGATGGTGATCGCTCACACCAAATCCTTGGACCCCTCCCGGCCTGTGACC
TTTGTGAGCAACTCTAACTATGCAGCAGACAAGGGGGCTCCGTATGTGGATGTGATCTGT
TTGAACAGCTACTACTCTTGGTATCACGACTACGGGCACCTGGAGTTGATTCAGCTGCAG
CTGGCCACCCAGTTTGAGAACTGGTATAAGAAGTATCAGAAGCCCATTATTCAGAGCGAG
TATGGAGCAGAAACGATTGCAGGGTTTCACCAGGATCCACCTCTGATGTTCACTGAAGAG
TACCAGAAAAGTCTGCTAGAGCAGTACCATCTGGGTCTGGATCAAAAACGCAGAAAATAC
GTGGTTGGAGAGCTCATTTGGAATTTTGCCGATTTCATGACTGAACAGTCACCGACGAGA
GTGCTGGGGAATAAAAAGGGGATCTTCACTCGGCAGAGACAACCAAAAAGTGCAGCGTTC
CTTTTGCGAGAGAGATACTGGAAGATTGCCAATGAAACCAGGTATCCCCACTCAGTAGCC
AAGTCACAATGTTTGGAAAACAGCCTGTTTACTTGA
Chromosome Location
7
Locus
7q21.11
External Identifiers
ResourceLink
UniProtKB IDP08236
UniProtKB Entry NameBGLR_HUMAN
GenBank Protein ID183233
GenBank Gene IDM15182
GenAtlas IDGUSB
HGNC IDHGNC:4696
General References
  1. Oshima A, Kyle JW, Miller RD, Hoffmann JW, Powell PP, Grubb JH, Sly WS, Tropak M, Guise KS, Gravel RA: Cloning, sequencing, and expression of cDNA for human beta-glucuronidase. Proc Natl Acad Sci U S A. 1987 Feb;84(3):685-9. [PubMed:3468507]
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  6. Shipley JM, Miller RD, Wu BM, Grubb JH, Christensen SG, Kyle JW, Sly WS: Analysis of the 5' flanking region of the human beta-glucuronidase gene. Genomics. 1991 Aug;10(4):1009-18. [PubMed:1916806]
  7. Tanaka J, Gasa S, Sakurada K, Miyazaki T, Kasai M, Makita A: Characterization of the subunits and sugar moiety of human placental and leukemic beta-glucuronidase. Biol Chem Hoppe Seyler. 1992 Jan;373(1):57-62. [PubMed:1311180]
  8. Guise KS, Korneluk RG, Waye J, Lamhonwah AM, Quan F, Palmer R, Ganschow RE, Sly WS, Gravel RA: Isolation and expression in Escherichia coli of a cDNA clone encoding human beta-glucuronidase. Gene. 1985;34(1):105-10. [PubMed:3924735]
  9. Kreamer BL, Siegel FL, Gourley GR: A novel inhibitor of beta-glucuronidase: L-aspartic acid. Pediatr Res. 2001 Oct;50(4):460-6. [PubMed:11568288]
  10. 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]
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  15. Jain S, Drendel WB, Chen ZW, Mathews FS, Sly WS, Grubb JH: Structure of human beta-glucuronidase reveals candidate lysosomal targeting and active-site motifs. Nat Struct Biol. 1996 Apr;3(4):375-81. [PubMed:8599764]
  16. Tomatsu S, Montano AM, Dung VC, Grubb JH, Sly WS: Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome). Hum Mutat. 2009 Apr;30(4):511-9. doi: 10.1002/humu.20828. [PubMed:19224584]
  17. Vervoort R, Lissens W, Liebaers I: Molecular analysis of a patient with hydrops fetalis caused by beta-glucuronidase deficiency, and evidence for additional pseudogenes. Hum Mutat. 1993;2(6):443-5. [PubMed:8111412]
  18. Wu BM, Sly WS: Mutational studies in a patient with the hydrops fetalis form of mucopolysaccharidosis type VII. Hum Mutat. 1993;2(6):446-57. [PubMed:8111413]
  19. Tomatsu S, Fukuda S, Sukegawa K, Ikedo Y, Yamada S, Yamada Y, Sasaki T, Okamoto H, Kuwahara T, Yamaguchi S, et al.: Mucopolysaccharidosis type VII: characterization of mutations and molecular heterogeneity. Am J Hum Genet. 1991 Jan;48(1):89-96. [PubMed:1702266]
  20. Shipley JM, Klinkenberg M, Wu BM, Bachinsky DR, Grubb JH, Sly WS: Mutational analysis of a patient with mucopolysaccharidosis type VII, and identification of pseudogenes. Am J Hum Genet. 1993 Mar;52(3):517-26. [PubMed:7680524]
  21. Wu BM, Tomatsu S, Fukuda S, Sukegawa K, Orii T, Sly WS: Overexpression rescues the mutant phenotype of L176F mutation causing beta-glucuronidase deficiency mucopolysaccharidosis in two Mennonite siblings. J Biol Chem. 1994 Sep 23;269(38):23681-8. [PubMed:8089138]
  22. Vervoort R, Islam MR, Sly W, Chabas A, Wevers R, de Jong J, Liebaers I, Lissens W: A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene. Am J Hum Genet. 1995 Oct;57(4):798-804. [PubMed:7573038]
  23. Yamada S, Tomatsu S, Sly WS, Islam R, Wenger DA, Fukuda S, Sukegawa K, Orii T: Four novel mutations in mucopolysaccharidosis type VII including a unique base substitution in exon 10 of the beta-glucuronidase gene that creates a novel 5'-splice site. Hum Mol Genet. 1995 Apr;4(4):651-5. [PubMed:7633414]
  24. Vervoort R, Islam MR, Sly WS, Zabot MT, Kleijer WJ, Chabas A, Fensom A, Young EP, Liebaers I, Lissens W: Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am J Hum Genet. 1996 Mar;58(3):457-71. [PubMed:8644704]
  25. Islam MR, Vervoort R, Lissens W, Hoo JJ, Valentino LA, Sly WS: beta-Glucuronidase P408S, P415L mutations: evidence that both mutations combine to produce an MPS VII allele in certain Mexican patients. Hum Genet. 1996 Sep;98(3):281-4. [PubMed:8707294]
  26. Vervoort R, Buist NR, Kleijer WJ, Wevers R, Fryns JP, Liebaers I, Lissens W: Molecular analysis of the beta-glucuronidase gene: novel mutations in mucopolysaccharidosis type VII and heterogeneity of the polyadenylation region. Hum Genet. 1997 Apr;99(4):462-8. [PubMed:9099834]
  27. Vervoort R, Gitzelmann R, Bosshard N, Maire I, Liebaers I, Lissens W: Low beta-glucuronidase enzyme activity and mutations in the human beta-glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency and a heterozygote. Hum Genet. 1998 Jan;102(1):69-78. [PubMed:9490302]
  28. Schwartz I, Silva LR, Leistner S, Todeschini LA, Burin MG, Pina-Neto JM, Islam RM, Shah GN, Sly WS, Giugliani R: Mucopolysaccharidosis VII: clinical, biochemical and molecular investigation of a Brazilian family. Clin Genet. 2003 Aug;64(2):172-5. [PubMed:12859417]
  29. Storch S, Wittenstein B, Islam R, Ullrich K, Sly WS, Braulke T: Mutational analysis in longest known survivor of mucopolysaccharidosis type VII. Hum Genet. 2003 Feb;112(2):190-4. Epub 2002 Nov 5. [PubMed:12522561]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11793Niraparibapproved, investigationalyessubstrateDetails
DB09301Chondroitin sulfateapproved, investigational, nutraceuticalnosubstrateDetails
DB09340Tyropanoic acidapprovedunknownsubstrateDetails