ADH1B
| ADH1B | |||
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Gene ontology | |||
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Ensembl |
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| RefSeq (protein) |
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| Location (UCSC) | Chr 4: 99.3 – 99.35 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
| View/Edit Human | |||
Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1B gene.[3][4]
The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol (beverage alcohol), retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein, known as ADH1B or beta-ADH, can form homodimers and heterodimers with ADH1A and ADH1C subunits, exhibits high activity for ethanol oxidation[5][6] and plays a major role in ethanol catabolism (oxidizing ethanol into acetaldehyde). The acetaldehyde is further metabolized to acetate by aldehyde dehydrogenase genes. Three genes encoding the closely related alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster.[7]
The human gene is located on chromosome 4 in 4q22.
Previously ADH1B was called ADH2. There are more genes in the family of alcohol dehydrogenase. These genes are now referred to as ADH1A, ADH1C, and ADH4, ADH5, ADH6 and ADH7.[8]
Variants
A
single nucleotide polymorphism (SNP) in ADH1B is rs1229984, that changes arginine to histidine at residue 47 of the mature protein;[9] standard nomenclature now includes the initiating methionine, so the position is officially 48. The 'typical' variant of this has been referred to as ADH2(1) or ADH2*1 while the 'atypical' has been referred to as, e.g., ADH2(2), ADH2*2, ADH1B*48His. This SNP is associated with the risk for alcohol dependence, alcohol use disorders and alcohol consumption, with the atypical genotype having reduced risk of alcoholism.[10][11][12] The atypical genotype produces a more active enzyme and is associated with rice domestication.[13]
Another SNP is rs2066702 [Arg370Cys].[14] originally called position 369. This SNP is at high frequencies in populations from Africa, and also reduces risk for alcohol dependence.[15]
Role in pathology
A marked decrease of ADH1B
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000196616 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 3006456.
- PMID 23134050.
- PMID 2398055.
- PMID 23134050.
- ^ "Entrez Gene: ADH1B alcohol dehydrogenase IB (class I), beta polypeptide". Retrieved 2019-12-19.
- PMID 23134050.
- PMID 2547609.
- PMID 23134050.
- PMID 2014795.
- PMID 21968928.
- PMID 20089146.
- PMID 3619918.
- .
- PMID 19365573.
Further reading
- Harada S (April 2001). "[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese]". Nihon Arukoru Yakubutsu Igakkai Zasshi = Japanese Journal of Alcohol Studies & Drug Dependence. 36 (2): 85–106. PMID 11398342.
- Green RF, Stoler JM (July 2007). "Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview". American Journal of Obstetrics and Gynecology. 197 (1): 12–25. PMID 17618743.
- Lange LG, Sytkowski AJ, Vallee BL (October 1976). "Human liver alcohol dehydrogenase: purification, composition, and catalytic features". Biochemistry. 15 (21): 4687–93. PMID 9982.
- Hurley TD, Bosron WF, Hamilton JA, Amzel LM (September 1991). "Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non-active-site substitutions". Proceedings of the National Academy of Sciences of the United States of America. 88 (18): 8149–53. PMID 1896463.
- Stewart MJ, McBride MS, Winter LA, Duester G (June 1990). "Promoters for the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3: interaction of CCAAT/enhancer-binding protein with elements flanking the ADH2 TATA box". Gene. 90 (2): 271–9. PMID 2169444.
- Winter LA, Stewart MJ, Shean ML, Dong Y, Poellinger L, Okret S, Gustafsson JA, Duester G (July 1990). "A hormone response element upstream from the human alcohol dehydrogenase gene ADH2 consists of three tandem glucocorticoid receptor binding sites". Gene. 91 (2): 233–40. PMID 2210383.
- Carr LG, Edenberg HJ (January 1990). "cis-acting sequences involved in protein binding and in vitro transcription of the human alcohol dehydrogenase gene ADH2". The Journal of Biological Chemistry. 265 (3): 1658–64. PMID 2295648.
- Yasunami M, Kikuchi I, Sarapata D, Yoshida A (June 1990). "The human class I alcohol dehydrogenase gene cluster: three genes are tandemly organized in an 80-kb-long segment of the genome". Genomics. 7 (2): 152–8. PMID 2347582.
- Hurley TD, Edenberg HJ, Bosron WF (September 1990). "Expression and kinetic characterization of variants of human beta 1 beta 1 alcohol dehydrogenase containing substitutions at amino acid 47". The Journal of Biological Chemistry. 265 (27): 16366–72. PMID 2398055.
- Carr LG, Xu Y, Ho WH, Edenberg HJ (August 1989). "Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit". Alcoholism: Clinical and Experimental Research. 13 (4): 594–6. PMID 2679216.
- Tsukahara M, Yoshida A (February 1989). "Chromosomal assignment of the alcohol dehydrogenase cluster locus to human chromosome 4q21-23 by in situ hybridization". Genomics. 4 (2): 218–20. PMID 2737681.
- Duester G, Smith M, Bilanchone V, Hatfield GW (February 1986). "Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit". The Journal of Biological Chemistry. 261 (5): 2027–33. PMID 2935533.
- Ikuta T, Szeto S, Yoshida A (February 1986). "Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence". Proceedings of the National Academy of Sciences of the United States of America. 83 (3): 634–8. PMID 2935875.
- Ikuta T, Fujiyoshi T, Kurachi K, Yoshida A (May 1985). "Molecular cloning of a full-length cDNA for human alcohol dehydrogenase". Proceedings of the National Academy of Sciences of the United States of America. 82 (9): 2703–7. PMID 2986130.
- Hedén LO, Höög JO, Larsson K, Lake M, Lagerholm E, Holmgren A, Vallee BL, Jörnvall H, von Bahr-Lindström H (January 1986). "cDNA clones coding for the beta-subunit of human liver alcohol dehydrogenase have differently sized 3'-non-coding regions". FEBS Letters. 194 (2): 327–32. S2CID 39171264.
- Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ (April 1988). "Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification". Genomics. 2 (3): 209–14. PMID 3397059.
External links
- Human ADH1B genome location and ADH1B gene details page in the UCSC Genome Browser.
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