ADH1B
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesADH1B, ADH2, HEL-S-117, alcohol dehydrogenase 1B (class I), beta polypeptide
External IDsOMIM: 103720 HomoloGene: 133563 GeneCards: ADH1B
Orthologs
SpeciesHumanMouse
Entrez

125

n/a

Ensembl

ENSG00000196616

n/a

UniProt

P00325

n/a

RefSeq (mRNA)

NM_001286650
NM_000668

n/a

RefSeq (protein)

NP_000659
NP_001273579

n/a

Location (UCSC)Chr 4: 99.3 – 99.35 Mbn/a
PubMed search[2]n/a
Wikidata
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 mRNA was detected in corneal fibroblasts taken from persons suffering from keratoconus.[16]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196616 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Smith M (Mar 1986). "Genetics of Human Alcohol and Aldehyde Dehydrogenases". Advances in Human Genetics 15. Vol. 15. pp. 249–90. doi:10.1007/978-1-4615-8356-1_5. ISBN 978-1-4615-8358-5. PMID 3006456.
  4. ^ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC 3756590. PMID 23134050.
  5. ^ Hurley TD, Edenberg HJ, Bosron WF (1990). "Expression and kinetic characterization of variants of human beta 1 beta 1 alcohol dehydrogenase containing substitutions at amino acid 47". J. Biol. Chem. 265 (27): 16366–72. doi:10.1016/S0021-9258(17)46232-6. PMID 2398055.
  6. ^ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC 3756590. PMID 23134050.
  7. ^ "Entrez Gene: ADH1B alcohol dehydrogenase IB (class I), beta polypeptide". Retrieved 2019-12-19.
  8. ^ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC 3756590. PMID 23134050.
  9. ^ Matsuo Y, Yokoyama R, Yokoyama S (August 1989). "The genes for human alcohol dehydrogenases beta 1 and beta 2 differ by only one nucleotide". European Journal of Biochemistry. 183 (2): 317–20. doi:10.1111/j.1432-1033.1989.tb14931.x. PMID 2547609.
  10. ^ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC 3756590. PMID 23134050.
  11. ^ Thomasson HR, Edenberg HJ, Crabb DW, Mai XL, Jerome RE, Li TK, Wang SP, Lin YT, Lu RB, Yin SJ (April 1991). "Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men". American Journal of Human Genetics. 48 (4): 677–81. PMC 1682953. PMID 2014795.
  12. ^ Bierut LJ, Goate AM, Breslau N, Johnson EO, Bertelsen S, Fox L, Agrawal A, Bucholz KK, Grucza R, Hesselbrock V, Kramer J, Kuperman S, Nurnberger J, Porjesz B, Saccone NL, Schuckit M, Tischfield J, Wang JC, Foroud T, Rice JP, Edenberg HJ (April 2012). "ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry". Molecular Psychiatry. 17 (4): 445–50. doi:10.1038/mp.2011.124. PMC 3252425. PMID 21968928.
  13. ^ Peng Y, et al. (2010). "The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history". BMC Evolutionary Biology. 10 (1): 15. Bibcode:2010BMCEE..10...15P. doi:10.1186/1471-2148-10-15. PMC 2823730. PMID 20089146.
  14. ^ Burnell JC, Carr LG, Dwulet FE, Edenberg HJ, Li TK, Bosron WF (August 1987). "The human beta 3 alcohol dehydrogenase subunit differs from beta 1 by a Cys for Arg-369 substitution which decreases NAD(H) binding". Biochemical and Biophysical Research Communications. 146 (3): 1227–33. doi:10.1016/0006-291x(87)90779-0. PMID 3619918.
  15. ^ Walters RK, Adams MJ, Adkins AE, Aliev F, Bacanu SA, Batzler A, et al. (2018-03-10). "Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders". bioRxiv: 257311. doi:10.1101/257311. hdl:1871.1/c28775f1-af5b-4205-93cc-8fc89d2429b3.
  16. ^ Mootha VV, Kanoff JM, Shankardas J, Dimitrijevich S (2009). "Marked reduction of alcohol dehydrogenase in keratoconus corneal fibroblasts". Molecular Vision. 15: 706–12. PMC 2666775. PMID 19365573.

Further reading

External links

PDB gallery
Category