ADH5

ADH5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1M6H, 1M6W, 1MA0, 1MC5, 1MP0, 1TEH, 2FZE, 2FZW, 3QJ5
Identifiers
Aliases	ADH5 , ADH-3, ADHX, FALDH, FDH, GSH-FDH, GSNOR, HEL-S-60p, alcohol dehydrogenase 5 (class III), chi polypeptide, BMFS7, AMEDS
External IDs	OMIM: 103710; MGI: 87929; HomoloGene: 68076; GeneCards: ADH5; OMA:ADH5 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q23 Start 99,070,978 bp [1] End 99,088,801 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3|3 G3 Start 138,148,854 bp [2] End 138,161,260 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastric mucosa Descending thoracic aorta stromal cell of endometrium kidney tubule corpus epididymis ascending aorta Achilles tendon popliteal artery tibial arteries ventricular zone Top expressed in primitive streak left lobe of liver Gonadal ridge endocardial cushion medullary collecting duct ureter medial ganglionic eminence vas deferens olfactory epithelium atrioventricular valve More reference expression data BioGPS n/a
Gene ontology Molecular function protein homodimerization activity zinc ion binding metal ion binding fatty acid binding formaldehyde dehydrogenase activity electron transfer activity oxidoreductase activity S-(hydroxymethyl)glutathione dehydrogenase activity alcohol dehydrogenase (NAD+) activity alcohol dehydrogenase activity, zinc-dependent Cellular component cytoplasm cytosol mitochondrion extracellular exosome Biological process respiratory system process retinoid metabolic process response to redox state positive regulation of blood pressure response to lipopolysaccharide peptidyl-cysteine S-nitrosylation response to nitrosative stress formaldehyde catabolic process ethanol oxidation electron transport chain Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 128 11532 Ensembl ENSG00000197894 ENSMUSG00000028138 UniProt P11766 P28474 RefSeq (mRNA) NM_000671 NM_001288578 NM_007410 RefSeq (protein) NP_000662 NP_001275507 NP_031436 Location (UCSC) Chr 4: 99.07 – 99.09 Mb Chr 3: 138.15 – 138.16 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Alcohol dehydrogenase class-3 is an enzyme that in humans is encoded by the ADH5 gene. ^{[5] [6] [7]}

This gene encodes glutathione-dependent formaldehyde dehydrogenase or the class III alcohol dehydrogenase chi subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class III alcohol dehydrogenase is a homodimer composed of 2 chi subunits. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione.

This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. ^[7]

Clinical significance

Mutations of the ADH5 gene and ALDH2 gene cause AMED syndrome, an autosomal recessive digenic multisystem disorder characterized by global developmental delay with impaired intellectual development, short stature, growth impairment and early development of myelodysplastic syndrome and bone marrow failure. The syndrome was first described in 2020. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000197894 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028138 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hur MW, Edenberg HJ (Dec 1992). "Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase". Gene. 121 (2): 305–11. doi:10.1016/0378-1119(92)90135-C. PMID   1446828.
6. Adinolfi A, Adinolfi M, Hopkinson DA (May 1984). "Immunological and biochemical characterization of the human alcohol dehydrogenase chi-ADH isozyme". Ann Hum Genet. 48 (Pt 1): 1–10. doi:10.1111/j.1469-1809.1984.tb00828.x. PMID   6424546. S2CID   85113864.
7. "Entrez Gene: ADH5 alcohol dehydrogenase 5 (class III), chi polypeptide".
8. Kniffin CL (27 November 2023) [Originally published on 13 January 2021]. "AMED SYNDROME, DIGENIC; AMEDS". Online Mendelian Inheritance in Man. Johns Hopkins University. #619151. Retrieved 1 May 2024.

Further reading

• Iborra FJ, Renau-Piqueras J, Portoles M, et al. (1992). "Immunocytochemical and biochemical demonstration of formaldhyde dehydrogenase (class III alcohol dehydrogenase) in the nucleus". J. Histochem. Cytochem. 40 (12): 1865–78. doi: 10.1177/40.12.1453005 . PMID   1453005.
• Giri PR, Krug JF, Kozak C, et al. (1989). "Cloning and comparative mapping of a human class III (chi) alcohol dehydrogenase cDNA". Biochem. Biophys. Res. Commun. 164 (1): 453–60. doi:10.1016/0006-291X(89)91741-5. PMID   2679557.
• Sharma CP, Fox EA, Holmquist B, et al. (1989). "cDNA sequence of human class III alcohol dehydrogenase". Biochem. Biophys. Res. Commun. 164 (2): 631–7. doi:10.1016/0006-291X(89)91507-6. PMID   2818582.
• Beisswenger TB, Holmquist B, Vallee BL (1986). "chi-ADH is the sole alcohol dehydrogenase isozyme of mammalian brains: implications and inferences". Proc. Natl. Acad. Sci. U.S.A. 82 (24): 8369–73. doi: 10.1073/pnas.82.24.8369 . PMC   390917 . PMID   2934732.
• Dafeldecker WP, Vallee BL (1986). "Organ-specific human alcohol dehydrogenase: isolation and characterization of isozymes from testis". Biochem. Biophys. Res. Commun. 134 (3): 1056–63. doi:10.1016/0006-291X(86)90358-X. PMID   2936344.
• Kaiser R, Holmquist B, Hempel J, et al. (1988). "Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes". Biochemistry. 27 (4): 1132–40. doi:10.1021/bi00404a009. PMID   3365377.
• Khokha AM, Voronov PP, Zimatkin SM (1994). "[Immunoenzyme and immunohistochemical analysis of class III alcohol dehydrogenase from human testis]". Biokhimiia. 59 (7): 997–1002. PMID   7948423.
• Engeland K, Höög JO, Holmquist B, et al. (1993). "Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation". Proc. Natl. Acad. Sci. U.S.A. 90 (6): 2491–4. Bibcode:1993PNAS...90.2491E. doi: 10.1073/pnas.90.6.2491 . PMC   46113 . PMID   8460164.
• Holmquist B, Moulis JM, Engeland K, Vallee BL (1993). "Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase". Biochemistry. 32 (19): 5139–44. doi:10.1021/bi00070a024. PMID   8494891.
• Engeland K, Maret W (1993). "Extrahepatic, differential expression of four classes of human alcohol dehydrogenase". Biochem. Biophys. Res. Commun. 193 (1): 47–53. doi:10.1006/bbrc.1993.1588. PMID   8503936.
• Yang ZN, Bosron WF, Hurley TD (1997). "Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase". J. Mol. Biol. 265 (3): 330–43. doi:10.1006/jmbi.1996.0731. PMID   9018047.
• Mori O, Haseba T, Kameyama K, et al. (2000). "Histological distribution of class III alcohol dehydrogenase in human brain". Brain Res. 852 (1): 186–90. doi:10.1016/S0006-8993(99)02201-5. PMID   10661511. S2CID   23510523.
• Sanghani PC, Stone CL, Ray BD, et al. (2000). "Kinetic mechanism of human glutathione-dependent formaldehyde dehydrogenase". Biochemistry. 39 (35): 10720–9. doi:10.1021/bi9929711. PMID   10978156.
• Lee DK, Suh D, Edenberg HJ, Hur MW (2002). "POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1". J. Biol. Chem. 277 (30): 26761–8. doi: 10.1074/jbc.M202078200 . PMID   12004059.
• Jelski W, Chrostek L, Szmitkowski M, Laszewicz W (2002). "Activity of class I, II, III, and IV alcohol dehydrogenase isoenzymes in human gastric mucosa". Dig. Dis. Sci. 47 (7): 1554–7. doi:10.1023/A:1015871219922. PMID   12141816. S2CID   31197228.
• Sanghani PC, Robinson H, Bosron WF, Hurley TD (2002). "Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes". Biochemistry. 41 (35): 10778–86. doi:10.1021/bi0257639. PMID   12196016.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Sanghani PC, Bosron WF, Hurley TD (2003). "Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation". Biochemistry. 41 (51): 15189–94. doi:10.1021/bi026705q. PMID   12484756.

External links

• Human ADH5 genome location and ADH5 gene details page in the UCSC Genome Browser .