Alcohol dehydrogenase class-3

UniProt P11766 Organism Homo sapiens Gene ADH5, ADHX, FDH EC 1.1.1.1, 1.1.1.-, 1.1.1.284

Also known as: ADH5, ADHX, FDH

Function

Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione. Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate. Class-III ADH is remarkably ineffective in oxidizing ethanol. Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. Also acts as a S-nitroso-glutathione reductase by catalyzing the NADH-dependent reduction of S-nitrosoglutathione, thereby regulating protein S-nitrosylation (By similarity).

Classification

Family (Pfam): PF08240 ADH_N, PF00107 ADH_zinc_N
InterPro: ADH-like_C, ADH-like_N, ADH_3, ADH_Zn_CS, GroES-like_sf, NAD(P)-bd_dom_sf
Functional cluster: Oxidoreductases & Polyketide Synthases

Experimental structures · PDB · 10

1M6H X-ray 2.00A
1M6W X-ray 2.30A
1MA0 X-ray 2.30A
1MC5 X-ray 2.60A
1MP0 X-ray 2.20A
1TEH X-ray 2.70A
2FZE X-ray 1.90A
2FZW X-ray 1.84A
3QJ5 X-ray 1.90A
8GV3 EM 3.05A

A predicted model is available from AlphaFold.

Gene Ontology · 14

Disease associations

AMED syndrome, digenic MONDO:0030894

Drugs targeting this protein · 3

N6022 inhibitor
NITREFAZOLE inhibitor
CAVOSONSTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Aldehyde dehydrogenase, mitochondrial 1 shared papers
All-trans-retinol dehydrogenase [NAD(+)] ADH4 1 shared papers
All-trans-retinol dehydrogenase [NAD(+)] ADH4 1 shared papers

Literature · 14 cited papers

Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome. Sci. Adv. · 2020
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
Omega-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4. J. Biol. Chem. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase. J. Mol. Biol. · 1997
Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase. Biochemistry · 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. · 1993
Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes. Biochemistry · 1988
cDNA sequence of human class III alcohol dehydrogenase. Biochem. Biophys. Res. Commun. · 1989
… and 2 more in the literature graph

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