All-trans-retinol dehydrogenase [NAD(+)] ADH4

Function

Catalyzes the NAD-dependent oxidation of either all-trans-retinol or 9-cis-retinol. 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. Also catalyzes the reduction of benzoquinones.

Classification

Family (Pfam)

PF08240 ADH_N, PF00107 ADH_zinc_N

InterPro

ADH-like_C, ADH-like_N, ADH_Zn_CS, ER, GroES-like_sf, NAD(P)-bd_dom_sf

Functional cluster

Oxidoreductases & Polyketide Synthases

Experimental structures · PDB · 1

• 3COS X-ray 2.10A

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0005829 cytosol
• GO:0004022 alcohol dehydrogenase (NAD+) activity
• GO:0004032 aldose reductase (NADPH) activity
• GO:0005503 all-trans retinal binding
• GO:0004745 all-trans-retinol dehydrogenase (NAD+) activity
• GO:0018479 benzaldehyde dehydrogenase (NAD+) activity
• GO:0051287 NAD binding
• GO:0003960 quinone reductase (NADPH) activity
• GO:0019841 retinol binding
• GO:0051903 S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity
• GO:0008270 zinc ion binding
• GO:0046164 alcohol catabolic process
• GO:0006066 alcohol metabolic process
• GO:0006081 aldehyde metabolic process
• GO:0010430 fatty acid omega-oxidation
• GO:0046294 formaldehyde catabolic process
• GO:1901661 quinone metabolic process
• GO:0001523 retinoid metabolic process
• GO:0042572 retinol metabolic process

Drugs targeting this protein · 1

• NITREFAZOLE inhibitor

Related proteins · sequence + function similarity

• Alcohol dehydrogenase class-2 isozyme 1 0.98
• Alcohol dehydrogenase class-2 isozyme 2 0.98
• All-trans-retinol dehydrogenase [NAD(+)] ADH4 0.97
• NADP-dependent alcohol dehydrogenase 0.97
• All-trans-retinol dehydrogenase [NAD(+)] ADH4 0.96
• Alcohol dehydrogenase 6 0.96
• All-trans-retinol dehydrogenase [NAD(+)] ADH4 0.96
• Alcohol dehydrogenase 1 0.96
• Alcohol dehydrogenase 1 0.96
• Alcohol dehydrogenase 6 0.96
• Alcohol dehydrogenase 1 0.96
• Alcohol dehydrogenase 1 0.95

Co-cited proteins · studied together in the literature

• All-trans-retinol dehydrogenase [NAD(+)] ADH4 3 shared papers
• All-trans-retinol dehydrogenase [NAD(+)] ADH4 1 shared papers
• Alcohol dehydrogenase class-3 1 shared papers

Literature · 9 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism. Cell. Mol. Life Sci. · 2007
• Omega-oxidation of 20-hydroxyeicosatetraenoic acid (20-HETE) in cerebral microvascular smooth muscle and endothelium by alcohol dehydrogenase 4. J. Biol. Chem. · 2005
• Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• A novel subtype of class II alcohol dehydrogenase in rodents. Unique Pro(47) and Ser(182) modulates hydride transfer in the mouse enzyme. J. Biol. Chem. · 1999
• Structure of the class II enzyme of human liver alcohol dehydrogenase: combined cDNA and protein sequence determination of the pi subunit. Biochemistry · 1987
• Cloning and characterization of the human ADH4 gene. Gene · 1991