UniProt functional annotation for P40394

UniProt code: P40394.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, and omega-hydroxy fatty acids and their derivatives (PubMed:15369820, PubMed:16787387, PubMed:9600267). Oxidizes preferentially all trans-retinol, all-trans-4-hydroxyretinol, 9-cis- retinol, 2-hexenol, and long chain omega-hydroxy fatty acids such as juniperic acid (PubMed:15369820, PubMed:16787387, PubMed:9600267). In vitro can also catalyzes the NADH-dependent reduction of all-trans- retinal and aldehydes and their derivatives (PubMed:15369820, PubMed:16787387, PubMed:9600267). Reduces preferentially all trans- retinal, all-trans-4-oxoretinal and hexanal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:16787387, PubMed:15369820). Therefore may participate in retinoid metabolism, fatty acid omega-oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation (PubMed:9600267, PubMed:15369820, PubMed:16787387). {ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:16787387, ECO:0000269|PubMed:9600267}.
 
Catalytic activity: Reaction=a primary alcohol + NAD(+) = an aldehyde + H(+) + NADH; Xref=Rhea:RHEA:10736, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, ChEBI:CHEBI:17478, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.1; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10737; Evidence={ECO:0000305|PubMed:9600267}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10738; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=10-hydroxydecanoate + NAD(+) = 10-oxodecanoate + H(+) + NADH; Xref=Rhea:RHEA:20880, ChEBI:CHEBI:11305, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58022; EC=1.1.1.66; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20881; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=all-trans-retinol + NAD(+) = all-trans-retinal + H(+) + NADH; Xref=Rhea:RHEA:21284, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.105; Evidence={ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:16787387, ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21285; Evidence={ECO:0000305|PubMed:16787387};
Catalytic activity: Reaction=9-cis-retinol + NAD(+) = 9-cis-retinal + H(+) + NADH; Xref=Rhea:RHEA:42052, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42053; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=all-trans-3,4-didehydroretinol + NAD(+) = all-trans-3,4- didehydroretinal + H(+) + NADH; Xref=Rhea:RHEA:55940, ChEBI:CHEBI:15378, ChEBI:CHEBI:28537, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132246; Evidence={ECO:0000269|PubMed:15369820}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55941; Evidence={ECO:0000305|PubMed:15369820};
Catalytic activity: Reaction=all-trans-4-hydroxyretinol + NAD(+) = all-trans-4- hydroxyretinal + H(+) + NADH; Xref=Rhea:RHEA:55936, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:132259, ChEBI:CHEBI:139346; Evidence={ECO:0000269|PubMed:15369820}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55937; Evidence={ECO:0000305|PubMed:15369820};
Catalytic activity: Reaction=all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal + H(+) + NADH; Xref=Rhea:RHEA:60632, ChEBI:CHEBI:15378, ChEBI:CHEBI:44597, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:139347; Evidence={ECO:0000269|PubMed:15369820}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60634; Evidence={ECO:0000305|PubMed:15369820};
Catalytic activity: Reaction=12-hydroxydodecanoate + NAD(+) = 12-oxododecanoate + H(+) + NADH; Xref=Rhea:RHEA:60980, ChEBI:CHEBI:15378, ChEBI:CHEBI:36204, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:144067; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60981; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=16-hydroxyhexadecanoate + NAD(+) = 16-oxohexadecanoate + H(+) + NADH; Xref=Rhea:RHEA:60984, ChEBI:CHEBI:15378, ChEBI:CHEBI:55329, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:144068; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60985; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=hexan-1-ol + NAD(+) = H(+) + hexanal + NADH; Xref=Rhea:RHEA:60972, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:87393, ChEBI:CHEBI:88528; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60973; Evidence={ECO:0000305|PubMed:9600267}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60974; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=(E)-hex-2-en-1-ol + NAD(+) = (E)-hex--2-enal + H(+) + NADH; Xref=Rhea:RHEA:60988, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:141205; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60989; Evidence={ECO:0000305|PubMed:9600267}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60990; Evidence={ECO:0000305|PubMed:9600267};
Catalytic activity: Reaction=(E)-4-hydroxynon-2-en-1-ol + NAD(+) = (E)-4-hydroxynon-2-enal + H(+) + NADH; Xref=Rhea:RHEA:60976, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58968, ChEBI:CHEBI:142617; Evidence={ECO:0000269|PubMed:9600267}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:60978; Evidence={ECO:0000305|PubMed:9600267};
Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:10631979}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:10631979};
Activity regulation: Retinol oxidation is inhibited by the detergent Tween 80 (PubMed:15369820). Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation (PubMed:9600267). 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation (PubMed:9600267). All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (PubMed:9600267). 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (PubMed:9600267). Cimetidine competitively inhibited ethanol oxidation (PubMed:9600267). {ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:9600267}.
Biophysicochemical properties: Kinetic parameters: KM=23 uM for all-trans-retinol {ECO:0000269|PubMed:15369820}; KM=15 uM for all-trans-4-hydroxyretinol {ECO:0000269|PubMed:15369820}; KM=28 uM for all-trans-3,4-didehydroretinol {ECO:0000269|PubMed:15369820}; KM=34 uM for all-trans-retinal {ECO:0000269|PubMed:15369820, ECO:0000269|PubMed:9600267}; KM=17 uM for all-trans-4-oxoretinal {ECO:0000269|PubMed:15369820}; KM=26 uM for all-trans-3,4-didehydroretinal {ECO:0000269|PubMed:15369820}; KM=0.3 uM for all-trans-retinol {ECO:0000269|PubMed:16787387}; KM=0.8 uM for all-trans-retinal {ECO:0000269|PubMed:16787387}; KM=0.1 mM for 10-OH-decanoic acid (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=0.17 mM for 12-OH-dodecanoic acid (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=0.07 mM for 12-OH-dodecanoic acid (with 0.1 M glycine/NaOH at pH 10) {ECO:0000269|PubMed:9600267}; KM=0.035 mM for 16-OH-hexadecanoic acid (with 0.1 M glycine/NaOH at pH 10) {ECO:0000269|PubMed:9600267}; KM=0.14 mM for hexanol (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=0.02 mM for hexanal (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=0.017 mM for 2-hexenol (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=0.025 mM for 2-hexenal (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=0.038 mM for 4-hydroxynonenal (with 0.1 M sodium phosphate at pH 7.5) {ECO:0000269|PubMed:9600267}; KM=15 uM for all-trans-retinol {ECO:0000269|PubMed:9600267}; KM=36 uM for 9-cis-retinol {ECO:0000269|PubMed:9600267}; KM=21 uM for 9-cis-retinal {ECO:0000269|PubMed:9600267};
Subunit: Homodimer. {ECO:0000269|PubMed:10631979}.
Subcellular location: Cytoplasm.
Tissue specificity: Preferentially expressed in stomach.
Miscellaneous: There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.
Similarity: Belongs to the zinc-containing alcohol dehydrogenase family. Class-IV subfamily. {ECO:0000305}.
Sequence caution: Sequence=AAA19002.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAC51351.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAG35707.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA53960.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAA53961.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.