UniProt functional annotation for O60218

UniProt code: O60218.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:9565553, PubMed:18087047, PubMed:12732097, PubMed:19013440, PubMed:19563777). Displays strong enzymatic activity toward all-trans- retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:18087047). Plays a critical role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4- hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:19013440, PubMed:19563777). Displays no reductase activity towards glucose (PubMed:12732097). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047, ECO:0000269|PubMed:19013440, ECO:0000269|PubMed:19563777, ECO:0000269|PubMed:9565553}.
 
Catalytic activity: Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + H(+) + NADPH; Xref=Rhea:RHEA:25033, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.300; Evidence={ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047};
Catalytic activity: Reaction=9-cis-retinol + NADP(+) = 9-cis-retinal + H(+) + NADPH; Xref=Rhea:RHEA:54916, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273; Evidence={ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047};
Catalytic activity: Reaction=13-cis-retinol + NADP(+) = 13-cis-retinal + H(+) + NADPH; Xref=Rhea:RHEA:54920, ChEBI:CHEBI:15378, ChEBI:CHEBI:45479, ChEBI:CHEBI:45487, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:12732097};
Catalytic activity: Reaction=allyl alcohol + NADP(+) = acrolein + H(+) + NADPH; Xref=Rhea:RHEA:12168, ChEBI:CHEBI:15368, ChEBI:CHEBI:15378, ChEBI:CHEBI:16605, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.54; Evidence={ECO:0000269|PubMed:19563777};
Catalytic activity: Reaction=(E)-4-hydroxynon-2-en-1-ol + NADP(+) = (E)-4-hydroxynon-2-enal + H(+) + NADPH; Xref=Rhea:RHEA:58416, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:58968, ChEBI:CHEBI:142617; Evidence={ECO:0000269|PubMed:19013440};
Catalytic activity: Reaction=a 4-hydroxynonen-1-ol + NADP(+) = a 4-hydroxynonenal + H(+) + NADPH; Xref=Rhea:RHEA:58336, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:142593, ChEBI:CHEBI:142606; Evidence={ECO:0000269|PubMed:19563777};
Catalytic activity: Reaction=NADP(+) + prenol = 3-methyl-2-butenal + H(+) + NADPH; Xref=Rhea:RHEA:58420, ChEBI:CHEBI:15378, ChEBI:CHEBI:15825, ChEBI:CHEBI:16019, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:19563777};
Catalytic activity: Reaction=(E)-hex-2-en-1-ol + NADP(+) = (E)-hex--2-enal + H(+) + NADPH; Xref=Rhea:RHEA:58424, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:141205; Evidence={ECO:0000269|PubMed:19563777};
Catalytic activity: Reaction=(E,E)-2,4-hexadien-1-ol + NADP(+) = (E,E)-2,4-hexadienal + H(+) + NADPH; Xref=Rhea:RHEA:58428, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:82334, ChEBI:CHEBI:142625; Evidence={ECO:0000269|PubMed:19563777};
Catalytic activity: Reaction=(E)-4-oxonon-2-en-1-ol + NADP(+) = (E)-4-oxonon-2-enal + H(+) + NADPH; Xref=Rhea:RHEA:58432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:58972, ChEBI:CHEBI:142624; Evidence={ECO:0000269|PubMed:19013440};
Catalytic activity: Reaction=4-methylpentan-1-ol + NADP(+) = 4-methylpentanal + H(+) + NADPH; Xref=Rhea:RHEA:58436, ChEBI:CHEBI:15378, ChEBI:CHEBI:17998, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:63910; Evidence={ECO:0000269|PubMed:19013440};
Activity regulation: Retinaldehyde reductase activity is inhibited by tolrestat. {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047}.
Biophysicochemical properties: Kinetic parameters: KM=6000 uM for D,L-glyceraldehyde {ECO:0000269|PubMed:18087047}; KM=0.6 uM for all-trans-retinal {ECO:0000269|PubMed:18087047}; KM=0.7 uM for 9-cis-retinal {ECO:0000269|PubMed:18087047}; KM=37 uM for pyridine-3-aldehyde {ECO:0000269|PubMed:12732097}; KM=110 uM for acrolein {ECO:0000269|PubMed:19563777}; KM=87 uM for 3-methyl-2-butenal {ECO:0000269|PubMed:19563777}; KM=30 uM for 4-hydroxynonenal {ECO:0000269|PubMed:19563777}; KM=61 uM for (E)-2-hexenal {ECO:0000269|PubMed:19563777}; KM=95 uM for (E,E)-2,4-hexadienal {ECO:0000269|PubMed:19563777}; KM=532 uM for GS-acrolein {ECO:0000269|PubMed:19563777}; KM=245 uM for GS-3-methyl-2-butenal {ECO:0000269|PubMed:19563777}; KM=145 uM for GS-(E)-2-hexenal {ECO:0000269|PubMed:19563777}; KM=77 uM for GS-(E,E)-2,4-hexadienal {ECO:0000269|PubMed:19563777}; KM=330 uM for (E)-4-hydroxynon-2-enal {ECO:0000269|PubMed:19013440}; KM=300 uM for (E)-4-oxonon-2-enal {ECO:0000269|PubMed:19013440}; KM=50 uM for 4-methylpentanal {ECO:0000269|PubMed:19013440}; Vmax=3122 nmol/min/mg enzyme with acrolein {ECO:0000269|PubMed:19563777}; Vmax=2647 nmol/min/mg enzyme with 3-methyl-2-butenal as substrate {ECO:0000269|PubMed:19563777}; Vmax=2658 nmol/min/mg enzyme with (E)-2-hexenal as substrate {ECO:0000269|PubMed:19563777}; Vmax=2160 nmol/min/mg enzyme with (E,E)-2,4-hexadienal as substrate {ECO:0000269|PubMed:19563777}; Vmax=3298 nmol/min/mg enzyme with 4-hydroxynonenal {ECO:0000269|PubMed:19563777}; Vmax=64 nmol/min/mg enzyme with GS-acrolein {ECO:0000269|PubMed:19563777}; Vmax=1960 nmol/min/mg enzyme with GS-3-methyl-2-butenal as substrate {ECO:0000269|PubMed:19563777}; Vmax=2049 nmol/min/mg enzyme with GS-(E)-2-hexenal {ECO:0000269|PubMed:19563777}; Vmax=4004 nmol/min/mg enzyme with GS-(E,E)-2,4-hexadienal as substrate {ECO:0000269|PubMed:19563777}; Note=kcat is 640 min(-1) for glyceraldehyde as substrate (PubMed:12732097). kcat is 185 min(-1) for pyridine-3-aldehyde as substrate (PubMed:12732097). kcat is 116 min(-1) for acrolein as substrate. kcat is 103 min(-1) for 3-methyl-2-butenal as substrate. kcat is 97 min(-1) for(E)-2-hexenal as substrate. kcat is 82 min(-1) for (E,E)-2,4-hexadienal as substrate. kcat is 120 min(-1) for 4- hydroxynonenal as substrate. kcat is 3 min(-1) for GS-acrolein as substrate. kcat is 70 min(-1) for GS-3-methyl-2-butenal as substrate. kcat is 71 min(-1) for GS-(E)-2-hexenal as substrate. kcat is 147 min(-1) for (E,E)-2,4-hexadienal as substrate (PubMed:19563777). kcat is 35 min(-1) for D,L-glyceraldehyde as substrate. kcat is 27 min(-1) for all-trans-retinal as substrate. kcat is 1 min(-1) for 9-cis- retinal as substrate (PubMed:18087047). kcat is 43 min(-1) for 4- hydroxynon-2-enal (PubMed:19013440). kcat is 40 min(-1) for (E)-4- oxonon-2-enal (PubMed:19013440). kcat is 25 min(-1) for 4- methylpentanal (PubMed:19013440). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047, ECO:0000269|PubMed:19013440, ECO:0000269|PubMed:19563777};
Pathway: Cofactor metabolism; retinol metabolism. {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:18087047}.
Subcellular location: Lysosome {ECO:0000269|PubMed:21585341}. Secreted {ECO:0000269|PubMed:21585341}. Note=Secreted through a lysosome- mediated non-classical pathway.
Tissue specificity: Found in many tissues. Highly expressed in small intestine, colon and adrenal gland. {ECO:0000269|PubMed:9565553}.
Induction: Overexpressed in certain types of cancers, including hepatocellular carcinoma and lung cancer associated with tobacco smoking. {ECO:0000269|PubMed:15755999, ECO:0000269|PubMed:9565553}.
Miscellaneous: Has no counterpart in murine and rat species. {ECO:0000305}.
Similarity: Belongs to the aldo/keto reductase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.