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UniProt functional annotation for P15121 | ||
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| UniProt code: P15121. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia (PubMed:1936586). Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis- retinal (PubMed:12732097, PubMed:19010934, PubMed:8343525). Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2- (5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a 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:21329684). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:17381426, ECO:0000269|PubMed:19010934, ECO:0000269|PubMed:1936586, ECO:0000269|PubMed:21329684, ECO:0000269|PubMed:8343525}. |
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| Catalytic activity: | |
Reaction=an alditol + NADP(+) = an aldose + H(+) + NADPH; Xref=Rhea:RHEA:12789, Rhea:RHEA-COMP:9554, Rhea:RHEA-COMP:9555, ChEBI:CHEBI:15378, ChEBI:CHEBI:15693, ChEBI:CHEBI:17522, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.21; Evidence={ECO:0000269|PubMed:8245005}; |
| 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:21329680}; |
| 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:21329680}; |
| 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=glycerol + NADP(+) = D-glyceraldehyde + H(+) + NADPH; Xref=Rhea:RHEA:23592, ChEBI:CHEBI:15378, ChEBI:CHEBI:17378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.372; Evidence={ECO:0000269|PubMed:10510318, ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:1936586, ECO:0000269|PubMed:21329680, ECO:0000269|PubMed:8245005}; |
| Catalytic activity: | |
Reaction=glycerol + NADP(+) = H(+) + L-glyceraldehyde + NADPH; Xref=Rhea:RHEA:38111, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:27975, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.372; Evidence={ECO:0000269|PubMed:10510318, ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:1936586, ECO:0000269|PubMed:21329680, ECO:0000269|PubMed:8245005}; |
| 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:21329684}; |
| 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:21329684}; |
| 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:21329684}; |
| 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:21329684}; |
| Catalytic activity: | |
Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin H2; Xref=Rhea:RHEA:45312, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404, ChEBI:CHEBI:57405, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:19010934}; |
| 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:10510318, ECO:0000269|PubMed:21329684}; |
| Catalytic activity: | |
Reaction=NADP(+) + pyridine 3-methanol = H(+) + NADPH + pyridine-3- carbaldehyde; Xref=Rhea:RHEA:58776, ChEBI:CHEBI:15378, ChEBI:CHEBI:28345, ChEBI:CHEBI:45213, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:12732097}; |
| Catalytic activity: | |
Reaction=1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine + H(+) + NADPH = 1-hexadecanoyl-2-(5-hydroxypentanoyl)-sn-glycero-3- phosphocholine + NADP(+); Xref=Rhea:RHEA:58512, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:77890, ChEBI:CHEBI:142747; Evidence={ECO:0000269|PubMed:17381426}; |
| Catalytic activity: | |
Reaction=1-hexadecanoyl-2-(7-oxoheptanoyl)-sn-glycero-3-phosphocholine + H(+) + NADPH = 1-hexadecanoyl-2-(7-hydroxyheptanoyl)-sn-glycero-3- phosphocholine + NADP(+); Xref=Rhea:RHEA:58752, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:134601, ChEBI:CHEBI:142748; Evidence={ECO:0000269|PubMed:17381426}; |
| Catalytic activity: | |
Reaction=1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine + H(+) + NADPH = 1-hexadecanoyl-2-(9-hydroxynonanoyl)-sn-glycero-3- phosphocholine + NADP(+); Xref=Rhea:RHEA:58592, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61042, ChEBI:CHEBI:142749; Evidence={ECO:0000269|PubMed:17381426}; |
| Catalytic activity: | |
Reaction=1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3- phosphoethanolamine + H(+) + NADPH = 1-hexadecanoyl-2-(5- hydroxypentanoyl)-sn-glycero-3-phosphoethanolamine + NADP(+); Xref=Rhea:RHEA:58756, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:142750, ChEBI:CHEBI:142751; Evidence={ECO:0000269|PubMed:17381426}; |
| Activity regulation: | |
Cys-299 may regulate the kinetic and inhibition properties of the enzyme, but does not participate in catalysis (PubMed:8343525). Tolrestat inhibits retinal reduction (PubMed:12732097). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:8343525}. |
| Biophysicochemical properties: | |
Kinetic parameters: KM=44 uM for D,L-glyceraldehyde {ECO:0000269|PubMed:12732097}; KM=76000 uM for glucose {ECO:0000269|PubMed:12732097}; KM=14 uM for pyridine-3-carbaldehyde {ECO:0000269|PubMed:12732097}; KM=10 uM for all-trans-retinal {ECO:0000269|PubMed:12732097}; KM=12 uM for 9-cis-retinal {ECO:0000269|PubMed:12732097}; KM=14 uM for 13-cis-retinal {ECO:0000269|PubMed:12732097}; KM=8.8 uM for 1-O-palmitoyl-2-O-(5-oxovaleryl)-sn-glycero-3- phosphocholine (POVPC) {ECO:0000269|PubMed:17381426}; KM=16 uM for 1-hexadecanoyl-2-(7-oxoheptanoyl)-sn-glycero-3- phosphocholine {ECO:0000269|PubMed:17381426}; KM=13 uM for 1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3- phosphocholine {ECO:0000269|PubMed:17381426}; KM=11 uM for 1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3- phosphoethanolamine {ECO:0000269|PubMed:17381426}; KM=884 uM for acrolein {ECO:0000269|PubMed:21329684}; KM=9643 uM for 3-methyl-2-butenal {ECO:0000269|PubMed:21329684}; KM=878 uM for (E)-2-hexenal {ECO:0000269|PubMed:21329684}; KM=905 uM for (E,E)-2,4-hexadienal {ECO:0000269|PubMed:21329684}; KM=716 uM for 4-hydroxynonenal {ECO:0000269|PubMed:21329684}; KM=122 uM for GS-(E)-4-hexenal {ECO:0000269|PubMed:21329684}; KM=7 uM for GS-hexenal {ECO:0000269|PubMed:21329684}; KM=5 uM for GS-4-hydroxynonenal {ECO:0000269|PubMed:21329684}; KM=1.9 uM for prostaglandin H2 {ECO:0000269|PubMed:19010934}; Vmax=26 nmol/min/mg enzyme for prostaglandin H2 {ECO:0000269|PubMed:19010934}; Note=kcat is 15 min(-1) for all-trans-retinal as substrate. kcat is 30 min(-1) for 9-cis-retinal as substrate. kcat is 94 min(-1) for 13- cis-retinal as substrate (PubMed:12732097). kcat is 11 min(-1) for acrolein as substrate. kcat is 31 min(-1) for 3-methyl-2-butenal as substrate. kcat is 41 min(-1) for (E)-2-hexenal as substrate. kcat is 43 min(-1) for (E,E)-2,4-hexadienal as substrate. kcat is 50 min(-1) for 4-hydroxynonenal as substrate. kcat is 16 min(-1) for GS-(E)-4- hexenal as substrate. kcat is 16 min(-1) for GS-hexenal as substrate. kcat is 13 min(-1) for GS-4-hydroxynonenal as substrate (PubMed:21329684). kcat is 31 min(-1) for D,L-glyceraldehyde (PubMed:21329680). {ECO:0000269|PubMed:12732097, ECO:0000269|PubMed:21329680, ECO:0000269|PubMed:21329684}; |
| Subunit: | |
Monomer. {ECO:0000269|PubMed:15146478, ECO:0000269|PubMed:15272156, ECO:0000269|PubMed:16337231, ECO:0000269|PubMed:17368668, ECO:0000269|PubMed:17418233, ECO:0000269|PubMed:17505104}. |
| Subcellular location: | |
Cytoplasm. |
| Tissue specificity: | |
Highly expressed in embryonic epithelial cells (EUE) in response to osmotic stress. {ECO:0000269|PubMed:8435445}. |
| Similarity: | |
Belongs to the aldo/keto reductase family. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.