C9JRZ8 · AK1BF_HUMAN
- ProteinAldo-keto reductase family 1 member B15
- GeneAKR1B15
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids316 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Isoform 1
Catalyzes the NADPH-dependent reduction of a variety of carbonyl substrates, like aromatic aldehydes, alkenals, ketones and alpha-dicarbonyl compounds (PubMed:21276782, PubMed:26222439).
In addition, catalyzes the reduction of androgens and estrogens with high positional selectivity (shows 17-beta-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoAs (PubMed:25577493).
Displays strong enzymatic activity toward all-trans-retinal and 9-cis-retinal (PubMed:26222439).
May play a physiological role in retinoid metabolism (PubMed:26222439).
In addition, catalyzes the reduction of androgens and estrogens with high positional selectivity (shows 17-beta-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoAs (PubMed:25577493).
Displays strong enzymatic activity toward all-trans-retinal and 9-cis-retinal (PubMed:26222439).
May play a physiological role in retinoid metabolism (PubMed:26222439).
Isoform 2
No oxidoreductase activity observed with the tested substrates.
Miscellaneous
Has no counterpart in murine species.
Catalytic activity
- 17beta-estradiol + NADP+ = estrone + H+ + NADPH
- 17beta-hydroxy-5alpha-androstan-3-one + NADP+ = 5alpha-androstan-3,17-dione + H+ + NADPH
- 3beta-hydroxyandrost-5-en-17-one + H+ + NADPH = androst-5-en-3beta,17beta-diol + NADP+
- androsterone + H+ + NADPH = 5alpha-androstane-3alpha,17beta-diol + NADP+
- 9-cis-retinol + NADP+ = 9-cis-retinal + H+ + NADPH
- (E)-hex-2-en-1-ol + NADP+ = (E)-hex-2-enal + H+ + NADPH
- NADP+ + nonan-2-one = (3E)-nonen-2-one + H+ + NADPH
- acetoin + NADP+ = diacetyl + H+ + NADPH
- (E)-4-hydroxynon-2-en-1-ol + NADP+ = (E)-4-hydroxynon-2-enal + H+ + NADPH
Activity regulation
Inhibited by the inhibitor JF0064.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.8 μM | androsterone | tested with isoform 1 in the reductive reaction | ||||
1.9 μM | delta-4-androstenedione | tested with isoform 1 in the reductive reaction | ||||
2.5 μM | estrone | tested with isoform 1 in the reductive reaction | ||||
63.4 μM | acetoacetyl-CoA | tested with isoform 1 in the reductive reaction | ||||
19.2 μM | 3-alpha,17-beta-androstandiol | tested with isoform 1 in the oxidative reaction | ||||
7.1 μM | testosterone | tested with isoform 1 in the oxidative reaction | ||||
9.1 μM | 17-beta-estradiol | tested with isoform 1 in the oxidative reaction | ||||
1 μM | all-trans-retinal | |||||
0.16 μM | 9-cis-retinal | |||||
880 μM | D,L-glyceraldehyde | |||||
2.9 μM | pyridine-3-aldehyde | |||||
3.1 μM | hexanal | |||||
36 μM | acrolein | |||||
5 μM | trans-2-hexenal | |||||
2.2 μM | 4-hydroxy-2-nonenal | |||||
1.7 μM | 3-nonen-2-one | |||||
1 μM | 2,3-butanedione | |||||
1 μM | farnesal | |||||
5.7 μM | NADPH |
kcat is 1.7 min-1 using isoform 1 for the reduction of androsterone. kcat is 1.1 min-1 using isoform 1 for the reduction of delta-4-androstenedione. kcat is 1.0 min-1 using isoform 1 for the reduction of estrone. kcat is 0.5 min-1 using isoform 1 for the reduction of acetoacetyl-CoA. kcat is 3.0 min-1 using isoform 1 for the oxidation of 3-alpha,17-beta-androstandiol. kcat is 0.6 min-1 using isoform 1 for the oxidation of testosterone. kcat is 0.5 min-1 using isoform 1 for the oxidation of 17-beta-estradiol (PubMed:25577493).
kcat is 10.7 min-1 with D,L-glyceraldehyde as substrate. kcat is 9 min-1 with pyridine-3-aldehyde as substrate. kcat is 7.3 min-1 with hexanal as substrate. kcat is 9 min-1 with acrolein as substrate. kcat is 11.3 min-1 with trans-2-hexenal as substrate. kcat is 5.2 min-1 with 4-hydroxy-2-nonenal as substrate. kcat is 4.8 min-1 with farnesal as substrate. kcat is 1.7 min-1 with 2,3-butanedione as substrate. kcat is 5.4 min-1 with all-trans-retinaldehyde as substrate. kcat is 3.8 min-1 with 9-cis-retinal as substrate (PubMed:26222439).
kcat is 10.7 min-1 with D,L-glyceraldehyde as substrate. kcat is 9 min-1 with pyridine-3-aldehyde as substrate. kcat is 7.3 min-1 with hexanal as substrate. kcat is 9 min-1 with acrolein as substrate. kcat is 11.3 min-1 with trans-2-hexenal as substrate. kcat is 5.2 min-1 with 4-hydroxy-2-nonenal as substrate. kcat is 4.8 min-1 with farnesal as substrate. kcat is 1.7 min-1 with 2,3-butanedione as substrate. kcat is 5.4 min-1 with all-trans-retinaldehyde as substrate. kcat is 3.8 min-1 with 9-cis-retinal as substrate (PubMed:26222439).
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 20-22 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: TWR | ||||||
Binding site | 44 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 49 | Proton donor | ||||
Sequence: Y | ||||||
Site | 78 | Lowers pKa of active site Tyr | ||||
Sequence: K | ||||||
Binding site | 111 | substrate | ||||
Sequence: H | ||||||
Binding site | 160-161 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SN | ||||||
Binding site | 184 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 210-217 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: YSPLGSPD | ||||||
Binding site | 261-273 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: IPKSMTPAHIVEN |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | aldose reductase (NADPH) activity | |
Molecular Function | all-trans-retinol dehydrogenase (NADP+) activity | |
Molecular Function | allyl-alcohol dehydrogenase activity | |
Molecular Function | estradiol 17-beta-dehydrogenase [NAD(P)+] activity | |
Molecular Function | farnesol dehydrogenase activity | |
Molecular Function | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | |
Molecular Function | testosterone 17-beta-dehydrogenase (NADP+) activity | |
Biological Process | estrogen biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameAldo-keto reductase family 1 member B15
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionC9JRZ8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
Isoform 2
Keywords
- Cellular component
Disease & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 419 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000395341 | 1-316 | UniProt | Aldo-keto reductase family 1 member B15 | |||
Sequence: MATFVELSTKAKMPIVGLGTWRSLLGKVKEAVKVAIDAEYRHIDCAYFYENQHEVGEAIQEKIQEKAVMREDLFIVSKVWPTFFERPLVRKAFEKTLKDLKLSYLDVYLIHWPQGFKTGDDFFPKDDKGNMISGKGTFLDAWEAMEELVDEGLVKALGVSNFNHFQIERLLNKPGLKYKPVTNQVECHPYLTQEKLIQYCHSKGITVTAYSPLGSPDRPWAKPEDPSLLEDPKIKEIAAKHKKTTAQVLIRFHIQRNVTVIPKSMTPAHIVENIQVFDFKLSDEEMATILSFNRNWRAFDFKEFSHLEDFPFDAEY | |||||||
Modified residue (large scale data) | 8 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 9 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 125 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 190 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 192 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 215 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 263 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Monomer.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | C9JRZ8 | AKR1B10 O60218 | 2 | EBI-51935374, EBI-1572139 | |
BINARY | C9JRZ8-2 | TRAF2 Q12933 | 3 | EBI-17190479, EBI-355744 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
C9JRZ8-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsAKR1B15.1
- Length316
- Mass (Da)36,537
- Last updated2015-04-01 v2
- Checksum5FB6CBFA7190C740
C9JRZ8-2
- Name2
- SynonymsAKR1B15.2
- Differences from canonical
- 1-22: MATFVELSTKAKMPIVGLGTWR → MVLQMEPQVNSTNNFHQGPLDQPVGPLTGLKSSLLKDTTSAGPLLRPYPA
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_041606 | 1-22 | in isoform 2 | |||
Sequence: MATFVELSTKAKMPIVGLGTWR → MVLQMEPQVNSTNNFHQGPLDQPVGPLTGLKSSLLKDTTSAGPLLRPYPA |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC078847 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471070 EMBL· GenBank· DDBJ | EAW83819.1 EMBL· GenBank· DDBJ | Genomic DNA |