Q95JH7 · AK1C1_MACFA
- ProteinAldo-keto reductase family 1 member C1
- GeneAKR1C1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids323 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids (PubMed:15618685).
Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (By similarity).
Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:15618685).
May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate. Displays affinity for bile acids (By similarity).
Can also act on non-steroidal substrates such as S-indan-1-ol, S-tetralol and 4-chromanol (PubMed:15618685).
Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH (By similarity).
Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens (PubMed:15618685).
May also reduce conjugated steroids such as 5alpha-dihydrotestosterone sulfate. Displays affinity for bile acids (By similarity).
Can also act on non-steroidal substrates such as S-indan-1-ol, S-tetralol and 4-chromanol (PubMed:15618685).
Catalytic activity
- a 3alpha-hydroxysteroid + NADP+ = a 3-oxosteroid + H+ + NADPH
- (20S)-hydroxypregn-4-en-3-one + NADP+ = H+ + NADPH + progesteroneThis reaction proceeds in the forward and the backward directions.
- (20S)-hydroxypregn-4-en-3-one + NAD+ = H+ + NADH + progesteroneThis reaction proceeds in the forward and the backward directions.
- 5alpha-androstane-3alpha,17beta-diol + NADP+ = 17beta-hydroxy-5alpha-androstan-3-one + H+ + NADPHThis reaction proceeds in the backward direction.
- 17beta-hydroxy-5alpha-androstan-3-one + NADP+ = 5alpha-androstan-3,17-dione + H+ + NADPHThis reaction proceeds in the backward direction.
- androsterone + H+ + NADPH = 5alpha-androstane-3alpha,17beta-diol + NADP+This reaction proceeds in the forward and the backward directions.
- 5alpha-androstane-3alpha,17beta-diol + NAD+ = androsterone + H+ + NADHThis reaction proceeds in the backward direction.
- 20alpha-hydroxy-5beta-pregnan-3-one + NADP+ = 5beta-pregnan-3,20-dione + H+ + NADPHThis reaction proceeds in the backward direction.
- 3beta-hydroxy-5beta-pregnane-20-one + NADP+ = 5beta-pregnan-3,20-dione + H+ + NADPHThis reaction proceeds in the backward direction.
- 3beta-hydroxy-5beta-pregnane-20-one + H+ + NADPH = 3beta,20alpha-dihydroxy-5beta-pregnane + NADP+This reaction proceeds in the forward direction.
- (3beta,5alpha,17beta)-3-hydroxyandrostan-17-yl sulfate + NADP+ = 5alpha-dihydrotestosterone sulfate + H+ + NADPHThis reaction proceeds in the backward direction.
Activity regulation
Potently inhibited by benzbromarone and 3',3'',5',5''-tetrabromophenolphthalein (TBPP).
Pathway
Steroid metabolism.
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 20-24 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: GFGTY | ||||||
Binding site | 24 | substrate | ||||
Sequence: Y | ||||||
Binding site | 50 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Site | 54 | Important for substrate specificity | ||||
Sequence: L | ||||||
Active site | 55 | Proton donor | ||||
Sequence: Y | ||||||
Site | 84 | Lowers pKa of active site Tyr | ||||
Sequence: K | ||||||
Binding site | 117 | substrate | ||||
Sequence: H | ||||||
Binding site | 166-167 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SN | ||||||
Binding site | 190 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 216-222 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: FSALGSH | ||||||
Binding site | 222 | substrate | ||||
Sequence: H | ||||||
Binding site | 227 | substrate | ||||
Sequence: W | ||||||
Binding site | 270-280 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: KSYNEQRIREN |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAldo-keto reductase family 1 member C1
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionQ95JH7
Proteomes
Subcellular Location
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000124634 | 1-323 | Aldo-keto reductase family 1 member C1 | |||
Sequence: MDSKHQCVKLNDGHFMPVLGFGTYAPAEVPKNKALEATKLAIEAGFRHIDSAHLYNNEEYVGLAIRSKIADGTVKREDIFYTSKLWCNSHRPEFVRPALERSLKNLQLDYVDLYLIHFPVSLKPGEELIPKDENGKLLFDTVDLCATWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYLNQRKLLDFCKSKDIVLVAFSALGSHREKPWVDQNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRENMKVFEFQLTSEDMKAIDGLDRNIRYLTLDIFAGPPNYPFSDEY |
Interaction
Structure
Sequence
- Sequence statusComplete
- Length323
- Mass (Da)36,947
- Last updated2001-12-01 v1
- ChecksumD632ACC1C65D3744
Keywords
- Technical term