AKR1C3 - Aldo-keto reductase family 1 member C3 - human protein (Function)
 
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AKR1C3 »  Aldo-keto reductase family 1 member C3   [ EC 1.-.-.- ]
 
Protein also known as:  Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase [EC 1.3.1.20].
Gene name:  AKR1C3
Family name: Aldo/keto reductase
Entry whose protein(s) existence is based on evidence at protein level
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1 92 1
GENE REF ISO

Function

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Overview 
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.  
  • CuratedUniProtKB
GO molecular function 
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activitydefinition[GO:0047020]  
1
  • IDAUniProtKB
Alditol:NADP+ 1-oxidoreductase activitydefinition[GO:0004032]  
1
  • IDAUniProtKB
Aldo-keto reductase (NADP) activitydefinition[GO:0004033]  
1
  • TASUniProtKB
Androsterone dehydrogenase activitydefinition[GO:0047023]  
1
  • IDAUniProtKB
Delta4-3-oxosteroid 5beta-reductase activitydefinition[GO:0047787]  
1
  • IDAUniProtKB
Dihydrotestosterone 17-beta-dehydrogenase activitydefinition[GO:0035410]  
1
  • IDAUniProtKB
Geranylgeranyl reductase activitydefinition[GO:0045550]  
1
  • IDAUniProtKB
Indanol dehydrogenase activitydefinition[GO:0047718]  
  • IEAEC 2 GO
Ketoreductase activitydefinition[GO:0045703]  
1
  • IDAUniProtKB
Ketosteroid monooxygenase activitydefinition[GO:0047086]  
1
  • IDAUniProtKB
Oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptordefinition[GO:0016655]  
2
  • IDAUniProtKB
Phenanthrene 9,10-monooxygenase activitydefinition[GO:0018636]  
1
  • IDAUniProtKB
Prostaglandin D2 11-ketoreductase activitydefinition[GO:0036131]  
  • IEAEC 2 GO
Prostaglandin F receptor activitydefinition[GO:0004958]  
1
  • IDAUniProtKB
Prostaglandin-F synthase activitydefinition[GO:0047017]  
  • IEAEC 2 GO
Retinal dehydrogenase activitydefinition[GO:0001758]  
1
  • IDAUniProtKB
Retinol dehydrogenase activitydefinition[GO:0004745]  
1
  • IDAUniProtKB
Testosterone 17-beta-dehydrogenase (NADP+) activitydefinition[GO:0047045]  
  • IEAEC 2 GO
Testosterone dehydrogenase (NAD+) activitydefinition[GO:0047035]  
  • IEAEC 2 GO
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activitydefinition[GO:0047115]  
  • IEAEC 2 GO
GO biological process 
Cellular response to cadmium iondefinition[GO:0071276]  
1
  • IDAUniProtKB
Cellular response to calcium iondefinition[GO:0071277]  
1
  • IDAUniProtKB
Cellular response to corticosteroid stimulusdefinition[GO:0071384]  
1
  • IDAUniProtKB
Cellular response to jasmonic acid stimulusdefinition[GO:0071395]  
1
  • IDAUniProtKB
Cellular response to prostaglandin stimulusdefinition[GO:0071379]  
1
  • IDAUniProtKB
Cellular response to reactive oxygen speciesdefinition[GO:0034614]  
1
  • IDAUniProtKB
Cellular response to starvationdefinition[GO:0009267]  
1
  • IEPUniProtKB
Daunorubicin metabolic processdefinition[GO:0044597]  
1
  • IMPUniProtKB
Doxorubicin metabolic processdefinition[GO:0044598]  
1
  • IMPUniProtKB
Farnesol catabolic processdefinition[GO:0016488]  
1
  • IDAUniProtKB
G-protein coupled receptor signaling pathwaydefinition[GO:0007186]  
1
  • IDAUniProtKB
Keratinocyte differentiationdefinition[GO:0030216]  
1
  • IEPUniProtKB
Male gonad developmentdefinition[GO:0008584]  
1
  • IEPUniProtKB
Multicellular organismal macromolecule metabolic processdefinition[GO:0044259]  
1
  • IEPUniProtKB
Negative regulation of retinoic acid biosynthetic processdefinition[GO:1900053]  
1
  • IDAUniProtKB
Oxidation-reduction processdefinition[GO:0055114]  
4
  • IDAUniProtKB
Positive regulation of cell deathdefinition[GO:0010942]  
1
  • IDAUniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
3
  • IMPUniProtKB
Positive regulation of endothelial cell apoptotic processdefinition[GO:2000353]  
1
  • IDAUniProtKB
Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
1
  • IDAUniProtKB
Positive regulation of reactive oxygen species metabolic processdefinition[GO:2000379]  
1
  • IDAUniProtKB
Progesterone metabolic processdefinition[GO:0042448]  
1
  • IDAUniProtKB
Prostaglandin metabolic processdefinition[GO:0006693]  
2
  • IEPUniProtKB
Protein import into nucleus, translocationdefinition[GO:0000060]  
1
  • IDAUniProtKB
Regulation of retinoic acid receptor signaling pathwaydefinition[GO:0048385]  
1
  • IDAUniProtKB
Regulation of testosterone biosynthetic processdefinition[GO:2000224]  
1
  • IMPUniProtKB
Renal absorptiondefinition[GO:0070293]  
1
  • NASUniProtKB
Response to nutrientdefinition[GO:0007584]  
1
  • IEPUniProtKB
Response to prostaglandindefinition[GO:0034694]  
1
  • IDAUniProtKB
Retinal metabolic processdefinition[GO:0042574]  
1
  • IDAUniProtKB
Steroid metabolic processdefinition[GO:0008202]  
1
  • IEPUniProtKB
Testosterone biosynthetic processdefinition[GO:0061370]  
1
  • IMPUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 1.3.1.20: Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) catechol + NADPH.  
  • CuratedUniProtKB
EC 1.1.1.357: A 3-alpha-hydroxysteroid + NAD(P)(+) a 3-oxosteroid + NAD(P)H.  
  • CuratedUniProtKB
EC 1.1.1.188: (5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP(+) (5Z,13E)-(15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH.  
  • CuratedUniProtKB
EC 1.1.1.239: Testosterone + NAD(+) androstenedione + NADH.  
  • CuratedUniProtKB
EC 1.1.1.64: Testosterone + NADP(+) androst-4-ene-3,17-dione + NADPH.  
  • CuratedUniProtKB
EC 1.1.1.112: Indan-1-ol + NAD(P)(+) indanone + NAD(P)H.  
  • CuratedUniProtKB
It is regulated in the following manner
Strongly inhibited by nonsteroidal anti-inflammatory drugs (NSAID) including flufenamic acid and indomethacin. Also inhibited by the flavinoid, rutin, and by selective serotonin inhibitors (SSRIs).  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Arachidonic acid metabolism  hsa00590+8644  
Metabolism of xenobiotics by cytochrome P450  hsa00980+8644  
Steroid hormone biosynthesis  hsa00140+8644  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Metabolism  REACT_111217  
Signal Transduction  REACT_111102  
 

Biophysicochemical properties

Kinetic parameters
KM 142.1 uM for progesterone
KM 2.37 uM for 5-alpha-dihydrotestosterone
KM 1.0 uM for androstanediol
Vmax 20.1 nmol/min/mg enzyme with progesterone as substrate
Vmax 4.4 nmol/min/mg enzyme with androstanediol as substrate
Vmax 1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as substrate

Keywords

Molecular function 
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: P42330
Other
GeneWiki: AKR1C3
GenomeRNAi: 8644
PRO: PR:P42330