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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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.  
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GO molecular function 
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activitydefinition[GO:0047020]  
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Alditol:NADP+ 1-oxidoreductase activitydefinition[GO:0004032]  
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  • UniProtKB
Aldo-keto reductase (NADP) activitydefinition[GO:0004033]  
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  • UniProtKB
Androsterone dehydrogenase activitydefinition[GO:0047023]  
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  • UniProtKB
Delta4-3-oxosteroid 5beta-reductase activitydefinition[GO:0047787]  
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Dihydrotestosterone 17-beta-dehydrogenase activitydefinition[GO:0035410]  
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Geranylgeranyl reductase activitydefinition[GO:0045550]  
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Indanol dehydrogenase activitydefinition[GO:0047718]  
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  • EC 2 GO
Ketoreductase activitydefinition[GO:0045703]  
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Ketosteroid monooxygenase activitydefinition[GO:0047086]  
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Oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptordefinition[GO:0016655]  
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Phenanthrene 9,10-monooxygenase activitydefinition[GO:0018636]  
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Prostaglandin D2 11-ketoreductase activitydefinition[GO:0036131]  
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  • EC 2 GO
Prostaglandin-F synthase activitydefinition[GO:0047017]  
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  • EC 2 GO
Retinal dehydrogenase activitydefinition[GO:0001758]  
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Retinol dehydrogenase activitydefinition[GO:0004745]  
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Testosterone 17-beta-dehydrogenase (NADP+) activitydefinition[GO:0047045]  
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  • EC 2 GO
Testosterone dehydrogenase (NAD+) activitydefinition[GO:0047035]  
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  • EC 2 GO
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activitydefinition[GO:0047115]  
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  • EC 2 GO
GO biological process 
Cellular response to cadmium iondefinition[GO:0071276]  
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Cellular response to calcium iondefinition[GO:0071277]  
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Cellular response to corticosteroid stimulusdefinition[GO:0071384]  
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Cellular response to jasmonic acid stimulusdefinition[GO:0071395]  
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Cellular response to prostaglandin D stimulusdefinition[GO:0071799]  
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Cellular response to prostaglandin stimulusdefinition[GO:0071379]  
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Cellular response to reactive oxygen speciesdefinition[GO:0034614]  
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Cellular response to starvationdefinition[GO:0009267]  
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Daunorubicin metabolic processdefinition[GO:0044597]  
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Doxorubicin metabolic processdefinition[GO:0044598]  
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Farnesol catabolic processdefinition[GO:0016488]  
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G-protein coupled receptor signaling pathwaydefinition[GO:0007186]  
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Keratinocyte differentiationdefinition[GO:0030216]  
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Male gonad developmentdefinition[GO:0008584]  
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Multicellular organismal macromolecule metabolic processdefinition[GO:0044259]  
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Negative regulation of retinoic acid biosynthetic processdefinition[GO:1900053]  
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Oxidation-reduction processdefinition[GO:0055114]  
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Positive regulation of cell deathdefinition[GO:0010942]  
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Positive regulation of cell proliferationdefinition[GO:0008284]  
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Positive regulation of endothelial cell apoptotic processdefinition[GO:2000353]  
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Positive regulation of protein kinase B signalingdefinition[GO:0051897]  
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Positive regulation of reactive oxygen species metabolic processdefinition[GO:2000379]  
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Progesterone metabolic processdefinition[GO:0042448]  
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Prostaglandin metabolic processdefinition[GO:0006693]  
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Protein import into nucleus, translocationdefinition[GO:0000060]  
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Regulation of retinoic acid receptor signaling pathwaydefinition[GO:0048385]  
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Regulation of testosterone biosynthetic processdefinition[GO:2000224]  
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Renal absorptiondefinition[GO:0070293]  
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Response to nutrientdefinition[GO:0007584]  
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Retinal metabolic processdefinition[GO:0042574]  
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Steroid metabolic processdefinition[GO:0008202]  
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Testosterone biosynthetic processdefinition[GO:0061370]  
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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.  
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EC 1.1.1.357: A 3-alpha-hydroxysteroid + NAD(P)(+) a 3-oxosteroid + NAD(P)H.  
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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.  
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EC 1.1.1.239: Testosterone + NAD(+) androstenedione + NADH.  
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EC 1.1.1.64: Testosterone + NADP(+) androst-4-ene-3,17-dione + NADPH.  
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EC 1.1.1.112: Indan-1-ol + NAD(P)(+) indanone + NAD(P)H.  
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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).  
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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:
Retinoid metabolism and transport  REACT_24968  
Synthesis of bile acids and bile salts via 24-hydroxycholesterol  REACT_11053  
Synthesis of bile acids and bile salts via 27-hydroxycholesterol  REACT_11048  
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol  REACT_11041  
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)  REACT_150149  
 

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