Names & Taxonomy

Uniprot ID:
P42330
Entry Name:
AK1C3_HUMAN
Status:
reviewed
Protein Names:
Aldo-keto reductase family 1 member C3 (EC 1.-.-.-) (17-beta-hydroxysteroid dehydrogenase type 5) (17-beta-HSD 5) (3-alpha-HSD type II, brain) (3-alpha-hydroxysteroid dehydrogenase type 2) (3-alpha-HSD type 2) (EC 1.1.1.357) (Chlordecone reductase homolog HAKRb) (Dihydrodiol dehydrogenase 3) (DD-3) (DD3) (Dihydrodiol dehydrogenase type I) (HA1753) (Indanol dehydrogenase) (EC 1.1.1.112) (Prostaglandin F synthase) (PGFS) (EC 1.1.1.188) (Testosterone 17-beta-dehydrogenase 5) (EC 1.1.1.239) (EC 1.1.1.64) (Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase) (EC 1.3.1.20)
Gene Names:
AKR1C3 DDH1 HSD17B5 KIAA0119 PGFS
Gene Names Primary:
AKR1C3
Organism:
Homo sapiens (Human)

Structure

Length:
323
Sequence:
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPMSLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLDRNLHYFNSDSFASHPNYPYSDEY
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm.

Function

Function:
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.
Catalytic Activity:
Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol + NADPH.; A 3-alpha-hydroxysteroid + NAD(P)(+) = a 3-oxosteroid + NAD(P)H.
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=142.1 uM for progesterone
Enzyme Regulation:
ENZYME REGULATION: 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).
Active Site:
ACT_SITE 55 55 Proton donor.
Cross Reference Drug Bank:
DB00905 DB00997
Gene Ontology Go:
cytoplasm
cytosol
extracellular exosome
intracellular
nucleus
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
alditol:NADP+ 1-oxidoreductase activity
aldo-keto reductase (NADP) activity
androsterone dehydrogenase activity
delta4-3-oxosteroid 5beta-reductase activity
dihydrotestosterone 17-beta-dehydrogenase activity
geranylgeranyl reductase activity
indanol dehydrogenase activity
ketoreductase activity
ketosteroid monooxygenase activity
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
phenanthrene 9,10-monooxygenase activity
prostaglandin D2 11-ketoreductase activity
prostaglandin-F synthase activity
retinal dehydrogenase activity
retinol dehydrogenase activity
testosterone 17-beta-dehydrogenase (NADP+) activity
testosterone dehydrogenase (NAD+) activity
trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
arachidonic acid metabolic process
cellular response to cadmium ion
cellular response to calcium ion
cellular response to corticosteroid stimulus
cellular response to jasmonic acid stimulus
cellular response to prostaglandin D stimulus
cellular response to prostaglandin stimulus
cellular response to reactive oxygen species
cellular response to starvation
cyclooxygenase pathway
daunorubicin metabolic process
doxorubicin metabolic process
farnesol catabolic process
fat-soluble vitamin metabolic process
G-protein coupled receptor signaling pathway
keratinocyte differentiation
male gonad development
multicellular organismal macromolecule metabolic process
negative regulation of retinoic acid biosynthetic process
oxidation-reduction process
phototransduction, visible light
positive regulation of cell death
positive regulation of cell proliferation
positive regulation of endothelial cell apoptotic process
positive regulation of protein kinase B signaling
positive regulation of reactive oxygen species metabolic process
progesterone metabolic process
prostaglandin metabolic process
protein import into nucleus, translocation
regulation of retinoic acid receptor signaling pathway
regulation of testosterone biosynthetic process
renal absorption
response to nutrient
retinal metabolic process
retinoid metabolic process
small molecule metabolic process
steroid metabolic process
testosterone biosynthetic process
vitamin metabolic process
Gene Ontology Biological Process:
arachidonic acid metabolic process
cellular response to cadmium ion
cellular response to calcium ion
cellular response to corticosteroid stimulus
cellular response to jasmonic acid stimulus
cellular response to prostaglandin D stimulus
cellular response to prostaglandin stimulus
cellular response to reactive oxygen species
cellular response to starvation
cyclooxygenase pathway
daunorubicin metabolic process
doxorubicin metabolic process
farnesol catabolic process
fat-soluble vitamin metabolic process
G-protein coupled receptor signaling pathway
keratinocyte differentiation
male gonad development
multicellular organismal macromolecule metabolic process
negative regulation of retinoic acid biosynthetic process
oxidation-reduction process
phototransduction, visible light
positive regulation of cell death
positive regulation of cell proliferation
positive regulation of endothelial cell apoptotic process
positive regulation of protein kinase B signaling
positive regulation of reactive oxygen species metabolic process
progesterone metabolic process
prostaglandin metabolic process
protein import into nucleus, translocation
regulation of retinoic acid receptor signaling pathway
regulation of testosterone biosynthetic process
renal absorption
response to nutrient
retinal metabolic process
retinoid metabolic process
small molecule metabolic process
steroid metabolic process
testosterone biosynthetic process
vitamin metabolic process
Gene Ontology Molecular Function:
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
alditol:NADP+ 1-oxidoreductase activity
aldo-keto reductase (NADP) activity
androsterone dehydrogenase activity
delta4-3-oxosteroid 5beta-reductase activity
dihydrotestosterone 17-beta-dehydrogenase activity
geranylgeranyl reductase activity
indanol dehydrogenase activity
ketoreductase activity
ketosteroid monooxygenase activity
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
phenanthrene 9,10-monooxygenase activity
prostaglandin D2 11-ketoreductase activity
prostaglandin-F synthase activity
retinal dehydrogenase activity
retinol dehydrogenase activity
testosterone 17-beta-dehydrogenase (NADP+) activity
testosterone dehydrogenase (NAD+) activity
trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Gene Ontology Cellular Component:
cytoplasm
cytosol
extracellular exosome
intracellular
nucleus
Keywords:
3D-structure
Alternative splicing
Complete proteome
Cytoplasm
NAD
NADP
Oxidoreductase
Polymorphism
Reference proteome

Publication

PubMed ID:
8274401 7650035 7626489 9415401 10622721 10557352 10672042 11165022 7788527 14702039 15164054 15489334 9927279 21269460 24275569 14979715 14996743 15087468