Gene/Proteome Database (LMPD)

LMPD ID
LMP006772
Gene ID
8644
Species
Homo sapiens (Human)
Gene Name
aldo-keto reductase family 1, member C3
Gene Symbol
AKR1C3
Synonyms
DD3; DDX; HA1753; HAKRB; HAKRe; HSD17B5; PGFS; hluPGFS
Chromosome
10
Map Location
10p15-p14
EC Number
1.-.-.-
Summary
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
Orthologs
View orthologs and multiple alignments for AKR1C3

Proteins

aldo-keto reductase family 1 member C3 isoform 1
Refseq ID NP_003730
Protein GI 24497583
UniProt ID P42330
mRNA ID NM_003739
Length 323
RefSeq Status REVIEWED
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPMSLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLDRNLHYFNSDSFASHPNYPYSDEY
aldo-keto reductase family 1 member C3 isoform 2
Refseq ID NP_001240837
Protein GI 359806990
UniProt ID P42330
mRNA ID NM_001253908
Length 323
RefSeq Status REVIEWED
MDSKHQCLKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPMSLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLDRNLHYFNSDSFASHPNYPYSDEY
aldo-keto reductase family 1 member C3 isoform 3
Refseq ID NP_001240838
Protein GI 359806998
UniProt ID B4DKT3
mRNA ID NM_001253909
Length 138
RefSeq Status REVIEWED
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPMSLKVCSLYEHKIALLLSL

Gene Information

Entrez Gene ID
8644
Gene Name
aldo-keto reductase family 1, member C3
Gene Symbol
AKR1C3
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0005829 TAS:Reactome C cytosol
GO:0070062 IDA:UniProtKB C extracellular vesicular exosome
GO:0005622 IDA:LIFEdb C intracellular
GO:0005634 IDA:UniProtKB C nucleus
GO:0047020 IDA:UniProtKB F 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
GO:0004032 IDA:UniProtKB F alditol:NADP+ 1-oxidoreductase activity
GO:0004033 TAS:UniProtKB F aldo-keto reductase (NADP) activity
GO:0047023 IDA:UniProtKB F androsterone dehydrogenase activity
GO:0047787 IDA:UniProtKB F delta4-3-oxosteroid 5beta-reductase activity
GO:0035410 IDA:UniProtKB F dihydrotestosterone 17-beta-dehydrogenase activity
GO:0045550 IDA:UniProtKB F geranylgeranyl reductase activity
GO:0047718 IEA:UniProtKB-EC F indanol dehydrogenase activity
GO:0045703 IDA:UniProtKB F ketoreductase activity
GO:0047086 IDA:UniProtKB F ketosteroid monooxygenase activity
GO:0016655 IDA:UniProtKB F oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
GO:0018636 IDA:UniProtKB F phenanthrene 9,10-monooxygenase activity
GO:0036131 IEA:UniProtKB-EC F prostaglandin D2 11-ketoreductase activity
GO:0004958 IDA:UniProtKB F prostaglandin F receptor activity
GO:0047017 IEA:UniProtKB-EC F prostaglandin-F synthase activity
GO:0001758 IDA:UniProtKB F retinal dehydrogenase activity
GO:0004745 IDA:UniProtKB F retinol dehydrogenase activity
GO:0047045 IEA:UniProtKB-EC F testosterone 17-beta-dehydrogenase (NADP+) activity
GO:0047035 IEA:UniProtKB-EC F testosterone dehydrogenase (NAD+) activity
GO:0047115 IEA:UniProtKB-EC F trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
GO:0007186 IDA:UniProtKB P G-protein coupled receptor signaling pathway
GO:0019369 TAS:Reactome P arachidonic acid metabolic process
GO:0071276 IDA:UniProtKB P cellular response to cadmium ion
GO:0071277 IDA:UniProtKB P cellular response to calcium ion
GO:0071384 IDA:UniProtKB P cellular response to corticosteroid stimulus
GO:0071395 IDA:UniProtKB P cellular response to jasmonic acid stimulus
GO:0071379 IDA:UniProtKB P cellular response to prostaglandin stimulus
GO:0034614 IDA:UniProtKB P cellular response to reactive oxygen species
GO:0009267 IEP:UniProtKB P cellular response to starvation
GO:0019371 TAS:Reactome P cyclooxygenase pathway
GO:0044597 IMP:UniProtKB P daunorubicin metabolic process
GO:0044598 IMP:UniProtKB P doxorubicin metabolic process
GO:0016488 IDA:UniProtKB P farnesol catabolic process
GO:0030216 IEP:UniProtKB P keratinocyte differentiation
GO:0008584 IEP:UniProtKB P male gonad development
GO:0044259 IEP:UniProtKB P multicellular organismal macromolecule metabolic process
GO:1900053 IDA:UniProtKB P negative regulation of retinoic acid biosynthetic process
GO:0055114 IDA:UniProtKB P oxidation-reduction process
GO:0007603 TAS:Reactome P phototransduction, visible light
GO:0010942 IDA:UniProtKB P positive regulation of cell death
GO:0008284 IDA:UniProtKB P positive regulation of cell proliferation
GO:2000353 IDA:UniProtKB P positive regulation of endothelial cell apoptotic process
GO:0051897 IDA:UniProtKB P positive regulation of protein kinase B signaling
GO:2000379 IDA:UniProtKB P positive regulation of reactive oxygen species metabolic process
GO:0042448 IDA:UniProtKB P progesterone metabolic process
GO:0006693 IEP:UniProtKB P prostaglandin metabolic process
GO:0000060 IDA:UniProtKB P protein import into nucleus, translocation
GO:0048385 IDA:UniProtKB P regulation of retinoic acid receptor signaling pathway
GO:2000224 IMP:UniProtKB P regulation of testosterone biosynthetic process
GO:0070293 NAS:UniProtKB P renal absorption
GO:0007584 IEP:UniProtKB P response to nutrient
GO:0034694 IDA:UniProtKB P response to prostaglandin
GO:0042574 IDA:UniProtKB P retinal metabolic process
GO:0001523 TAS:Reactome P retinoid metabolic process
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0008202 IEP:UniProtKB P steroid metabolic process
GO:0061370 IMP:UniProtKB P testosterone biosynthetic process

KEGG Pathway Links

KEGG Pathway ID Description
hsa04913 Ovarian steroidogenesis
hsa00140 Steroid hormone biosynthesis

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_150149 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

Domain Information

InterPro Annotations

Accession Description
IPR001395 Aldo/keto reductase
IPR020471 Aldo/keto reductase subgroup
IPR018170 Aldo/keto reductase, conserved site
IPR023210 NADP-dependent oxidoreductase domain

UniProt Annotations

Entry Information

Gene Name
aldo-keto reductase family 1, member C3
Protein Entry
AK1C3_HUMAN
UniProt ID
P42330
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P42330-1; Sequence=Displayed; Name=2; IsoId=P42330-2; Sequence=VSP_055798; Note=No experimental confirmation available.;
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=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as substrate ; Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate ;
Catalytic Activity (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.
Catalytic Activity A 3-alpha-hydroxysteroid + NAD(P)(+) = a 3- oxosteroid + NAD(P)H.
Catalytic Activity Indan-1-ol + NAD(P)(+) = indanone + NAD(P)H.
Catalytic Activity Testosterone + NAD(+) = androstenedione + NADH.
Catalytic Activity Testosterone + NADP(+) = androst-4-ene-3,17- dione + NADPH.
Catalytic Activity Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol + NADPH.
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).
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.
Sequence Caution Sequence=BAA04619.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ;
Similarity Belongs to the aldo/keto reductase family.
Subcellular Location Cytoplasm.
Tissue Specificity Expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. The dominant HSD in prostate and mammary gland. In the prostate, higher levels in epithelial cells than in stromal cells. In the brain, expressed in medulla, spinal cord, frontotemporal lobes, thalamus, subthalamic nuclei and amygdala. Weaker expression in the hippocampus, substantia nigra and caudate. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AKR1C3ID612ch10p15.html";

Identical and Related Proteins

Unique RefSeq proteins for LMP006772 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
24497583 RefSeq NP_003730 323 aldo-keto reductase family 1 member C3 isoform 1
359806990 RefSeq NP_001240837 323 aldo-keto reductase family 1 member C3 isoform 2
359806998 RefSeq NP_001240838 138 aldo-keto reductase family 1 member C3 isoform 3

Identical Sequences to LMP006772 proteins

Reference Database Accession Length Protein Name
GI:24497583 DBBJ BAF83054.1 323 unnamed protein product [Homo sapiens]
GI:359806998 DBBJ BAG59295.1 138 unnamed protein product [Homo sapiens]
GI:24497583 GenBank ABM84786.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II), partial [synthetic construct]
GI:24497583 GenBank ACT64585.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) protein, partial [synthetic construct]
GI:24497583 GenBank AIC50170.1 323 AKR1C3, partial [synthetic construct]
GI:24497583 GenBank AIC55449.1 323 AKR1C3, partial [synthetic construct]
GI:24497583 SwissProt P42330.4 323 RecName: Full=Aldo-keto reductase family 1 member C3; AltName: Full=17-beta-hydroxysteroid dehydrogenase type 5; Short=17-beta-HSD 5; AltName: Full=3-alpha-HSD type II, brain; AltName: Full=3-alpha-hydroxysteroid dehydrogenase type 2; Short=3-alpha-HSD type 2; AltName: Full=Chlordecone reductase homolog HAKRb; AltName: Full=Dihydrodiol dehydrogenase 3; Short=DD-3; Short=DD3; AltName: Full=Dihydrodiol dehydrogenase type I; AltName: Full=HA1753; AltName: Full=Indanol dehydrogenase; AltName: Full=Prostaglandin F synthase; Short=PGFS; AltName: Full=Testosterone 17-beta-dehydrogenase 5; AltName: Full=Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase [Homo sapiens]

Related Sequences to LMP006772 proteins

Reference Database Accession Length Protein Name
GI:359806998 GenBank AAH01479.1 323 Aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) [Homo sapiens]
GI:359806990 GenBank AAH01479.1 323 Aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) [Homo sapiens]
GI:359806998 GenBank AAP35950.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) [Homo sapiens]
GI:359806990 GenBank AAP35950.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) [Homo sapiens]
GI:24497583 GenBank AAP36169.1 324 Homo sapiens aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II), partial [synthetic construct]
GI:24497583 GenBank AAX29580.1 324 aldo-keto reductase family 1 member C3, partial [synthetic construct]
GI:24497583 GenBank AAX29581.1 324 aldo-keto reductase family 1 member C3, partial [synthetic construct]
GI:359806990 GenBank ABM81605.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) [synthetic construct]
GI:359806998 GenBank ABM81605.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) [synthetic construct]
GI:359806990 GenBank ABM84786.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II), partial [synthetic construct]
GI:359806998 GenBank ABM84786.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II), partial [synthetic construct]
GI:359806998 GenBank ACT64585.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) protein, partial [synthetic construct]
GI:359806990 GenBank ACT64585.1 323 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II) protein, partial [synthetic construct]
GI:24497583 PDB 3R58 331 Chain A, Akr1c3 Complex With Naproxen
GI:24497583 PDB 3R6I 331 Chain A, Akr1c3 Complex With Meclofenamic Acid
GI:24497583 PDB 3R7M 331 Chain A, Akr1c3 Complex With Sulindac
GI:359806998 RefSeq NP_003730.4 323 aldo-keto reductase family 1 member C3 isoform 1 [Homo sapiens]
GI:359806990 RefSeq NP_003730.4 323 aldo-keto reductase family 1 member C3 isoform 1 [Homo sapiens]