Aldo-keto reductase family 1 member C3

Details

Name
Aldo-keto reductase family 1 member C3
Synonyms
  • 1.-.-.-
  • 17-beta-HSD 5
  • 17-beta-hydroxysteroid dehydrogenase type 5
  • 3-alpha-HSD type 2
  • 3-alpha-HSD type II, brain
  • 3-alpha-hydroxysteroid dehydrogenase type 2
  • Chlordecone reductase homolog HAKRb
  • DD-3
  • DD3
  • DDH1
  • Dihydrodiol dehydrogenase 3
  • Dihydrodiol dehydrogenase type I
  • HA1753
  • HSD17B5
  • Indanol dehydrogenase
  • KIAA0119
  • PGFS
  • Prostaglandin F synthase
  • Testosterone 17-beta-dehydrogenase 5
  • Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
Gene Name
AKR1C3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037052|Aldo-keto reductase family 1 member C3
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY
Number of residues
323
Molecular Weight
36852.89
Theoretical pI
8.06
GO Classification
Functions
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / alditol / 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
Processes
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 / 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
Components
cytoplasm / cytosol / extracellular exosome / intracellular / nucleus
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0018982|Aldo-keto reductase family 1 member C3 (AKR1C3)
ATGGATTCAAAACATCAGTGTTTGAAGCTAAATGATGGTCACTTCATGCCTGTCCTGGGA
TTTGGCACCTATGCACCTCCAGAGGTTCCGAGAAGTAAAGCTTTGGAGGTCACAAAATTA
GCAATAGAAGCTGGGTTCCGCCATATAGATTCTGCTCATTTATACAATAATGAGGAGCAG
GTTGGACTGGCCATCCGAAGCAAGATTGCAGATGGCAGTGTGAAGAGAGAAGACATATTC
TACACTTCAAAGCTTTGGTCCACTTTTCATCGACCAGAGTTGGTCCGACCAGCCTTGGAA
AACTCACTGAAGAAAGCTCAATTGGACTATGTTGACCTCTATCTTATTCATTCTCCAATG
TCTCTAAAGCCAGGTGAGGAACTTTCACCAACAGATGAAAATGGAAAAGTAATATTTGAC
ATAGTGGATCTCTGTACCACCTGGGAGGCCATGGAGAAGTGTAAGGATGCAGGATTGGCC
AAGTCCATTGGGGTGTCAAACTTCAACCGCAGGCAGCTGGAGATGATCCTCAACAAGCCA
GGACTCAAGTACAAGCCTGTCTGCAACCAGGTAGAATGTCATCCGTATTTCAACCGGAGT
AAATTGCTAGATTTCTGCAAGTCGAAAGATATTGTTCTGGTTGCCTATAGTGCTCTGGGA
TCTCAACGAGACAAACGATGGGTGGACCCGAACTCCCCGGTGCTCTTGGAGGACCCAGTC
CTTTGTGCCTTGGCAAAAAAGCACAAGCGAACCCCAGCCCTGATTGCCCTGCGCTACCAG
CTGCAGCGTGGGGTTGTGGTCCTGGCCAAGAGCTACAATGAGCAGCGCATCAGACAGAAC
GTGCAGGTTTTTGAGTTCCAGTTGACTGCAGAGGACATGAAAGCCATAGATGGCCTAGAC
AGAAATCTCCACTATTTTAACAGTGATAGTTTTGCTAGCCACCCTAATTATCCATATTCA
GATGAATATTAA
Chromosome Location
10
Locus
10p15-p14
External Identifiers
ResourceLink
UniProtKB IDP42330
UniProtKB Entry NameAK1C3_HUMAN
GenBank Protein ID4261711
GenBank Gene IDS68288
GenAtlas IDAKR1C3
HGNC IDHGNC:386
General References
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  3. Khanna M, Qin KN, Cheng KC: Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):41-6. [PubMed:7626489]
  4. Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA, Penning TM: Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution. Mol Endocrinol. 1997 Dec;11(13):1971-84. [PubMed:9415401]
  5. Suzuki-Yamamoto T, Nishizawa M, Fukui M, Okuda-Ashitaka E, Nakajima T, Ito S, Watanabe K: cDNA cloning, expression and characterization of human prostaglandin F synthase. FEBS Lett. 1999 Dec 3;462(3):335-40. [PubMed:10622721]
  6. Griffin LD, Mellon SH: Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13512-7. [PubMed:10557352]
  7. Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S: Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes. Genes Cells. 2000 Feb;5(2):111-25. [PubMed:10672042]
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  11. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [PubMed:15164054]
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  13. Dufort I, Rheault P, Huang XF, Soucy P, Luu-The V: Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase. Endocrinology. 1999 Feb;140(2):568-74. [PubMed:9927279]
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  17. Lovering AL, Ride JP, Bunce CM, Desmond JC, Cummings SM, White SA: Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin. Cancer Res. 2004 Mar 1;64(5):1802-10. [PubMed:14996743]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB01698Rutinapproved, experimental, investigationalunknownDetails
DB02056Prostaglandin D2investigationalunknownDetails
DB02266Flufenamic acidapprovedunknownDetails
DB01536Androstenedioneexperimental, illicitunknowninducerDetails
DB034612'-Monophosphoadenosine 5'-DiphosphoriboseexperimentalunknownDetails
DB077003-CARBOXAMIDO-1,3,5(10)-ESTRATRIEN-17(R)-SPIRO-2'(5',5'-DIMETHYL-6'OXO)TETRAHYDROPYRANexperimentalunknownDetails
DB00997Doxorubicinapproved, investigationalunknownsubstrateDetails
DB00328Indomethacinapproved, investigationalunknowninhibitorDetails
DB13751Glycyrrhizic acidapproved, experimentalnosubstrateDetails
DB01039FenofibrateapprovedunknownsubstrateDetails
DB00776OxcarbazepineapprovedunknownsubstrateDetails