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Database: UniProt
Entry: P42330
LinkDB: P42330
Original site: P42330 
ID   AK1C3_HUMAN             Reviewed;         323 AA.
AC   P42330; A8K2V0; B4DL37; Q5T2L1; Q96DJ1; Q96KI8; Q99530; Q9UCX1;
AC   Q9UII3; Q9UKL9;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   05-OCT-2010, sequence version 4.
DT   29-OCT-2014, entry version 160.
DE   RecName: Full=Aldo-keto reductase family 1 member C3;
DE            EC=1.-.-.-;
DE   AltName: Full=17-beta-hydroxysteroid dehydrogenase type 5;
DE            Short=17-beta-HSD 5;
DE   AltName: Full=3-alpha-HSD type II, brain;
DE   AltName: Full=3-alpha-hydroxysteroid dehydrogenase type 2;
DE            Short=3-alpha-HSD type 2;
DE            EC=1.1.1.357;
DE   AltName: Full=Chlordecone reductase homolog HAKRb;
DE   AltName: Full=Dihydrodiol dehydrogenase 3;
DE            Short=DD-3;
DE            Short=DD3;
DE   AltName: Full=Dihydrodiol dehydrogenase type I;
DE   AltName: Full=HA1753;
DE   AltName: Full=Indanol dehydrogenase;
DE            EC=1.1.1.112;
DE   AltName: Full=Prostaglandin F synthase;
DE            Short=PGFS;
DE            EC=1.1.1.188;
DE   AltName: Full=Testosterone 17-beta-dehydrogenase 5;
DE            EC=1.1.1.239;
DE            EC=1.1.1.64;
DE   AltName: Full=Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase;
DE            EC=1.3.1.20;
GN   Name=AKR1C3; Synonyms=DDH1, HSD17B5, KIAA0119, PGFS;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS GLN-5 AND
RP   ILE-175.
RC   TISSUE=Liver;
RX   PubMed=8274401; DOI=10.1016/0960-0760(93)90308-J;
RA   Qin K.-N., New M.I., Cheng K.-C.;
RT   "Molecular cloning of multiple cDNAs encoding human enzymes
RT   structurally related to 3 alpha-hydroxysteroid dehydrogenase.";
RL   J. Steroid Biochem. Mol. Biol. 46:673-679(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, TISSUE
RP   SPECIFICITY, AND VARIANTS GLN-5 AND ILE-175.
RX   PubMed=7650035; DOI=10.1074/jbc.270.34.20162;
RA   Khanna M., Qin K.-N., Wang R.W., Cheng K.-C.;
RT   "Substrate specificity, gene structure, and tissue-specific
RT   distribution of multiple human 3 alpha-hydroxysteroid
RT   dehydrogenases.";
RL   J. Biol. Chem. 270:20162-20168(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-5.
RC   TISSUE=Liver;
RX   PubMed=7626489; DOI=10.1016/0960-0760(95)00019-V;
RA   Khanna M., Qin K.-N., Cheng K.-C.;
RT   "Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and
RT   molecular cloning of multiple cDNAs encoding structurally related
RT   proteins in humans.";
RL   J. Steroid Biochem. Mol. Biol. 53:41-46(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, TISSUE
RP   SPECIFICITY, AND VARIANT GLN-5.
RC   TISSUE=Prostate;
RX   PubMed=9415401; DOI=10.1210/me.11.13.1971;
RA   Lin H.-K., Jez J.M., Schlegel B.P., Peehl D.M., Pachter J.A.,
RA   Penning T.M.;
RT   "Expression and characterization of recombinant type 2 3 alpha-
RT   hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration
RT   of bifunctional 3 alpha/17 beta-HSD activity and cellular
RT   distribution.";
RL   Mol. Endocrinol. 11:1971-1984(1997).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC
RP   DNA] OF 124-190, CHARACTERIZATION, TISSUE SPECIFICITY, AND VARIANT
RP   GLN-5.
RC   TISSUE=Lung;
RX   PubMed=10622721; DOI=10.1016/S0014-5793(99)01551-3;
RA   Suzuki-Yamamoto T., Nishizawa M., Fukui M., Okuda-Ashitaka E.,
RA   Nakajima T., Ito S., Watanabe K.;
RT   "cDNA cloning, expression and characterization of human prostaglandin
RT   F synthase.";
RL   FEBS Lett. 462:335-340(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES,
RP   TISSUE SPECIFICITY, AND VARIANT GLN-5.
RC   TISSUE=Brain;
RX   PubMed=10557352; DOI=10.1073/pnas.96.23.13512;
RA   Griffin L.D., Mellon S.H.;
RT   "Selective serotonin reuptake inhibitors directly alter activity of
RT   neurosteroidogenic enzymes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:13512-13517(1999).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Liver;
RX   PubMed=10672042; DOI=10.1046/j.1365-2443.2000.00310.x;
RA   Nishizawa M., Nakajima T., Yasuda K., Kanzaki H., Sasaguri Y.,
RA   Watanabe K., Ito S.;
RT   "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with
RT   three aldo-keto reductase genes.";
RL   Genes Cells 5:111-125(2000).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Prostate;
RX   PubMed=11165022; DOI=10.1016/S0303-7207(00)00426-3;
RA   Penning T.M., Burczynski M.E., Jez J.M., Lin H.-K., Ma H., Moore M.,
RA   Ratnam K., Palackal N.;
RT   "Structure-function aspects and inhibitor design of type 5 17beta-
RT   hydroxysteroid dehydrogenase (AKR1C3).";
RL   Mol. Cell. Endocrinol. 171:137-149(2001).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-5.
RC   TISSUE=Bone marrow;
RX   PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA   Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S.,
RA   Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT   "Prediction of the coding sequences of unidentified human genes. III.
RT   The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by
RT   analysis of cDNA clones from human cell line KG-1.";
RL   DNA Res. 2:37-43(1995).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA   Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA   Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA   Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA   Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA   Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA   Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA   Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA   Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA   Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA   Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA   Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA   Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA   Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA   Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA   Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA   Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [13]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [14]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Colon, and Urinary bladder;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [15]
RP   CHARACTERIZATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT
RP   ILE-175, AND MUTAGENESIS OF LYS-75.
RX   PubMed=9927279; DOI=10.1210/en.140.2.568;
RA   Dufort I., Rheault P., Huang X.-F., Soucy P., Luu-The V.;
RT   "Characteristics of a highly labile human type 5 17beta-hydroxysteroid
RT   dehydrogenase.";
RL   Endocrinology 140:568-574(1999).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH PROSTAGLANDIN
RP   H(2); NADPH AND RUTIN.
RX   PubMed=14979715; DOI=10.1021/bi036046x;
RA   Komoto J., Yamada T., Watanabe K., Takusagawa F.;
RT   "Crystal structure of human prostaglandin F synthase (AKR1C3).";
RL   Biochemistry 43:2188-2198(2004).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH FLUFENAMIC ACID
RP   AND INDOMETHACIN.
RX   PubMed=14996743; DOI=10.1158/0008-5472.CAN-03-2847;
RA   Lovering A.L., Ride J.P., Bunce C.M., Desmond J.C., Cummings S.M.,
RA   White S.A.;
RT   "Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in
RT   complex with the nonsteroidal anti-inflammatory drugs flufenamic acid
RT   and indomethacin.";
RL   Cancer Res. 64:1802-1810(2004).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH NADP AND DELTA4
RP   -3 ANDROSTENE-3,17-DIONE, AND IMPORTANCE OF TRP-227 AND PHE-306 IN
RP   LIGAND RECOGNITION AND PRODUCT RELEASE.
RX   PubMed=15087468; DOI=10.1210/me.2004-0032;
RA   Qiu W., Zhou M., Labrie F., Lin S.-X.;
RT   "Crystal structures of the multispecific 17beta-hydroxysteroid
RT   dehydrogenase type 5: critical androgen regulation in human peripheral
RT   tissues.";
RL   Mol. Endocrinol. 18:1798-1807(2004).
CC   -!- FUNCTION: Catalyzes the conversion of aldehydes and ketones to
CC       alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2
CC       and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-
CC       PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and
CC       20-alpha HSD. Can interconvert active androgens, estrogens and
CC       progestins with their cognate inactive metabolites. Preferentially
CC       transforms androstenedione (4-dione) to testosterone.
CC   -!- CATALYTIC ACTIVITY: Trans-1,2-dihydrobenzene-1,2-diol + NADP(+) =
CC       catechol + NADPH.
CC   -!- CATALYTIC ACTIVITY: A 3-alpha-hydroxysteroid + NAD(P)(+) = a 3-
CC       oxosteroid + NAD(P)H.
CC   -!- CATALYTIC ACTIVITY: (5Z,13E)-(15S)-9-alpha,11-alpha,15-
CC       trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-9-
CC       alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH.
CC   -!- CATALYTIC ACTIVITY: Testosterone + NAD(+) = androstenedione +
CC       NADH.
CC   -!- CATALYTIC ACTIVITY: Testosterone + NADP(+) = androst-4-ene-3,17-
CC       dione + NADPH.
CC   -!- CATALYTIC ACTIVITY: Indan-1-ol + NAD(P)(+) = indanone + NAD(P)H.
CC   -!- ENZYME REGULATION: Strongly inhibited by nonsteroidal anti-
CC       inflammatory drugs (NSAID) including flufenamic acid and
CC       indomethacin. Also inhibited by the flavinoid, rutin, and by
CC       selective serotonin inhibitors (SSRIs).
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=142.1 uM for progesterone {ECO:0000269|PubMed:10557352};
CC         KM=2.37 uM for 5-alpha-dihydrotestosterone
CC         {ECO:0000269|PubMed:10557352};
CC         KM=1.0 uM for androstanediol {ECO:0000269|PubMed:10557352};
CC         Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate
CC         {ECO:0000269|PubMed:10557352};
CC         Vmax=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as
CC         substrate {ECO:0000269|PubMed:10557352};
CC         Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate
CC         {ECO:0000269|PubMed:10557352};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P42330-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P42330-2; Sequence=VSP_055798;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Expressed in many tissues including adrenal
CC       gland, brain, kidney, liver, lung, mammary gland, placenta, small
CC       intestine, colon, spleen, prostate and testis. The dominant HSD in
CC       prostate and mammary gland. In the prostate, higher levels in
CC       epithelial cells than in stromal cells. In the brain, expressed in
CC       medulla, spinal cord, frontotemporal lobes, thalamus, subthalamic
CC       nuclei and amygdala. Weaker expression in the hippocampus,
CC       substantia nigra and caudate. {ECO:0000269|PubMed:10557352,
CC       ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:11165022,
CC       ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401,
CC       ECO:0000269|PubMed:9927279}.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA04619.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/AKR1C3ID612ch10p15.html";
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DR   EMBL; S68288; AAD14011.1; -; mRNA.
DR   EMBL; L43839; AAB41916.1; -; Genomic_DNA.
DR   EMBL; L43831; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43832; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43833; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43834; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43835; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43836; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43837; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; L43838; AAB41916.1; JOINED; Genomic_DNA.
DR   EMBL; AB018580; BAA88488.1; -; mRNA.
DR   EMBL; AB028065; BAA88489.1; -; Genomic_DNA.
DR   EMBL; AF149416; AAF07272.2; -; mRNA.
DR   EMBL; AB032157; BAA92892.1; -; Genomic_DNA.
DR   EMBL; D17793; BAA04619.2; ALT_INIT; mRNA.
DR   EMBL; BT007286; AAP35950.1; -; mRNA.
DR   EMBL; AK290365; BAF83054.1; -; mRNA.
DR   EMBL; AK296829; BAG59399.1; -; mRNA.
DR   EMBL; AL391427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471072; EAW86454.1; -; Genomic_DNA.
DR   EMBL; BC001479; AAH01479.1; -; mRNA.
DR   EMBL; BC019230; AAH19230.1; -; mRNA.
DR   CCDS; CCDS7063.1; -. [P42330-1]
DR   PIR; B57407; B57407.
DR   PIR; I73674; I73674.
DR   RefSeq; NP_001240837.1; NM_001253908.1.
DR   RefSeq; NP_003730.4; NM_003739.5. [P42330-1]
DR   UniGene; Hs.78183; -.
DR   PDB; 1RY0; X-ray; 1.69 A; A/B=1-323.
DR   PDB; 1RY8; X-ray; 1.69 A; A/B=1-323.
DR   PDB; 1S1P; X-ray; 1.20 A; A=1-323.
DR   PDB; 1S1R; X-ray; 2.00 A; A=1-323.
DR   PDB; 1S2A; X-ray; 1.70 A; A=1-323.
DR   PDB; 1S2C; X-ray; 1.80 A; A=1-323.
DR   PDB; 1XF0; X-ray; 2.00 A; A=1-323.
DR   PDB; 1ZQ5; X-ray; 1.30 A; A=1-323.
DR   PDB; 2F38; X-ray; 2.00 A; A=1-323.
DR   PDB; 2FGB; X-ray; 1.35 A; A=1-323.
DR   PDB; 3R43; X-ray; 2.00 A; A=1-323.
DR   PDB; 3R58; X-ray; 2.30 A; A=1-323.
DR   PDB; 3R6I; X-ray; 1.95 A; A=1-323.
DR   PDB; 3R7M; X-ray; 2.10 A; A=1-323.
DR   PDB; 3R8G; X-ray; 1.80 A; A=1-323.
DR   PDB; 3R8H; X-ray; 1.90 A; A=1-323.
DR   PDB; 3R94; X-ray; 2.01 A; A=1-323.
DR   PDB; 3UFY; X-ray; 1.90 A; A=1-323.
DR   PDB; 3UG8; X-ray; 1.73 A; A=1-323.
DR   PDB; 3UGR; X-ray; 1.65 A; A=1-323.
DR   PDB; 3UWE; X-ray; 1.68 A; A=1-323.
DR   PDB; 4DBS; X-ray; 1.85 A; A/B=1-323.
DR   PDB; 4DBU; X-ray; 2.53 A; A/B=1-323.
DR   PDB; 4DBW; X-ray; 1.80 A; A/B=1-323.
DR   PDB; 4DZ5; X-ray; 1.70 A; A=1-323.
DR   PDB; 4FA3; X-ray; 2.20 A; A=1-323.
DR   PDB; 4FAL; X-ray; 2.00 A; A=1-323.
DR   PDB; 4FAM; X-ray; 2.00 A; A/B=1-323.
DR   PDB; 4H7C; X-ray; 1.97 A; A=1-323.
DR   PDB; 4HMN; X-ray; 2.40 A; A=1-323.
DR   PDBsum; 1RY0; -.
DR   PDBsum; 1RY8; -.
DR   PDBsum; 1S1P; -.
DR   PDBsum; 1S1R; -.
DR   PDBsum; 1S2A; -.
DR   PDBsum; 1S2C; -.
DR   PDBsum; 1XF0; -.
DR   PDBsum; 1ZQ5; -.
DR   PDBsum; 2F38; -.
DR   PDBsum; 2FGB; -.
DR   PDBsum; 3R43; -.
DR   PDBsum; 3R58; -.
DR   PDBsum; 3R6I; -.
DR   PDBsum; 3R7M; -.
DR   PDBsum; 3R8G; -.
DR   PDBsum; 3R8H; -.
DR   PDBsum; 3R94; -.
DR   PDBsum; 3UFY; -.
DR   PDBsum; 3UG8; -.
DR   PDBsum; 3UGR; -.
DR   PDBsum; 3UWE; -.
DR   PDBsum; 4DBS; -.
DR   PDBsum; 4DBU; -.
DR   PDBsum; 4DBW; -.
DR   PDBsum; 4DZ5; -.
DR   PDBsum; 4FA3; -.
DR   PDBsum; 4FAL; -.
DR   PDBsum; 4FAM; -.
DR   PDBsum; 4H7C; -.
DR   PDBsum; 4HMN; -.
DR   ProteinModelPortal; P42330; -.
DR   SMR; P42330; 6-320.
DR   BioGrid; 114196; 9.
DR   IntAct; P42330; 5.
DR   MINT; MINT-1379107; -.
DR   BindingDB; P42330; -.
DR   ChEMBL; CHEMBL4681; -.
DR   DrugBank; DB00905; Bimatoprost.
DR   DrugBank; DB00997; Doxorubicin.
DR   PhosphoSite; P42330; -.
DR   DMDM; 308153646; -.
DR   DOSAC-COBS-2DPAGE; P42330; -.
DR   MaxQB; P42330; -.
DR   PaxDb; P42330; -.
DR   PRIDE; P42330; -.
DR   DNASU; 8644; -.
DR   Ensembl; ENST00000380554; ENSP00000369927; ENSG00000196139. [P42330-1]
DR   GeneID; 8644; -.
DR   KEGG; hsa:8644; -.
DR   UCSC; uc001ihr.3; human. [P42330-1]
DR   CTD; 8644; -.
DR   GeneCards; GC10P005077; -.
DR   HGNC; HGNC:386; AKR1C3.
DR   HPA; CAB010874; -.
DR   MIM; 603966; gene.
DR   neXtProt; NX_P42330; -.
DR   PharmGKB; PA24679; -.
DR   eggNOG; COG0656; -.
DR   GeneTree; ENSGT00760000119041; -.
DR   HOVERGEN; HBG000020; -.
DR   InParanoid; P42330; -.
DR   KO; K04119; -.
DR   OMA; FDIVDLC; -.
DR   PhylomeDB; P42330; -.
DR   TreeFam; TF106492; -.
DR   Reactome; REACT_11041; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR   Reactome; REACT_11048; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR   Reactome; REACT_11053; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR   Reactome; REACT_150149; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR   Reactome; REACT_24968; Retinoid metabolism and transport.
DR   SABIO-RK; P42330; -.
DR   EvolutionaryTrace; P42330; -.
DR   GeneWiki; AKR1C3; -.
DR   GenomeRNAi; 8644; -.
DR   NextBio; 32407; -.
DR   PRO; PR:P42330; -.
DR   Bgee; P42330; -.
DR   CleanEx; HS_AKR1C3; -.
DR   ExpressionAtlas; P42330; baseline and differential.
DR   Genevestigator; P42330; -.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR   GO; GO:0005622; C:intracellular; IDA:LIFEdb.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:UniProtKB.
DR   GO; GO:0004033; F:aldo-keto reductase (NADP) activity; TAS:UniProtKB.
DR   GO; GO:0047023; F:androsterone dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0047787; F:delta4-3-oxosteroid 5beta-reductase activity; IDA:UniProtKB.
DR   GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0045550; F:geranylgeranyl reductase activity; IDA:UniProtKB.
DR   GO; GO:0047718; F:indanol dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0045703; F:ketoreductase activity; IDA:UniProtKB.
DR   GO; GO:0047086; F:ketosteroid monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR   GO; GO:0018636; F:phenanthrene 9,10-monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0036131; F:prostaglandin D2 11-ketoreductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004958; F:prostaglandin F receptor activity; IDA:UniProtKB.
DR   GO; GO:0047017; F:prostaglandin-F synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0001758; F:retinal dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0004745; F:retinol dehydrogenase activity; IDA:UniProtKB.
DR   GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IEA:UniProtKB-EC.
DR   GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR   GO; GO:0071276; P:cellular response to cadmium ion; IDA:UniProtKB.
DR   GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR   GO; GO:0071384; P:cellular response to corticosteroid stimulus; IDA:UniProtKB.
DR   GO; GO:0071395; P:cellular response to jasmonic acid stimulus; IDA:UniProtKB.
DR   GO; GO:0071379; P:cellular response to prostaglandin stimulus; IDA:UniProtKB.
DR   GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:UniProtKB.
DR   GO; GO:0009267; P:cellular response to starvation; IEP:UniProtKB.
DR   GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome.
DR   GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB.
DR   GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB.
DR   GO; GO:0016488; P:farnesol catabolic process; IDA:UniProtKB.
DR   GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0030216; P:keratinocyte differentiation; IEP:UniProtKB.
DR   GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR   GO; GO:0044259; P:multicellular organismal macromolecule metabolic process; IEP:UniProtKB.
DR   GO; GO:1900053; P:negative regulation of retinoic acid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0055114; P:oxidation-reduction process; IDA:UniProtKB.
DR   GO; GO:0007603; P:phototransduction, visible light; TAS:Reactome.
DR   GO; GO:0010942; P:positive regulation of cell death; IDA:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
DR   GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IDA:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR   GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR   GO; GO:0042448; P:progesterone metabolic process; IDA:UniProtKB.
DR   GO; GO:0006693; P:prostaglandin metabolic process; IEP:UniProtKB.
DR   GO; GO:0000060; P:protein import into nucleus, translocation; IDA:UniProtKB.
DR   GO; GO:0048385; P:regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:2000224; P:regulation of testosterone biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0070293; P:renal absorption; NAS:UniProtKB.
DR   GO; GO:0007584; P:response to nutrient; IEP:UniProtKB.
DR   GO; GO:0034694; P:response to prostaglandin; IDA:UniProtKB.
DR   GO; GO:0042574; P:retinal metabolic process; IDA:UniProtKB.
DR   GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0008202; P:steroid metabolic process; IEP:UniProtKB.
DR   GO; GO:0061370; P:testosterone biosynthetic process; IMP:UniProtKB.
DR   Gene3D; 3.20.20.100; -; 1.
DR   InterPro; IPR001395; Aldo/ket_red.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   InterPro; IPR020471; Aldo/keto_reductase_subgr.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   PANTHER; PTHR11732; PTHR11732; 1.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   PIRSF; PIRSF000097; AKR; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF51430; SSF51430; 1.
DR   PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR   PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; Cytoplasm; NAD;
KW   NADP; Oxidoreductase; Polymorphism; Reference proteome.
FT   CHAIN         1    323       Aldo-keto reductase family 1 member C3.
FT                                /FTId=PRO_0000124638.
FT   NP_BIND      13     22       NADP. {ECO:0000255}.
FT   NP_BIND     217    280       NADP. {ECO:0000250}.
FT   ACT_SITE     55     55       Proton donor. {ECO:0000250}.
FT   BINDING     117    117       Substrate. {ECO:0000250}.
FT   SITE         54     54       Important for substrate specificity.
FT                                {ECO:0000250}.
FT   SITE         84     84       Lowers pKa of active site Tyr.
FT                                {ECO:0000250}.
FT   SITE        227    227       Involved in ligand recognition and
FT                                product release.
FT   SITE        306    306       Involved in ligand recognition and
FT                                product release.
FT   VAR_SEQ       1    119       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_055798.
FT   VARIANT       5      5       H -> Q (in dbSNP:rs12529).
FT                                {ECO:0000269|PubMed:10557352,
FT                                ECO:0000269|PubMed:10622721,
FT                                ECO:0000269|PubMed:7626489,
FT                                ECO:0000269|PubMed:7650035,
FT                                ECO:0000269|PubMed:7788527,
FT                                ECO:0000269|PubMed:8274401,
FT                                ECO:0000269|PubMed:9415401}.
FT                                /FTId=VAR_013288.
FT   VARIANT      66     66       R -> Q (in dbSNP:rs35961894).
FT                                /FTId=VAR_032767.
FT   VARIANT      77     77       E -> G (in dbSNP:rs41306308).
FT                                /FTId=VAR_061001.
FT   VARIANT     170    170       R -> C (in dbSNP:rs35575889).
FT                                /FTId=VAR_032768.
FT   VARIANT     175    175       M -> I (no effect on 17beta-HSD activity;
FT                                dbSNP:rs1131132).
FT                                {ECO:0000269|PubMed:7650035,
FT                                ECO:0000269|PubMed:8274401}.
FT                                /FTId=VAR_013289.
FT   VARIANT     180    180       P -> S (in dbSNP:rs34186955).
FT                                /FTId=VAR_032769.
FT   MUTAGEN      75     75       K->E: No effect on 17beta-HSD activity.
FT                                {ECO:0000269|PubMed:9927279}.
FT   CONFLICT      3      3       S -> P (in Ref. 3; no nucleotide entry).
FT                                {ECO:0000305}.
FT   CONFLICT      6      6       Q -> K (in Ref. 3; no nucleotide entry).
FT                                {ECO:0000305}.
FT   CONFLICT     38     38       T -> S (in Ref. 6; AAF07272).
FT                                {ECO:0000305}.
FT   CONFLICT     75     75       K -> E (in Ref. 1; AAD14011 and 3; no
FT                                nucleotide entry). {ECO:0000305}.
FT   CONFLICT     75     75       K -> M (in Ref. 2; AAB41916).
FT                                {ECO:0000305}.
FT   CONFLICT     89     89       F -> S (in Ref. 6; AAF07272).
FT                                {ECO:0000305}.
FT   CONFLICT    270    270       K -> R (in Ref. 6; AAF07272).
FT                                {ECO:0000305}.
FT   STRAND        7      9
FT   STRAND       15     22
FT   HELIX        33     44
FT   STRAND       48     50
FT   HELIX        53     55
FT   HELIX        58     70
FT   HELIX        76     78
FT   STRAND       80     85
FT   HELIX        87     89
FT   HELIX        92     94
FT   HELIX        95    106
FT   STRAND      111    116
FT   STRAND      124    126
FT   STRAND      133    135
FT   HELIX       144    156
FT   STRAND      159    167
FT   HELIX       170    177
FT   STRAND      187    192
FT   HELIX       200    208
FT   STRAND      212    217
FT   TURN        225    227
FT   HELIX       235    237
FT   HELIX       239    248
FT   HELIX       252    262
FT   STRAND      266    270
FT   HELIX       274    280
FT   HELIX       281    285
FT   HELIX       290    297
FT   HELIX       309    312
FT   HELIX       318    320
SQ   SEQUENCE   323 AA;  36853 MW;  86A7690D9498C6FD CRC64;
     MDSKHQCVKL NDGHFMPVLG FGTYAPPEVP RSKALEVTKL AIEAGFRHID SAHLYNNEEQ
     VGLAIRSKIA DGSVKREDIF YTSKLWSTFH RPELVRPALE NSLKKAQLDY VDLYLIHSPM
     SLKPGEELSP TDENGKVIFD IVDLCTTWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNKP
     GLKYKPVCNQ VECHPYFNRS KLLDFCKSKD IVLVAYSALG SQRDKRWVDP NSPVLLEDPV
     LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTA EDMKAIDGLD
     RNLHYFNSDS FASHPNYPYS DEY
//
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