Full text data of AKR1C3
AKR1C3
(DDH1, HSD17B5, KIAA0119, PGFS)
[Confidence: low (only semi-automatic identification from reviews)]
Aldo-keto reductase family 1 member C3; 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; 1.1.1.357; Chlordecone reductase homolog HAKRb; Dihydrodiol dehydrogenase 3; DD-3; DD3; Dihydrodiol dehydrogenase type I; HA1753; Indanol dehydrogenase; 1.1.1.112; Prostaglandin F synthase; PGFS; 1.1.1.188; Testosterone 17-beta-dehydrogenase 5; 1.1.1.239; 1.1.1.64; Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; 1.3.1.20)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Aldo-keto reductase family 1 member C3; 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; 1.1.1.357; Chlordecone reductase homolog HAKRb; Dihydrodiol dehydrogenase 3; DD-3; DD3; Dihydrodiol dehydrogenase type I; HA1753; Indanol dehydrogenase; 1.1.1.112; Prostaglandin F synthase; PGFS; 1.1.1.188; Testosterone 17-beta-dehydrogenase 5; 1.1.1.239; 1.1.1.64; Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; 1.3.1.20)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P42330
ID AK1C3_HUMAN Reviewed; 323 AA.
AC P42330; A8K2V0; Q5T2L1; Q96DJ1; Q96KI8; Q99530; Q9UCX1; Q9UII3;
read moreAC Q9UKL9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 4.
DT 22-JAN-2014, entry version 153.
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], AND VARIANTS GLN-5 AND 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], 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], CHARACTERIZATION, TISSUE SPECIFICITY, AND
RP 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], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF
RP 124-190, CHARACTERIZATION, TISSUE SPECIFICITY, AND VARIANT 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], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP 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], CHARACTERIZATION, AND TISSUE 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], 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].
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].
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 MRNA].
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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;
CC KM=2.37 uM for 5-alpha-dihydrotestosterone;
CC KM=1.0 uM for androstanediol;
CC Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate;
CC Vmax=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as
CC substrate;
CC Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04619.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
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; AL391427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001479; AAH01479.1; -; mRNA.
DR EMBL; BC019230; AAH19230.1; -; mRNA.
DR PIR; B57407; B57407.
DR PIR; I73674; I73674.
DR RefSeq; NP_001240837.1; NM_001253908.1.
DR RefSeq; NP_003730.4; NM_003739.5.
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 IntAct; P42330; 5.
DR MINT; MINT-1379107; -.
DR BindingDB; P42330; -.
DR ChEMBL; CHEMBL4681; -.
DR DrugBank; DB01093; Dimethyl sulfoxide.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P42330; -.
DR DMDM; 308153646; -.
DR DOSAC-COBS-2DPAGE; P42330; -.
DR PaxDb; P42330; -.
DR PRIDE; P42330; -.
DR DNASU; 8644; -.
DR Ensembl; ENST00000380554; ENSP00000369927; ENSG00000196139.
DR Ensembl; ENST00000583876; ENSP00000464178; ENSG00000265685.
DR GeneID; 8644; -.
DR KEGG; hsa:8644; -.
DR UCSC; uc001ihr.3; human.
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 HOVERGEN; HBG000020; -.
DR InParanoid; P42330; -.
DR KO; K04119; -.
DR OMA; FDIVDLC; -.
DR PhylomeDB; P42330; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; P42330; -.
DR EvolutionaryTrace; P42330; -.
DR GeneWiki; AKR1C3; -.
DR GenomeRNAi; 8644; -.
DR NextBio; 32407; -.
DR PRO; PR:P42330; -.
DR ArrayExpress; P42330; -.
DR Bgee; P42330; -.
DR CleanEx; HS_AKR1C3; -.
DR Genevestigator; P42330; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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: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: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: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:0007603; P:phototransduction, visible light; TAS:Reactome.
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 cascade; 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: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:0042574; P:retinal metabolic process; IDA: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; Complete proteome; Cytoplasm; NAD; NADP; Oxidoreductase;
KW Polymorphism; Reference proteome.
FT CHAIN 1 323 Aldo-keto reductase family 1 member C3.
FT /FTId=PRO_0000124638.
FT NP_BIND 13 22 NADP (Potential).
FT NP_BIND 217 280 NADP (By similarity).
FT ACT_SITE 55 55 Proton donor (By similarity).
FT BINDING 117 117 Substrate (By similarity).
FT SITE 54 54 Important for substrate specificity (By
FT similarity).
FT SITE 84 84 Lowers pKa of active site Tyr (By
FT similarity).
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 VARIANT 5 5 H -> Q (in dbSNP:rs12529).
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 /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 CONFLICT 3 3 S -> P (in Ref. 3; no nucleotide entry).
FT CONFLICT 6 6 Q -> K (in Ref. 3; no nucleotide entry).
FT CONFLICT 38 38 T -> S (in Ref. 6; AAF07272).
FT CONFLICT 75 75 K -> E (in Ref. 1; AAD14011 and 3; no
FT nucleotide entry).
FT CONFLICT 75 75 K -> M (in Ref. 2; AAB41916).
FT CONFLICT 89 89 F -> S (in Ref. 6; AAF07272).
FT CONFLICT 270 270 K -> R (in Ref. 6; AAF07272).
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
//
ID AK1C3_HUMAN Reviewed; 323 AA.
AC P42330; A8K2V0; Q5T2L1; Q96DJ1; Q96KI8; Q99530; Q9UCX1; Q9UII3;
read moreAC Q9UKL9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 4.
DT 22-JAN-2014, entry version 153.
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], AND VARIANTS GLN-5 AND 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], 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], CHARACTERIZATION, TISSUE SPECIFICITY, AND
RP 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], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF
RP 124-190, CHARACTERIZATION, TISSUE SPECIFICITY, AND VARIANT 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], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP 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], CHARACTERIZATION, AND TISSUE 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], 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].
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].
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 MRNA].
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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;
CC KM=2.37 uM for 5-alpha-dihydrotestosterone;
CC KM=1.0 uM for androstanediol;
CC Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate;
CC Vmax=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as
CC substrate;
CC Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04619.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
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; AL391427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001479; AAH01479.1; -; mRNA.
DR EMBL; BC019230; AAH19230.1; -; mRNA.
DR PIR; B57407; B57407.
DR PIR; I73674; I73674.
DR RefSeq; NP_001240837.1; NM_001253908.1.
DR RefSeq; NP_003730.4; NM_003739.5.
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 IntAct; P42330; 5.
DR MINT; MINT-1379107; -.
DR BindingDB; P42330; -.
DR ChEMBL; CHEMBL4681; -.
DR DrugBank; DB01093; Dimethyl sulfoxide.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; P42330; -.
DR DMDM; 308153646; -.
DR DOSAC-COBS-2DPAGE; P42330; -.
DR PaxDb; P42330; -.
DR PRIDE; P42330; -.
DR DNASU; 8644; -.
DR Ensembl; ENST00000380554; ENSP00000369927; ENSG00000196139.
DR Ensembl; ENST00000583876; ENSP00000464178; ENSG00000265685.
DR GeneID; 8644; -.
DR KEGG; hsa:8644; -.
DR UCSC; uc001ihr.3; human.
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 HOVERGEN; HBG000020; -.
DR InParanoid; P42330; -.
DR KO; K04119; -.
DR OMA; FDIVDLC; -.
DR PhylomeDB; P42330; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; P42330; -.
DR EvolutionaryTrace; P42330; -.
DR GeneWiki; AKR1C3; -.
DR GenomeRNAi; 8644; -.
DR NextBio; 32407; -.
DR PRO; PR:P42330; -.
DR ArrayExpress; P42330; -.
DR Bgee; P42330; -.
DR CleanEx; HS_AKR1C3; -.
DR Genevestigator; P42330; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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: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: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: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:0007603; P:phototransduction, visible light; TAS:Reactome.
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 cascade; 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: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:0042574; P:retinal metabolic process; IDA: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; Complete proteome; Cytoplasm; NAD; NADP; Oxidoreductase;
KW Polymorphism; Reference proteome.
FT CHAIN 1 323 Aldo-keto reductase family 1 member C3.
FT /FTId=PRO_0000124638.
FT NP_BIND 13 22 NADP (Potential).
FT NP_BIND 217 280 NADP (By similarity).
FT ACT_SITE 55 55 Proton donor (By similarity).
FT BINDING 117 117 Substrate (By similarity).
FT SITE 54 54 Important for substrate specificity (By
FT similarity).
FT SITE 84 84 Lowers pKa of active site Tyr (By
FT similarity).
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 VARIANT 5 5 H -> Q (in dbSNP:rs12529).
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 /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 CONFLICT 3 3 S -> P (in Ref. 3; no nucleotide entry).
FT CONFLICT 6 6 Q -> K (in Ref. 3; no nucleotide entry).
FT CONFLICT 38 38 T -> S (in Ref. 6; AAF07272).
FT CONFLICT 75 75 K -> E (in Ref. 1; AAD14011 and 3; no
FT nucleotide entry).
FT CONFLICT 75 75 K -> M (in Ref. 2; AAB41916).
FT CONFLICT 89 89 F -> S (in Ref. 6; AAF07272).
FT CONFLICT 270 270 K -> R (in Ref. 6; AAF07272).
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
//
MIM
603966
*RECORD*
*FIELD* NO
603966
*FIELD* TI
*603966 ALDO-KETO REDUCTASE FAMILY 1, MEMBER C3; AKR1C3
;;ALDO-KETO REDUCTASE B; HAKRB;;
read moreDIHYDRODIOL DEHYDROGENASE 3; DD3;;
3-@ALPHA-HYDROXYSTEROID DEHYDROGENASE, TYPE II;;
17-@BETA-HYDROXYSTEROID DEHYDROGENASE V; HSD17B5
*FIELD* TX
CLONING
The aldo-keto reductase family includes 3-alpha-hydroxysteroid
dehydrogenase (3-alpha-HSD) as well as dihydrodiol dehydrogenase
(AKR1C3) and human chlordecone reductase (CHDR, or AKR1C4; 600451).
Aldo-keto reductases catalyze the conversion of aldehydes and ketones to
alcohols by utilizing NADH and/or NADPH as a cofactor. 3-Alpha-HSD is a
versatile aldo-keto reductase, able to utilize a large array of
substrates. By screening a human liver expression library with an
antibody against rat 3-alpha-HSD, Qin et al. (1993) isolated cDNAs
encoding 4 distinct human aldo-keto reductases: HAKRa (AKR1C4), HAKRb,
HAKRc (AKR1C1; 600449), and HAKRd (AKR1C2; 600450). The predicted
323-amino acid HAKR proteins share more than 85% identity. Northern blot
analysis revealed that HAKRb is expressed as 1.4- and 1.2-kb mRNAs in
several human tissues.
Nagase et al. (1995) isolated KIAA0119, an HAKRb cDNA, from a human
immature myeloid cell line. Mills et al. (1998) isolated an identical
cDNA, which they designated HAKRe.
GENE FUNCTION
Khanna et al. (1995) reported that recombinant type I (AKR1C4) and type
II (AKR1C3) human 3-alpha-HSD proteins exhibited both reductase and
dehydrogenase activities.
GENE STRUCTURE
By sequence analysis, Khanna et al. (1995) demonstrated that the AKR1C3
and AKR1C4 genes contain 9 exons and span 15 to 20 kb. The sizes and
boundaries of the exons are identical in both genes.
MAPPING
By analysis of somatic cell hybrids, Nagase et al. (1995) mapped the
KIAA0119 gene to chromosome 10. Khanna et al. (1995) isolated 2 genes
encoding dihydrodiol dehydrogenase, referred to as type I or DDH1, and
type II or DDH2, as well as 1 gene for chlordecone reductase. However,
sequence analysis revealed that the type I gene of Khanna et al. (1995)
corresponded to either AKR1C1 or AKR1C2, the type II gene corresponded
to AKR1C3, and the CHDR gene corresponded to AKR1C4 (White, 1999). By a
combination of somatic cell hybrid analysis and fluorescence in situ
hybridization, Khanna et al. (1995) mapped all 3 genes to 10p15-p14.
MOLECULAR GENETICS
Qin et al. (2006) identified a functional polymorphism in the promoter
region of the HSD17B5 gene (-71G) that may contribute to testosterone
excess in a subset of patients with polycystic ovary syndrome (see
184700).
*FIELD* RF
1. Khanna, M.; Qin, K.-N.; Klisak, I.; Belkin, S.; Sparkes, R. S.;
Cheng, K.-C.: Localization of multiple human dihydrodiol dehydrogenase
(DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome
10 by the polymerase chain reaction and fluorescence in situ hybridization. Genomics 25:
588-590, 1995.
2. Khanna, M.; Qin, K.-N.; Wang, R. W.; Cheng, K.-C.: Substrate specificity,
gene structure, and tissue-specific distribution of multiple human
3-alpha-hydroxysteroid dehydrogenases. J. Biol. Chem. 270: 20162-20168,
1995.
3. Mills, K. I.; Gilkes, A. F.; Sweeney, M.; Choudhry, M. A.; Woodgate,
L. J.; Bunce, C. M.; Brown, G.; Burnett, A. K.: Identification of
a retinoic acid responsive aldoketoreductase expressed in HL60 leukaemic
cells. FEBS Lett. 440: 158-162, 1998.
4. Nagase, T; Miyajima, N; Tanaka, A.; Sazuka, T.; Seki, N.; Sato,
S.; Tabata, S.; Ishikawa, K.; Kawarabayashi, Y.; Kotani, H.; Nomura,
N.: Prediction of the coding sequences of unidentified human genes.
III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced
by analysis of cDNA clones from human cell line KG-1. DNA Res. 2:
37-43, 1995.
5. Qin, K.; Ehrmann, D. A.; Cox, N.; Refetoff, S.; Rosenfield, R.
L.: Identification of a functional polymorphism of the human type
5 17-beta-hydroxysteroid dehydrogenase gene associated with polycystic
ovary syndrome. J. Clin. Endocr. Metab. 91: 270-276, 2006. Note:
Erratum: J. Clin. Endocr. Metab. 91: 529 only, 2006.
6. Qin, K.-N.; New, M. I.; Cheng, K.-C.: Molecular cloning of multiple
cDNAs encoding human enzymes structurally related to 3-alpha-hydroxysteroid
dehydrogenase. J. Steroid Biochem. Molec. Biol. 46: 673-679, 1993.
7. White, J.: Personal Communication. London, England 6/14/1999.
*FIELD* CN
John A. Phillips, III - updated: 5/31/2007
*FIELD* CD
Rebekah S. Rasooly: 7/7/1999
*FIELD* ED
terry: 09/14/2012
carol: 12/21/2007
carol: 5/31/2007
alopez: 7/7/1999
*RECORD*
*FIELD* NO
603966
*FIELD* TI
*603966 ALDO-KETO REDUCTASE FAMILY 1, MEMBER C3; AKR1C3
;;ALDO-KETO REDUCTASE B; HAKRB;;
read moreDIHYDRODIOL DEHYDROGENASE 3; DD3;;
3-@ALPHA-HYDROXYSTEROID DEHYDROGENASE, TYPE II;;
17-@BETA-HYDROXYSTEROID DEHYDROGENASE V; HSD17B5
*FIELD* TX
CLONING
The aldo-keto reductase family includes 3-alpha-hydroxysteroid
dehydrogenase (3-alpha-HSD) as well as dihydrodiol dehydrogenase
(AKR1C3) and human chlordecone reductase (CHDR, or AKR1C4; 600451).
Aldo-keto reductases catalyze the conversion of aldehydes and ketones to
alcohols by utilizing NADH and/or NADPH as a cofactor. 3-Alpha-HSD is a
versatile aldo-keto reductase, able to utilize a large array of
substrates. By screening a human liver expression library with an
antibody against rat 3-alpha-HSD, Qin et al. (1993) isolated cDNAs
encoding 4 distinct human aldo-keto reductases: HAKRa (AKR1C4), HAKRb,
HAKRc (AKR1C1; 600449), and HAKRd (AKR1C2; 600450). The predicted
323-amino acid HAKR proteins share more than 85% identity. Northern blot
analysis revealed that HAKRb is expressed as 1.4- and 1.2-kb mRNAs in
several human tissues.
Nagase et al. (1995) isolated KIAA0119, an HAKRb cDNA, from a human
immature myeloid cell line. Mills et al. (1998) isolated an identical
cDNA, which they designated HAKRe.
GENE FUNCTION
Khanna et al. (1995) reported that recombinant type I (AKR1C4) and type
II (AKR1C3) human 3-alpha-HSD proteins exhibited both reductase and
dehydrogenase activities.
GENE STRUCTURE
By sequence analysis, Khanna et al. (1995) demonstrated that the AKR1C3
and AKR1C4 genes contain 9 exons and span 15 to 20 kb. The sizes and
boundaries of the exons are identical in both genes.
MAPPING
By analysis of somatic cell hybrids, Nagase et al. (1995) mapped the
KIAA0119 gene to chromosome 10. Khanna et al. (1995) isolated 2 genes
encoding dihydrodiol dehydrogenase, referred to as type I or DDH1, and
type II or DDH2, as well as 1 gene for chlordecone reductase. However,
sequence analysis revealed that the type I gene of Khanna et al. (1995)
corresponded to either AKR1C1 or AKR1C2, the type II gene corresponded
to AKR1C3, and the CHDR gene corresponded to AKR1C4 (White, 1999). By a
combination of somatic cell hybrid analysis and fluorescence in situ
hybridization, Khanna et al. (1995) mapped all 3 genes to 10p15-p14.
MOLECULAR GENETICS
Qin et al. (2006) identified a functional polymorphism in the promoter
region of the HSD17B5 gene (-71G) that may contribute to testosterone
excess in a subset of patients with polycystic ovary syndrome (see
184700).
*FIELD* RF
1. Khanna, M.; Qin, K.-N.; Klisak, I.; Belkin, S.; Sparkes, R. S.;
Cheng, K.-C.: Localization of multiple human dihydrodiol dehydrogenase
(DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome
10 by the polymerase chain reaction and fluorescence in situ hybridization. Genomics 25:
588-590, 1995.
2. Khanna, M.; Qin, K.-N.; Wang, R. W.; Cheng, K.-C.: Substrate specificity,
gene structure, and tissue-specific distribution of multiple human
3-alpha-hydroxysteroid dehydrogenases. J. Biol. Chem. 270: 20162-20168,
1995.
3. Mills, K. I.; Gilkes, A. F.; Sweeney, M.; Choudhry, M. A.; Woodgate,
L. J.; Bunce, C. M.; Brown, G.; Burnett, A. K.: Identification of
a retinoic acid responsive aldoketoreductase expressed in HL60 leukaemic
cells. FEBS Lett. 440: 158-162, 1998.
4. Nagase, T; Miyajima, N; Tanaka, A.; Sazuka, T.; Seki, N.; Sato,
S.; Tabata, S.; Ishikawa, K.; Kawarabayashi, Y.; Kotani, H.; Nomura,
N.: Prediction of the coding sequences of unidentified human genes.
III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced
by analysis of cDNA clones from human cell line KG-1. DNA Res. 2:
37-43, 1995.
5. Qin, K.; Ehrmann, D. A.; Cox, N.; Refetoff, S.; Rosenfield, R.
L.: Identification of a functional polymorphism of the human type
5 17-beta-hydroxysteroid dehydrogenase gene associated with polycystic
ovary syndrome. J. Clin. Endocr. Metab. 91: 270-276, 2006. Note:
Erratum: J. Clin. Endocr. Metab. 91: 529 only, 2006.
6. Qin, K.-N.; New, M. I.; Cheng, K.-C.: Molecular cloning of multiple
cDNAs encoding human enzymes structurally related to 3-alpha-hydroxysteroid
dehydrogenase. J. Steroid Biochem. Molec. Biol. 46: 673-679, 1993.
7. White, J.: Personal Communication. London, England 6/14/1999.
*FIELD* CN
John A. Phillips, III - updated: 5/31/2007
*FIELD* CD
Rebekah S. Rasooly: 7/7/1999
*FIELD* ED
terry: 09/14/2012
carol: 12/21/2007
carol: 5/31/2007
alopez: 7/7/1999