AK1C3_HUMAN
ID AK1C3_HUMAN Reviewed; 323 AA.
AC P42330; A8K2V0; B4DL37; Q5T2L1; Q96DJ1; Q96KI8; Q99530; Q9UCX1; Q9UII3;
AC Q9UKL9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 4.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Aldo-keto reductase family 1 member C3;
DE EC=1.1.1.- {ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279};
DE EC=1.1.1.210 {ECO:0000269|PubMed:14672942};
DE EC=1.1.1.53 {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942};
DE EC=1.1.1.62 {ECO:0000269|PubMed:10998348};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase type 5 {ECO:0000303|PubMed:11165022};
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 {ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279};
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=Prostaglandin F synthase {ECO:0000303|PubMed:10622721};
DE Short=PGFS {ECO:0000303|PubMed:10622721};
DE EC=1.1.1.188 {ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279};
DE AltName: Full=Testosterone 17-beta-dehydrogenase 5;
DE EC=1.1.1.239 {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279};
DE EC=1.1.1.64 {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279};
GN Name=AKR1C3;
GN Synonyms=DDH1, HSD17B5, KIAA0119, PGFS {ECO:0000303|PubMed:10622721};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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 structurally
RT related to 3 alpha-hydroxysteroid dehydrogenase.";
RL J. Steroid Biochem. Mol. Biol. 46:673-679(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, FUNCTION, 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 distribution of
RT multiple human 3 alpha-hydroxysteroid 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 proteins
RT in humans.";
RL J. Steroid Biochem. Mol. Biol. 53:41-46(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY,
RP AND VARIANT GLN-5.
RC TISSUE=Prostate;
RX PubMed=9415401; DOI=10.1210/mend.11.13.0026;
RA Lin H.-K., Jez J.M., Schlegel B.P., Peehl D.M., Pachter J.A., Penning T.M.;
RT "Expression and characterization of recombinant type 2 3 alpha-
RT hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of
RT bifunctional 3 alpha/17 beta-HSD activity and cellular distribution.";
RL Mol. Endocrinol. 11:1971-1984(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA]
RP OF 124-190, FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, VARIANT
RP GLN-5, AND SUBCELLULAR LOCATION.
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., Nakajima T.,
RA Ito S., Watanabe K.;
RT "cDNA cloning, expression and characterization of human prostaglandin F
RT synthase.";
RL FEBS Lett. 462:335-340(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES,
RP TISSUE SPECIFICITY, VARIANT GLN-5, CATALYTIC ACTIVITY, AND FUNCTION.
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., Watanabe K.,
RA 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), CATALYTIC ACTIVITY, FUNCTION,
RP TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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., Tabata S.,
RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III. The
RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of
RT 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 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, TISSUE SPECIFICITY,
RP CHARACTERIZATION OF VARIANT ILE-175, AND MUTAGENESIS OF LYS-75.
RX PubMed=9927279; DOI=10.1210/endo.140.2.6531;
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 CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=10998348; DOI=10.1042/0264-6021:3510067;
RA Penning T.M., Burczynski M.E., Jez J.M., Hung C.F., Lin H.K., Ma H.,
RA Moore M., Palackal N., Ratnam K.;
RT "Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the
RT aldo-keto reductase superfamily: functional plasticity and tissue
RT distribution reveals roles in the inactivation and formation of male and
RT female sex hormones.";
RL Biochem. J. 351:67-77(2000).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15047184; DOI=10.1016/j.abb.2004.02.009;
RA Koda N., Tsutsui Y., Niwa H., Ito S., Woodward D.F., Watanabe K.;
RT "Synthesis of prostaglandin F ethanolamide by prostaglandin F synthase and
RT identification of Bimatoprost as a potent inhibitor of the enzyme: new
RT enzyme assay method using LC/ESI/MS.";
RL Arch. Biochem. Biophys. 424:128-136(2004).
RN [18]
RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=14672942; DOI=10.1074/jbc.m313308200;
RA Steckelbroeck S., Jin Y., Gopishetty S., Oyesanmi B., Penning T.M.;
RT "Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto
RT reductase superfamily display significant 3beta-hydroxysteroid
RT dehydrogenase activity: implications for steroid hormone metabolism and
RT action.";
RL J. Biol. Chem. 279:10784-10795(2004).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19010934; DOI=10.1093/jb/mvn152;
RA Kabututu Z., Manin M., Pointud J.C., Maruyama T., Nagata N., Lambert S.,
RA Lefrancois-Martinez A.M., Martinez A., Urade Y.;
RT "Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3
RT and 1B7.";
RL J. Biochem. 145:161-168(2009).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20036328; DOI=10.1016/j.jsbmb.2009.12.009;
RA Byrns M.C., Duan L., Lee S.H., Blair I.A., Penning T.M.;
RT "Aldo-keto reductase 1C3 expression in MCF-7 cells reveals roles in steroid
RT hormone and prostaglandin metabolism that may explain its over-expression
RT in breast cancer.";
RL J. Steroid Biochem. Mol. Biol. 118:177-187(2010).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF ARG-226.
RX PubMed=21851338; DOI=10.1042/bj20111286;
RA Ruiz F.X., Porte S., Gallego O., Moro A., Ardevol A., Del Rio-Espinola A.,
RA Rovira C., Farres J., Pares X.;
RT "Retinaldehyde is a substrate for human aldo-keto reductases of the 1C
RT subfamily.";
RL Biochem. J. 440:335-344(2011).
RN [22]
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., Buerckstuemmer T.,
RA 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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24] {ECO:0007744|PDB:1RY0, ECO:0007744|PDB:1RY8}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH PROSTAGLANDIN H(2);
RP NADPH AND RUTIN, AND ACTIVITY REGULATION.
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 [25] {ECO:0007744|PDB:1S1P, ECO:0007744|PDB:1S1R, ECO:0007744|PDB:1S2A, ECO:0007744|PDB:1S2C}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADP; NADPFLUFENAMIC
RP ACID AND INDOMETHACIN, AND ACTIVITY REGULATION.
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 and
RT indomethacin.";
RL Cancer Res. 64:1802-1810(2004).
RN [26] {ECO:0007744|PDB:1XF0}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH NADP AND DELTA4-3
RP ANDROSTENE-3,17-DIONE, AND IMPORTANCE OF TRP-227 AND PHE-306 IN LIGAND
RP 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: Cytosolic aldo-keto reductase that catalyzes the NADH and
CC NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a
CC NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid
CC nucleus and side chain and regulates the metabolism of androgens,
CC estrogens and progesterone (PubMed:10622721, PubMed:11165022,
CC PubMed:7650035, PubMed:9415401, PubMed:9927279). Displays the ability
CC to catalyze both oxidation and reduction in vitro, but most probably
CC acts as a reductase in vivo since the oxidase activity measured in
CC vitro is inhibited by physiological concentration of NADPH
CC (PubMed:14672942, PubMed:11165022). Acts preferentially as a 17-
CC ketosteroid reductase and has the highest catalytic efficiency of the
CC AKR1C enzyme for the reduction of delta4-androstenedione to form
CC testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to
CC 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone
CC and estrone to 17beta-estradiol (PubMed:15047184, PubMed:20036328,
CC PubMed:10622721, PubMed:11165022, PubMed:10998348, PubMed:19010934).
CC Catalyzes the transformation of the potent androgen dihydrotestosterone
CC (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol
CC (3-alpha-diol) (PubMed:10998348, PubMed:14672942, PubMed:11165022,
CC PubMed:7650035, PubMed:9415401, PubMed:10557352). Also displays
CC retinaldehyde reductase activity toward 9-cis-retinal
CC (PubMed:21851338). {ECO:0000269|PubMed:10557352,
CC ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:14672942,
CC ECO:0000269|PubMed:15047184, ECO:0000269|PubMed:19010934,
CC ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:21851338,
CC ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401,
CC ECO:0000269|PubMed:9927279}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:34783, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.357; Evidence={ECO:0000269|PubMed:11165022,
CC ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401,
CC ECO:0000269|PubMed:9927279};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3alpha-hydroxysteroid + NAD(+) = a 3-oxosteroid + H(+) +
CC NADH; Xref=Rhea:RHEA:34779, ChEBI:CHEBI:15378, ChEBI:CHEBI:36835,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.357; Evidence={ECO:0000269|PubMed:11165022,
CC ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401,
CC ECO:0000269|PubMed:9927279};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin
CC D2; Xref=Rhea:RHEA:10140, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404,
CC ChEBI:CHEBI:57406, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.188; Evidence={ECO:0000269|PubMed:10622721,
CC ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035,
CC ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin
CC H2; Xref=Rhea:RHEA:45312, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:15047184, ECO:0000269|PubMed:19010934};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45314;
CC Evidence={ECO:0000305|PubMed:15047184, ECO:0000305|PubMed:19010934};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + prostaglandin D2 = 11beta-prostaglandin F2 +
CC NADP(+); Xref=Rhea:RHEA:45316, ChEBI:CHEBI:15378, ChEBI:CHEBI:57406,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:85173;
CC Evidence={ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:15047184,
CC ECO:0000269|PubMed:20036328};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45317;
CC Evidence={ECO:0000305|PubMed:10622721, ECO:0000305|PubMed:20036328};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45318;
CC Evidence={ECO:0000305|PubMed:10622721};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + prostaglandin D2-ethanolamide = 11beta-
CC prostaglandin F2-ethanolamide + NADP(+); Xref=Rhea:RHEA:45308,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:85174, ChEBI:CHEBI:85175;
CC Evidence={ECO:0000269|PubMed:15047184};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45309;
CC Evidence={ECO:0000305|PubMed:15047184};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADH; Xref=Rhea:RHEA:14929, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.239; Evidence={ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:9415401,
CC ECO:0000269|PubMed:9927279};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14930;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14931;
CC Evidence={ECO:0000305|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADPH; Xref=Rhea:RHEA:14981, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.64;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022,
CC ECO:0000269|PubMed:20036328, ECO:0000269|PubMed:9415401,
CC ECO:0000269|PubMed:9927279};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14982;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983;
CC Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022,
CC ECO:0000269|PubMed:20036328};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24617;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24613;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614;
CC Evidence={ECO:0000305|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20S)-hydroxypregn-4-en-3-one + NADP(+) = H(+) + NADPH +
CC progesterone; Xref=Rhea:RHEA:42112, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:20036328};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42114;
CC Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(20S)-hydroxypregn-4-en-3-one + NAD(+) = H(+) + NADH +
CC progesterone; Xref=Rhea:RHEA:42108, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:28453, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42109;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110;
CC Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:20036328};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:42116,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:14672942,
CC ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:9415401};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118;
CC Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:14672942};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADH; Xref=Rhea:RHEA:42004,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.53;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
CC Evidence={ECO:0000305|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + H(+) + NADPH =
CC 5alpha-androstane-3alpha,17beta-diol + NADP(+); Xref=Rhea:RHEA:42156,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:9415401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157;
CC Evidence={ECO:0000305|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42158;
CC Evidence={ECO:0000305|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3alpha,17beta-diol + NAD(+) = 3alpha-
CC hydroxy-5alpha-androstan-17-one + H(+) + NADH; Xref=Rhea:RHEA:42124,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942,
CC ECO:0000269|PubMed:9415401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125;
CC Evidence={ECO:0000305|PubMed:10998348, ECO:0000305|PubMed:14672942};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:16297,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.210;
CC Evidence={ECO:0000269|PubMed:14672942};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16299;
CC Evidence={ECO:0000305|PubMed:14672942};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-cis-retinol + NADP(+) = 9-cis-retinal + H(+) + NADPH;
CC Xref=Rhea:RHEA:54916, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273;
CC Evidence={ECO:0000269|PubMed:21851338};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54918;
CC Evidence={ECO:0000305|PubMed:21851338};
CC -!- ACTIVITY REGULATION: Strongly inhibited by nonsteroidal anti-
CC inflammatory drugs (NSAID) including flufenamic acid and indomethacin.
CC Also inhibited by the flavinoid, rutin, and by selective serotonin
CC inhibitors (SSRIs) (PubMed:14979715, PubMed:14996743, PubMed:10557352).
CC The oxidation reaction is inhibited by low micromolar concentrations of
CC NADPH (PubMed:14672942). {ECO:0000269|PubMed:10557352,
CC ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:14979715,
CC ECO:0000269|PubMed:14996743}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11.9 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the
CC oxidation assay) {ECO:0000269|PubMed:10998348};
CC KM=26.2 uM for 17beta-hydroxy-5alpha-androstan-3-one
CC {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11165022};
CC KM=19 uM for 17beta-hydroxy-5alpha-androstan-3-one
CC {ECO:0000269|PubMed:9415401};
CC KM=8.96 uM for 3alpha-hydroxy-5alpha-androstan-17-one (in the
CC reduction assay) {ECO:0000269|PubMed:10998348};
CC KM=17.5 uM for prostaglandin H2 {ECO:0000269|PubMed:19010934};
CC KM=0.3 uM for 9-cis-retinol {ECO:0000269|PubMed:21851338};
CC KM=0.4 uM for 9-cis-retinal {ECO:0000269|PubMed:21851338};
CC KM=142.1 uM for progesterone {ECO:0000269|PubMed:10557352};
CC KM=2.37 uM for 17beta-hydroxy-5alpha-androstan-3-one
CC {ECO:0000269|PubMed:10557352};
CC KM=1.0 uM for androstanediol {ECO:0000269|PubMed:10557352};
CC KM=5 uM for 5alpha-androstan-3,17-dione
CC {ECO:0000269|PubMed:10998348};
CC KM=24.3 uM for testosterone (in the oxidation assay)
CC {ECO:0000269|PubMed:10998348};
CC KM=27.2 uM for 5alpha-androstane-3alpha,17beta-diol
CC {ECO:0000269|PubMed:10998348};
CC Vmax=3.9 nmol/min/mg enzyme with prostaglandin H2 as substrate
CC {ECO:0000269|PubMed:19010934};
CC Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate
CC {ECO:0000269|PubMed:10557352};
CC Vmax=2.45 nmol/min/mg enzyme for 7beta-hydroxy-5alpha-androstan-3-one
CC {ECO:0000269|PubMed:9415401};
CC Vmax=1.8 nmol/min/mg enzyme with 17beta-hydroxy-5alpha-androstan-3-
CC one as substrate {ECO:0000269|PubMed:10557352};
CC Vmax=4.18 nmol/min/mg enzyme for 17beta-hydroxy-5alpha-androstan-3-
CC one reduction {ECO:0000269|PubMed:10998348};
CC Vmax=3.99 nmol/min/mg enzyme for 5alpha-androstane-3alpha,17beta-diol
CC oxidation {ECO:0000269|PubMed:10998348};
CC Vmax=48.4 nmol/min/mg enzyme for 5alpha-androstan-3,17-dione
CC reduction {ECO:0000269|PubMed:10998348};
CC Vmax=10.2 nmol/min/mg enzyme for 3alpha-hydroxy-5alpha-androstan-17-
CC one reduction {ECO:0000269|PubMed:10998348};
CC Vmax=1.34 nmol/min/mg enzyme for testosterone oxydation
CC {ECO:0000269|PubMed:10998348};
CC Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate
CC {ECO:0000269|PubMed:10557352};
CC Note=kcat is 0.044 min(-1) for testosterone oxydation
CC (PubMed:10998348). kcat is 13 min(-1) for 9-cis-retinal as substrate
CC (PubMed:21851338). kcat is 4.18 min(-1) for 17beta-hydroxy-5alpha-
CC androstan-3-one reduction (PubMed:10998348). kcat is 0.37 min(-1) for
CC 3alpha-hydroxy-5alpha-androstan-17-one reduction (PubMed:10998348).
CC kcat is 0.046 min(-1) for 17beta-hydroxy-5alpha-androstan-3-one
CC oxydation (PubMed:10998348). {ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:21851338};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:14672942}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10622721}.
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 -!- TISSUE SPECIFICITY: Expressed in many tissues including adrenal gland,
CC brain, kidney, liver, lung, mammary gland, placenta, small intestine,
CC colon, spleen, prostate and testis. High expression in prostate and
CC mammary gland. In the prostate, higher levels in epithelial cells than
CC in stromal cells. In the brain, expressed in medulla, spinal cord,
CC frontotemporal lobes, thalamus, subthalamic nuclei and amygdala. Weaker
CC expression in the hippocampus, substantia nigra and caudate.
CC {ECO:0000269|PubMed:10557352, ECO:0000269|PubMed:10622721,
CC ECO:0000269|PubMed:11165022, ECO:0000269|PubMed:7650035,
CC ECO:0000269|PubMed:9415401, ECO:0000269|PubMed:9927279}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04619.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC 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 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 PDB; 4WDT; X-ray; 1.50 A; A=1-323.
DR PDB; 4WDU; X-ray; 1.70 A; A=1-323.
DR PDB; 4WDW; X-ray; 1.94 A; A/B=1-323.
DR PDB; 4WDX; X-ray; 1.64 A; A/B=1-323.
DR PDB; 4WRH; X-ray; 1.60 A; A=1-323.
DR PDB; 4XVD; X-ray; 2.81 A; A/B=1-323.
DR PDB; 4XVE; X-ray; 1.55 A; A=1-323.
DR PDB; 4YVV; X-ray; 2.30 A; A/B=1-323.
DR PDB; 4YVX; X-ray; 2.30 A; A/B=1-323.
DR PDB; 4ZFC; X-ray; 2.00 A; A/B=1-323.
DR PDB; 5HNT; X-ray; 2.00 A; A/C=6-320.
DR PDB; 5HNU; X-ray; 2.00 A; A/C=6-320.
DR PDB; 6A7B; X-ray; 2.37 A; A/B=1-323.
DR PDB; 6F2U; X-ray; 1.88 A; A/B=6-319.
DR PDB; 6F78; X-ray; 1.30 A; A/B=6-323.
DR PDB; 6GXK; X-ray; 1.70 A; A/B=6-323.
DR PDB; 7C7F; X-ray; 1.70 A; A/B=1-323.
DR PDB; 7C7G; X-ray; 1.86 A; A/B=1-323.
DR PDB; 7C7H; X-ray; 1.86 A; A/B=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 PDBsum; 4WDT; -.
DR PDBsum; 4WDU; -.
DR PDBsum; 4WDW; -.
DR PDBsum; 4WDX; -.
DR PDBsum; 4WRH; -.
DR PDBsum; 4XVD; -.
DR PDBsum; 4XVE; -.
DR PDBsum; 4YVV; -.
DR PDBsum; 4YVX; -.
DR PDBsum; 4ZFC; -.
DR PDBsum; 5HNT; -.
DR PDBsum; 5HNU; -.
DR PDBsum; 6A7B; -.
DR PDBsum; 6F2U; -.
DR PDBsum; 6F78; -.
DR PDBsum; 6GXK; -.
DR PDBsum; 7C7F; -.
DR PDBsum; 7C7G; -.
DR PDBsum; 7C7H; -.
DR AlphaFoldDB; P42330; -.
DR SMR; P42330; -.
DR BioGRID; 114196; 18.
DR IntAct; P42330; 10.
DR STRING; 9606.ENSP00000369927; -.
DR BindingDB; P42330; -.
DR ChEMBL; CHEMBL4681; -.
DR DrugBank; DB07700; 3-carboxamido-1,3,5(10)-estratrien-17(R)-spiro-2'(5',5'-dimethyl-6'oxo)tetrahydropyran.
DR DrugBank; DB01536; Androstenedione.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB02266; Flufenamic acid.
DR DrugBank; DB13751; Glycyrrhizic acid.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB06077; Lumateperone.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB02056; Prostaglandin D2.
DR DrugBank; DB01698; Rutin.
DR DrugCentral; P42330; -.
DR GuidetoPHARMACOLOGY; 1382; -.
DR SwissLipids; SLP:000000804; -.
DR SwissLipids; SLP:000001647; -. [P42330-1]
DR GlyGen; P42330; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P42330; -.
DR PhosphoSitePlus; P42330; -.
DR SwissPalm; P42330; -.
DR BioMuta; AKR1C3; -.
DR DMDM; 308153646; -.
DR DOSAC-COBS-2DPAGE; P42330; -.
DR EPD; P42330; -.
DR jPOST; P42330; -.
DR MassIVE; P42330; -.
DR MaxQB; P42330; -.
DR PaxDb; P42330; -.
DR PeptideAtlas; P42330; -.
DR PRIDE; P42330; -.
DR ProteomicsDB; 4506; -.
DR ProteomicsDB; 55504; -. [P42330-1]
DR Antibodypedia; 4389; 397 antibodies from 37 providers.
DR DNASU; 8644; -.
DR Ensembl; ENST00000380554.5; ENSP00000369927.3; ENSG00000196139.14. [P42330-1]
DR GeneID; 8644; -.
DR KEGG; hsa:8644; -.
DR MANE-Select; ENST00000380554.5; ENSP00000369927.3; NM_003739.6; NP_003730.4.
DR UCSC; uc001ihu.4; human. [P42330-1]
DR CTD; 8644; -.
DR DisGeNET; 8644; -.
DR GeneCards; AKR1C3; -.
DR HGNC; HGNC:386; AKR1C3.
DR HPA; ENSG00000196139; Tissue enhanced (intestine).
DR MIM; 603966; gene.
DR neXtProt; NX_P42330; -.
DR OpenTargets; ENSG00000196139; -.
DR PharmGKB; PA24679; -.
DR VEuPathDB; HostDB:ENSG00000196139; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000163208; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; P42330; -.
DR OMA; QIAMERG; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; P42330; -.
DR TreeFam; TF106492; -.
DR BioCyc; MetaCyc:HS03054-MON; -.
DR BRENDA; 1.1.1.188; 2681.
DR BRENDA; 1.1.1.21; 2681.
DR BRENDA; 1.1.1.213; 2681.
DR BRENDA; 1.1.1.239; 2681.
DR BRENDA; 1.1.1.357; 2681.
DR BRENDA; 1.1.1.51; 2681.
DR BRENDA; 1.1.1.62; 2681.
DR BRENDA; 1.1.1.64; 2681.
DR BRENDA; 1.3.1.20; 2681.
DR PathwayCommons; P42330; -.
DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-HSA-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SABIO-RK; P42330; -.
DR SignaLink; P42330; -.
DR SIGNOR; P42330; -.
DR BioGRID-ORCS; 8644; 9 hits in 1042 CRISPR screens.
DR ChiTaRS; AKR1C3; human.
DR EvolutionaryTrace; P42330; -.
DR GeneWiki; AKR1C3; -.
DR GenomeRNAi; 8644; -.
DR Pharos; P42330; Tchem.
DR PRO; PR:P42330; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P42330; protein.
DR Bgee; ENSG00000196139; Expressed in jejunal mucosa and 197 other tissues.
DR ExpressionAtlas; P42330; baseline and differential.
DR Genevisible; P42330; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IDA:UniProtKB.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0032052; F:bile acid binding; IBA:GO_Central.
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:0045703; F:ketoreductase activity; IDA:UniProtKB.
DR GO; GO:0047086; F:ketosteroid monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; TAS:Reactome.
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; TAS:Reactome.
DR GO; GO:0036130; F:prostaglandin H2 endoperoxidase reductase activity; TAS:Reactome.
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:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
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: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:0071799; P:cellular response to prostaglandin D 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:0043170; P:macromolecule metabolic process; IEP:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR GO; GO:1900053; P:negative regulation of retinoic acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0010942; P:positive regulation of cell death; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population 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; 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:0001523; P:retinoid 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 CDD; cd19108; AKR_AKR1C1-35; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044482; AKR1C.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
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; Cytoplasm; Lipid metabolism; NAD; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C3"
FT /id="PRO_0000124638"
FT ACT_SITE 55
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 23..24
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT BINDING 50
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT BINDING 117
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 166..167
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT BINDING 190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT BINDING 216..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT BINDING 270..272
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT BINDING 276..280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:14979715,
FT ECO:0000269|PubMed:14996743, ECO:0000269|PubMed:15087468"
FT SITE 54
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000250"
FT SITE 84
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT SITE 227
FT /note="Involved in ligand recognition and product release"
FT /evidence="ECO:0000269|PubMed:15087468"
FT SITE 306
FT /note="Involved in ligand recognition and product release"
FT /evidence="ECO:0000269|PubMed:15087468"
FT VAR_SEQ 1..119
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055798"
FT VARIANT 5
FT /note="H -> Q (in dbSNP:rs12529)"
FT /evidence="ECO:0000269|PubMed:10557352,
FT ECO:0000269|PubMed:10622721, ECO:0000269|PubMed:7626489,
FT ECO:0000269|PubMed:7650035, ECO:0000269|PubMed:7788527,
FT ECO:0000269|PubMed:8274401, ECO:0000269|PubMed:9415401"
FT /id="VAR_013288"
FT VARIANT 66
FT /note="R -> Q (in dbSNP:rs35961894)"
FT /id="VAR_032767"
FT VARIANT 77
FT /note="E -> G (in dbSNP:rs11551177)"
FT /id="VAR_061001"
FT VARIANT 170
FT /note="R -> C (in dbSNP:rs35575889)"
FT /id="VAR_032768"
FT VARIANT 175
FT /note="M -> I (no effect on 17beta-HSD activity;
FT dbSNP:rs1131132)"
FT /evidence="ECO:0000269|PubMed:7650035,
FT ECO:0000269|PubMed:8274401, ECO:0000269|PubMed:9927279"
FT /id="VAR_013289"
FT VARIANT 180
FT /note="P -> S (in dbSNP:rs34186955)"
FT /id="VAR_032769"
FT MUTAGEN 75
FT /note="K->E: No effect on 17beta-HSD activity."
FT /evidence="ECO:0000269|PubMed:9927279"
FT MUTAGEN 226
FT /note="R->P: Decreases in the retinaldehyde reductase
FT activity. 3-fold decrease in the kcat value, whereas the KM
FT value does not vary."
FT /evidence="ECO:0000269|PubMed:21851338"
FT MUTAGEN 226
FT /note="R->Q: Decrease in the retinaldehyde reductase
FT activity. Exhibits changes in both KM and kcat values."
FT /evidence="ECO:0000269|PubMed:21851338"
FT CONFLICT 3
FT /note="S -> P (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 6
FT /note="Q -> K (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="T -> S (in Ref. 6; AAF07272)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="K -> E (in Ref. 1; AAD14011 and 3; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="K -> M (in Ref. 2; AAB41916)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="F -> S (in Ref. 6; AAF07272)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="K -> R (in Ref. 6; AAF07272)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 33..44
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 95..106
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:1ZQ5"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4WDU"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:1S1P"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:1S1P"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 274..280
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:1S1P"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:4WRH"
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
