AK1C1_HUMAN
ID AK1C1_HUMAN Reviewed; 323 AA.
AC Q04828; P52896; Q5SR15; Q7M4N2; Q9UCX2;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Aldo-keto reductase family 1 member C1 {ECO:0000305};
DE EC=1.1.1.- {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699, ECO:0000269|PubMed:8573067};
DE EC=1.1.1.112 {ECO:0000269|PubMed:8573067};
DE EC=1.1.1.209 {ECO:0000269|PubMed:10998348};
DE EC=1.1.1.210 {ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247};
DE EC=1.1.1.357 {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348};
DE EC=1.1.1.51 {ECO:0000269|PubMed:10998348};
DE EC=1.1.1.53 {ECO:0000269|PubMed:10998348};
DE EC=1.1.1.62 {ECO:0000269|PubMed:10998348};
DE EC=1.3.1.20 {ECO:0000269|PubMed:8486699, ECO:0000269|PubMed:8573067};
DE AltName: Full=20-alpha-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:11013348};
DE Short=20-alpha-HSD {ECO:0000303|PubMed:11013348};
DE EC=1.1.1.149 {ECO:0000305|PubMed:11013348};
DE AltName: Full=Chlordecone reductase homolog HAKRC;
DE AltName: Full=Dihydrodiol dehydrogenase 1 {ECO:0000303|PubMed:8573067};
DE Short=DD1 {ECO:0000303|PubMed:8573067};
DE AltName: Full=High-affinity hepatic bile acid-binding protein;
DE Short=HBAB;
GN Name=AKR1C1; Synonyms=DDH, DDH1;
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], CATALYTIC ACTIVITY, PARTIAL PROTEIN SEQUENCE,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=8486699; DOI=10.1016/s0021-9258(18)82220-7;
RA Stolz A., Hammond L., Lou H., Takikawa H., Ronk M., Shively J.E.;
RT "cDNA cloning and expression of the human hepatic bile acid-binding
RT protein. A member of the monomeric reductase gene family.";
RL J. Biol. Chem. 268:10448-10457(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=8132567; DOI=10.1016/s0021-9258(17)37210-1;
RA Lou H., Hammond L., Sharma V., Sparkes R.S., Lusis A.J., Stolz A.;
RT "Genomic organization and chromosomal localization of a novel human hepatic
RT dihydrodiol dehydrogenase with high affinity bile acid binding.";
RL J. Biol. Chem. 269:8416-8422(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Colon;
RX PubMed=7515059; DOI=10.1016/s0021-9258(17)40716-2;
RA Ciaccio P.J., Jaiswal A.K., Tew K.D.;
RT "Regulation of human dihydrodiol dehydrogenase by Michael acceptor
RT xenobiotics.";
RL J. Biol. Chem. 269:15558-15562(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Skin fibroblast;
RX PubMed=11013348; DOI=10.1677/jme.0.0250221;
RA Zhang Y., Dufort I., Rheault P., Luu-The V.;
RT "Characterization of a human 20alpha-hydroxysteroid dehydrogenase.";
RL J. Mol. Endocrinol. 25:221-228(2000).
RN [7]
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 vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Testis;
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-323.
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 [11]
RP PROTEIN SEQUENCE OF 10-31; 40-61; 69-126; 137-153; 162-206; 209-230;
RP 250-267; 271-289 AND 295-323, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8573067; DOI=10.1042/bj3130373;
RA Hara A., Matsuura K., Tamada Y., Sato K., Miyabe Y., Deyashiki Y.,
RA Ishida N.;
RT "Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-
RT acid-binding protein and an oxidoreductase of human colon cells.";
RL Biochem. J. 313:373-376(1996).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-323, AND PROTEIN SEQUENCE OF 18-31;
RP 105-131; 176-193 AND 271-294.
RC TISSUE=Liver;
RX PubMed=8172617; DOI=10.1042/bj2990545;
RA Deyashiki Y., Ogasawara A., Nakayama T., Nakanishi M., Miyabe Y., Sato K.,
RA Hara A.;
RT "Molecular cloning of two human liver 3 alpha-hydroxysteroid/dihydrodiol
RT dehydrogenase isoenzymes that are identical with chlordecone reductase and
RT bile-acid binder.";
RL Biochem. J. 299:545-552(1994).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND TISSUE SPECIFICITY.
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, 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 [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19218247; DOI=10.1074/jbc.m809465200;
RA Jin Y., Duan L., Lee S.H., Kloosterboer H.J., Blair I.A., Penning T.M.;
RT "Human cytosolic hydroxysteroid dehydrogenases of the aldo-ketoreductase
RT superfamily catalyze reduction of conjugated steroids: implications for
RT phase I and phase II steroid hormone metabolism.";
RL J. Biol. Chem. 284:10013-10022(2009).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH NADP AND
RP 20ALPHA-HYDROXY-PROGESTERONE, AND MUTAGENESIS OF GLU-127; HIS-222; ARG-304;
RP TYR-305; THR-307 AND ASP-309.
RX PubMed=12899831; DOI=10.1016/s0022-2836(03)00762-9;
RA Couture J.-F., Legrand P., Cantin L., Luu-The V., Labrie F., Breton R.;
RT "Human 20alpha-hydroxysteroid dehydrogenase: crystallographic and site-
RT directed mutagenesis studies lead to the identification of an alternative
RT binding site for C21-steroids.";
RL J. Mol. Biol. 331:593-604(2003).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) IN COMPLEX WITH NADP AND
RP 3-CHLORO-5-PHENYLSALICYLIC ACID.
RX PubMed=21414777; DOI=10.1016/j.bmcl.2011.01.076;
RA El-Kabbani O., Dhagat U., Soda M., Endo S., Matsunaga T., Hara A.;
RT "Probing the inhibitor selectivity pocket of human 20alpha-hydroxysteroid
RT dehydrogenase (AKR1C1) with X-ray crystallography and site-directed
RT mutagenesis.";
RL Bioorg. Med. Chem. Lett. 21:2564-2567(2011).
CC -!- FUNCTION: Cytosolic aldo-keto reductase that catalyzes the NADH and
CC NADPH-dependent reduction of ketosteroids to hydroxysteroids
CC (PubMed:19218247). Most probably acts as a reductase in vivo since the
CC oxidase activity measured in vitro is inhibited by physiological
CC concentrations of NADPH (PubMed:14672942). Displays a broad positional
CC specificity acting on positions 3, 17 and 20 of steroids and regulates
CC the metabolism of hormones like estrogens and androgens
CC (PubMed:10998348). May also reduce conjugated steroids such as 5alpha-
CC dihydrotestosterone sulfate (PubMed:19218247). Displays affinity for
CC bile acids (PubMed:8486699). {ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247,
CC ECO:0000269|PubMed:8486699}.
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:10998348,
CC ECO:0000269|PubMed:11013348};
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:10998348,
CC ECO:0000269|PubMed:11013348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NADP(+) = 17alpha-
CC hydroxyprogesterone + H(+) + NADPH; Xref=Rhea:RHEA:15857,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16418, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.149;
CC Evidence={ECO:0000305|PubMed:11013348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15859;
CC Evidence={ECO:0000305|PubMed:11013348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NAD(+) = 17alpha-
CC hydroxyprogesterone + H(+) + NADH; Xref=Rhea:RHEA:15853,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16418, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.149;
CC Evidence={ECO:0000305|PubMed:11013348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15855;
CC Evidence={ECO:0000305|PubMed:11013348};
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:11013348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42114;
CC Evidence={ECO:0000269|PubMed:10998348};
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:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol +
CC H(+) + NADPH; Xref=Rhea:RHEA:16729, ChEBI:CHEBI:10702,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18135, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.20; Evidence={ECO:0000269|PubMed:8486699,
CC ECO:0000269|PubMed:8573067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-indan-1-ol + NAD(+) = H(+) + indan-1-one + NADH;
CC Xref=Rhea:RHEA:16317, ChEBI:CHEBI:15378, ChEBI:CHEBI:17404,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:156384;
CC EC=1.1.1.112; Evidence={ECO:0000269|PubMed:8573067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-indan-1-ol + NADP(+) = H(+) + indan-1-one + NADPH;
CC Xref=Rhea:RHEA:16321, ChEBI:CHEBI:15378, ChEBI:CHEBI:17404,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:156384;
CC EC=1.1.1.112; Evidence={ECO:0000269|PubMed:8573067};
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:10998348, ECO:0000269|PubMed:14672942};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|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, ECO:0000269|PubMed:19218247};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16299;
CC Evidence={ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:19218247};
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:0000269|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:42120,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42121;
CC Evidence={ECO:0000269|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:20377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.209;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20378;
CC Evidence={ECO:0000269|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:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42158;
CC Evidence={ECO:0000269|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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125;
CC Evidence={ECO:0000269|PubMed:10998348};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24617;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000269|PubMed:10998348};
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:0000269|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24614;
CC Evidence={ECO:0000269|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=1.1.1.51;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14982;
CC Evidence={ECO:0000269|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20alpha-hydroxy-5beta-pregnan-3-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:42168, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30154, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78666; Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42169;
CC Evidence={ECO:0000269|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-
CC 3,20-dione + H(+) + NADPH; Xref=Rhea:RHEA:22944, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16229, ChEBI:CHEBI:30154, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5beta-pregnane-20-one + H(+) + NADPH =
CC 3beta,20alpha-dihydroxy-5beta-pregnane + NADP(+);
CC Xref=Rhea:RHEA:65496, ChEBI:CHEBI:15378, ChEBI:CHEBI:16229,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:156526;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65497;
CC Evidence={ECO:0000269|PubMed:10998348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3beta,5alpha,17beta)-3-hydroxyandrostan-17-yl sulfate +
CC NADP(+) = 5alpha-dihydrotestosterone sulfate + H(+) + NADPH;
CC Xref=Rhea:RHEA:53120, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:136982, ChEBI:CHEBI:136983;
CC Evidence={ECO:0000269|PubMed:19218247};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53122;
CC Evidence={ECO:0000269|PubMed:19218247};
CC -!- ACTIVITY REGULATION: Inhibited by hexestrol with an IC(50) of 9.5 uM,
CC 1,10-phenanthroline with an IC(50) of 55 uM, 1,7-phenanthroline with an
CC IC(50) of 72 uM, flufenamic acid with an IC(50) of 6.0 uM, indomethacin
CC with an IC(50) of 140 uM, ibuprofen with an IC(50) of 950 uM,
CC lithocholic acid with an IC(50) of 25 uM, ursodeoxycholic acid with an
CC IC(50) of 340 uM and chenodeoxycholic acid with an IC(50) of 570 uM
CC (PubMed:8573067). The oxidation reaction is inhibited by low micromolar
CC concentrations of NADPH (PubMed:14672942).
CC {ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:8573067}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for (s)-tetralol {ECO:0000269|PubMed:8573067};
CC KM=38 uM for (s)-indan-1-ol {ECO:0000269|PubMed:8573067};
CC KM=580 uM for benzene dihydrodiol ((1R,2R)-1,2-dihydrobenzene-1,2-
CC diol) {ECO:0000269|PubMed:8573067};
CC KM=3 uM for 5-beta-pregnane-3-alpha,20-alpha-diol
CC {ECO:0000269|PubMed:8573067};
CC KM=3 uM for 5-beta-pregnan-20-alpha-ol-3-one
CC {ECO:0000269|PubMed:8573067};
CC KM=12 uM for 4-pregnen-20-alpha-ol-3-one
CC {ECO:0000269|PubMed:8573067};
CC KM=133 uM for 9-alpha,11-beta-prostaglandin F(2)
CC {ECO:0000269|PubMed:8573067};
CC KM=2 uM for 5-beta-pregnan-3-alpha-ol-20-one
CC {ECO:0000269|PubMed:8573067};
CC KM=1 uM for 5-beta-androstane-3,17-dione
CC {ECO:0000269|PubMed:8573067};
CC KM=12 uM for prostaglandin D(2) {ECO:0000269|PubMed:8573067};
CC KM=2.65 uM for progesterone (in the reduction assay)
CC {ECO:0000269|PubMed:10998348};
CC KM=16.2 uM for 3beta-hydroxy-5beta-pregnane-20-one (in the reduction
CC assay) {ECO:0000269|PubMed:10998348};
CC KM=14.7 uM for (20S)-hydroxypregn-4-en-3-one (in the oxidation assay)
CC {ECO:0000269|PubMed:10998348};
CC KM=80.6 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the
CC reduction assay) {ECO:0000269|PubMed:10998348};
CC KM=4.2 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction
CC assay) {ECO:0000269|PubMed:19218247};
CC KM=31.7 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the
CC oxidation assay) {ECO:0000269|PubMed:10998348};
CC KM=6.77 uM for 5alpha-androstan-3,17-dione (in the reduction assay)
CC {ECO:0000269|PubMed:10998348};
CC KM=41.7 uM for 3alpha-hydroxy-5alpha-androstan-17-one/androsterone
CC (in the oxidation assay) {ECO:0000269|PubMed:10998348};
CC KM=21.0 uM for 3alpha-hydroxy-5alpha-androstan-17-one/androsterone
CC (in the reduction assay) {ECO:0000269|PubMed:10998348};
CC KM=39.8 uM for testosterone (in the oxidation assay)
CC {ECO:0000269|PubMed:10998348};
CC KM=19.4 uM for 20alpha-hydroxy-5beta-pregnan-3-one (in the oxidation
CC assay) {ECO:0000269|PubMed:10998348};
CC KM=5.2 uM for 5alpha-dihydrotestosterone sulfate (in the reduction
CC assay) {ECO:0000269|PubMed:19218247};
CC Vmax=7.85 nmol/min/mg enzyme for the reduction of progesterone
CC {ECO:0000269|PubMed:10998348};
CC Vmax=29.7 nmol/min/mg enzyme for the reduction of 3beta-hydroxy-
CC 5beta-pregnane-20-one {ECO:0000269|PubMed:10998348};
CC Vmax=31.9 nmol/min/mg enzyme for the oxidation of (20S)-hydroxypregn-
CC 4-en-3-one {ECO:0000269|PubMed:10998348};
CC Vmax=18.0 nmol/min/mg enzyme for the reduction of 17beta-hydroxy-
CC 5alpha-androstan-3-one {ECO:0000269|PubMed:10998348};
CC Vmax=0.72 nmol/min/mg enzyme for the oxidation of 17beta-hydroxy-
CC 5alpha-androstan-3-one {ECO:0000269|PubMed:10998348};
CC Vmax=12.8 nmol/min/mg enzyme for the reduction of 5alpha-androstan-
CC 3,17-dione {ECO:0000269|PubMed:10998348};
CC Vmax=1.59 nmol/min/mg enzyme for the oxidation of 3alpha-hydroxy-
CC 5alpha-androstan-17-one/androsterone {ECO:0000269|PubMed:10998348};
CC Vmax=4.79 nmol/min/mg enzyme for the reduction of 3alpha-hydroxy-
CC 5alpha-androstan-17-one/androsterone {ECO:0000269|PubMed:10998348};
CC Vmax=1.2 nmol/min/mg enzyme for the oxidation of testosterone
CC {ECO:0000269|PubMed:10998348};
CC Vmax=87.5 nmol/min/mg enzyme for the oxidation of 20alpha-hydroxy-
CC 5beta-pregnan-3-one {ECO:0000269|PubMed:10998348};
CC Note=kcat is 0.29 min-1 for the reduction of progesterone
CC (PubMed:10998348). kcat is 1.1 min-1 for the reduction of 3beta-
CC hydroxy-5beta-pregnane-20-one (PubMed:10998348). kcat is 1.2 min-1
CC for the oxidation of (20S)-hydroxypregn-4-en-3-one (PubMed:10998348).
CC kcat is 0.66 min-1 for the reduction of 17beta-hydroxy-5alpha-
CC androstan-3-one (PubMed:10998348). kcat is 0.026 min-1 for the
CC oxidation of 17beta-hydroxy-5alpha-androstan-3-one (PubMed:10998348).
CC kcat is 0.47 min-1 for the reduction of 5alpha-androstan-3,17-dione
CC (PubMed:10998348). kcat is 0.06 min-1 for the oxidation of 3alpha-
CC hydroxy-5alpha-androstan-17-one/androsterone (PubMed:10998348). kcat
CC is 0.18 min-1 for the reduction of 3alpha-hydroxy-5alpha-androstan-
CC 17-one/androsterone (PubMed:10998348). kcat is 0.044 min-1 for the
CC oxidation of testosterone (PubMed:10998348). kcat is 3.23 min-1 for
CC the oxidation of 20alpha-hydroxy-5beta-pregnan-3-one
CC (PubMed:10998348). kcat is 0.74 min-1 for the reduction of 17beta-
CC hydroxy-5alpha-androstan-3-one (PubMed:19218247). kcat is 0.75 min-1
CC for the reduction of 5alpha-dihydrotestosterone sulfate
CC (PubMed:19218247). {ECO:0000269|PubMed:10998348,
CC ECO:0000269|PubMed:19218247};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:14672942}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12899831,
CC ECO:0000269|PubMed:21414777}.
CC -!- INTERACTION:
CC Q04828; P26045: PTPN3; NbExp=6; IntAct=EBI-2116455, EBI-1047946;
CC Q04828; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-2116455, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:8486699}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested including liver,
CC prostate, testis, adrenal gland, brain, uterus, mammary gland and
CC keratinocytes. Highest levels found in liver, mammary gland and brain.
CC {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:11013348}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; M86609; AAB02880.1; -; mRNA.
DR EMBL; U05861; AAA18115.1; -; Genomic_DNA.
DR EMBL; U05853; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05854; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05855; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05857; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05858; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05859; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05860; AAA18115.1; JOINED; Genomic_DNA.
DR EMBL; U05684; AAA16227.1; -; mRNA.
DR EMBL; AB031083; BAA92883.1; -; mRNA.
DR EMBL; AB032150; BAA92886.1; -; Genomic_DNA.
DR EMBL; BT007197; AAP35861.1; -; mRNA.
DR EMBL; AC091817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713867; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015490; AAH15490.1; -; mRNA.
DR EMBL; BC020216; AAH20216.1; -; mRNA.
DR EMBL; BC040210; AAH40210.1; -; mRNA.
DR EMBL; S68290; AAD14012.1; -; mRNA.
DR EMBL; D26124; BAA05121.1; -; mRNA.
DR CCDS; CCDS7061.1; -.
DR PIR; A53436; A53436.
DR PIR; I73675; I73675.
DR PIR; S59619; S59619.
DR PIR; S61515; S61515.
DR RefSeq; NP_001344.2; NM_001353.5.
DR PDB; 1MRQ; X-ray; 1.59 A; A=2-323.
DR PDB; 3C3U; X-ray; 1.80 A; A=1-323.
DR PDB; 3GUG; X-ray; 1.90 A; A=1-323.
DR PDB; 3NTY; X-ray; 1.87 A; A=1-323.
DR PDB; 4YVP; X-ray; 2.60 A; A/B=1-323.
DR PDB; 6A7A; X-ray; 2.37 A; A=1-323.
DR PDB; 6IJX; X-ray; 2.20 A; A=1-323.
DR PDBsum; 1MRQ; -.
DR PDBsum; 3C3U; -.
DR PDBsum; 3GUG; -.
DR PDBsum; 3NTY; -.
DR PDBsum; 4YVP; -.
DR PDBsum; 6A7A; -.
DR PDBsum; 6IJX; -.
DR AlphaFoldDB; Q04828; -.
DR SMR; Q04828; -.
DR BioGRID; 108012; 19.
DR IntAct; Q04828; 8.
DR MINT; Q04828; -.
DR STRING; 9606.ENSP00000370254; -.
DR BindingDB; Q04828; -.
DR ChEMBL; CHEMBL5905; -.
DR DrugBank; DB04674; 2-HYDROXY-3,5-DIIODOBENZOIC ACID.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB07768; Epitestosterone.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB07931; Hexestrol.
DR DrugBank; DB06077; Lumateperone.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB00461; Nabumetone.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03467; Naringenin.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB12612; Ozanimod.
DR DrugBank; DB00936; Salicylic acid.
DR DrugCentral; Q04828; -.
DR SwissLipids; SLP:000000802; -.
DR iPTMnet; Q04828; -.
DR PhosphoSitePlus; Q04828; -.
DR SwissPalm; Q04828; -.
DR BioMuta; AKR1C1; -.
DR DMDM; 416877; -.
DR EPD; Q04828; -.
DR jPOST; Q04828; -.
DR MassIVE; Q04828; -.
DR MaxQB; Q04828; -.
DR PaxDb; Q04828; -.
DR PeptideAtlas; Q04828; -.
DR PRIDE; Q04828; -.
DR ProteomicsDB; 58285; -.
DR Antibodypedia; 23969; 329 antibodies from 37 providers.
DR CPTC; Q04828; 2 antibodies.
DR DNASU; 1645; -.
DR Ensembl; ENST00000380872.9; ENSP00000370254.4; ENSG00000187134.14.
DR GeneID; 1645; -.
DR KEGG; hsa:1645; -.
DR MANE-Select; ENST00000380872.9; ENSP00000370254.4; NM_001353.6; NP_001344.2.
DR UCSC; uc001ihq.4; human.
DR CTD; 1645; -.
DR DisGeNET; 1645; -.
DR GeneCards; AKR1C1; -.
DR HGNC; HGNC:384; AKR1C1.
DR HPA; ENSG00000187134; Tissue enriched (liver).
DR MalaCards; AKR1C1; -.
DR MIM; 600449; gene.
DR neXtProt; NX_Q04828; -.
DR OpenTargets; ENSG00000187134; -.
DR PharmGKB; PA24677; -.
DR VEuPathDB; HostDB:ENSG00000187134; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000163208; -.
DR InParanoid; Q04828; -.
DR OMA; RMNFPAR; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; Q04828; -.
DR TreeFam; TF106492; -.
DR BioCyc; MetaCyc:HS10741-MON; -.
DR BRENDA; 1.1.1.149; 2681.
DR BRENDA; 1.1.1.270; 2681.
DR BRENDA; 1.1.1.357; 2681.
DR BRENDA; 1.1.1.50; 2681.
DR BRENDA; 1.3.1.20; 2681.
DR PathwayCommons; Q04828; -.
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-975634; Retinoid metabolism and transport.
DR SABIO-RK; Q04828; -.
DR SignaLink; Q04828; -.
DR SIGNOR; Q04828; -.
DR BioGRID-ORCS; 1645; 13 hits in 1001 CRISPR screens.
DR ChiTaRS; AKR1C1; human.
DR EvolutionaryTrace; Q04828; -.
DR GeneWiki; AKR1C1; -.
DR GenomeRNAi; 1645; -.
DR Pharos; Q04828; Tchem.
DR PRO; PR:Q04828; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q04828; protein.
DR Bgee; ENSG00000187134; Expressed in islet of Langerhans and 98 other tissues.
DR ExpressionAtlas; Q04828; baseline and differential.
DR Genevisible; Q04828; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0047006; F:17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0033703; F:3beta-hydroxy-5beta-steroid dehydrogenase 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; TAS:UniProtKB.
DR GO; GO:0047044; F:androstan-3-alpha,17-beta-diol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047042; F:androsterone dehydrogenase (B-specific) activity; IDA:UniProtKB.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0032052; F:bile acid binding; IDA:UniProtKB.
DR GO; GO:0031406; F:carboxylic acid binding; IDA:UniProtKB.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047718; F:indanol dehydrogenase activity; IEA:UniProtKB-EC.
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:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; IEA:UniProtKB-EC.
DR GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0015721; P:bile acid and bile salt transport; TAS:UniProtKB.
DR GO; GO:0008206; P:bile acid metabolic process; IDA:UniProtKB.
DR GO; GO:0071395; P:cellular response to jasmonic acid stimulus; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; TAS:UniProtKB.
DR GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB.
DR GO; GO:0007586; P:digestion; IDA:UniProtKB.
DR GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; TAS: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; IBA:GO_Central.
DR GO; GO:0046683; P:response to organophosphorus; 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; IBA:GO_Central.
DR GO; GO:0006805; P:xenobiotic metabolic process; NAS: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; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C1"
FT /id="PRO_0000124633"
FT ACT_SITE 55
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 20..24
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12899831,
FT ECO:0000269|PubMed:21414777"
FT BINDING 24
FT /ligand="substrate"
FT BINDING 50
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12899831,
FT ECO:0000269|PubMed:21414777"
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:12899831,
FT ECO:0000269|PubMed:21414777"
FT BINDING 190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12899831,
FT ECO:0000269|PubMed:21414777"
FT BINDING 216..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12899831,
FT ECO:0000269|PubMed:21414777"
FT BINDING 222
FT /ligand="substrate"
FT BINDING 227
FT /ligand="substrate"
FT BINDING 270..280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:12899831,
FT ECO:0000269|PubMed:21414777"
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"
FT SITE 222
FT /note="May be involved in the mediating step between the
FT transformation of progesterone and the release of the
FT cofactor"
FT VARIANT 170
FT /note="R -> H (in dbSNP:rs139588200)"
FT /id="VAR_048214"
FT VARIANT 172
FT /note="Q -> L (in dbSNP:rs760575583)"
FT /id="VAR_048215"
FT MUTAGEN 127
FT /note="E->D: 30-fold decrease in k(cat)/K(m) value for
FT progesterone reduction; no effect on the K(m) value."
FT /evidence="ECO:0000269|PubMed:12899831"
FT MUTAGEN 222
FT /note="H->I: Marked decrease in k(cat)/K(m) value for
FT progesterone; 24-fold decrease for progesterone reduction;
FT 18-fold decrease for 20alpha-OHProg oxidation. 95-fold
FT decrease in K(m) value for NADPH."
FT /evidence="ECO:0000269|PubMed:12899831"
FT MUTAGEN 222
FT /note="H->S: Marked decrease in k(cat)/K(m) value for
FT progesterone; 10-fold decrease for progesterone reduction;
FT 3-fold decrease for 20alpha-OHProg oxidation. 10-fold
FT decrease in K(m) value for NADPH."
FT /evidence="ECO:0000269|PubMed:12899831"
FT MUTAGEN 304
FT /note="R->L: 70-fold decrease in progesterone reduction. No
FT effect on DHT reduction."
FT /evidence="ECO:0000269|PubMed:12899831"
FT MUTAGEN 305
FT /note="Y->F: No effect on progesterone reduction."
FT /evidence="ECO:0000269|PubMed:12899831"
FT MUTAGEN 307
FT /note="T->V: No effect on progesterone reduction."
FT /evidence="ECO:0000269|PubMed:12899831"
FT MUTAGEN 309
FT /note="D->V: No effect on progesterone reduction."
FT /evidence="ECO:0000269|PubMed:12899831"
FT CONFLICT 3
FT /note="S -> A (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="V -> D (in Ref. 4; no nucleotide entry and 10;
FT AAD14012)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="G -> E (in Ref. 4; no nucleotide entry and 10;
FT AAD14012)"
FT /evidence="ECO:0000305"
FT CONFLICT 171..172
FT /note="RQ -> ST (in Ref. 4; no nucleotide entry and 10;
FT AAD14012)"
FT /evidence="ECO:0000305"
FT CONFLICT 183..184
FT /note="KY -> QV (in Ref. 4; no nucleotide entry and 10;
FT AAD14012)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="H -> L (in Ref. 4; no nucleotide entry and 10;
FT AAD14012)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="F -> I (in Ref. 4; no nucleotide entry and 10;
FT AAD14012)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 33..44
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 92..106
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:3C3U"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4YVP"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:3GUG"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:1MRQ"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:1MRQ"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 274..280
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:1MRQ"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:6IJX"
SQ SEQUENCE 323 AA; 36788 MW; 9CB215478FBD29D5 CRC64;
MDSKYQCVKL NDGHFMPVLG FGTYAPAEVP KSKALEATKL AIEAGFRHID SAHLYNNEEQ
VGLAIRSKIA DGSVKREDIF YTSKLWCNSH RPELVRPALE RSLKNLQLDY VDLYLIHFPV
SVKPGEEVIP KDENGKILFD TVDLCATWEA VEKCKDAGLA KSIGVSNFNR RQLEMILNKP
GLKYKPVCNQ VECHPYFNQR KLLDFCKSKD IVLVAYSALG SHREEPWVDP NSPVLLEDPV
LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTS EEMKAIDGLN
RNVRYLTLDI FAGPPNYPFS DEY
