AK1C2_HUMAN
ID AK1C2_HUMAN Reviewed; 323 AA.
AC P52895; A8K2N9; B4DKR9; Q14133; Q5SR16; Q7M4N1; Q96A71;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Aldo-keto reductase family 1 member C2 {ECO:0000305};
DE EC=1.-.-.- {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:19218247, 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=1.1.1.53 {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942};
DE EC=1.1.1.62 {ECO:0000269|PubMed:10998348};
DE EC=1.3.1.20 {ECO:0000269|PubMed:8573067};
DE AltName: Full=3-alpha-HSD3;
DE AltName: Full=Chlordecone reductase homolog HAKRD;
DE AltName: Full=Dihydrodiol dehydrogenase 2 {ECO:0000303|PubMed:8573067};
DE Short=DD-2 {ECO:0000303|PubMed:8573067};
DE Short=DD2 {ECO:0000303|PubMed:8573067};
DE AltName: Full=Dihydrodiol dehydrogenase/bile acid-binding protein;
DE Short=DD/BABP;
DE AltName: Full=Type III 3-alpha-hydroxysteroid dehydrogenase;
DE EC=1.1.1.357 {ECO:0000269|PubMed:15929998, ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338, ECO:0000269|PubMed:8573067};
GN Name=AKR1C2; Synonyms=DDH2;
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).
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 [MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=8011662; DOI=10.1016/0005-2728(94)90144-9;
RA Ciaccio P.J., Tew K.D.;
RT "cDNA and deduced amino acid sequences of a human colon dihydrodiol
RT dehydrogenase.";
RL Biochim. Biophys. Acta 1186:129-132(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT TYR-46.
RX PubMed=7959017; DOI=10.1016/0378-1119(94)90176-7;
RA Qin K.-N., Khanna M., Cheng K.-C.;
RT "Structure of a gene coding for human dihydrodiol dehydrogenase/bile acid-
RT binding protein.";
RL Gene 149:357-361(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=8920937; DOI=10.1006/bbrc.1996.1684;
RA Dufort I., Soucy P., Labrie F., Luu-The V.;
RT "Molecular cloning of human type 3 3 alpha-hydroxysteroid dehydrogenase
RT that differs from 20 alpha-hydroxysteroid dehydrogenase by seven amino
RT acids.";
RL Biochem. Biophys. Res. Commun. 228:474-479(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=9716498; DOI=10.1042/bj3340399;
RA Shiraishi H., Ishikura S., Matsuura K., Deyashiki Y., Ninomiya M.,
RA Sakai S., Hara A.;
RT "Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2)
RT and tissue distribution of its mRNA.";
RL Biochem. J. 334:399-405(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
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 [7]
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 [8]
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 [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, 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 [11]
RP PROTEIN SEQUENCE OF 2-31; 40-62; 69-100; 105-131; 137-153; 162-206;
RP 209-231; 250-269 AND 271-323, 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 PROTEIN SEQUENCE OF 10-29; 40-55; 76-101; 105-128; 137-146; 162-197;
RP 208-223; 259-270 AND 305-322, 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 [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP 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 TISSUE SPECIFICITY, VARIANTS SRXY8 VAL-79; GLN-90; GLN-222 AND THR-300, AND
RP CHARACTERIZATION OF VARIANTS SRXY8 VAL-79; GLN-90; GLN-222 AND THR-300.
RX PubMed=21802064; DOI=10.1016/j.ajhg.2011.06.009;
RA Fluck C.E., Meyer-Boni M., Pandey A.V., Kempna P., Miller W.L.,
RA Schoenle E.J., Biason-Lauber A.;
RT "Why boys will be boys: two pathways of fetal testicular androgen
RT biosynthesis are needed for male sexual differentiation.";
RL Am. J. Hum. Genet. 89:201-218(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH NADP AND
RP URSODEOXYCHOLATE.
RX PubMed=11513593; DOI=10.1021/bi010919a;
RA Jin Y., Stayrook S.E., Albert R.H., Palackal N.T., Penning T.M., Lewis M.;
RT "Crystal structure of human type III 3alpha-hydroxysteroid
RT dehydrogenase/bile acid binding protein complexed with NADP(+) and
RT ursodeoxycholate.";
RL Biochemistry 40:10161-10168(2001).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH NADP AND
RP TESTOSTERONE.
RX PubMed=11514561; DOI=10.1074/jbc.m105610200;
RA Nahoum V., Gangloff A., Legrand P., Zhu D.-W., Cantin L., Zhorov B.S.,
RA Luu-The V., Labrie F., Breton R., Lin S.X.;
RT "Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in
RT complex with testosterone and NADP at 1.25-A resolution.";
RL J. Biol. Chem. 276:42091-42098(2001).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-323 IN COMPLEX WITH NADP,
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-301 AND ARG-304.
RX PubMed=15929998; DOI=10.1110/ps.051353205;
RA Couture J.F., de Jesus-Tran K.P., Roy A.M., Cantin L., Cote P.L.,
RA Legrand P., Luu-The V., Labrie F., Breton R.;
RT "Comparison of crystal structures of human type 3 3alpha-hydroxysteroid
RT dehydrogenase reveals an 'induced-fit' mechanism and a conserved basic
RT motif involved in the binding of androgen.";
RL Protein Sci. 14:1485-1497(2005).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=17034817; DOI=10.1016/j.jmb.2006.09.030;
RA Faucher F., Pereira de Jesus-Tran K., Cantin L., Luu-The V., Labrie F.,
RA Breton R.;
RT "Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase
RT (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular
RT determinants responsible for the unique 17alpha-reductive activity of this
RT enzyme.";
RL J. Mol. Biol. 364:747-763(2006).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 3-323 IN COMPLEX WITH NADP AND
RP HYDROXYANDROSTERONE, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP TYR-24 AND LYS-31.
RX PubMed=17442338; DOI=10.1016/j.jmb.2007.03.058;
RA Faucher F., Cantin L., Pereira de Jesus-Tran K., Lemieux M., Luu-The V.,
RA Labrie F., Breton R.;
RT "Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids
RT differently from other aldo-keto reductases: identification and
RT characterization of amino acid residues critical for substrate binding.";
RL J. Mol. Biol. 369:525-540(2007).
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). Works in concert with the 5-alpha/5-beta-steroid
CC reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-
CC alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most
CC potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-
CC androstane-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:15929998,
CC PubMed:17034817, PubMed:17442338, PubMed:8573067). Also specifically
CC able to produce 17beta-hydroxy-5alpha-androstan-3-one/5alphaDHT
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:15929998,
CC ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338,
CC ECO:0000269|PubMed:19218247, ECO:0000269|PubMed:8486699,
CC ECO:0000269|PubMed:8573067}.
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:15929998,
CC ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338,
CC ECO:0000269|PubMed:8573067};
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:15929998,
CC ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338,
CC 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 ECO:0000269|PubMed:19218247};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42117;
CC Evidence={ECO:0000269|PubMed:10998348};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42118;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942,
CC 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, ECO:0000269|PubMed:14672942};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42005;
CC Evidence={ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:14672942};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42006;
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:14672942};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42125;
CC Evidence={ECO:0000269|PubMed:14672942};
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=(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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42113;
CC Evidence={ECO:0000269|PubMed:10998348};
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};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42110;
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=(3beta,5alpha,17beta)-3-hydroxy-androstan-17-yl sulfate +
CC NADP(+) = 5alpha-dihydrotestosterone sulfate + H(+) + NADPH;
CC Xref=Rhea:RHEA:53136, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:133105, ChEBI:CHEBI:136982;
CC Evidence={ECO:0000269|PubMed:19218247};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53138;
CC Evidence={ECO:0000269|PubMed:19218247};
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;
CC Evidence={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 -!- ACTIVITY REGULATION: Inhibited by hexestrol with an IC(50) of 2.8 uM,
CC 1,10-phenanthroline with an IC(50) of 2100 uM, 1,7-phenanthroline with
CC an IC(50) of 1500 uM, flufenamic acid with an IC(50) of 0.9 uM,
CC indomethacin with an IC(50) of 75 uM, ibuprofen with an IC(50) of 6.9
CC uM, lithocholic acid with an IC(50) of 0.07 uM, ursodeoxycholic acid
CC with an IC(50) of 0.08 uM and chenodeoxycholic acid with an IC(50) of
CC 0.13 uM (PubMed:8573067). The oxidation reaction is inhibited by low
CC micromolar concentrations of NADPH (PubMed:14672942).
CC {ECO:0000269|PubMed:14672942, ECO:0000269|PubMed:8573067}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=260 uM for (s)-tetralol {ECO:0000269|PubMed:8573067};
CC KM=520 uM for (s)-indan-1-ol {ECO:0000269|PubMed:8573067};
CC KM=5000 uM for benzene dihydrodiol {ECO:0000269|PubMed:8573067};
CC KM=1 uM for 5-beta-pregnane-3-alpha,20-alpha-diol
CC {ECO:0000269|PubMed:8573067};
CC KM=208 uM for 9-alpha,11-beta-prostaglandin F(2)
CC {ECO:0000269|PubMed:8573067};
CC KM=0.3 uM for 5-beta-androstane-3,17-dione
CC {ECO:0000269|PubMed:8573067};
CC KM=79 uM for prostaglandin D2 {ECO:0000269|PubMed:8573067};
CC KM=26 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction
CC assay) {ECO:0000269|PubMed:10998348};
CC KM=2.9 uM for 17beta-hydroxy-5alpha-androstan-3-one (in the reduction
CC assay) {ECO:0000269|PubMed:19218247};
CC KM=6.26 uM for 5alpha-androstan-3,17-dione (in the reduction assay)
CC {ECO:0000269|PubMed:10998348};
CC KM=9.73 uM for 3alpha-hydroxy-5alpha-androstan-17-one/androsterone
CC (in the oxidation assay) {ECO:0000269|PubMed:10998348};
CC KM=22.0 uM for 5alpha-androstane-3alpha,17beta-diol (in the oxidation
CC assay) {ECO:0000269|PubMed:10998348};
CC KM=4.2 uM for 5alpha-dihydrotestosterone sulfate (in the reduction
CC assay) {ECO:0000269|PubMed:19218247};
CC Vmax=6.24 nmol/min/mg enzyme for the reduction of 17beta-hydroxy-
CC 5alpha-androstan-3-one {ECO:0000269|PubMed:10998348};
CC Vmax=37.8 nmol/min/mg enzyme for the reduction of 5alpha-androstan-
CC 3,17-dione {ECO:0000269|PubMed:10998348};
CC Vmax=11.3 nmol/min/mg enzyme for the oxidation of 3alpha-hydroxy-
CC 5alpha-androstan-17-one/androsterone {ECO:0000269|PubMed:10998348};
CC Vmax=6.58 nmol/min/mg enzyme for the oxidation of 5alpha-androstane-
CC 3alpha,17beta-diol {ECO:0000269|PubMed:10998348};
CC Note=kcat is 0.66 min-1 for the reduction of 17beta-hydroxy-5alpha-
CC androstan-3-one (PubMed:10998348). kcat is 1.98 min-1 for the
CC reduction of 17beta-hydroxy-5alpha-androstan-3-one (PubMed:19218247).
CC kcat is 1.39 min-1 for the reduction of 5alpha-androstan-3,17-dione
CC (PubMed:10998348). kcat is 0.42 min-1 for the oxidation of 3alpha-
CC hydroxy-5alpha-androstan-17-one/androsterone (PubMed:10998348). kcat
CC is 0.24 min-1 for the oxidation of 5alpha-androstane-3alpha,17beta-
CC diol (PubMed:10998348). kcat is 1.0 min-1 for the reduction of
CC 5alpha-dihydrotestosterone sulfate (PubMed:19218247).
CC {ECO:0000269|PubMed:10998348, ECO:0000269|PubMed:19218247};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:14672942}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:8486699}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P52895-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P52895-2; Sequence=VSP_043779, VSP_043780;
CC -!- TISSUE SPECIFICITY: Expressed in fetal testes. Expressed in fetal and
CC adult adrenal glands. {ECO:0000269|PubMed:21802064}.
CC -!- DISEASE: 46,XY sex reversal 8 (SRXY8) [MIM:614279]: A disorder of sex
CC development. Affected individuals have a 46,XY karyotype but present as
CC phenotypically normal females. {ECO:0000269|PubMed:21802064}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; S68330; AAD14013.1; -; mRNA.
DR EMBL; U05598; AAA20937.1; -; mRNA.
DR EMBL; L32592; AAB38486.1; -; Genomic_DNA.
DR EMBL; AB021654; BAA36169.1; -; mRNA.
DR EMBL; AB031084; BAA92884.1; -; mRNA.
DR EMBL; AB032153; BAA92891.1; -; Genomic_DNA.
DR EMBL; AK290304; BAF82993.1; -; mRNA.
DR EMBL; AK296686; BAG59281.1; -; mRNA.
DR EMBL; BT006653; AAP35299.1; -; mRNA.
DR EMBL; AL391427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713867; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007024; AAH07024.1; -; mRNA.
DR EMBL; BC063574; AAH63574.1; -; mRNA.
DR CCDS; CCDS44350.1; -. [P52895-2]
DR CCDS; CCDS7062.1; -. [P52895-1]
DR PIR; I73676; I73676.
DR PIR; JC5240; JC5240.
DR PIR; S61516; S61516.
DR RefSeq; NP_001128713.1; NM_001135241.2. [P52895-2]
DR RefSeq; NP_001345.1; NM_001354.5. [P52895-1]
DR RefSeq; NP_995317.1; NM_205845.2. [P52895-1]
DR PDB; 1IHI; X-ray; 3.00 A; A/B=1-323.
DR PDB; 1J96; X-ray; 1.25 A; A/B=2-323.
DR PDB; 1XJB; X-ray; 1.90 A; A/B=2-323.
DR PDB; 2HDJ; X-ray; 2.00 A; A/B=1-323.
DR PDB; 2IPJ; X-ray; 1.80 A; A/B=3-323.
DR PDB; 4JQ1; X-ray; 1.60 A; A/B=1-323.
DR PDB; 4JQ2; X-ray; 1.75 A; A/B=1-323.
DR PDB; 4JQ3; X-ray; 1.75 A; A/B=1-323.
DR PDB; 4JQ4; X-ray; 1.52 A; A/B=1-323.
DR PDB; 4JQA; X-ray; 1.45 A; A/B=1-323.
DR PDB; 4JTQ; X-ray; 1.60 A; A/B=1-323.
DR PDB; 4JTR; X-ray; 1.30 A; A/B=1-323.
DR PDB; 4L1W; X-ray; 2.20 A; A/B=2-323.
DR PDB; 4L1X; X-ray; 2.00 A; A/B=2-323.
DR PDB; 4XO6; X-ray; 1.20 A; A/B=2-323.
DR PDB; 4XO7; X-ray; 1.75 A; A/B=1-323.
DR PDBsum; 1IHI; -.
DR PDBsum; 1J96; -.
DR PDBsum; 1XJB; -.
DR PDBsum; 2HDJ; -.
DR PDBsum; 2IPJ; -.
DR PDBsum; 4JQ1; -.
DR PDBsum; 4JQ2; -.
DR PDBsum; 4JQ3; -.
DR PDBsum; 4JQ4; -.
DR PDBsum; 4JQA; -.
DR PDBsum; 4JTQ; -.
DR PDBsum; 4JTR; -.
DR PDBsum; 4L1W; -.
DR PDBsum; 4L1X; -.
DR PDBsum; 4XO6; -.
DR PDBsum; 4XO7; -.
DR AlphaFoldDB; P52895; -.
DR SMR; P52895; -.
DR BioGRID; 108013; 30.
DR IntAct; P52895; 6.
DR STRING; 9606.ENSP00000370129; -.
DR BindingDB; P52895; -.
DR ChEMBL; CHEMBL5847; -.
DR DrugBank; DB06777; Chenodeoxycholic acid.
DR DrugBank; DB07768; Epitestosterone.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB13751; Glycyrrhizic acid.
DR DrugBank; DB06077; Lumateperone.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB00461; Nabumetone.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB12612; Ozanimod.
DR DrugBank; DB01586; Ursodeoxycholic acid.
DR DrugCentral; P52895; -.
DR SwissLipids; SLP:000000803; -.
DR iPTMnet; P52895; -.
DR PhosphoSitePlus; P52895; -.
DR SwissPalm; P52895; -.
DR BioMuta; AKR1C2; -.
DR DMDM; 20532374; -.
DR EPD; P52895; -.
DR jPOST; P52895; -.
DR MassIVE; P52895; -.
DR MaxQB; P52895; -.
DR PaxDb; P52895; -.
DR PeptideAtlas; P52895; -.
DR PRIDE; P52895; -.
DR ProteomicsDB; 56548; -. [P52895-1]
DR ProteomicsDB; 56549; -. [P52895-2]
DR Antibodypedia; 23996; 294 antibodies from 33 providers.
DR CPTC; P52895; 3 antibodies.
DR DNASU; 1646; -.
DR Ensembl; ENST00000380753.9; ENSP00000370129.4; ENSG00000151632.18. [P52895-1]
DR Ensembl; ENST00000455190.2; ENSP00000408440.1; ENSG00000151632.18. [P52895-2]
DR GeneID; 1646; -.
DR KEGG; hsa:1646; -.
DR MANE-Select; ENST00000380753.9; ENSP00000370129.4; NM_001393392.1; NP_001380321.1.
DR UCSC; uc010qao.2; human. [P52895-1]
DR CTD; 1646; -.
DR DisGeNET; 1646; -.
DR GeneCards; AKR1C2; -.
DR HGNC; HGNC:385; AKR1C2.
DR HPA; ENSG00000151632; Tissue enhanced (adipose tissue, liver, skeletal muscle).
DR MalaCards; AKR1C2; -.
DR MIM; 600450; gene.
DR MIM; 614279; phenotype.
DR neXtProt; NX_P52895; -.
DR OpenTargets; ENSG00000151632; -.
DR Orphanet; 443087; 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency.
DR PharmGKB; PA24678; -.
DR VEuPathDB; HostDB:ENSG00000151632; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000167640; -.
DR HOGENOM; CLU_023205_19_2_1; -.
DR InParanoid; P52895; -.
DR OMA; DMMINPQ; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; P52895; -.
DR TreeFam; TF106492; -.
DR BioCyc; MetaCyc:HS07754-MON; -.
DR BRENDA; 1.1.1.213; 2681.
DR BRENDA; 1.1.1.357; 2681.
DR BRENDA; 1.1.1.50; 2681.
DR BRENDA; 1.3.1.20; 2681.
DR PathwayCommons; P52895; -.
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 SABIO-RK; P52895; -.
DR SignaLink; P52895; -.
DR SIGNOR; P52895; -.
DR BioGRID-ORCS; 1646; 19 hits in 1007 CRISPR screens.
DR ChiTaRS; AKR1C2; human.
DR EvolutionaryTrace; P52895; -.
DR GenomeRNAi; 1646; -.
DR Pharos; P52895; Tchem.
DR PRO; PR:P52895; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P52895; protein.
DR Bgee; ENSG00000151632; Expressed in islet of Langerhans and 92 other tissues.
DR ExpressionAtlas; P52895; baseline and differential.
DR Genevisible; P52895; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase 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; 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: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:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; 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: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; IEP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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:0008202; P:steroid metabolic process; IDA: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; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Disease variant; Lipid metabolism; NADP; Oxidoreductase;
KW Reference proteome; Steroid metabolism.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C2"
FT /id="PRO_0000124637"
FT ACT_SITE 55
FT /note="Proton donor"
FT BINDING 20..24
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11513593,
FT ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:15929998,
FT ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"
FT BINDING 24
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 50
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11513593,
FT ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:15929998,
FT ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"
FT BINDING 117
FT /ligand="substrate"
FT BINDING 166..167
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11513593,
FT ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:15929998,
FT ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"
FT BINDING 190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11513593,
FT ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:15929998,
FT ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"
FT BINDING 216..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11513593,
FT ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:15929998,
FT ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"
FT BINDING 222
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 227
FT /ligand="substrate"
FT BINDING 270..280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:11513593,
FT ECO:0000269|PubMed:11514561, ECO:0000269|PubMed:15929998,
FT ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338"
FT SITE 84
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT VAR_SEQ 124..139
FT /note="PGEEVIPKDENGKILF -> EDIGILTWKKSPKHNS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043779"
FT VAR_SEQ 140..323
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043780"
FT VARIANT 46
FT /note="F -> Y (in dbSNP:rs2854482)"
FT /evidence="ECO:0000269|PubMed:7959017"
FT /id="VAR_048216"
FT VARIANT 79
FT /note="I -> V (in SRXY8; partially impaired activity;
FT dbSNP:rs387906750)"
FT /evidence="ECO:0000269|PubMed:21802064"
FT /id="VAR_066632"
FT VARIANT 90
FT /note="H -> Q (in SRXY8; partially impaired activity;
FT dbSNP:rs797044460)"
FT /evidence="ECO:0000269|PubMed:21802064"
FT /id="VAR_066633"
FT VARIANT 172
FT /note="L -> Q (in dbSNP:rs11474)"
FT /id="VAR_014748"
FT VARIANT 222
FT /note="H -> Q (in SRXY8; partially impaired activity;
FT dbSNP:rs13222)"
FT /evidence="ECO:0000269|PubMed:21802064"
FT /id="VAR_066634"
FT VARIANT 300
FT /note="N -> T (in SRXY8; partially impaired activity;
FT dbSNP:rs387906751)"
FT /evidence="ECO:0000269|PubMed:21802064"
FT /id="VAR_066635"
FT MUTAGEN 24
FT /note="Y->A: Strongly decreases affinity for
FT androstenedione. Decreases androstenedione reductase
FT activity about 60-fold."
FT /evidence="ECO:0000269|PubMed:17442338"
FT MUTAGEN 31
FT /note="K->A,M: Increases the low androstenedione reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:17442338"
FT MUTAGEN 301
FT /note="R->A: Decreases 3-alpha-hydroxysteroid reductase
FT activity about 50-fold."
FT /evidence="ECO:0000269|PubMed:15929998"
FT MUTAGEN 304
FT /note="R->A: Decreases 3-alpha-hydroxysteroid reductase
FT activity about 500-fold."
FT /evidence="ECO:0000269|PubMed:15929998"
FT CONFLICT 76
FT /note="R -> S (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="S -> C (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="E -> EE (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="V -> A (in Ref. 3; AAB38486)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="G -> R (in Ref. 7; BAF82993)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="K -> E (in Ref. 1; AAD14013 and 3; AAB38486)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="K -> E (in Ref. 1; AAD14013 and 3; AAB38486)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="C -> H (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="C -> H (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="F -> I (in Ref. 1; AAD14013 and 3; AAB38486)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 32..44
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 92..106
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:4JQA"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4JQA"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:4XO6"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 274..281
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:4XO6"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:4XO6"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:4XO6"
SQ SEQUENCE 323 AA; 36735 MW; 0D7B6F983FCE85E1 CRC64;
MDSKYQCVKL NDGHFMPVLG FGTYAPAEVP KSKALEAVKL AIEAGFHHID SAHVYNNEEQ
VGLAIRSKIA DGSVKREDIF YTSKLWSNSH RPELVRPALE RSLKNLQLDY VDLYLIHFPV
SVKPGEEVIP KDENGKILFD TVDLCATWEA MEKCKDAGLA KSIGVSNFNH RLLEMILNKP
GLKYKPVCNQ VECHPYFNQR KLLDFCKSKD IVLVAYSALG SHREEPWVDP NSPVLLEDPV
LCALAKKHKR TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTS EEMKAIDGLN
RNVRYLTLDI FAGPPNYPFS DEY
