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 24-JAN-2024, entry version 213. 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(+) = androsterone + CC H(+) + NADH; Xref=Rhea:RHEA:42124, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16032, ChEBI:CHEBI:36713, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945; 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=androsterone + NADP(+) = 5alpha-androstan-3,17-dione + H(+) + CC NADPH; Xref=Rhea:RHEA:20377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, CC ChEBI:CHEBI:16032, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.209; 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 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 CC 17beta-hydroxy-5alpha-androstan-3-one {ECO:0000269|PubMed:10998348}; CC Vmax=37.8 nmol/min/mg enzyme for the reduction of CC 5alpha-androstan-3,17-dione {ECO:0000269|PubMed:10998348}; CC Vmax=11.3 nmol/min/mg enzyme for the oxidation of CC 3alpha-hydroxy-5alpha-androstan-17-one/androsterone CC {ECO:0000269|PubMed:10998348}; CC Vmax=6.58 nmol/min/mg enzyme for the oxidation of CC 5alpha-androstane-3alpha,17beta-diol {ECO:0000269|PubMed:10998348}; CC Note=kcat is 0.66 min-1 for the reduction of CC 17beta-hydroxy-5alpha-androstan-3-one (PubMed:10998348). kcat is 1.98 CC min-1 for the reduction of 17beta-hydroxy-5alpha-androstan-3-one CC (PubMed:19218247). kcat is 1.39 min-1 for the reduction of CC 5alpha-androstan-3,17-dione (PubMed:10998348). kcat is 0.42 min-1 for CC the oxidation of 3alpha-hydroxy-5alpha-androstan-17-one/androsterone CC (PubMed:10998348). kcat is 0.24 min-1 for the oxidation of CC 5alpha-androstane-3alpha,17beta-diol (PubMed:10998348). kcat is 1.0 CC min-1 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 -!- 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 59. 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; 9606-ENSP00000370129; -. DR PeptideAtlas; P52895; -. DR ProteomicsDB; 56548; -. [P52895-1] DR ProteomicsDB; 56549; -. [P52895-2] DR Pumba; P52895; -. DR Antibodypedia; 23996; 323 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 AGR; HGNC:385; -. DR CTD; 1646; -. DR DisGeNET; 1646; -. DR GeneCards; AKR1C2; -. DR HGNC; HGNC:385; AKR1C2. DR HPA; ENSG00000151632; Tissue enhanced (adipose tissue, liver). DR MalaCards; AKR1C2; -. DR MIM; 600450; gene. DR MIM; 614279; phenotype. DR neXtProt; NX_P52895; -. DR OpenTargets; ENSG00000151632; -. DR Orphanet; 443087; 46,XY difference 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; KLWGTEQ; -. DR OrthoDB; 890110at2759; -. DR PhylomeDB; P52895; -. DR TreeFam; TF106492; -. DR BioCyc; MetaCyc:HS07754-MONOMER; -. 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 1091 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 94 other cell types or tissues. DR ExpressionAtlas; P52895; baseline and differential. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. 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:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] 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: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 phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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; NADP-dependent oxidoreductase domain; 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 PANTHER; PTHR11732:SF153; ALDO-KETO REDUCTASE FAMILY 1 MEMBER C1-RELATED; 1. DR PANTHER; PTHR11732; ALDO/KETO REDUCTASE; 1. DR Pfam; PF00248; Aldo_ket_red; 1. DR PIRSF; PIRSF000097; AKR; 1. DR PRINTS; PR00069; ALDKETRDTASE. DR SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1. DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1. DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1. DR Genevisible; P52895; HS. 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 //