AK1CL_MOUSE
ID AK1CL_MOUSE Reviewed; 323 AA.
AC Q91WR5; Q6P8V0; Q9CX32;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Aldo-keto reductase family 1 member C21;
DE EC=1.1.1.-;
DE AltName: Full=17-alpha-hydroxysteroid dehydrogenase;
DE Short=17-alpha-HSD;
DE AltName: Full=3(or 17)-alpha-hydroxysteroid dehydrogenase;
DE EC=1.1.1.209;
DE AltName: Full=3-alpha-hydroxysteroid dehydrogenase;
DE AltName: Full=Dihydrodiol dehydrogenase type 1;
DE Short=DD1;
DE AltName: Full=Dihydrodiol dehydrogenase type 3;
DE Short=DD3;
GN Name=Akr1c21;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=ICR; TISSUE=Kidney;
RX PubMed=15577209; DOI=10.1248/bpb.27.1939;
RA Ishikura S., Usami N., Nakajima S., Shiraishi H., El-Kabbani O., Hara A.;
RT "Characterization of two isoforms of mouse 3(17)alpha-hydroxysteroid
RT dehydrogenases of the aldo-keto reductase family.";
RL Biol. Pharm. Bull. 27:1939-1945(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=16018803; DOI=10.1186/1471-2091-6-12;
RA Bellemare V., Faucher F., Breton R., Luu-The V.;
RT "Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17-
RT alpha-HSD) and its involvement in the biosynthesis of epitestosterone.";
RL BMC Biochem. 6:12-12(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION, AND
RP MUTAGENESIS OF ALA-24.
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH NADP.
RX PubMed=17909281; DOI=10.1107/s1744309107040985;
RA Dhagat U., Carbone V., Chung R.P.-T., Schulze-Briese C., Endo S., Hara A.,
RA El-Kabbani O.;
RT "Structure of 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) holoenzyme
RT from an orthorhombic crystal form: an insight into the bifunctionality of
RT the enzyme.";
RL Acta Crystallogr. F 63:825-830(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 6-323 IN COMPLEX WITH
RP EPITESTOSTERONE, MUTAGENESIS OF LYS-31, BIOPHYSICOCHEMICAL PROPERTIES,
RP CATALYTIC ACTIVITY, AND FUNCTION.
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).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH NADP.
RX PubMed=19237748; DOI=10.1107/s0907444908044028;
RA Dhagat U., Endo S., Mamiya H., Hara A., El-Kabbani O.;
RT "Structure of the G225P/G226P mutant of mouse 3(17)alpha-hydroxysteroid
RT dehydrogenase (AKR1C21) ternary complex: implications for the binding of
RT inhibitor and substrate.";
RL Acta Crystallogr. D 65:257-265(2009).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF MUTANT ASP-224, CATALYTIC
RP ACTIVITY, FUNCTION, AND MUTAGENESIS OF GLN-222 AND TYR-224.
RX PubMed=20124700; DOI=10.1107/s0907444909051464;
RA Dhagat U., Endo S., Mamiya H., Hara A., El-Kabbani O.;
RT "Studies on a Tyr residue critical for the binding of coenzyme and
RT substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21):
RT structure of the Y224D mutant enzyme.";
RL Acta Crystallogr. D 66:198-204(2010).
CC -!- FUNCTION: NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that
CC converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-
CC alpha-hydroxysteroid dehydrogenase activity. Has broad substrate
CC specificity and acts on various 17-alpha-hydroxysteroids, 17-
CC ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of
CC keto groups is strictly stereoselective. Reduction of 17-ketosteroids
CC yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-
CC ketosteroids yields only 3-alpha-hydroxysteroids.
CC {ECO:0000269|PubMed:15577209, ECO:0000269|PubMed:16018803,
CC ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338,
CC ECO:0000269|PubMed:20124700}.
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:15577209, ECO:0000269|PubMed:17442338,
CC ECO:0000269|PubMed:20124700};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + NAD(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADH; Xref=Rhea:RHEA:20381,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16032,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.209;
CC Evidence={ECO:0000269|PubMed:15577209, ECO:0000269|PubMed:17442338,
CC ECO:0000269|PubMed:20124700};
CC -!- ACTIVITY REGULATION: Inhibited by high concentrations of substrate.
CC {ECO:0000269|PubMed:15577209}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.8 uM for NADP {ECO:0000269|PubMed:15577209,
CC ECO:0000269|PubMed:17442338};
CC KM=19 uM for androstenedione {ECO:0000269|PubMed:15577209,
CC ECO:0000269|PubMed:17442338};
CC KM=0.5 uM for 5-beta-pregnane-3-alpha,20-alpha-diol
CC {ECO:0000269|PubMed:15577209, ECO:0000269|PubMed:17442338};
CC KM=0.5 uM for 5-beta-pregnane-3,20-dione
CC {ECO:0000269|PubMed:15577209, ECO:0000269|PubMed:17442338};
CC KM=0.6 uM for epitestosterone {ECO:0000269|PubMed:15577209,
CC ECO:0000269|PubMed:17442338};
CC KM=0.3 uM for androst-4-ene-3,17-dione {ECO:0000269|PubMed:15577209,
CC ECO:0000269|PubMed:17442338};
CC pH dependence:
CC Optimum pH is 10.0. {ECO:0000269|PubMed:15577209,
CC ECO:0000269|PubMed:17442338};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15577209,
CC ECO:0000269|PubMed:17034817, ECO:0000269|PubMed:17442338,
CC ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in kidney and brain.
CC {ECO:0000269|PubMed:15577209, ECO:0000269|PubMed:16018803}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; AB178898; BAD18929.1; -; mRNA.
DR EMBL; AY742217; AAW65159.1; -; mRNA.
DR EMBL; AK020439; BAB32101.1; -; mRNA.
DR EMBL; BC013531; AAH13531.1; -; mRNA.
DR EMBL; BC061057; AAH61057.1; -; mRNA.
DR EMBL; BC091761; AAH91761.1; -; mRNA.
DR CCDS; CCDS26225.1; -.
DR RefSeq; NP_084177.2; NM_029901.2.
DR PDB; 2HE5; X-ray; 2.90 A; A/B/C/D=1-323.
DR PDB; 2HE8; X-ray; 1.90 A; A/B=1-323.
DR PDB; 2HEJ; X-ray; 1.35 A; A/B=1-323.
DR PDB; 2IPF; X-ray; 1.85 A; A/B=6-323.
DR PDB; 2IPG; X-ray; 1.90 A; A/B=5-323.
DR PDB; 2P5N; X-ray; 1.80 A; A/B=1-323.
DR PDB; 3CV6; X-ray; 2.10 A; A/B=1-323.
DR PDB; 3FJN; X-ray; 2.30 A; A/B=1-323.
DR PDBsum; 2HE5; -.
DR PDBsum; 2HE8; -.
DR PDBsum; 2HEJ; -.
DR PDBsum; 2IPF; -.
DR PDBsum; 2IPG; -.
DR PDBsum; 2P5N; -.
DR PDBsum; 3CV6; -.
DR PDBsum; 3FJN; -.
DR AlphaFoldDB; Q91WR5; -.
DR SMR; Q91WR5; -.
DR STRING; 10090.ENSMUSP00000021628; -.
DR BindingDB; Q91WR5; -.
DR ChEMBL; CHEMBL1075270; -.
DR DrugCentral; Q91WR5; -.
DR iPTMnet; Q91WR5; -.
DR PhosphoSitePlus; Q91WR5; -.
DR jPOST; Q91WR5; -.
DR MaxQB; Q91WR5; -.
DR PaxDb; Q91WR5; -.
DR PeptideAtlas; Q91WR5; -.
DR PRIDE; Q91WR5; -.
DR ProteomicsDB; 296382; -.
DR DNASU; 77337; -.
DR Ensembl; ENSMUST00000021628; ENSMUSP00000021628; ENSMUSG00000021207.
DR GeneID; 77337; -.
DR KEGG; mmu:77337; -.
DR UCSC; uc007pjr.1; mouse.
DR CTD; 77337; -.
DR MGI; MGI:1924587; Akr1c21.
DR VEuPathDB; HostDB:ENSMUSG00000021207; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000153677; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; Q91WR5; -.
DR OMA; QIAMERG; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; Q91WR5; -.
DR TreeFam; TF106492; -.
DR BRENDA; 1.1.1.148; 3474.
DR BRENDA; 1.1.1.209; 3474.
DR BRENDA; 1.1.1.50; 3474.
DR SABIO-RK; Q91WR5; -.
DR BioGRID-ORCS; 77337; 1 hit in 73 CRISPR screens.
DR EvolutionaryTrace; Q91WR5; -.
DR PRO; PR:Q91WR5; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q91WR5; protein.
DR Bgee; ENSMUSG00000021207; Expressed in right kidney and 40 other tissues.
DR ExpressionAtlas; Q91WR5; baseline and differential.
DR Genevisible; Q91WR5; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; ISO:MGI.
DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) activity; IMP:CAFA.
DR GO; GO:0072555; F:17-beta-ketosteroid reductase activity; IMP:CAFA.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IMP:CAFA.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; ISO:MGI.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; ISA:MGI.
DR GO; GO:0047042; F:androsterone dehydrogenase (B-specific) activity; ISO:MGI.
DR GO; GO:0047023; F:androsterone dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0032052; F:bile acid binding; ISO:MGI.
DR GO; GO:0031406; F:carboxylic acid binding; ISO:MGI.
DR GO; GO:0047743; F:chlordecone reductase activity; ISO:MGI.
DR GO; GO:0047787; F:delta4-3-oxosteroid 5beta-reductase activity; ISO:MGI.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; ISO:MGI.
DR GO; GO:0045550; F:geranylgeranyl reductase activity; ISO:MGI.
DR GO; GO:0045703; F:ketoreductase activity; ISO:MGI.
DR GO; GO:0047086; F:ketosteroid monooxygenase activity; ISO:MGI.
DR GO; GO:1902121; F:lithocholic acid binding; IMP:CAFA.
DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; ISO:MGI.
DR GO; GO:0070401; F:NADP+ binding; IMP:CAFA.
DR GO; GO:0070402; F:NADPH binding; IMP:CAFA.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; ISO:MGI.
DR GO; GO:0018636; F:phenanthrene 9,10-monooxygenase activity; ISO:MGI.
DR GO; GO:0001758; F:retinal dehydrogenase activity; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; IMP:CAFA.
DR GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0033764; F:steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:MGI.
DR GO; GO:0047115; F:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity; ISO:MGI.
DR GO; GO:0044597; P:daunorubicin metabolic process; IBA:GO_Central.
DR GO; GO:0044598; P:doxorubicin metabolic process; IBA:GO_Central.
DR GO; GO:0042448; P:progesterone metabolic process; IBA:GO_Central.
DR GO; GO:0006693; P:prostaglandin metabolic process; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; ISA:MGI.
DR GO; GO:0008202; P:steroid metabolic process; IMP:CAFA.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Lipid metabolism; NADP; Oxidoreductase;
KW Reference proteome; Steroid metabolism.
FT CHAIN 1..323
FT /note="Aldo-keto reductase family 1 member C21"
FT /id="PRO_0000326222"
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:17034817,
FT ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748"
FT BINDING 31
FT /ligand="substrate"
FT BINDING 50
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17034817,
FT ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748"
FT BINDING 117
FT /ligand="substrate"
FT BINDING 166..167
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17034817,
FT ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748"
FT BINDING 190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17034817,
FT ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748"
FT BINDING 216..224
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17034817,
FT ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748"
FT BINDING 270..280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17034817,
FT ECO:0000269|PubMed:17909281, ECO:0000269|PubMed:19237748"
FT SITE 84
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MUTAGEN 24
FT /note="A->Y: Reduces enzyme activity and affinity for
FT substrate. Alters the stereospecificity, so that
FT androstenedione is converted to testosterone."
FT /evidence="ECO:0000269|PubMed:17034817"
FT MUTAGEN 31
FT /note="K->A: No effect on affinity for androstenedione.
FT Slight increase of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17442338"
FT MUTAGEN 222
FT /note="Q->N: Decreases affinity for NADP. Changes enzyme
FT activity, leading to the production of testosterone and
FT concomitantly reducing the production of epi-testosterone."
FT /evidence="ECO:0000269|PubMed:20124700"
FT MUTAGEN 224
FT /note="Y->D: Decreases affinity for NADP. Changes enzyme
FT activity, leading to the production of testosterone and
FT concomitantly reducing the production of epi-testosterone."
FT /evidence="ECO:0000269|PubMed:20124700"
FT MUTAGEN 224
FT /note="Y->F: No effect on enzyme activity. Decreases
FT affinity for NADP."
FT /evidence="ECO:0000269|PubMed:20124700"
FT CONFLICT 27
FT /note="L -> V (in Ref. 1; BAD18929 and 4; AAH13531/
FT AAH91761)"
FT /evidence="ECO:0000305"
FT CONFLICT 60
FT /note="H -> R (in Ref. 1; BAD18929 and 4; AAH13531/
FT AAH91761)"
FT /evidence="ECO:0000305"
FT CONFLICT 91
FT /note="H -> R (in Ref. 1; BAD18929 and 4; AAH13531/
FT AAH91761)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="E -> V (in Ref. 1; BAD18929 and 4; AAH13531/
FT AAH91761)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="Y -> S (in Ref. 1; BAD18929 and 4; AAH13531/
FT AAH91761)"
FT /evidence="ECO:0000305"
FT CONFLICT 294
FT /note="K -> E (in Ref. 4; AAH61057)"
FT /evidence="ECO:0000305"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:2HE5"
FT HELIX 33..44
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:2HEJ"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 95..106
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:3FJN"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:3FJN"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:3CV6"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:2HEJ"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:3FJN"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 252..261
FT /evidence="ECO:0007829|PDB:2HEJ"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 274..280
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:2HEJ"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:2HEJ"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:2P5N"
SQ SEQUENCE 323 AA; 36877 MW; 0D598A0559EFBF11 CRC64;
MNSKCHCVIL NDGNFIPVLG FGTALPLECP KSKAKELTKI AIDAGFHHFD SASVYNTEDH
VGEAIRSKIA DGTVRREDIF YTSKVWCTSL HPELVRASLE RSLQKLQFDY VDLYLIHYPM
ALKPGEENFP VDEHGKLIFD RVDLCATWEA MEKCKDAGLT KSIGVSNFNY RQLEMILNKP
GLKYKPVCNQ VECHPYLNQM KLLDFCKSKD IVLVAYGVLG TQRYGGWVDQ NSPVLLDEPV
LGSMAKKYNR TPALIALRYQ LQRGIVVLNT SLKEERIKEN MQVFEFQLSS EDMKVLDGLN
RNMRYIPAAI FKGHPNWPFL DEY
