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Database: UniProt
Entry: P51857
LinkDB: P51857
Original site: P51857 
ID   AK1D1_HUMAN             Reviewed;         326 AA.
AC   P51857; A1L4P6; A8K060; B4DPN3; B4DPN8;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   02-JUN-2021, entry version 172.
DE   RecName: Full=Aldo-keto reductase family 1 member D1;
DE            EC=1.3.1.3 {ECO:0000269|PubMed:11342103, ECO:0000269|PubMed:18407998, ECO:0000269|PubMed:20522910, ECO:0000269|PubMed:21255593, ECO:0000269|PubMed:7508385};
DE   AltName: Full=3-oxo-5-beta-steroid 4-dehydrogenase;
DE   AltName: Full=Delta(4)-3-ketosteroid 5-beta-reductase;
DE   AltName: Full=Delta(4)-3-oxosteroid 5-beta-reductase;
GN   Name=AKR1D1; Synonyms=SRD5B1;
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), CATALYTIC ACTIVITY, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Liver;
RX   PubMed=7508385; DOI=10.1111/j.1432-1033.1994.tb19947.x;
RA   Kondo K.-H., Kai M.-H., Setoguchi Y., Eggertsen G., Sjoeblom P.,
RA   Setoguchi T., Okuda K., Bjoerkhem I.;
RT   "Cloning and expression of cDNA of human delta 4-3-oxosteroid 5 beta-
RT   reductase and substrate specificity of the expressed enzyme.";
RL   Eur. J. Biochem. 219:357-363(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, FUNCTION, TISSUE
RP   SPECIFICITY, SUBSTRATE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX   PubMed=11342103; DOI=10.1016/s0167-4781(00)00278-5;
RA   Charbonneau A., The V.L.;
RT   "Genomic organization of a human 5beta-reductase and its pseudogene and
RT   substrate selectivity of the expressed enzyme.";
RL   Biochim. Biophys. Acta 1517:228-235(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC   TISSUE=Liver, and Mammary gland;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [9]
RP   CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS CBAS2 PHE-106; ARG-133;
RP   LEU-198; GLU-223 AND CYS-261, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=20522910; DOI=10.1074/jbc.m110.127779;
RA   Drury J.E., Mindnich R., Penning T.M.;
RT   "Characterization of disease-related 5beta-reductase (AKR1D1) mutations
RT   reveals their potential to cause bile acid deficiency.";
RL   J. Biol. Chem. 285:24529-24537(2010).
RN   [10]
RP   CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP   AND ACTIVITY REGULATION.
RX   PubMed=21255593; DOI=10.1016/j.steroids.2011.01.003;
RA   Chen M., Drury J.E., Penning T.M.;
RT   "Substrate specificity and inhibitor analyses of human steroid 5beta-
RT   reductase (AKR1D1).";
RL   Steroids 76:484-490(2011).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH NADP.
RX   PubMed=18624455; DOI=10.1021/bi800572s;
RA   Faucher F., Cantin L., Luu-The V., Labrie F., Breton R.;
RT   "The crystal structure of human Delta4-3-ketosteroid 5beta-reductase
RT   defines the functional role of the residues of the catalytic tetrad in the
RT   steroid double bond reduction mechanism.";
RL   Biochemistry 47:8261-8270(2008).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH NADP.
RX   PubMed=19075558; DOI=10.1021/bi801276h;
RA   Faucher F., Cantin L., Luu-The V., Labrie F., Breton R.;
RT   "Crystal structures of human Delta4-3-ketosteroid 5beta-reductase (AKR1D1)
RT   reveal the presence of an alternative binding site responsible for
RT   substrate inhibition.";
RL   Biochemistry 47:13537-13546(2008).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEXES WITH NADP;
RP   TESTOSTERONE; PROGESTERONE AND CORTISONE, MUTAGENESIS OF TYR-58 AND
RP   GLU-120, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=18407998; DOI=10.1074/jbc.m801778200;
RA   Di Costanzo L., Drury J.E., Penning T.M., Christianson D.W.;
RT   "Crystal structure of human liver delta(4)-3-ketosteroid 5beta-reductase
RT   (AKR1D1) and implications for substrate binding and catalysis.";
RL   J. Biol. Chem. 283:16830-16839(2008).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH NADP.
RX   PubMed=19515843; DOI=10.1074/jbc.c109.016931;
RA   Drury J.E., Di Costanzo L., Penning T.M., Christianson D.W.;
RT   "Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and
RT   structure of the enzyme-inhibitor complex.";
RL   J. Biol. Chem. 284:19786-19790(2009).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH NADP.
RX   PubMed=18848863; DOI=10.1016/j.mce.2008.09.013;
RA   Di Costanzo L., Drury J.E., Christianson D.W., Penning T.M.;
RT   "Structure and catalytic mechanism of human steroid 5beta-reductase
RT   (AKR1D1).";
RL   Mol. Cell. Endocrinol. 301:191-198(2009).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) IN COMPLEX WITH NADP AND
RP   TESTOSTERONE.
RX   PubMed=22437839; DOI=10.1074/jbc.m111.338780;
RA   Chen M., Drury J.E., Christianson D.W., Penning T.M.;
RT   "Conversion of human steroid 5beta-reductase (AKR1D1) into 3beta-
RT   hydroxysteroid dehydrogenase by single point mutation E120H: example of
RT   perfect enzyme engineering.";
RL   J. Biol. Chem. 287:16609-16622(2012).
RN   [18]
RP   VARIANTS CBAS2 PHE-106 AND LEU-198.
RX   PubMed=12970144; DOI=10.1136/gut.52.10.1494;
RA   Lemonde H.A., Custard E.J., Bouquet J., Duran M., Overmars H.,
RA   Scambler P.J., Clayton P.T.;
RT   "Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid
RT   5beta-reductase, in hepatitis and liver failure in infancy.";
RL   Gut 52:1494-1499(2003).
RN   [19]
RP   VARIANTS CBAS2 ARG-133 AND CYS-261.
RX   PubMed=15030995; DOI=10.1016/j.jhep.2003.12.024;
RA   Gonzales E., Cresteil D., Baussan C., Dabadie A., Gerhardt M.F.,
RA   Jacquemin E.;
RT   "SRD5B1 (AKR1D1) gene analysis in delta(4)-3-oxosteroid 5beta-reductase
RT   deficiency: evidence for primary genetic defect.";
RL   J. Hepatol. 40:716-718(2004).
RN   [20]
RP   VARIANTS CBAS2 50-ARG--TYR-326 DEL AND GLU-223.
RX   PubMed=19175828; DOI=10.1111/j.1440-1746.2008.05669.x;
RA   Ueki I., Kimura A., Chen H.L., Yorifuji T., Mori J., Itoh S., Maruyama K.,
RA   Ishige T., Takei H., Nittono H., Kurosawa T., Kage M., Matsuishi T.;
RT   "SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-
RT   Delta4-steroid 5beta-reductase deficiency.";
RL   J. Gastroenterol. Hepatol. 24:776-785(2009).
CC   -!- FUNCTION: Catalyzes the stereospecific NADPH-dependent reduction of the
CC       C4-C5 double bond of bile acid intermediates and steroid hormones
CC       carrying a delta(4)-3-one structure to yield an A/B cis-ring junction.
CC       This cis-configuration is crucial for bile acid biosynthesis and plays
CC       important roles in steroid metabolism. Capable of reducing a broad
CC       range of delta-(4)-3-ketosteroids from C18 (such as, 17beta-
CC       hydroxyestr-4-en-3-one) to C27 (such as, 7alpha-hydroxycholest-4-en-3-
CC       one). {ECO:0000269|PubMed:11342103, ECO:0000269|PubMed:18407998,
CC       ECO:0000269|PubMed:20522910, ECO:0000269|PubMed:21255593,
CC       ECO:0000269|PubMed:7508385}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5beta-cholestan-3-one + NADP(+) = cholest-4-en-3-one + H(+) +
CC         NADPH; Xref=Rhea:RHEA:11524, ChEBI:CHEBI:15378, ChEBI:CHEBI:16074,
CC         ChEBI:CHEBI:16175, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.3;
CC         Evidence={ECO:0000269|PubMed:18407998, ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11526;
CC         Evidence={ECO:0000305|PubMed:18407998};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4,5beta-dihydrocortisone + NADP(+) = cortisone + H(+) + NADPH;
CC         Xref=Rhea:RHEA:14037, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962,
CC         ChEBI:CHEBI:18093, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.3;
CC         Evidence={ECO:0000269|PubMed:18407998, ECO:0000269|PubMed:20522910,
CC         ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14039;
CC         Evidence={ECO:0000305|PubMed:18407998};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cortisol + H(+) + NADPH = 5beta-dihydrocortisol + NADP(+);
CC         Xref=Rhea:RHEA:46644, ChEBI:CHEBI:732, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17650, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46645;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=corticosterone + H(+) + NADPH = 5beta-dihydrocorticosterone +
CC         NADP(+); Xref=Rhea:RHEA:46664, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:86381;
CC         Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46665;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7alpha,12alpha-dihydroxycholest-4-en-3-one + H(+) + NADPH =
CC         7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADP(+);
CC         Xref=Rhea:RHEA:46632, ChEBI:CHEBI:2288, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:28477, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46633;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7alpha-hydroxycholest-4-en-3-one + H(+) + NADPH = 7alpha-
CC         hydroxy-5beta-cholestan-3-one + NADP(+); Xref=Rhea:RHEA:46640,
CC         ChEBI:CHEBI:2290, ChEBI:CHEBI:15378, ChEBI:CHEBI:17899,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:20522910, ECO:0000269|PubMed:21255593,
CC         ECO:0000269|PubMed:7508385};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46641;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=epitestosterone + H(+) + NADPH = 5beta-dihydroepitestosterone
CC         + NADP(+); Xref=Rhea:RHEA:46652, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:42534, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:86377; Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46653;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=androst-4-ene-3,17-dione + H(+) + NADPH = 5beta-androstane-
CC         3,17-dione + NADP(+); Xref=Rhea:RHEA:46656, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16422, ChEBI:CHEBI:16985, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46657;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+) + NADPH + progesterone = 5beta-pregnan-3,20-dione +
CC         NADP(+); Xref=Rhea:RHEA:46660, ChEBI:CHEBI:15378, ChEBI:CHEBI:17026,
CC         ChEBI:CHEBI:30154, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:11342103, ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46661;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=21-hydroxyprogesterone + H(+) + NADPH = 5beta-
CC         dihydrodeoxycorticosterone + NADP(+); Xref=Rhea:RHEA:46668,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16973, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:86384;
CC         Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46669;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=aldosterone + H(+) + NADPH = 5beta-dihydroaldosterone +
CC         NADP(+); Xref=Rhea:RHEA:46672, ChEBI:CHEBI:15378, ChEBI:CHEBI:27584,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:86389;
CC         Evidence={ECO:0000269|PubMed:11342103, ECO:0000269|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=17beta-hydroxyandrosta-1,4-dien-3-one + H(+) + NADPH = 17beta-
CC         hydroxy-5beta-androst-1-en-3-one + NADP(+); Xref=Rhea:RHEA:47076,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:34584, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:87331;
CC         Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47077;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=17beta-hydroxyestr-4-en-3-one + H(+) + NADPH = 17beta-hydroxy-
CC         5beta-estran-3-one + NADP(+); Xref=Rhea:RHEA:47080, ChEBI:CHEBI:7466,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:87333; Evidence={ECO:0000269|PubMed:21255593};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47081;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5beta-dihydrotestosterone + NADP(+) = H(+) + NADPH +
CC         testosterone; Xref=Rhea:RHEA:46636, ChEBI:CHEBI:2150,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:17347, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.3.1.3; Evidence={ECO:0000269|PubMed:11342103,
CC         ECO:0000269|PubMed:20522910, ECO:0000269|PubMed:21255593,
CC         ECO:0000269|PubMed:7508385};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=androst-4-ene-3,11,17-trione + H(+) + NADPH = 17beta-
CC         hydroxyandrost-4-ene-3,11-dione + NADP(+); Xref=Rhea:RHEA:53484,
CC         ChEBI:CHEBI:2495, ChEBI:CHEBI:15378, ChEBI:CHEBI:34133,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC         Evidence={ECO:0000269|PubMed:11342103};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53485;
CC         Evidence={ECO:0000305|PubMed:21255593};
CC   -!- ACTIVITY REGULATION: Subject to inhibition by high substrate
CC       concentrations. Inhibited by testosterone concentrations above 10 uM
CC       (PubMed:18407998). Inhibited by the primary and secondary bile acids
CC       chenodeoxycholic acid and ursodeoxycholic acid (PubMed:21255593).
CC       {ECO:0000269|PubMed:18407998, ECO:0000269|PubMed:21255593}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.2 uM for corticosterone {ECO:0000269|PubMed:21255593};
CC         KM=2.9 uM for epitestosterone {ECO:0000269|PubMed:21255593};
CC         KM=3.0 uM for 17beta-hydroxyestr-4-en-3-one
CC         {ECO:0000269|PubMed:21255593};
CC         KM=0.8 uM for 7alpha-hydroxycholest-4-en-3-one
CC         {ECO:0000269|PubMed:21255593};
CC         KM=0.3 uM for cholest-4-en-3-one {ECO:0000269|PubMed:21255593};
CC         KM=3.2 uM for 17beta-hydroxyandrosta-1,4-dien-3-one
CC         {ECO:0000269|PubMed:20522910};
CC         KM=0.9 uM for androst-4-ene-3,17-dione {ECO:0000269|PubMed:21255593};
CC         KM=15.1 uM for cortisone {ECO:0000269|PubMed:20522910,
CC         ECO:0000269|PubMed:21255593};
CC         KM=13.1 uM for cortisol {ECO:0000269|PubMed:21255593};
CC         KM=2.5 uM for aldosterone {ECO:0000269|PubMed:21255593};
CC         KM=2.7 uM for testosterone {ECO:0000269|PubMed:18407998,
CC         ECO:0000269|PubMed:20522910};
CC         Note=kcat is 2.7 min(-1) with 17beta-hydroxyestr-4-en-3-one as
CC         substrate. kcat is 6.0 min(-1) with androst-4-ene-3,17-dione as
CC         substrate. kcat is 8.4 min(-1) with testosterone as substrate. kcat
CC         is 6.0 min(-1) with epitestosterone as substrate. kcat is 3.2 min(-1)
CC         with 17beta-hydroxyandrosta-1,4-dien-3-one as substrate. kcat is 9.0
CC         min(-1) with aldosterone as substrate. kcat is 1.9 min(-1) with
CC         corticosterone as substrate. kcat is 2.7 min(-1) with cortisol as
CC         substrate. kcat is 11.2 min(-1) with cortisone as substrate. kcat is
CC         2.0 min(-1) with 7alpha-hydroxycholest-4-en-3-one as substrate. kcat
CC         is 0.6 min(-1) with cholest-4-en-3-one as substrate.
CC         {ECO:0000269|PubMed:21255593};
CC       pH dependence:
CC         Optimum pH is 6. {ECO:0000269|PubMed:21255593};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7508385}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P51857-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P51857-2; Sequence=VSP_042901;
CC       Name=3;
CC         IsoId=P51857-3; Sequence=VSP_042913;
CC   -!- TISSUE SPECIFICITY: Highly expressed in liver. Expressed in testis and
CC       weakly in colon. {ECO:0000269|PubMed:11342103}.
CC   -!- DISEASE: Congenital bile acid synthesis defect 2 (CBAS2) [MIM:235555]:
CC       A condition characterized by jaundice, intrahepatic cholestasis and
CC       hepatic failure. Patients with this liver disease show absence or low
CC       levels of chenodeoxycholic acid and cholic acid in plasma and urine.
CC       {ECO:0000269|PubMed:12970144, ECO:0000269|PubMed:15030995,
CC       ECO:0000269|PubMed:19175828, ECO:0000269|PubMed:20522910}. 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; Z28339; CAA82193.1; -; mRNA.
DR   EMBL; AF283659; AAG39381.1; -; Genomic_DNA.
DR   EMBL; AF283651; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283652; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283653; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283654; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283655; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283656; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283657; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AF283658; AAG39381.1; JOINED; Genomic_DNA.
DR   EMBL; AK289425; BAF82114.1; -; mRNA.
DR   EMBL; AK298421; BAG60645.1; -; mRNA.
DR   EMBL; AK298428; BAG60650.1; -; mRNA.
DR   EMBL; AC009263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC024082; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC083867; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH236950; EAL24049.1; -; Genomic_DNA.
DR   EMBL; CH471070; EAW83881.1; -; Genomic_DNA.
DR   EMBL; BC130625; AAI30626.1; -; mRNA.
DR   EMBL; BC130627; AAI30628.1; -; mRNA.
DR   CCDS; CCDS55169.1; -. [P51857-2]
DR   CCDS; CCDS55170.1; -. [P51857-3]
DR   CCDS; CCDS5846.1; -. [P51857-1]
DR   PIR; S41120; S41120.
DR   RefSeq; NP_001177835.1; NM_001190906.1. [P51857-3]
DR   RefSeq; NP_001177836.1; NM_001190907.1. [P51857-2]
DR   RefSeq; NP_005980.1; NM_005989.3. [P51857-1]
DR   PDB; 3BUR; X-ray; 1.62 A; A/B=1-326.
DR   PDB; 3BUV; X-ray; 1.35 A; A/B=1-326.
DR   PDB; 3BV7; X-ray; 1.79 A; A/B=1-326.
DR   PDB; 3CAQ; X-ray; 2.20 A; A/B=1-326.
DR   PDB; 3CAS; X-ray; 2.00 A; A/B=1-326.
DR   PDB; 3CAV; X-ray; 1.90 A; A/B=1-326.
DR   PDB; 3CMF; X-ray; 1.90 A; A/B=1-326.
DR   PDB; 3COT; X-ray; 2.03 A; A/B=1-326.
DR   PDB; 3DOP; X-ray; 2.00 A; A/B=1-326.
DR   PDB; 3G1R; X-ray; 1.70 A; A/B=1-326.
DR   PDB; 3UZW; X-ray; 1.89 A; A/B=1-326.
DR   PDB; 3UZX; X-ray; 1.64 A; A/B=1-326.
DR   PDB; 3UZY; X-ray; 1.83 A; A/B=1-326.
DR   PDB; 3UZZ; X-ray; 1.82 A; A/B=1-326.
DR   PDBsum; 3BUR; -.
DR   PDBsum; 3BUV; -.
DR   PDBsum; 3BV7; -.
DR   PDBsum; 3CAQ; -.
DR   PDBsum; 3CAS; -.
DR   PDBsum; 3CAV; -.
DR   PDBsum; 3CMF; -.
DR   PDBsum; 3COT; -.
DR   PDBsum; 3DOP; -.
DR   PDBsum; 3G1R; -.
DR   PDBsum; 3UZW; -.
DR   PDBsum; 3UZX; -.
DR   PDBsum; 3UZY; -.
DR   PDBsum; 3UZZ; -.
DR   SMR; P51857; -.
DR   BioGRID; 112596; 8.
DR   IntAct; P51857; 7.
DR   STRING; 9606.ENSP00000242375; -.
DR   DrugBank; DB07557; 3,20-Pregnanedione.
DR   DrugBank; DB07447; 5beta-dihydrotestosterone.
DR   DrugBank; DB00548; Azelaic acid.
DR   DrugBank; DB01216; Finasteride.
DR   DrugBank; DB00741; Hydrocortisone.
DR   DrugBank; DB06077; Lumateperone.
DR   DrugBank; DB00717; Norethisterone.
DR   SwissLipids; SLP:000001272; -. [P51857-1]
DR   iPTMnet; P51857; -.
DR   PhosphoSitePlus; P51857; -.
DR   BioMuta; AKR1D1; -.
DR   DMDM; 1703007; -.
DR   EPD; P51857; -.
DR   jPOST; P51857; -.
DR   MassIVE; P51857; -.
DR   MaxQB; P51857; -.
DR   PaxDb; P51857; -.
DR   PeptideAtlas; P51857; -.
DR   PRIDE; P51857; -.
DR   ProteomicsDB; 56436; -. [P51857-1]
DR   ProteomicsDB; 56437; -. [P51857-2]
DR   ProteomicsDB; 56438; -. [P51857-3]
DR   Antibodypedia; 32317; 249 antibodies.
DR   DNASU; 6718; -.
DR   Ensembl; ENST00000242375; ENSP00000242375; ENSG00000122787. [P51857-1]
DR   Ensembl; ENST00000411726; ENSP00000402374; ENSG00000122787. [P51857-3]
DR   Ensembl; ENST00000432161; ENSP00000389197; ENSG00000122787. [P51857-2]
DR   GeneID; 6718; -.
DR   KEGG; hsa:6718; -.
DR   UCSC; uc003vtz.4; human. [P51857-1]
DR   CTD; 6718; -.
DR   DisGeNET; 6718; -.
DR   GeneCards; AKR1D1; -.
DR   HGNC; HGNC:388; AKR1D1.
DR   HPA; ENSG00000122787; Tissue enriched (liver).
DR   MalaCards; AKR1D1; -.
DR   MIM; 235555; phenotype.
DR   MIM; 604741; gene.
DR   neXtProt; NX_P51857; -.
DR   OpenTargets; ENSG00000122787; -.
DR   Orphanet; 79303; Congenital bile acid synthesis defect type 2.
DR   PharmGKB; PA24681; -.
DR   VEuPathDB; HostDB:ENSG00000122787.14; -.
DR   eggNOG; KOG1577; Eukaryota.
DR   GeneTree; ENSGT00940000155961; -.
DR   HOGENOM; CLU_023205_0_0_1; -.
DR   InParanoid; P51857; -.
DR   OMA; RNPSWVN; -.
DR   OrthoDB; 1016440at2759; -.
DR   PhylomeDB; P51857; -.
DR   TreeFam; TF106492; -.
DR   BRENDA; 1.3.1.3; 2681.
DR   PathwayCommons; P51857; -.
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; P51857; -.
DR   BioGRID-ORCS; 6718; 27 hits in 985 CRISPR screens.
DR   ChiTaRS; AKR1D1; human.
DR   EvolutionaryTrace; P51857; -.
DR   GenomeRNAi; 6718; -.
DR   Pharos; P51857; Tbio.
DR   PRO; PR:P51857; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P51857; protein.
DR   Bgee; ENSG00000122787; Expressed in liver and 67 other tissues.
DR   ExpressionAtlas; P51857; baseline and differential.
DR   Genevisible; P51857; HS.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0047834; F:D-threo-aldose 1-dehydrogenase activity; IEA:InterPro.
DR   GO; GO:0047787; F:delta4-3-oxosteroid 5beta-reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0047086; F:ketosteroid monooxygenase activity; IBA:GO_Central.
DR   GO; GO:0005496; F:steroid binding; TAS:UniProtKB.
DR   GO; GO:0016229; F:steroid dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0008209; P:androgen metabolic process; IDA:UniProtKB.
DR   GO; GO:0006699; P:bile acid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0030573; P:bile acid catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0008207; P:C21-steroid hormone metabolic process; IDA:UniProtKB.
DR   GO; GO:0006707; P:cholesterol catabolic process; IDA:UniProtKB.
DR   GO; GO:0007586; P:digestion; IDA:UniProtKB.
DR   GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR   CDD; cd19109; AKR_AKR1D1-3; 1.
DR   Gene3D; 3.20.20.100; -; 1.
DR   InterPro; IPR020471; AKR.
DR   InterPro; IPR044483; AKR1D1.
DR   InterPro; IPR018170; Aldo/ket_reductase_CS.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   PIRSF; PIRSF000097; AKR; 1.
DR   PRINTS; PR00069; ALDKETRDTASE.
DR   SUPFAM; SSF51430; SSF51430; 1.
DR   PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR   PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR   PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Bile acid catabolism; Cytoplasm;
KW   Disease variant; Intrahepatic cholestasis; Lipid degradation;
KW   Lipid metabolism; NADP; Oxidoreductase; Reference proteome;
KW   Steroid metabolism.
FT   CHAIN           1..326
FT                   /note="Aldo-keto reductase family 1 member D1"
FT                   /id="PRO_0000124669"
FT   NP_BIND         22..26
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:18624455,
FT                   ECO:0000269|PubMed:18848863, ECO:0000269|PubMed:19075558,
FT                   ECO:0000269|PubMed:19515843, ECO:0000269|PubMed:22437839"
FT   NP_BIND         169..170
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:18624455,
FT                   ECO:0000269|PubMed:18848863, ECO:0000269|PubMed:19075558,
FT                   ECO:0000269|PubMed:19515843, ECO:0000269|PubMed:22437839"
FT   NP_BIND         219..224
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:18624455,
FT                   ECO:0000269|PubMed:18848863, ECO:0000269|PubMed:19075558,
FT                   ECO:0000269|PubMed:19515843, ECO:0000269|PubMed:22437839"
FT   NP_BIND         273..283
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:18624455,
FT                   ECO:0000269|PubMed:18848863, ECO:0000269|PubMed:19075558,
FT                   ECO:0000269|PubMed:19515843, ECO:0000269|PubMed:22437839"
FT   ACT_SITE        58
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000305|PubMed:18407998"
FT   BINDING         26
FT                   /note="Substrate"
FT   BINDING         53
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:18624455,
FT                   ECO:0000269|PubMed:18848863, ECO:0000269|PubMed:19075558,
FT                   ECO:0000269|PubMed:19515843, ECO:0000269|PubMed:22437839"
FT   BINDING         58
FT                   /note="Substrate"
FT   BINDING         89
FT                   /note="Substrate"
FT   BINDING         120
FT                   /note="Substrate"
FT   BINDING         132
FT                   /note="Substrate"
FT   BINDING         193
FT                   /note="NADP"
FT                   /evidence="ECO:0000269|PubMed:18624455,
FT                   ECO:0000269|PubMed:18848863, ECO:0000269|PubMed:19075558,
FT                   ECO:0000269|PubMed:19515843, ECO:0000269|PubMed:22437839"
FT   BINDING         230
FT                   /note="Substrate"
FT   VAR_SEQ         153..193
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_042913"
FT   VAR_SEQ         286..326
FT                   /note="IFDFSLTEEEMKDIEALNKNVRFVELLMWRDHPEYPFHDEY -> VARSS
FT                   (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_042901"
FT   VARIANT         50..326
FT                   /note="Missing (in CBAS2)"
FT                   /evidence="ECO:0000269|PubMed:19175828"
FT                   /id="VAR_081755"
FT   VARIANT         106
FT                   /note="L -> F (in CBAS2; decreases protein level;
FT                   accumulates in inclusion bodies; acks of 5-beta-reductase
FT                   activity; dbSNP:rs121918343)"
FT                   /evidence="ECO:0000269|PubMed:12970144,
FT                   ECO:0000269|PubMed:20522910"
FT                   /id="VAR_033007"
FT   VARIANT         133
FT                   /note="P -> R (in CBAS2; highly reduced KM and Vmax with
FT                   cortisone as substrate. Increases KM and decreases kcat
FT                   with testosterone as substrate. No change in NADPH
FT                   affinity. More thermolabile in the absence of NADPH.
FT                   Reduces 5-beta-reductase activity; dbSNP:rs267606649)"
FT                   /evidence="ECO:0000269|PubMed:15030995,
FT                   ECO:0000269|PubMed:20522910"
FT                   /id="VAR_044430"
FT   VARIANT         198
FT                   /note="P -> L (in CBAS2; decreases protein level;
FT                   accumulates in inclusion bodies; decreases 5-beta-reductase
FT                   activity; dbSNP:rs121918342)"
FT                   /evidence="ECO:0000269|PubMed:12970144,
FT                   ECO:0000269|PubMed:20522910"
FT                   /id="VAR_033008"
FT   VARIANT         223
FT                   /note="G -> E (in CBAS2; decreases protein level;
FT                   accumulates in inclusion bodies; decreases 5-beta-reductase
FT                   activity; dbSNP:rs1228918719)"
FT                   /evidence="ECO:0000269|PubMed:19175828,
FT                   ECO:0000269|PubMed:20522910"
FT                   /id="VAR_081756"
FT   VARIANT         261
FT                   /note="R -> C (in CBAS2; decreases protein level;
FT                   accumulates in inclusion bodies; lacks of 5-beta-reductase
FT                   activity; dbSNP:rs267606650)"
FT                   /evidence="ECO:0000269|PubMed:15030995,
FT                   ECO:0000269|PubMed:20522910"
FT                   /id="VAR_044431"
FT   MUTAGEN         58
FT                   /note="Y->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:18407998"
FT   MUTAGEN         120
FT                   /note="E->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:18407998"
FT   CONFLICT        14
FT                   /note="D -> V (in Ref. 3; BAF82114)"
FT                   /evidence="ECO:0000305"
FT   STRAND          9..11
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          17..21
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   TURN            29..31
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           36..47
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          51..53
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           56..58
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           61..73
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           79..81
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          83..88
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           90..92
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           95..97
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           98..109
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          114..120
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           147..159
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          162..170
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           173..180
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          191..195
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           203..211
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          215..220
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   TURN            228..230
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           238..240
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           242..250
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           255..265
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           277..284
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           293..300
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   HELIX           312..314
FT                   /evidence="ECO:0007829|PDB:3BUV"
FT   STRAND          321..324
FT                   /evidence="ECO:0007829|PDB:3UZX"
SQ   SEQUENCE   326 AA;  37377 MW;  1FE02B95398A0A6F CRC64;
     MDLSAASHRI PLSDGNSIPI IGLGTYSEPK STPKGACATS VKVAIDTGYR HIDGAYIYQN
     EHEVGEAIRE KIAEGKVRRE DIFYCGKLWA TNHVPEMVRP TLERTLRVLQ LDYVDLYIIE
     VPMAFKPGDE IYPRDENGKW LYHKSNLCAT WEAMEACKDA GLVKSLGVSN FNRRQLELIL
     NKPGLKHKPV SNQVECHPYF TQPKLLKFCQ QHDIVITAYS PLGTSRNPIW VNVSSPPLLK
     DALLNSLGKR YNKTAAQIVL RFNIQRGVVV IPKSFNLERI KENFQIFDFS LTEEEMKDIE
     ALNKNVRFVE LLMWRDHPEY PFHDEY
//
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