AK1D1_HUMAN
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 03-AUG-2022, entry version 176.
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}.
CC ---------------------------------------------------------------------------
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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 AlphaFoldDB; P51857; -.
DR SMR; P51857; -.
DR BioGRID; 112596; 9.
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; 260 antibodies from 26 providers.
DR DNASU; 6718; -.
DR Ensembl; ENST00000242375.8; ENSP00000242375.3; ENSG00000122787.15. [P51857-1]
DR Ensembl; ENST00000411726.6; ENSP00000402374.2; ENSG00000122787.15. [P51857-3]
DR Ensembl; ENST00000432161.5; ENSP00000389197.1; ENSG00000122787.15. [P51857-2]
DR GeneID; 6718; -.
DR KEGG; hsa:6718; -.
DR MANE-Select; ENST00000242375.8; ENSP00000242375.3; NM_005989.4; NP_005980.1.
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; -.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000155961; -.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; P51857; -.
DR OMA; AFKPGNE; -.
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 SignaLink; P51857; -.
DR BioGRID-ORCS; 6718; 31 hits in 1068 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 72 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:0004033; F:aldo-keto reductase (NADP) activity; TAS:Reactome.
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 ACT_SITE 58
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:18407998"
FT BINDING 22..26
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 26
FT /ligand="substrate"
FT BINDING 53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 /ligand="substrate"
FT BINDING 89
FT /ligand="substrate"
FT BINDING 120
FT /ligand="substrate"
FT BINDING 132
FT /ligand="substrate"
FT BINDING 169..170
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 219..224
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 /ligand="substrate"
FT BINDING 273..283
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
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 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
