ID DHB1_HUMAN Reviewed; 328 AA.
AC P14061; B3KXS1; Q2M2L8;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 27-MAR-2024, entry version 230.
DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 1 {ECO:0000305};
DE Short=17-beta-HSD 1;
DE EC=1.1.1.51 {ECO:0000250|UniProtKB:P51656};
DE AltName: Full=20 alpha-hydroxysteroid dehydrogenase;
DE Short=20-alpha-HSD;
DE AltName: Full=E2DH;
DE AltName: Full=Estradiol 17-beta-dehydrogenase 1 {ECO:0000305};
DE EC=1.1.1.62 {ECO:0000269|PubMed:8994190};
DE AltName: Full=Placental 17-beta-hydroxysteroid dehydrogenase;
DE AltName: Full=Short chain dehydrogenase/reductase family 28C member 1;
GN Name=HSD17B1 {ECO:0000312|HGNC:HGNC:5210};
GN Synonyms=E17KSR, EDH17B1, EDH17B2, EDHB17, SDR28C1;
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], AND VARIANT SER-313.
RC TISSUE=Placenta;
RX PubMed=2846351; DOI=10.1016/0014-5793(88)80548-9;
RA Peltoketo H., Isomaa V., Maeentausta O., Vihko R.;
RT "Complete amino acid sequence of human placental 17 beta-hydroxysteroid
RT dehydrogenase deduced from cDNA.";
RL FEBS Lett. 239:73-77(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-313.
RC TISSUE=Placenta;
RX PubMed=2779584; DOI=10.1210/mend-3-8-1301;
RA Luu-The V., Labrie C., Zhao H.F., Couet J., Lachance Y., Simard J.,
RA Leblanc G., Labrie F.;
RT "Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and
RT assignment of the gene to chromosome 17: evidence of two mRNA species with
RT distinct 5'-termini in human placenta.";
RL Mol. Endocrinol. 3:1301-1309(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-313.
RX PubMed=2330005; DOI=10.1210/mend-4-2-268;
RA Luu-The V., Labrie C., Simard J., Lachance Y., Zhao H.F., Couet J.,
RA Leblanc G., Labrie F.;
RT "Structure of two in tandem human 17 beta-hydroxysteroid dehydrogenase
RT genes.";
RL Mol. Endocrinol. 4:268-275(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-313.
RX PubMed=2197970; DOI=10.1111/j.1749-6632.1990.tb34281.x;
RA Luu-The V., Labrie C., Zhao H.F., Couet J., Lachance Y., Simard J.,
RA Cote J., Leblanc G., Lagace L., Berube D., Gagne R., Labrie F.;
RT "Purification, cloning, complementary DNA structure, and predicted amino
RT acid sequence of human estradiol 17 beta-dehydrogenase.";
RL Ann. N. Y. Acad. Sci. 595:40-52(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-313.
RX PubMed=1327779; DOI=10.1111/j.1432-1033.1992.tb17310.x;
RA Peltoketo H.E., Isomma V., Vihko R.;
RT "Genomic organization and DNA sequences of human 17 beta-hydroxysteroid
RT dehydrogenase genes and flanking regions. Localization of multiple Alu
RT sequences and putative cis-acting elements.";
RL Eur. J. Biochem. 209:459-466(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-313.
RA Shen Y., Gibbs R.A.;
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-313.
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-313.
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-313.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 2-6.
RX PubMed=5045524; DOI=10.1021/bi00764a023;
RA Burns D.J.W., Engel L.L., Bethune J.L.;
RT "Amino acid composition and subunit structure. Human placental 17
RT - estradiol dehydrogenase.";
RL Biochemistry 11:2699-2703(1972).
RN [12]
RP PROTEIN SEQUENCE OF 52-68.
RX PubMed=4719204; DOI=10.1016/0014-5793(73)80554-x;
RA Nicholas J.C., Harris J.I.;
RT "Human placental 17 -oestradiol dehydrogenase. Sequence of a tryptic
RT peptide containing an essential cysteine.";
RL FEBS Lett. 29:173-176(1973).
RN [13]
RP PROTEIN SEQUENCE OF 205-224.
RX PubMed=3456799; DOI=10.1021/bi00351a019;
RA Murdock G.L., Chin C.-C., Warren J.C.;
RT "Human placental estradiol 17 beta-dehydrogenase: sequence of a histidine-
RT bearing peptide in the catalytic region.";
RL Biochemistry 25:641-646(1986).
RN [14]
RP PROTEIN SEQUENCE OF 220-224.
RX PubMed=6578212; DOI=10.1016/s0021-9258(17)44248-7;
RA Murdock G.L., Chin C.C., Offord R.E., Bradshaw R.A., Warren J.C.;
RT "Human placental estradiol 17 beta-dehydrogenase. Identification of a
RT single histidine residue affinity-labeled by both 3-bromoacetoxyestrone and
RT 12 beta-bromoacetoxy-4-estrene-3,17-dione.";
RL J. Biol. Chem. 258:11460-11464(1983).
RN [15]
RP SIMILARITY TO SHORT CHAIN DEHYDROGENASES.
RX PubMed=2547159; DOI=10.1210/mend-3-5-881;
RA Baker M.E.;
RT "Human placental 17 beta-hydroxysteroid dehydrogenase is homologous to NodG
RT protein of Rhizobium meliloti.";
RL Mol. Endocrinol. 3:881-884(1989).
RN [16]
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP MUTAGENESIS OF 112-LEU--VAL-114; SER-135; SER-143; TYR-156; LYS-160;
RP ALA-171; HIS-222 AND GLU-283, AND PHOSPHORYLATION AT SER-135.
RX PubMed=8994190; DOI=10.1210/mend.11.1.9872;
RA Puranen T., Poutanen M., Ghosh D., Vihko P., Vihko R.;
RT "Characterization of structural and functional properties of human 17 beta-
RT hydroxysteroid dehydrogenase type 1 using recombinant enzymes and site-
RT directed mutagenesis.";
RL Mol. Endocrinol. 11:77-86(1997).
RN [17] {ECO:0007744|PDB:1BHS}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=7663947; DOI=10.1016/s0969-2126(01)00183-6;
RA Ghosh D., Pletnev V.Z., Zhu D.W., Wawrzak Z., Duax W.L., Pangborn W.,
RA Labrie F., Lin S.-X.;
RT "Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at
RT 2.20-A resolution.";
RL Structure 3:503-513(1995).
RN [18] {ECO:0007744|PDB:1IOL}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=8756321; DOI=10.1038/nsb0896-665;
RA Azzi A., Rehse P.H., Zhu D.W., Campbell R.L., Labrie F., Lin S.X.;
RT "Crystal structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase
RT complexed with 17 beta-estradiol.";
RL Nat. Struct. Biol. 3:665-668(1996).
RN [19] {ECO:0007744|PDB:1FDS, ECO:0007744|PDB:1FDT}
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND NADP.
RX PubMed=8805577; DOI=10.1016/s0969-2126(96)00098-6;
RA Breton R., Housset D., Mazza C., Fontecilla-Camps J.-C.;
RT "The structure of a complex of human 17beta-hydroxysteroid dehydrogenase
RT with estradiol and NADP+ identifies two principal targets for the design of
RT inhibitors.";
RL Structure 4:905-915(1996).
RN [20] {ECO:0007744|PDB:1FDU, ECO:0007744|PDB:1FDV, ECO:0007744|PDB:1FDW}
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=9525918; DOI=10.1074/jbc.273.14.8145;
RA Mazza C., Breton R., Housset D., Fontecilla-Camps J.-C.;
RT "Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid
RT dehydrogenase.";
RL J. Biol. Chem. 273:8145-8152(1998).
RN [21] {ECO:0007744|PDB:1EQU}
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=9927655; DOI=10.1073/pnas.96.3.840;
RA Sawicki M.W., Erman M., Puranen T., Vihko P., Ghosh D.;
RT "Structure of the ternary complex of human 17beta-hydroxysteroid
RT dehydrogenase type 1 with 3-hydroxyestra-1,3,5,7-tetraen-17-one (equilin)
RT and NADP+.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:840-845(1999).
RN [22] {ECO:0007744|PDB:1DHT, ECO:0007744|PDB:3DHE}
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 39-328, AND MUTAGENESIS OF
RP LEU-150.
RX PubMed=10625652; DOI=10.1074/jbc.275.2.1105;
RA Han Q., Campbell R.L., Gangloff A., Huang Y.-W., Lin S.-X.;
RT "Dehydroepiandrosterone and dihydrotestosterone recognition by human
RT estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid
RT discrimination and enzyme-induced strain.";
RL J. Biol. Chem. 275:1105-1111(2000).
RN [23] {ECO:0007744|PDB:1I5R}
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=12223444; DOI=10.1096/fj.02-0026fje;
RA Qiu W., Campbell R.L., Gangloff A., Dupuis P., Boivin R.P., Tremblay M.R.,
RA Poirier D., Lin S.X.;
RT "A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase
RT inhibitors: estradiol-adenosine hybrids with high affinity.";
RL FASEB J. 16:1829-1831(2002).
RN [24] {ECO:0007744|PDB:1JTV}
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS).
RX PubMed=12490543; DOI=10.1096/fj.02-0397fje;
RA Gangloff A., Shi R., Nahoum V., Lin S.X.;
RT "Pseudo-symmetry of C19 steroids, alternative binding orientations, and
RT multispecificity in human estrogenic 17beta-hydroxysteroid dehydrogenase.";
RL FASEB J. 17:274-276(2003).
RN [25] {ECO:0007744|PDB:1QYV, ECO:0007744|PDB:1QYW, ECO:0007744|PDB:1QYX}
RP X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS).
RX PubMed=14966133; DOI=10.1074/jbc.m313156200;
RA Shi R., Lin S.X.;
RT "Cofactor hydrogen bonding onto the protein main chain is conserved in the
RT short chain dehydrogenase/reductase family and contributes to nicotinamide
RT orientation.";
RL J. Biol. Chem. 279:16778-16785(2004).
RN [26]
RP VARIANTS VAL-238 AND SER-313.
RX PubMed=8389226; DOI=10.1093/hmg/2.4.479;
RA Normand T., Narod S., Labrie F., Simard J.;
RT "Detection of polymorphisms in the estradiol 17 beta-hydroxysteroid
RT dehydrogenase II gene at the EDH17B2 locus on 17q11-q21.";
RL Hum. Mol. Genet. 2:479-483(1993).
CC -!- FUNCTION: Favors the reduction of estrogens and androgens. Converts
CC estrone (E1) to a more potent estrogen, 17beta-estradiol (E2)
CC (PubMed:8994190). Also has 20-alpha-HSD activity. Uses preferentially
CC NADH. {ECO:0000269|PubMed:8994190}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000269|PubMed:8994190};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:P51656};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000250|UniProtKB:P51656};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + testosterone = androst-4-ene-3,17-dione + H(+) +
CC NADPH; Xref=Rhea:RHEA:14981, ChEBI:CHEBI:15378, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.51;
CC Evidence={ECO:0000250|UniProtKB:P51656};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983;
CC Evidence={ECO:0000250|UniProtKB:P51656};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.11 uM for 17beta-estradiol {ECO:0000269|PubMed:8994190};
CC KM=0.9 uM for estrone {ECO:0000269|PubMed:8994190};
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC {ECO:0000269|PubMed:8994190}.
CC -!- SUBUNIT: Homodimer. Exists predominantly as an homodimer but also exits
CC as monomer. {ECO:0000269|PubMed:8805577, ECO:0000269|PubMed:8994190}.
CC -!- INTERACTION:
CC P14061; P09917: ALOX5; NbExp=3; IntAct=EBI-12867244, EBI-79934;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; X13440; CAA31792.1; -; mRNA.
DR EMBL; M36263; AAA35600.1; -; mRNA.
DR EMBL; M27138; AAB16941.1; -; Genomic_DNA.
DR EMBL; M84472; AAB16942.1; -; Genomic_DNA.
DR EMBL; U34879; AAD05019.1; -; Genomic_DNA.
DR EMBL; AK127832; BAG54583.1; -; mRNA.
DR EMBL; AC067852; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60836.1; -; Genomic_DNA.
DR EMBL; BC104752; AAI04753.1; -; mRNA.
DR EMBL; BC111935; AAI11936.1; -; mRNA.
DR CCDS; CCDS11428.1; -.
DR PIR; A36081; DEHUE7.
DR RefSeq; NP_000404.2; NM_000413.3.
DR PDB; 1A27; X-ray; 1.90 A; A=2-290.
DR PDB; 1BHS; X-ray; 2.20 A; A=2-328.
DR PDB; 1DHT; X-ray; 2.24 A; A=2-328.
DR PDB; 1EQU; X-ray; 3.00 A; A/B=2-328.
DR PDB; 1FDS; X-ray; 1.70 A; A=2-328.
DR PDB; 1FDT; X-ray; 2.20 A; A=2-328.
DR PDB; 1FDU; X-ray; 2.70 A; A/B/C/D=2-328.
DR PDB; 1FDV; X-ray; 3.10 A; A/B/C/D=2-328.
DR PDB; 1FDW; X-ray; 2.70 A; A=2-328.
DR PDB; 1I5R; X-ray; 1.60 A; A=2-328.
DR PDB; 1IOL; X-ray; 2.30 A; A=2-328.
DR PDB; 1JTV; X-ray; 1.54 A; A=2-328.
DR PDB; 1QYV; X-ray; 1.81 A; A=2-328.
DR PDB; 1QYW; X-ray; 1.63 A; A=2-328.
DR PDB; 1QYX; X-ray; 1.89 A; A=2-328.
DR PDB; 3DEY; X-ray; 1.70 A; X=2-328.
DR PDB; 3DHE; X-ray; 2.30 A; A=2-328.
DR PDB; 3HB4; X-ray; 2.21 A; X=2-328.
DR PDB; 3HB5; X-ray; 2.00 A; X=2-328.
DR PDB; 3KLM; X-ray; 1.70 A; X=2-328.
DR PDB; 3KLP; X-ray; 2.50 A; X=2-328.
DR PDB; 3KM0; X-ray; 2.30 A; A/B=2-328.
DR PDB; 6CGC; X-ray; 2.10 A; A/B=1-328.
DR PDB; 6CGE; X-ray; 2.20 A; A/B=1-328.
DR PDB; 6DTP; X-ray; 2.00 A; A/B=1-328.
DR PDB; 6MNC; X-ray; 2.40 A; A/B=1-328.
DR PDB; 6MNE; X-ray; 1.86 A; A/B=1-328.
DR PDB; 7X3Z; X-ray; 2.25 A; A/B=1-328.
DR PDBsum; 1A27; -.
DR PDBsum; 1BHS; -.
DR PDBsum; 1DHT; -.
DR PDBsum; 1EQU; -.
DR PDBsum; 1FDS; -.
DR PDBsum; 1FDT; -.
DR PDBsum; 1FDU; -.
DR PDBsum; 1FDV; -.
DR PDBsum; 1FDW; -.
DR PDBsum; 1I5R; -.
DR PDBsum; 1IOL; -.
DR PDBsum; 1JTV; -.
DR PDBsum; 1QYV; -.
DR PDBsum; 1QYW; -.
DR PDBsum; 1QYX; -.
DR PDBsum; 3DEY; -.
DR PDBsum; 3DHE; -.
DR PDBsum; 3HB4; -.
DR PDBsum; 3HB5; -.
DR PDBsum; 3KLM; -.
DR PDBsum; 3KLP; -.
DR PDBsum; 3KM0; -.
DR PDBsum; 6CGC; -.
DR PDBsum; 6CGE; -.
DR PDBsum; 6DTP; -.
DR PDBsum; 6MNC; -.
DR PDBsum; 6MNE; -.
DR PDBsum; 7X3Z; -.
DR AlphaFoldDB; P14061; -.
DR SMR; P14061; -.
DR BioGRID; 109525; 58.
DR IntAct; P14061; 2.
DR STRING; 9606.ENSP00000225929; -.
DR BindingDB; P14061; -.
DR ChEMBL; CHEMBL3181; -.
DR DrugBank; DB01561; Androstanedione.
DR DrugBank; DB01536; Androstenedione.
DR DrugBank; DB02323; EM-1745.
DR DrugBank; DB02187; Equilin.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB02901; Stanolone.
DR DrugBank; DB13951; Stanolone acetate.
DR DrugCentral; P14061; -.
DR SwissLipids; SLP:000001218; -.
DR iPTMnet; P14061; -.
DR SwissPalm; P14061; -.
DR BioMuta; HSD17B1; -.
DR DMDM; 313104233; -.
DR jPOST; P14061; -.
DR MassIVE; P14061; -.
DR PaxDb; 9606-ENSP00000466799; -.
DR PeptideAtlas; P14061; -.
DR ProteomicsDB; 53018; -.
DR Antibodypedia; 16966; 347 antibodies from 33 providers.
DR DNASU; 3292; -.
DR Ensembl; ENST00000585807.6; ENSP00000466799.1; ENSG00000108786.11.
DR GeneID; 3292; -.
DR KEGG; hsa:3292; -.
DR MANE-Select; ENST00000585807.6; ENSP00000466799.1; NM_000413.4; NP_000404.2.
DR UCSC; uc002hzw.4; human.
DR AGR; HGNC:5210; -.
DR CTD; 3292; -.
DR DisGeNET; 3292; -.
DR GeneCards; HSD17B1; -.
DR HGNC; HGNC:5210; HSD17B1.
DR HPA; ENSG00000108786; Tissue enriched (placenta).
DR MIM; 109684; gene.
DR neXtProt; NX_P14061; -.
DR OpenTargets; ENSG00000108786; -.
DR PharmGKB; PA29478; -.
DR VEuPathDB; HostDB:ENSG00000108786; -.
DR eggNOG; KOG1205; Eukaryota.
DR GeneTree; ENSGT00940000160415; -.
DR HOGENOM; CLU_010194_2_9_1; -.
DR InParanoid; P14061; -.
DR OMA; KGLHRDT; -.
DR OrthoDB; 2898074at2759; -.
DR PhylomeDB; P14061; -.
DR BRENDA; 1.1.1.51; 2681.
DR BRENDA; 1.1.1.62; 2681.
DR PathwayCommons; P14061; -.
DR Reactome; R-HSA-193144; Estrogen biosynthesis.
DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision).
DR SABIO-RK; P14061; -.
DR SignaLink; P14061; -.
DR SIGNOR; P14061; -.
DR UniPathway; UPA00769; -.
DR BioGRID-ORCS; 3292; 8 hits in 1158 CRISPR screens.
DR ChiTaRS; HSD17B1; human.
DR EvolutionaryTrace; P14061; -.
DR GeneWiki; HSD17B1; -.
DR GenomeRNAi; 3292; -.
DR Pharos; P14061; Tchem.
DR PRO; PR:P14061; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P14061; Protein.
DR Bgee; ENSG00000108786; Expressed in placenta and 101 other cell types or tissues.
DR ExpressionAtlas; P14061; baseline and differential.
DR Genevisible; P14061; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR GO; GO:0035410; F:dihydrotestosterone 17-beta-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; IDA:UniProtKB.
DR GO; GO:1903924; F:estradiol binding; IDA:CAFA.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0070401; F:NADP+ binding; IMP:CAFA.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0036094; F:small molecule binding; EXP:DisProt.
DR GO; GO:0005496; F:steroid binding; IDA:CAFA.
DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; IEA:Ensembl.
DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; ISS:UniProtKB.
DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0071248; P:cellular response to metal ion; IEA:Ensembl.
DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; TAS:ProtInc.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl.
DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; TAS:ProtInc.
DR GO; GO:0061370; P:testosterone biosynthetic process; ISS:UniProtKB.
DR CDD; cd09806; type1_17beta-HSD-like_SDR_c; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR011348; 17beta_DH.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43391:SF15; 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1; 1.
DR PANTHER; PTHR43391; RETINOL DEHYDROGENASE-RELATED; 1.
DR Pfam; PF00106; adh_short; 1.
DR PIRSF; PIRSF000095; 17beta-HSD; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Lipid biosynthesis;
KW Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Steroid biosynthesis.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:5045524"
FT CHAIN 2..328
FT /note="17-beta-hydroxysteroid dehydrogenase type 1"
FT /id="PRO_0000054567"
FT REGION 291..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT BINDING 10..38
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:8805577"
FT BINDING 66
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:8805577"
FT BINDING 143
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8805577"
FT BINDING 160
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:8805577"
FT MOD_RES 135
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:8994190"
FT VARIANT 238
FT /note="A -> V (in dbSNP:rs147402365)"
FT /evidence="ECO:0000269|PubMed:8389226"
FT /id="VAR_006951"
FT VARIANT 313
FT /note="G -> S (in dbSNP:rs605059)"
FT /evidence="ECO:0000269|PubMed:1327779,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2197970, ECO:0000269|PubMed:2330005,
FT ECO:0000269|PubMed:2779584, ECO:0000269|PubMed:2846351,
FT ECO:0000269|PubMed:8389226, ECO:0000269|Ref.6,
FT ECO:0000269|Ref.9"
FT /id="VAR_006952"
FT MUTAGEN 112..114
FT /note="LDV->F: Loss of 17-beta-hydroxysteroid dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 135
FT /note="S->A: Abolishes phosphorylation. No effect on 17-
FT beta-hydroxysteroid dehydrogenase activity."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 143
FT /note="S->A: Loss of 17-beta-hydroxysteroid dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 150
FT /note="L->V: Alters substrate specificity."
FT /evidence="ECO:0000269|PubMed:10625652"
FT MUTAGEN 156
FT /note="Y->A: Loss of 17-beta-hydroxysteroid dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 160
FT /note="K->A: Loss of 17-beta-hydroxysteroid dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 171
FT /note="A->AEF: Loss of 17-beta-hydroxysteroid dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 222
FT /note="H->A: No effect on conversion of estrone to 17beta-
FT estradiol."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 283
FT /note="E->A: No effect on conversion of estrone to 17beta-
FT estradiol."
FT /evidence="ECO:0000269|PubMed:8994190"
FT MUTAGEN 283
FT /note="E->Q: No effect on conversion of estrone to 17beta-
FT estradiol."
FT /evidence="ECO:0000269|PubMed:8994190"
FT CONFLICT 3
FT /note="R -> E (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 31..38
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 44..52
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 70..78
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 117..133
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 154..174
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 179..186
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:1A27"
FT TURN 193..196
FT /evidence="ECO:0007829|PDB:1A27"
FT HELIX 201..206
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 210..230
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 234..246
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:1JTV"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:1EQU"
FT HELIX 261..269
FT /evidence="ECO:0007829|PDB:1JTV"
FT HELIX 274..285
FT /evidence="ECO:0007829|PDB:1JTV"
SQ SEQUENCE 328 AA; 34950 MW; 5B5C8909F9120832 CRC64;
MARTVVLITG CSSGIGLHLA VRLASDPSQS FKVYATLRDL KTQGRLWEAA RALACPPGSL
ETLQLDVRDS KSVAAARERV TEGRVDVLVC NAGLGLLGPL EALGEDAVAS VLDVNVVGTV
RMLQAFLPDM KRRGSGRVLV TGSVGGLMGL PFNDVYCASK FALEGLCESL AVLLLPFGVH
LSLIECGPVH TAFMEKVLGS PEEVLDRTDI HTFHRFYQYL AHSKQVFREA AQNPEEVAEV
FLTALRAPKP TLRYFTTERF LPLLRMRLDD PSGSNYVTAM HREVFGDVPA KAEAGAEAGG
GAGPGAEDEA GRGAVGDPEL GDPPAAPQ
//
