DHB7_HUMAN
ID DHB7_HUMAN Reviewed; 341 AA.
AC P56937; Q5T246; Q7Z4V9; Q8WWS2; Q9UF00;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 {ECO:0000305};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 7;
DE Short=17-beta-HSD 7;
DE AltName: Full=3-keto-steroid reductase;
DE EC=1.1.1.270 {ECO:0000269|PubMed:11165030, ECO:0000269|PubMed:12829805, ECO:0000269|PubMed:20659585};
DE AltName: Full=Dihydrotestosterone oxidoreductase;
DE EC=1.1.1.210 {ECO:0000269|PubMed:12574203, ECO:0000269|PubMed:12732193, ECO:0000269|PubMed:19772289};
DE AltName: Full=Estradiol 17-beta-dehydrogenase 7;
DE EC=1.1.1.62 {ECO:0000269|PubMed:12574203, ECO:0000269|PubMed:12732193, ECO:0000269|PubMed:19772289};
DE AltName: Full=Short chain dehydrogenase/reductase family 37C member 1;
GN Name=HSD17B7; Synonyms=17HSD7 {ECO:0000303|PubMed:12732193}, SDR37C1;
GN ORFNames=UNQ2563/PRO6243;
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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=10544267; DOI=10.1016/s0014-5793(99)01366-6;
RA Krazeisen A., Breitling R., Imai K., Fritz S., Moeller G., Adamski J.;
RT "Determination of cDNA, gene structure and chromosomal localization of the
RT novel human 17beta-hydroxysteroid dehydrogenase type 7.";
RL FEBS Lett. 460:373-379(1999).
RN [2]
RP SEQUENCE REVISION.
RA Krazeisen A., Breitling R., Imai K., Fritz S., Moeller G., Adamski J.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 3), CATALYTIC
RP ACTIVITY, FUNCTION, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Placenta;
RX PubMed=12732193; DOI=10.1016/s0006-291x(03)00694-6;
RA Toern S., Nokelainen P., Kurkela R., Pulkka A., Menjivar M., Ghosh S.,
RA Coca-Prados M., Peltoketo H., Isomaa V., Vihko P.;
RT "Production, purification, and functional analysis of recombinant human and
RT mouse 17beta-hydroxysteroid dehydrogenase type 7.";
RL Biochem. Biophys. Res. Commun. 305:37-45(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhou Y., Yu L., Zhao S.Y.;
RT "Cloning of a new human cDNA homologous to Rattus norvegicus ovarian-
RT specific protein.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin, and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11165030; DOI=10.1016/s0303-7207(00)00416-0;
RA Breitling R., Krazeisen A., Moeller G., Adamski J.;
RT "17beta-hydroxysteroid dehydrogenase type 7--an ancient 3-ketosteroid
RT reductase of cholesterogenesis.";
RL Mol. Cell. Endocrinol. 171:199-204(2001).
RN [12]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=12574203; DOI=10.1210/jc.2002-020236;
RA Haerkoenen P., Toern S., Kurkela R., Porvari K., Pulkka A., Lindfors A.,
RA Isomaa V., Vihko P.;
RT "Sex hormone metabolism in prostate cancer cells during transition to an
RT androgen-independent state.";
RL J. Clin. Endocrinol. Metab. 88:705-712(2003).
RN [13]
RP CATALYTIC ACTIVITY, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12829805; DOI=10.1210/me.2002-0436;
RA Marijanovic Z., Laubner D., Moeller G., Gege C., Husen B., Adamski J.,
RA Breitling R.;
RT "Closing the gap: identification of human 3-ketosteroid reductase, the last
RT unknown enzyme of mammalian cholesterol biosynthesis.";
RL Mol. Endocrinol. 17:1715-1725(2003).
RN [14]
RP ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=19772289; DOI=10.1021/jm900921c;
RA Bellavance E., Luu-The V., Poirier D.;
RT "Potent and selective steroidal inhibitors of 17beta-hydroxysteroid
RT dehydrogenase type 7, an enzyme that catalyzes the reduction of the key
RT hormones estrone and dihydrotestosterone.";
RL J. Med. Chem. 52:7488-7502(2009).
RN [15]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=20659585; DOI=10.1016/j.bbalip.2010.07.006;
RA Taramino S., Teske B., Oliaro-Bosso S., Bard M., Balliano G.;
RT "Divergent interactions involving the oxidosqualene cyclase and the
RT steroid-3-ketoreductase in the sterol biosynthetic pathway of mammals and
RT yeasts.";
RL Biochim. Biophys. Acta 1801:1232-1237(2010).
RN [16]
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 [17]
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).
CC -!- FUNCTION: Bifunctional enzyme involved in steroid-hormone metabolism
CC and cholesterol biosynthesis (PubMed:12574203, PubMed:12732193,
CC PubMed:12829805, PubMed:20659585, PubMed:19772289, PubMed:11165030).
CC Catalyzes the NADP(H)-dependent reduction of estrogens and androgens
CC and regulates the biological potency of these steroids. Converts
CC estrone (E1) to a more potent estrogen, 17beta-estradiol (E2)
CC (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts
CC dihydrotestosterone (DHT) to its inactive form 5a-androstane-3b,17b-
CC diol (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts
CC moderately progesterone to 3beta-hydroxypregn-4-ene-20-one, leading to
CC its inactivation (PubMed:12574203, PubMed:12732193). Additionally,
CC participates in the post-squalene cholesterol biosynthesis, as a 3-
CC ketosteroid reductase (PubMed:12829805, PubMed:20659585,
CC PubMed:11165030). {ECO:0000269|PubMed:11165030,
CC ECO:0000269|PubMed:12574203, ECO:0000269|PubMed:12732193,
CC ECO:0000269|PubMed:12829805, ECO:0000269|PubMed:19772289,
CC ECO:0000269|PubMed:20659585}.
CC -!- FUNCTION: [Isoform 3]: Does not have enzymatic activities toward E1 and
CC DHT. {ECO:0000269|PubMed:12732193}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000269|PubMed:12574203, ECO:0000269|PubMed:12732193,
CC ECO:0000269|PubMed:19772289};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000305|PubMed:12574203, ECO:0000305|PubMed:12732193};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxysteroid + NADP(+) = a 3-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:34787, ChEBI:CHEBI:15378, ChEBI:CHEBI:36836,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.270; Evidence={ECO:0000269|PubMed:12829805,
CC ECO:0000269|PubMed:20659585};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:34789;
CC Evidence={ECO:0000305|PubMed:12829805, ECO:0000305|PubMed:20659585};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-dehydro-4alpha-methylzymosterol + H(+) + NADPH = 4alpha-
CC methylzymosterol + NADP(+); Xref=Rhea:RHEA:36379, ChEBI:CHEBI:1949,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:136486; EC=1.1.1.270;
CC Evidence={ECO:0000269|PubMed:20659585};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36380;
CC Evidence={ECO:0000305|PubMed:20659585};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + zymosterone = NADP(+) + zymosterol;
CC Xref=Rhea:RHEA:33459, ChEBI:CHEBI:15378, ChEBI:CHEBI:18252,
CC ChEBI:CHEBI:52386, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:11165030, ECO:0000269|PubMed:12829805};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33460;
CC Evidence={ECO:0000305|PubMed:11165030, ECO:0000305|PubMed:12829805};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methyl-5alpha-cholest-8-en-3-one + H(+) + NADPH =
CC 4alpha-methyl-5alpha-cholest-8-en-3beta-ol + NADP(+);
CC Xref=Rhea:RHEA:46832, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87050, ChEBI:CHEBI:87051;
CC Evidence={ECO:0000305|PubMed:20659585};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46833;
CC Evidence={ECO:0000305|PubMed:20659585};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methyl-5alpha-cholest-7-en-3beta-ol + NADP(+) = 4alpha-
CC methyl-5alpha-cholest-7-en-3-one + H(+) + NADPH;
CC Xref=Rhea:RHEA:18409, ChEBI:CHEBI:15378, ChEBI:CHEBI:16495,
CC ChEBI:CHEBI:18378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.270; Evidence={ECO:0000250|UniProtKB:Q62904};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18411;
CC Evidence={ECO:0000250|UniProtKB:Q62904};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-cholest-8-en-3-one + H(+) + NADPH = 5alpha-cholest-8-
CC en-3beta-ol + NADP(+); Xref=Rhea:RHEA:46852, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:87056; Evidence={ECO:0000269|PubMed:11165030};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46853;
CC Evidence={ECO:0000305|PubMed:11165030};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-
CC hydroxy-5alpha-androstan-3-one + H(+) + NADPH; Xref=Rhea:RHEA:16297,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16330, ChEBI:CHEBI:18329,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.210;
CC Evidence={ECO:0000269|PubMed:12574203, ECO:0000269|PubMed:12732193,
CC ECO:0000269|PubMed:19772289};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16299;
CC Evidence={ECO:0000269|PubMed:12732193, ECO:0000305|PubMed:12574203};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + progesterone = 3beta-hydroxypregn-4-ene-20-one
CC + NADP(+); Xref=Rhea:RHEA:46216, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17026, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:85899; Evidence={ECO:0000269|PubMed:12574203,
CC ECO:0000269|PubMed:12732193};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46217;
CC Evidence={ECO:0000305|PubMed:12574203, ECO:0000305|PubMed:12732193};
CC -!- ACTIVITY REGULATION: Estradiol 17-beta-dehydrogenase and
CC dihydrotestosterone oxidoreductase activities are selectively inhibited
CC by 4-methyl-4-aza-5alpha-androstane derivatives, such as 17beta-[(N-
CC Heptyl)methylamino]-4-aza-5r-androstan-3-one and 17beta-(N-
CC Decylformamido)-4-aza-5r-androstan-3-one.
CC {ECO:0000269|PubMed:19772289}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.25 uM for estrone {ECO:0000269|PubMed:12732193};
CC KM=2.60 uM for 17beta-hydroxy-5alpha-androstan-3-one
CC {ECO:0000269|PubMed:12732193};
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC {ECO:0000269|PubMed:12574203, ECO:0000269|PubMed:12732193,
CC ECO:0000269|PubMed:19772289}.
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 5/6. {ECO:0000269|PubMed:11165030,
CC ECO:0000269|PubMed:12829805}.
CC -!- SUBUNIT: Binds to the short form of prolactin receptor.
CC {ECO:0000250|UniProtKB:Q62904}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12829805}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P56937-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56937-2; Sequence=VSP_006029;
CC Name=3;
CC IsoId=P56937-3; Sequence=VSP_012766;
CC -!- TISSUE SPECIFICITY: Highly expressed in adrenal gland, liver, lung and
CC thymus. Expressed in breast, ovaries, pituitary gland, pregnant uterus,
CC prostate, kidney, lymph node, small intestine, spinal cord and trachea.
CC Weakly expressed in all other tissues tested.
CC {ECO:0000269|PubMed:12732193}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in eye ciliary epithelial
CC cells and neuroendocrine cells. {ECO:0000269|PubMed:12732193}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q62904}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. ERG27 subfamily. {ECO:0000305}.
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DR EMBL; AF098786; AAF09266.2; -; mRNA.
DR EMBL; AF162767; AAF14537.1; -; Genomic_DNA.
DR EMBL; AF162759; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162760; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162761; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162762; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162763; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162764; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162765; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AF162766; AAF14537.1; JOINED; Genomic_DNA.
DR EMBL; AJ249179; CAC20418.1; -; mRNA.
DR EMBL; AJ250550; CAC88111.1; -; Genomic_DNA.
DR EMBL; AJ250551; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250552; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250553; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250554; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250555; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250556; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250557; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AJ250558; CAC88111.1; JOINED; Genomic_DNA.
DR EMBL; AF145023; AAP97275.1; -; mRNA.
DR EMBL; AY358962; AAQ89321.1; -; mRNA.
DR EMBL; AK290741; BAF83430.1; -; mRNA.
DR EMBL; BT007075; AAP35738.1; -; mRNA.
DR EMBL; AL392003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90716.1; -; Genomic_DNA.
DR EMBL; BC007068; AAH07068.1; -; mRNA.
DR EMBL; BC065246; AAH65246.1; -; mRNA.
DR CCDS; CCDS1242.1; -. [P56937-1]
DR RefSeq; NP_001291441.1; NM_001304512.1.
DR RefSeq; NP_001291442.1; NM_001304513.1.
DR RefSeq; NP_057455.1; NM_016371.3. [P56937-1]
DR AlphaFoldDB; P56937; -.
DR SMR; P56937; -.
DR BioGRID; 119563; 33.
DR IntAct; P56937; 14.
DR STRING; 9606.ENSP00000254521; -.
DR BindingDB; P56937; -.
DR ChEMBL; CHEMBL5999; -.
DR DrugBank; DB00157; NADH.
DR SwissLipids; SLP:000001214; -.
DR GlyGen; P56937; 3 sites.
DR iPTMnet; P56937; -.
DR PhosphoSitePlus; P56937; -.
DR SwissPalm; P56937; -.
DR BioMuta; HSD17B7; -.
DR DMDM; 8134404; -.
DR EPD; P56937; -.
DR jPOST; P56937; -.
DR MassIVE; P56937; -.
DR MaxQB; P56937; -.
DR PaxDb; P56937; -.
DR PeptideAtlas; P56937; -.
DR PRIDE; P56937; -.
DR ProteomicsDB; 56957; -. [P56937-1]
DR ProteomicsDB; 56958; -. [P56937-2]
DR ProteomicsDB; 56959; -. [P56937-3]
DR Antibodypedia; 34324; 170 antibodies from 26 providers.
DR DNASU; 51478; -.
DR Ensembl; ENST00000254521.8; ENSP00000254521.3; ENSG00000132196.16. [P56937-1]
DR GeneID; 51478; -.
DR KEGG; hsa:51478; -.
DR MANE-Select; ENST00000254521.8; ENSP00000254521.3; NM_016371.4; NP_057455.1.
DR UCSC; uc001gci.4; human. [P56937-1]
DR CTD; 51478; -.
DR DisGeNET; 51478; -.
DR GeneCards; HSD17B7; -.
DR HGNC; HGNC:5215; HSD17B7.
DR HPA; ENSG00000132196; Tissue enhanced (liver).
DR MIM; 606756; gene.
DR neXtProt; NX_P56937; -.
DR OpenTargets; ENSG00000132196; -.
DR PharmGKB; PA29483; -.
DR VEuPathDB; HostDB:ENSG00000132196; -.
DR eggNOG; KOG1478; Eukaryota.
DR GeneTree; ENSGT00390000013340; -.
DR HOGENOM; CLU_029944_2_0_1; -.
DR InParanoid; P56937; -.
DR OMA; ASYEGSK; -.
DR PhylomeDB; P56937; -.
DR TreeFam; TF105433; -.
DR BioCyc; MetaCyc:HS05604-MON; -.
DR BRENDA; 1.1.1.270; 2681.
DR BRENDA; 1.1.1.62; 2681.
DR PathwayCommons; P56937; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR SABIO-RK; P56937; -.
DR SignaLink; P56937; -.
DR UniPathway; UPA00769; -.
DR UniPathway; UPA00770; UER00758.
DR BioGRID-ORCS; 51478; 27 hits in 1050 CRISPR screens.
DR GeneWiki; HSD17B7; -.
DR GenomeRNAi; 51478; -.
DR Pharos; P56937; Tchem.
DR PRO; PR:P56937; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P56937; protein.
DR Bgee; ENSG00000132196; Expressed in adrenal tissue and 103 other tissues.
DR ExpressionAtlas; P56937; baseline and differential.
DR Genevisible; P56937; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IDA:UniProtKB.
DR GO; GO:0047024; F:5alpha-androstane-3beta,17beta-diol dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0102176; F:cycloeucalenone reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; IDA:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR CDD; cd08941; 3KS_SDR_c; 1.
DR InterPro; IPR042829; HSD17B7/Erg27.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NAD; NADP; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..341
FT /note="3-keto-steroid reductase/17-beta-hydroxysteroid
FT dehydrogenase 7"
FT /id="PRO_0000054586"
FT TOPO_DOM 1..229
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 8..15
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 112..119
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10544267"
FT /id="VSP_006029"
FT VAR_SEQ 215..249
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12732193"
FT /id="VSP_012766"
FT CONFLICT 52..53
FT /note="HP -> PT (in Ref. 1; AAF14537)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="Q -> P (in Ref. 1; AAF14537)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="C -> R (in Ref. 3; CAC88111)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="F -> L (in Ref. 3; CAC88111)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="L -> F (in Ref. 4; AAP97275)"
FT /evidence="ECO:0000305"
FT CONFLICT 273..276
FT /note="HQKP -> PPKA (in Ref. 4; AAP97275)"
FT /evidence="ECO:0000305"
FT CONFLICT 288..295
FT /note="ATTGFGRN -> GTTALEEI (in Ref. 4; AAP97275)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 341 AA; 38206 MW; FE4892B2602F549B CRC64;
MRKVVLITGA SSGIGLALCK RLLAEDDELH LCLACRNMSK AEAVCAALLA SHPTAEVTIV
QVDVSNLQSV FRASKELKQR FQRLDCIYLN AGIMPNPQLN IKALFFGLFS RKVIHMFSTA
EGLLTQGDKI TADGLQEVFE TNVFGHFILI RELEPLLCHS DNPSQLIWTS SRSARKSNFS
LEDFQHSKGK EPYSSSKYAT DLLSVALNRN FNQQGLYSNV ACPGTALTNL TYGILPPFIW
TLLMPAILLL RFFANAFTLT PYNGTEALVW LFHQKPESLN PLIKYLSATT GFGRNYIMTQ
KMDLDEDTAE KFYQKLLELE KHIRVTIQKT DNQARLSGSC L
