DHB3_MOUSE
ID DHB3_MOUSE Reviewed; 305 AA.
AC P70385; G3UWF9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 3;
DE Short=17-beta-HSD 3;
DE AltName: Full=Estradiol 17-beta-dehydrogenase 2;
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:P37058};
DE AltName: Full=Testicular 17-beta-hydroxysteroid dehydrogenase;
DE AltName: Full=Testosterone 17-beta-dehydrogenase 3 {ECO:0000305};
DE EC=1.1.1.64 {ECO:0000250|UniProtKB:P37058};
GN Name=Hsd17b3 {ECO:0000312|MGI:MGI:107177}; Synonyms=Edh17b3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=9182854; DOI=10.1016/s0960-0760(96)00165-3;
RA Sha J.A., Dudley K., Rajapaksha W.R.A.K.J.S., O'Shaughnessy P.J.;
RT "Sequence of mouse 17beta-hydroxysteroid dehydrogenase type 3 cDNA and
RT tissue distribution of the type 1 and type 3 isoform mRNAs.";
RL J. Steroid Biochem. Mol. Biol. 60:19-24(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 81-90, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=32190925; DOI=10.1096/fj.201902384r;
RA Sipilae P., Junnila A., Hakkarainen J., Huhtaniemi R., Mairinoja L.,
RA Zhang F.P., Strauss L., Ohlsson C., Kotaja N., Huhtaniemi I., Poutanen M.;
RT "The lack of HSD17B3 in male mice results in disturbed Leydig cell
RT maturation and endocrine imbalance akin to humans with HSD17B3
RT deficiency.";
RL FASEB J. 34:6111-6128(2020).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=32557858; DOI=10.1096/fj.202000361r;
RA Rebourcet D., Mackay R., Darbey A., Curley M.K., Joergensen A.,
RA Frederiksen H., Mitchell R.T., O'Shaughnessy P.J., Nef S., Smith L.B.;
RT "Ablation of the canonical testosterone production pathway via knockout of
RT the steroidogenic enzyme HSD17B3, reveals a novel mechanism of testicular
RT testosterone production.";
RL FASEB J. 34:10373-10386(2020).
CC -!- FUNCTION: Catalyzes the conversion of 17-oxosteroids to 17beta-
CC hydroxysteroids (PubMed:32557858). Favors the reduction of
CC androstenedione to testosterone (PubMed:32557858). Testosterone is the
CC key androgen driving male development and function (PubMed:32190925,
CC PubMed:32557858). Uses NADPH while the two other EDH17B enzymes use
CC NADH (By similarity). Androgens such as epiandrosterone,
CC dehydroepiandrosterone, androsterone and androstanedione are accepted
CC as substrates and reduced at C-17. Can reduce 11-ketoandrostenedione as
CC well as 11beta-hydroxyandrostenedione at C-17 to the respective
CC testosterone forms (By similarity). Plays a role in the rate-limiting-
CC step for the maximum level of testosterone production by the testis but
CC does not affect basal testosterone production (PubMed:32190925,
CC PubMed:32557858). {ECO:0000250|UniProtKB:P37058,
CC ECO:0000269|PubMed:32190925, ECO:0000269|PubMed:32557858,
CC ECO:0000303|PubMed:32190925, ECO:0000303|PubMed:32557858}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 17beta-hydroxy steroid + NADP(+) = a 17-oxo steroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:69284, ChEBI:CHEBI:15378, ChEBI:CHEBI:19168,
CC ChEBI:CHEBI:35343, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000305|PubMed:32190925, ECO:0000305|PubMed:32557858};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69286;
CC Evidence={ECO:0000305|PubMed:32190925, ECO:0000305|PubMed:32557858};
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=1.1.1.64;
CC Evidence={ECO:0000305|PubMed:32190925, ECO:0000305|PubMed:32557858};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983;
CC Evidence={ECO:0000305|PubMed:32190925, ECO:0000305|PubMed:32557858};
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:P37058};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + H(+) + NADPH = androst-5-
CC en-3beta,17beta-diol + NADP(+); Xref=Rhea:RHEA:46628,
CC ChEBI:CHEBI:2710, ChEBI:CHEBI:15378, ChEBI:CHEBI:28689,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46629;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = 5alpha-
CC androstan-3,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:42120,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15994, ChEBI:CHEBI:16330,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42122;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3alpha-hydroxy-5alpha-androstan-17-one + H(+) + NADPH =
CC 5alpha-androstane-3alpha,17beta-diol + NADP(+); Xref=Rhea:RHEA:42156,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16032, ChEBI:CHEBI:36713,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstan-17-one + H(+) + NADPH = 5alpha-
CC androstane-3beta,17beta-diol + NADP(+); Xref=Rhea:RHEA:53480,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18329, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:541975;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53481;
CC Evidence={ECO:0000250|UniProtKB:P37058};
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:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53485;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11beta-hydroxyandrost-4-ene-3,17-dione + H(+) + NADPH =
CC 11beta,17beta-dihydroxyandrost-4-ene-3-one + NADP(+);
CC Xref=Rhea:RHEA:53488, ChEBI:CHEBI:15378, ChEBI:CHEBI:27967,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:81481;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53489;
CC Evidence={ECO:0000250|UniProtKB:P37058};
CC -!- PATHWAY: Hormone biosynthesis; testosterone biosynthesis.
CC {ECO:0000269|PubMed:32190925, ECO:0000269|PubMed:32557858}.
CC -!- PATHWAY: Steroid metabolism. {ECO:0000269|PubMed:32190925,
CC ECO:0000269|PubMed:32557858}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P37058}.
CC -!- TISSUE SPECIFICITY: Expressed in the testes.
CC {ECO:0000269|PubMed:32190925, ECO:0000269|PubMed:32557858}.
CC -!- DEVELOPMENTAL STAGE: Expression is restricted to Sertoli cells in fetal
CC life, peaks in neonatal mice, declines thereafter until the age of 21
CC days, and appears in Leydig cells in adulthood.
CC {ECO:0000269|PubMed:32190925, ECO:0000269|PubMed:32557858}.
CC -!- DISRUPTION PHENOTYPE: Null males have increased circulating luteinizing
CC hormone (LH) levels (PubMed:32557858). Null males present mild
CC hypogonadism at adulthood represented by lowered weight of testes and
CC several other androgen-sensitive tissues, a shortened anogenital
CC distance, delayed puberty, and subfertility (fewer litters)
CC (PubMed:32190925). No phenotypic alterations in the null female
CC (PubMed:32190925, PubMed:32557858). {ECO:0000269|PubMed:32190925,
CC ECO:0000269|PubMed:32557858}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. 17-beta-HSD 3 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U66827; AAB06793.1; -; mRNA.
DR EMBL; CT009717; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466631; EDL16224.1; -; Genomic_DNA.
DR CCDS; CCDS26594.1; -.
DR RefSeq; NP_032317.2; NM_008291.3.
DR AlphaFoldDB; P70385; -.
DR SMR; P70385; -.
DR STRING; 10090.ENSMUSP00000132011; -.
DR BindingDB; P70385; -.
DR ChEMBL; CHEMBL1932905; -.
DR PhosphoSitePlus; P70385; -.
DR PaxDb; P70385; -.
DR PRIDE; P70385; -.
DR ProteomicsDB; 279413; -.
DR Antibodypedia; 3099; 195 antibodies from 26 providers.
DR DNASU; 15487; -.
DR Ensembl; ENSMUST00000039832; ENSMUSP00000044217; ENSMUSG00000033122.
DR Ensembl; ENSMUST00000166224; ENSMUSP00000132011; ENSMUSG00000033122.
DR Ensembl; ENSMUST00000222783; ENSMUSP00000152848; ENSMUSG00000033122.
DR GeneID; 15487; -.
DR KEGG; mmu:15487; -.
DR UCSC; uc007qyf.1; mouse.
DR CTD; 3293; -.
DR MGI; MGI:107177; Hsd17b3.
DR VEuPathDB; HostDB:ENSMUSG00000033122; -.
DR eggNOG; KOG1014; Eukaryota.
DR GeneTree; ENSGT00940000160266; -.
DR HOGENOM; CLU_010194_38_0_1; -.
DR InParanoid; P70385; -.
DR OMA; GNMPIPN; -.
DR OrthoDB; 895581at2759; -.
DR PhylomeDB; P70385; -.
DR TreeFam; TF314591; -.
DR Reactome; R-MMU-193048; Androgen biosynthesis.
DR Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00367; -.
DR BioGRID-ORCS; 15487; 0 hits in 77 CRISPR screens.
DR ChiTaRS; Hsd17b3; mouse.
DR PRO; PR:P70385; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P70385; protein.
DR Bgee; ENSMUSG00000033122; Expressed in gonadal ridge and 20 other tissues.
DR ExpressionAtlas; P70385; baseline and differential.
DR Genevisible; P70385; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0047035; F:testosterone dehydrogenase (NAD+) activity; ISO:MGI.
DR GO; GO:0030539; P:male genitalia development; IEA:InterPro.
DR GO; GO:0006694; P:steroid biosynthetic process; ISO:MGI.
DR GO; GO:0061370; P:testosterone biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR033281; HSD17B3.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR43899:SF7; PTHR43899:SF7; 1.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; NADP; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis.
FT CHAIN 1..305
FT /note="17-beta-hydroxysteroid dehydrogenase type 3"
FT /id="PRO_0000054574"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 44..73
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 95
FT /note="C -> G (in Ref. 1; AAB06793)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="I -> N (in Ref. 1; AAB06793)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="T -> S (in Ref. 1; AAB06793)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 305 AA; 34330 MW; 8EA9966B2777064D CRC64;
MEKLFIAAGL FVGLVCLVKC MRFSQHLFLR FCKALPSSFL RSMGQWAVIT GAGDGIGKAY
SFELARHGLN VVLISRTLEK LQTIAEEIER TTGSCVKIVQ ADFTREDIYD HIKEHLEGLE
IGILVNNVGM LPSFFPSHFL STSGESQNLI HCNITSVVKM TQLVLKHMES RRKGLILNIS
SGAALRPWPL YSLYSASKAF VYTFSKALSV EYRDKGIIIQ VLTPYSISTP MTKYLNNKMT
KTADEFVKES LKYVTIGAES CGCLAHEIIA IILNRIPSRI FYSSTAQRFL LTRYSDYLKR
NISNR
