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 27-MAR-2024, entry version 165. 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=androsterone + H(+) + NADPH = 5alpha-androstane-3alpha,17beta- CC diol + NADP(+); Xref=Rhea:RHEA:42156, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16032, ChEBI:CHEBI:36713, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349; 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 SwissPalm; P70385; -. DR PaxDb; 10090-ENSMUSP00000132011; -. DR ProteomicsDB; 279413; -. DR Antibodypedia; 3099; 245 antibodies from 26 providers. DR DNASU; 15487; -. DR Ensembl; ENSMUST00000039832.7; ENSMUSP00000044217.7; ENSMUSG00000033122.15. DR Ensembl; ENSMUST00000166224.8; ENSMUSP00000132011.2; ENSMUSG00000033122.15. DR Ensembl; ENSMUST00000222783.2; ENSMUSP00000152848.2; ENSMUSG00000033122.15. DR GeneID; 15487; -. DR KEGG; mmu:15487; -. DR UCSC; uc007qyf.1; mouse. DR AGR; MGI:107177; -. 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; CNIISVT; -. DR OrthoDB; 6845at2759; -. 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; 1 hit in 82 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 22 other cell types or tissues. DR ExpressionAtlas; P70385; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0072582; F:17-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:RHEA. DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; ISO:MGI. 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:0006694; P:steroid biosynthetic process; ISO:MGI. DR GO; GO:0061370; P:testosterone biosynthetic process; IEA:UniProtKB-UniPathway. DR CDD; cd05356; 17beta-HSD1_like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR020904; Sc_DH/Rdtase_CS. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR43899:SF7; 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 3; 1. DR PANTHER; PTHR43899; RH59310P; 1. DR Pfam; PF00106; adh_short; 1. DR PIRSF; PIRSF000126; 11-beta-HSD1; 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. DR Genevisible; P70385; MM. 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 //