ID DHB3_HUMAN Reviewed; 310 AA. AC P37058; Q5U0Q6; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 27-MAR-2024, entry version 211. DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 3; DE Short=17-beta-HSD 3 {ECO:0000303|PubMed:27927697}; DE AltName: Full=Estradiol 17-beta-dehydrogenase 2; DE EC=1.1.1.62 {ECO:0000269|PubMed:8075637}; DE AltName: Full=Short chain dehydrogenase/reductase family 12C member 2; 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:0000269|PubMed:16216911, ECO:0000269|PubMed:26545797, ECO:0000269|PubMed:27927697, ECO:0000269|PubMed:8075637}; GN Name=HSD17B3 {ECO:0000312|HGNC:HGNC:5212}; Synonyms=EDH17B3, SDR12C2; 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), VARIANTS MPH GLN-80; VAL-203; RP LEU-232 AND VAL-235, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF RP VARIANTS MPH GLN-80; VAL-203; LEU-232 AND VAL-235, TISSUE SPECIFICITY, AND RP INVOLVEMENT IN MPH. RC TISSUE=Testis; RX PubMed=8075637; DOI=10.1038/ng0594-34; RA Geissler W.M., Davis D.L., Wu L., Bradshaw K.D., Patel S., Mendonca B.B., RA Elliston K.O., Wilson J.D., Russell D.W., Andersson S.; RT "Male pseudohermaphroditism caused by mutations of testicular 17 beta- RT hydroxysteroid dehydrogenase 3."; RL Nat. Genet. 7:34-39(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-31 AND SER-289. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [6] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=16216911; DOI=10.1677/jme.1.01853; RA Mindnich R., Haller F., Halbach F., Moeller G., Hrabe de Angelis M., RA Adamski J.; RT "Androgen metabolism via 17beta-hydroxysteroid dehydrogenase type 3 in RT mammalian and non-mammalian vertebrates: comparison of the human and the RT zebrafish enzyme."; RL J. Mol. Endocrinol. 35:305-316(2005). RN [7] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=27927697; DOI=10.1530/joe-16-0495; RA Tsachaki M., Meyer A., Weger B., Kratschmar D.V., Tokarz J., Adamski J., RA Belting H.G., Affolter M., Dickmeis T., Odermatt A.; RT "Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the RT model organism zebrafish."; RL J. Endocrinol. 232:323-335(2017). RN [8] RP INVOLVEMENT IN MPH, AND VARIANTS MPH LEU-65; PRO-176; GLU-205; ILE-208; RP ASP-215 AND LEU-282. RX PubMed=8550739; DOI=10.1210/jcem.81.1.8550739; RA Andersson S., Geissler W.M., Wu L., Davis D.L., Grumbach M.M., New M.I., RA Schwarz H.P., Blethen S.L., Mendonca B.B., Bloise W., Witchel S.F., RA Cutler G.B. Jr., Griffin J.E., Wilson J.D., Russel D.W.; RT "Molecular genetics and pathophysiology of 17 beta-hydroxysteroid RT dehydrogenase 3 deficiency."; RL J. Clin. Endocrinol. Metab. 81:130-136(1996). RN [9] RP INVOLVEMENT IN MPH, AND VARIANT MPH TRP-80. RX PubMed=9758445; DOI=10.1530/eje.0.1390330; RA Bilbao J.R., Loridan L., Audi L., Gonzalo E., Castano L.; RT "A novel missense (R80W) mutation in 17-beta-hydroxysteroid dehydrogenase RT type 3 gene associated with male pseudohermaphroditism."; RL Eur. J. Endocrinol. 139:330-333(1998). RN [10] RP INVOLVEMENT IN MPH, VARIANTS MPH THR-56 AND SER-130, AND VARIANT SER-289. RX PubMed=9709959; DOI=10.1210/jcem.83.8.5052; RA Moghrabi N., Hughes I.A., Dunaif A., Andersson S.; RT "Deleterious missense mutations and silent polymorphism in the human RT 17beta-hydroxysteroid dehydrogenase 3 gene (HSD17B3)."; RL J. Clin. Endocrinol. Metab. 83:2855-2860(1998). RN [11] RP INVOLVEMENT IN MPH, AND VARIANT MPH TYR-268. RX PubMed=11158067; DOI=10.1210/jcem.86.2.7172; RA Lindqvist A., Hughes I.A., Andersson S.; RT "Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 RT deficiency."; RL J. Clin. Endocrinol. Metab. 86:921-923(2001). RN [12] RP VARIANT MPH ARG-133, CHARACTERIZATION OF VARIANT MPH ARG-133, FUNCTION, RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-133. RX PubMed=26545797; DOI=10.1016/j.jsbmb.2015.10.023; RA Engeli R.T., Rhouma B.B., Sager C.P., Tsachaki M., Birk J., Fakhfakh F., RA Keskes L., Belguith N., Odermatt A.; RT "Biochemical analyses and molecular modeling explain the functional loss of RT 17beta-hydroxysteroid dehydrogenase 3 mutant G133R in three Tunisian RT patients with 46, XY Disorders of Sex Development."; RL J. Steroid Biochem. Mol. Biol. 155:147-154(2016). CC -!- FUNCTION: Catalyzes the conversion of 17-oxosteroids to 17beta- CC hydroxysteroids (PubMed:8075637, PubMed:16216911, PubMed:27927697, CC PubMed:26545797). Favors the reduction of androstenedione to CC testosterone (PubMed:16216911, PubMed:27927697, PubMed:26545797). CC Testosterone is the key androgen driving male development and function CC (PubMed:8075637). Uses NADPH while the two other EDH17B enzymes use CC NADH (PubMed:26545797, PubMed:8075637, PubMed:16216911). Androgens such CC as epiandrosterone, dehydroepiandrosterone, androsterone and CC androstanedione are accepted as substrates and reduced at C-17 CC (PubMed:16216911). Can reduce 11-ketoandrostenedione as well as 11beta- CC hydroxyandrostenedione at C-17 to the respective testosterone forms CC (PubMed:16216911, PubMed:27927697). {ECO:0000269|PubMed:16216911, CC ECO:0000269|PubMed:26545797, ECO:0000269|PubMed:27927697, CC ECO:0000269|PubMed:8075637}. 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:0000269|PubMed:16216911, ECO:0000269|PubMed:26545797, CC ECO:0000269|PubMed:27927697, ECO:0000269|PubMed:8075637}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69286; CC Evidence={ECO:0000269|PubMed:26545797, ECO:0000305|PubMed:16216911, CC ECO:0000305|PubMed:27927697, ECO:0000305|PubMed:8075637}; 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:0000269|PubMed:16216911, ECO:0000269|PubMed:26545797, CC ECO:0000269|PubMed:27927697, ECO:0000269|PubMed:8075637}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983; CC Evidence={ECO:0000269|PubMed:26545797, ECO:0000305|PubMed:16216911, CC ECO:0000305|PubMed:27927697, ECO:0000305|PubMed:8075637}; 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:8075637}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24618; CC Evidence={ECO:0000305|PubMed:8075637}; 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:0000269|PubMed:16216911, ECO:0000269|PubMed:8075637}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46629; CC Evidence={ECO:0000305|PubMed:16216911, ECO:0000305|PubMed:8075637}; 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:0000269|PubMed:16216911}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42122; CC Evidence={ECO:0000305|PubMed:16216911}; 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:0000269|PubMed:16216911}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42157; CC Evidence={ECO:0000305|PubMed:16216911}; 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:0000269|PubMed:16216911}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53481; CC Evidence={ECO:0000305|PubMed:16216911}; 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:16216911, ECO:0000269|PubMed:27927697}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53485; CC Evidence={ECO:0000305|PubMed:16216911, ECO:0000305|PubMed:27927697}; 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:0000269|PubMed:16216911}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53489; CC Evidence={ECO:0000305|PubMed:16216911}; CC -!- PATHWAY: Hormone biosynthesis; testosterone biosynthesis. CC {ECO:0000305|PubMed:16216911, ECO:0000305|PubMed:26545797}. CC -!- PATHWAY: Steroid metabolism. {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:16216911, ECO:0000269|PubMed:26545797}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P37058-1; Sequence=Displayed; CC Name=2; CC IsoId=P37058-2; Sequence=VSP_056640; CC -!- TISSUE SPECIFICITY: Testis. {ECO:0000269|PubMed:8075637}. CC -!- DISEASE: Male pseudohermaphrodism with gynecomastia (MPH) [MIM:264300]: CC An autosomal recessive disorder that manifests, in males, as CC undermasculinization characterized by hypoplastic-to-normal internal CC genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory CC ducts) but female external genitalia and the absence of a prostate. CC This phenotype is caused by inadequate testicular synthesis of CC testosterone, which, in turn, results in insufficient formation of CC dihydrotestosterone in the anlage of the external genitalia and CC prostate during fetal development. At the expected time of puberty, CC there is a marked increase in plasma leuteinizing hormone and, CC consequently, in testicular secretion of androstenedione. Hence, a CC diagnostic hallmark of this disorder is a decreased plasma CC testosterone-to-androstenedione ratio. Significant amounts of the CC circulating androstenedione are, however, converted to testosterone, in CC peripheral tissues, thereby causing virilization. CC {ECO:0000269|PubMed:11158067, ECO:0000269|PubMed:26545797, CC ECO:0000269|PubMed:8075637, ECO:0000269|PubMed:8550739, CC ECO:0000269|PubMed:9709959, ECO:0000269|PubMed:9758445}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) CC family. 17-beta-HSD 3 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/hsd17b3/"; 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; U05659; AAC50066.1; -; mRNA. DR EMBL; AY341031; AAP88937.1; -; Genomic_DNA. DR EMBL; BT019371; AAV38178.1; -; mRNA. DR EMBL; AL160269; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034281; AAH34281.1; -; mRNA. DR CCDS; CCDS6716.1; -. [P37058-1] DR PIR; S43928; S43928. DR RefSeq; NP_000188.1; NM_000197.1. [P37058-1] DR RefSeq; XP_011516920.1; XM_011518618.2. DR RefSeq; XP_011516921.1; XM_011518619.2. DR RefSeq; XP_016870160.1; XM_017014671.1. DR RefSeq; XP_016870161.1; XM_017014672.1. DR AlphaFoldDB; P37058; -. DR SMR; P37058; -. DR BioGRID; 109526; 29. DR IntAct; P37058; 20. DR MINT; P37058; -. DR STRING; 9606.ENSP00000364412; -. DR BindingDB; P37058; -. DR ChEMBL; CHEMBL4234; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P37058; -. DR SwissLipids; SLP:000001270; -. [P37058-1] DR iPTMnet; P37058; -. DR PhosphoSitePlus; P37058; -. DR BioMuta; HSD17B3; -. DR DMDM; 1169300; -. DR MassIVE; P37058; -. DR PaxDb; 9606-ENSP00000364412; -. DR PeptideAtlas; P37058; -. DR ProteomicsDB; 55255; -. [P37058-1] DR ProteomicsDB; 65223; -. DR Antibodypedia; 3099; 245 antibodies from 26 providers. DR DNASU; 3293; -. DR Ensembl; ENST00000375262.4; ENSP00000364411.2; ENSG00000130948.10. [P37058-2] DR Ensembl; ENST00000375263.8; ENSP00000364412.3; ENSG00000130948.10. [P37058-1] DR GeneID; 3293; -. DR KEGG; hsa:3293; -. DR MANE-Select; ENST00000375263.8; ENSP00000364412.3; NM_000197.2; NP_000188.1. DR UCSC; uc010msc.1; human. [P37058-1] DR AGR; HGNC:5212; -. DR CTD; 3293; -. DR DisGeNET; 3293; -. DR GeneCards; HSD17B3; -. DR HGNC; HGNC:5212; HSD17B3. DR HPA; ENSG00000130948; Tissue enhanced (liver, testis). DR MalaCards; HSD17B3; -. DR MIM; 264300; phenotype. DR MIM; 605573; gene. DR neXtProt; NX_P37058; -. DR OpenTargets; ENSG00000130948; -. DR Orphanet; 752; 46,XY difference of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency. DR PharmGKB; PA29480; -. DR VEuPathDB; HostDB:ENSG00000130948; -. DR eggNOG; KOG1014; Eukaryota. DR GeneTree; ENSGT00940000160266; -. DR HOGENOM; CLU_010194_38_0_1; -. DR InParanoid; P37058; -. DR OMA; CNIISVT; -. DR OrthoDB; 6845at2759; -. DR PhylomeDB; P37058; -. DR TreeFam; TF314591; -. DR BioCyc; MetaCyc:HS05461-MONOMER; -. DR BRENDA; 1.1.1.51; 2681. DR BRENDA; 1.1.1.64; 2681. DR PathwayCommons; P37058; -. DR Reactome; R-HSA-193048; Androgen biosynthesis. DR Reactome; R-HSA-75876; Synthesis of very long-chain fatty acyl-CoAs. DR SignaLink; P37058; -. DR UniPathway; UPA00367; -. DR BioGRID-ORCS; 3293; 9 hits in 1142 CRISPR screens. DR ChiTaRS; HSD17B3; human. DR GeneWiki; HSD17B3_(gene); -. DR GenomeRNAi; 3293; -. DR Pharos; P37058; Tchem. DR PRO; PR:P37058; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P37058; Protein. DR Bgee; ENSG00000130948; Expressed in right testis and 92 other cell types or tissues. DR ExpressionAtlas; P37058; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc. 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; IEA:UniProtKB-EC. DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IDA:UniProtKB. DR GO; GO:0030283; F:testosterone dehydrogenase [NAD(P)] activity; TAS:Reactome. DR GO; GO:0006702; P:androgen biosynthetic process; TAS:Reactome. DR GO; GO:0030539; P:male genitalia development; TAS:ProtInc. DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central. 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; P37058; HS. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Endoplasmic reticulum; KW Lipid biosynthesis; Lipid metabolism; NADP; Oxidoreductase; KW Pseudohermaphroditism; Reference proteome; Steroid biosynthesis. FT CHAIN 1..310 FT /note="17-beta-hydroxysteroid dehydrogenase type 3" FT /id="PRO_0000054573" FT ACT_SITE 198 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001" FT BINDING 48..77 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 185 FT /ligand="substrate" FT /evidence="ECO:0000250" FT VAR_SEQ 225..274 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_056640" FT VARIANT 31 FT /note="V -> I (in dbSNP:rs2066480)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_014870" FT VARIANT 56 FT /note="A -> T (in MPH; Cambridge-2; affects NADPH cofactor FT binding; dbSNP:rs119481078)" FT /evidence="ECO:0000269|PubMed:9709959" FT /id="VAR_016067" FT VARIANT 65 FT /note="S -> L (in MPH; dbSNP:rs747329682)" FT /evidence="ECO:0000269|PubMed:8550739" FT /id="VAR_016068" FT VARIANT 80 FT /note="R -> Q (in MPH; Gaza; almost complete loss of FT testosterone 17-beta-dehydrogenase (NADP(+)) activity; FT dbSNP:rs119481075)" FT /evidence="ECO:0000269|PubMed:8075637" FT /id="VAR_006953" FT VARIANT 80 FT /note="R -> W (in MPH; dbSNP:rs119481077)" FT /evidence="ECO:0000269|PubMed:9758445" FT /id="VAR_006954" FT VARIANT 130 FT /note="N -> S (in MPH; Cambridge-1; complete loss of FT activity; dbSNP:rs119481079)" FT /evidence="ECO:0000269|PubMed:9709959" FT /id="VAR_016069" FT VARIANT 133 FT /note="G -> R (in MPH; almost complete loss of testosterone FT 17-beta-dehydrogenase (NADP(+)) activity; no effect on FT protein abundance; no effect on endoplasmic reticulum FT location; dbSNP:rs747724352)" FT /evidence="ECO:0000269|PubMed:26545797" FT /id="VAR_075369" FT VARIANT 176 FT /note="Q -> P (in MPH; dbSNP:rs767259718)" FT /evidence="ECO:0000269|PubMed:8550739" FT /id="VAR_016070" FT VARIANT 203 FT /note="A -> V (in MPH; loss of testosterone FT 17-beta-dehydrogenase (NADP(+)) activity; FT dbSNP:rs119481076)" FT /evidence="ECO:0000269|PubMed:8075637" FT /id="VAR_006955" FT VARIANT 205 FT /note="V -> E (in MPH; dbSNP:rs372027264)" FT /evidence="ECO:0000269|PubMed:8550739" FT /id="VAR_016071" FT VARIANT 208 FT /note="F -> I (in MPH)" FT /evidence="ECO:0000269|PubMed:8550739" FT /id="VAR_016072" FT VARIANT 215 FT /note="E -> D (in MPH; dbSNP:rs115063639)" FT /evidence="ECO:0000269|PubMed:8550739" FT /id="VAR_016203" FT VARIANT 232 FT /note="S -> L (in MPH; almost complete loss of testosterone FT 17-beta-dehydrogenase (NADP(+)) activity; FT dbSNP:rs28939085)" FT /evidence="ECO:0000269|PubMed:8075637" FT /id="VAR_006956" FT VARIANT 235 FT /note="M -> V (in MPH; almost complete loss of testosterone FT 17-beta-dehydrogenase (NADP(+)) activity; FT dbSNP:rs119481074)" FT /evidence="ECO:0000269|PubMed:8075637" FT /id="VAR_006957" FT VARIANT 268 FT /note="C -> Y (in MPH; complete loss of activity; FT dbSNP:rs119481080)" FT /evidence="ECO:0000269|PubMed:11158067" FT /id="VAR_016073" FT VARIANT 282 FT /note="P -> L (in MPH; dbSNP:rs144809928)" FT /evidence="ECO:0000269|PubMed:8550739" FT /id="VAR_016074" FT VARIANT 289 FT /note="G -> C (in dbSNP:rs2066479)" FT /id="VAR_061844" FT VARIANT 289 FT /note="G -> R (in dbSNP:rs2066479)" FT /id="VAR_061845" FT VARIANT 289 FT /note="G -> S (in dbSNP:rs2066479)" FT /evidence="ECO:0000269|PubMed:9709959, ECO:0000269|Ref.2" FT /id="VAR_014871" FT MUTAGEN 133 FT /note="G->A: Has 70% of wild-type testosterone FT 17-beta-dehydrogenase (NADP(+)) activity." FT /evidence="ECO:0000269|PubMed:26545797" FT MUTAGEN 133 FT /note="G->F: Almost complete loss of testosterone FT 17-beta-dehydrogenase (NADP(+)) activity." FT /evidence="ECO:0000269|PubMed:26545797" FT MUTAGEN 133 FT /note="G->Q: Almost complete loss of testosterone FT 17-beta-dehydrogenase (NADP(+)) activity." FT /evidence="ECO:0000269|PubMed:26545797" SQ SEQUENCE 310 AA; 34516 MW; 0643FF35ED979185 CRC64; MGDVLEQFFI LTGLLVCLAC LAKCVRFSRC VLLNYWKVLP KSFLRSMGQW AVITGAGDGI GKAYSFELAK RGLNVVLISR TLEKLEAIAT EIERTTGRSV KIIQADFTKD DIYEHIKEKL AGLEIGILVN NVGMLPNLLP SHFLNAPDEI QSLIHCNITS VVKMTQLILK HMESRQKGLI LNISSGIALF PWPLYSMYSA SKAFVCAFSK ALQEEYKAKE VIIQVLTPYA VSTAMTKYLN TNVITKTADE FVKESLNYVT IGGETCGCLA HEILAGFLSL IPAWAFYSGA FQRLLLTHYV AYLKLNTKVR //