DHB3_HUMAN
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 03-AUG-2022, entry version 202.
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=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: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/";
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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. [P37058-1]
DR RefSeq; XP_011516921.1; XM_011518619.2. [P37058-1]
DR RefSeq; XP_016870160.1; XM_017014671.1. [P37058-1]
DR RefSeq; XP_016870161.1; XM_017014672.1. [P37058-1]
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; P37058; -.
DR PeptideAtlas; P37058; -.
DR PRIDE; P37058; -.
DR ProteomicsDB; 55255; -. [P37058-1]
DR ProteomicsDB; 65223; -.
DR Antibodypedia; 3099; 195 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 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 disorder 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; GNMPIPN; -.
DR OrthoDB; 288325at2759; -.
DR PhylomeDB; P37058; -.
DR TreeFam; TF314591; -.
DR BioCyc; MetaCyc:HS05461-MON; -.
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; 7 hits in 1064 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 90 other tissues.
DR ExpressionAtlas; P37058; baseline and differential.
DR Genevisible; P37058; HS.
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:0016491; F:oxidoreductase activity; IBA:GO_Central.
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 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 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 17-beta-
FT dehydrogenase (NADP(+)) activity; 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 17-beta-
FT dehydrogenase (NADP(+)) activity."
FT /evidence="ECO:0000269|PubMed:26545797"
FT MUTAGEN 133
FT /note="G->F: Almost complete loss of testosterone 17-beta-
FT dehydrogenase (NADP(+)) activity."
FT /evidence="ECO:0000269|PubMed:26545797"
FT MUTAGEN 133
FT /note="G->Q: Almost complete loss of testosterone 17-beta-
FT 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
