DHB3_DANRE
ID DHB3_DANRE Reviewed; 307 AA.
AC Q6QA32;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=17-beta-hydroxysteroid dehydrogenase type 3;
DE Short=17-beta-HSD 3;
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:27927697};
GN Name=hsd17b3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAS58451.1};
RN [1] {ECO:0000312|EMBL:AAS58451.1}
RP NUCLEOTIDE SEQUENCE, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, FUNCTION, AND DEVELOPMENTAL STAGE.
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 [2] {ECO:0000312|Ensembl:ENSDARP00000151778}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Ensembl:ENSDARP00000151778};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
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).
CC -!- FUNCTION: Catalyzes the conversion of 17-oxosteroids to 17beta-
CC hydroxysteroids in the presence of NADPH (PubMed:16216911,
CC PubMed:27927697). Favors the reduction of androstenedione to
CC testosterone (PubMed:16216911, PubMed:27927697). Testosterone is the
CC key androgen driving male development and function (By similarity).
CC Among further tested androgens epiandrosterone and
CC dehydroepiandrosterone are accepted as substrates and reduced at C-17
CC (PubMed:16216911). Can also reduce 11-ketoandrostenedione as well as
CC 11beta-hydroxyandrostenedione at C-17 to the respective testosterone
CC forms (PubMed:16216911, PubMed:27927697). Cannot use androsterone and
CC androstanedione as substrates (PubMed:16216911).
CC {ECO:0000250|UniProtKB:P70385, ECO:0000269|PubMed:16216911,
CC ECO:0000269|PubMed:27927697}.
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:27927697};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:69286;
CC Evidence={ECO:0000305|PubMed:16216911, ECO:0000305|PubMed:27927697};
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:27927697};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:14983;
CC Evidence={ECO:0000305|PubMed:16216911, ECO:0000305|PubMed:27927697};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46629;
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}.
CC -!- PATHWAY: Steroid metabolism. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:16216911}. Membrane {ECO:0000255}; Single-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expression shows strong sexual dimorphism. In
CC female, highly expressed in ovaries, and at lower levels in skin
CC muscle, eyes and liver (PubMed:16216911). In males, strongly expresseed
CC in liver and at lower levels in testis, spleen, kidney, intestine and
CC muscle (PubMed:16216911). {ECO:0000269|PubMed:16216911}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryogenesis from sphere to 84 h
CC post-fertilization. {ECO:0000269|PubMed:16216911}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000255|RuleBase:RU000363}.
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DR EMBL; CR376747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY551081; AAS58451.1; -; mRNA.
DR RefSeq; XP_005167205.1; XM_005167148.3.
DR AlphaFoldDB; Q6QA32; -.
DR SMR; Q6QA32; -.
DR SwissLipids; SLP:000001726; -.
DR DNASU; 393335; -.
DR Ensembl; ENSDART00000186229; ENSDARP00000151778; ENSDARG00000115935.
DR GeneID; 393335; -.
DR CTD; 3293; -.
DR ZFIN; ZDB-GENE-040426-1339; hsd17b3.
DR InParanoid; Q6QA32; -.
DR OrthoDB; 895581at2759; -.
DR PhylomeDB; Q6QA32; -.
DR BRENDA; 1.1.1.51; 928.
DR UniPathway; UPA00367; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ZFIN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0047045; F:testosterone 17-beta-dehydrogenase (NADP+) activity; IDA:ZFIN.
DR GO; GO:0006702; P:androgen biosynthetic process; IDA:ZFIN.
DR GO; GO:0030539; P:male genitalia development; IEA:InterPro.
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 Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..307
FT /note="17-beta-hydroxysteroid dehydrogenase type 3"
FT /id="PRO_0000451342"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 200
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 47..76
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 307 AA; 34018 MW; D666B5904924C270 CRC64;
MTLTEIIFVL TGTCAILVFG GKIASLIMML ITKLFCPLPE AFFTSLGKWA VITGGSDGIG
RAYAEELSKQ GMSVIIISRN QEKLDRAAKK IELNTGGKVK VIAADFTKDD IYGHITENIE
GLDIGVLVNN VGILPSQIPC KLLETSDLEE RIYDIVNCNV KSMVKMCRIV LPGMQQRRRG
VILNVSSGIA KIPCPIYTLY AASKVFVERF SQGLQAEYIS KGIIIQTVAP FGVSTAMTGH
QKPDMVTFTA EEFVRSSLKY LKTGDQTYGS ITHTLLGRIV QSIPTWVLQS ETFQHHFQEY
VKNRDRR
