ID   SR5A3_DANRE             Reviewed;         309 AA.
AC   Q5RIU9; A4FVI8;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   02-OCT-2024, entry version 103.
DE   RecName: Full=Polyprenal reductase {ECO:0000305};
DE            EC=1.3.1.94 {ECO:0000250|UniProtKB:Q9H8P0};
DE   AltName: Full=3-oxo-5-alpha-steroid 4-dehydrogenase 3;
DE            EC=1.3.1.22 {ECO:0000250|UniProtKB:Q9H8P0};
DE   AltName: Full=Steroid 5-alpha-reductase 3;
DE            Short=S5AR 3;
DE            Short=SR type 3;
GN   Name=srd5a3; ORFNames=si:ch211-278f21.3;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Plays a key role in early steps of protein N-linked
CC       glycosylation by being involved in the conversion of polyprenol into
CC       dolichol (By similarity). Acts as a polyprenal reductase that mediates
CC       the reduction of polyprenal into dolichal in a NADP-dependent mechanism
CC       (By similarity). Dolichols are required for the synthesis of dolichol-
CC       linked monosaccharides and the oligosaccharide precursor used for N-
CC       glycosylation (By similarity). Also able to convert testosterone (T)
CC       into 5-alpha-dihydrotestosterone (DHT) (By similarity).
CC       {ECO:0000250|UniProtKB:Q9H8P0}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a di-trans,poly-cis-dolichal + NADP(+) = a di-trans,poly-cis-
CC         polyprenal + H(+) + NADPH; Xref=Rhea:RHEA:80727, Rhea:RHEA-
CC         COMP:19536, Rhea:RHEA-COMP:19537, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:231623,
CC         ChEBI:CHEBI:231637; EC=1.3.1.94;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:80729;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 3-oxo-5alpha-steroid + NADP(+) = a 3-oxo-Delta(4)-steroid +
CC         H(+) + NADPH; Xref=Rhea:RHEA:54384, ChEBI:CHEBI:13601,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:47909, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.3.1.22;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:54386;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=androst-4-ene-3,17-dione + H(+) + NADPH = 5alpha-androstan-
CC         3,17-dione + NADP(+); Xref=Rhea:RHEA:50816, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15994, ChEBI:CHEBI:16422, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50818;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = H(+) + NADPH
CC         + testosterone; Xref=Rhea:RHEA:50820, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16330, ChEBI:CHEBI:17347, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.3.1.22;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50822;
CC         Evidence={ECO:0000250|UniProtKB:Q9H8P0};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000250|UniProtKB:Q9H8P0}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q9H8P0}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q9H8P0}.
CC   -!- SIMILARITY: Belongs to the steroid 5-alpha reductase family. Polyprenal
CC       reductase subfamily. {ECO:0000305}.
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DR   EMBL; BX088688; CAI11971.1; -; Genomic_DNA.
DR   EMBL; BC133964; AAI33965.1; -; mRNA.
DR   RefSeq; NP_001038404.1; NM_001044939.1.
DR   AlphaFoldDB; Q5RIU9; -.
DR   SMR; Q5RIU9; -.
DR   STRING; 7955.ENSDARP00000063577; -.
DR   PaxDb; 7955-ENSDARP00000063577; -.
DR   Ensembl; ENSDART00000063578; ENSDARP00000063577; ENSDARG00000043307.
DR   GeneID; 560717; -.
DR   KEGG; dre:560717; -.
DR   AGR; ZFIN:ZDB-GENE-030131-7915; -.
DR   CTD; 79644; -.
DR   ZFIN; ZDB-GENE-030131-7915; srd5a3.
DR   eggNOG; KOG1640; Eukaryota.
DR   HOGENOM; CLU_044409_2_1_1; -.
DR   InParanoid; Q5RIU9; -.
DR   OMA; HMFFEVV; -.
DR   OrthoDB; 2896758at2759; -.
DR   PhylomeDB; Q5RIU9; -.
DR   TreeFam; TF315011; -.
DR   Reactome; R-DRE-193048; Androgen biosynthesis.
DR   Reactome; R-DRE-446199; Synthesis of Dolichyl-phosphate.
DR   UniPathway; UPA00378; -.
DR   PRO; PR:Q5RIU9; -.
DR   Proteomes; UP000000437; Chromosome 20.
DR   Bgee; ENSDARG00000043307; Expressed in ovary and 28 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0003865; F:3-oxo-5-alpha-steroid 4-dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0047751; F:3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR   GO; GO:0016628; F:oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; ISS:UniProtKB.
DR   GO; GO:0102389; F:polyprenol reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019408; P:dolichol biosynthetic process; IBA:GO_Central.
DR   GO; GO:0019348; P:dolichol metabolic process; ISS:UniProtKB.
DR   GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0016095; P:polyprenol catabolic process; ISS:UniProtKB.
DR   Gene3D; 1.20.120.1630; -; 1.
DR   InterPro; IPR001104; 3-oxo-5_a-steroid_4-DH_C.
DR   InterPro; IPR039698; Dfg10/SRD5A3.
DR   PANTHER; PTHR14624; DFG10 PROTEIN; 1.
DR   PANTHER; PTHR14624:SF0; POLYPRENOL REDUCTASE; 1.
DR   Pfam; PF02544; Steroid_dh; 1.
DR   PROSITE; PS50244; S5A_REDUCTASE; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..309
FT                   /note="Polyprenal reductase"
FT                   /id="PRO_0000398651"
FT   TOPO_DOM        1..3
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        4..24
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        25..67
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        68..88
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        89..114
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        115..135
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        136..150
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        151..171
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        172..185
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        186..206
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        207..255
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        256..276
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        277..309
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        69
FT                   /note="F -> S (in Ref. 2; AAI33965)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   309 AA;  35708 MW;  89513C21F5D7FEB6 CRC64;
     MFHILSIVNI IWLLLALCFG AAFCLNKFSV KLPNRVEHVF QDFIRYGKTK ENIKRASWQL
     VFDLSKRYFY HFYVVSVMWN GLLLLFSIRS VVMSEAFPDW IIDVLGSLTG RSRGAWNEIH
     LSTLLLQVLL WVHTLRRLLE CLFVSVFSDG VINVVQYAFG LSYYIILGLT VLCTNDSLPQ
     SESVSFFNQL TWYHVVGTLL FFWASFLQHQ SLSLLAKMRT DSSGKVETLA HKMPCGGWFE
     LVSCPHYLAE LLIYAAMCVC CGCASLTWWM VVLYVLCNQA LAAQLCHEYY RSKFKTYPHH
     RKAFIPFVL
//