PORED_MOUSE
ID PORED_MOUSE Reviewed; 330 AA.
AC Q9WUP4; D3YZB6; D3Z3J5; Q3UU82; Q8BGE3;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Polyprenol reductase {ECO:0000303|PubMed:20637498};
DE EC=1.3.1.94 {ECO:0000269|PubMed:20637498};
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 2-like;
DE AltName: Full=Steroid 5-alpha-reductase 3;
DE Short=S5AR 3;
DE Short=SR type 3;
GN Name=Srd5a3 {ECO:0000303|PubMed:20637498, ECO:0000312|MGI:MGI:1930252};
GN Synonyms=Srd5a2l;
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 [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=11116088; DOI=10.1101/gr.10.12.1928;
RA Wilsbacher L.D., Sangoram A.M., Antoch M.P., Takahashi J.S.;
RT "The mouse Clock locus: sequence and comparative analysis of 204 kb from
RT mouse chromosome 5.";
RL Genome Res. 10:1928-1940(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Thymus, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
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 [4]
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 [5]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=20637498; DOI=10.1016/j.cell.2010.06.001;
RA Cantagrel V., Lefeber D.J., Ng B.G., Guan Z., Silhavy J.L., Bielas S.L.,
RA Lehle L., Hombauer H., Adamowicz M., Swiezewska E., De Brouwer A.P.,
RA Blumel P., Sykut-Cegielska J., Houliston S., Swistun D., Ali B.R.,
RA Dobyns W.B., Babovic-Vuksanovic D., van Bokhoven H., Wevers R.A.,
RA Raetz C.R., Freeze H.H., Morava E., Al-Gazali L., Gleeson J.G.;
RT "SRD5A3 is required for converting polyprenol to dolichol and is mutated in
RT a congenital glycosylation disorder.";
RL Cell 142:203-217(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Plays a key role in early steps of protein N-linked
CC glycosylation by being required for the conversion of polyprenol into
CC dolichol (PubMed:20637498). Dolichols are required for the synthesis of
CC dolichol-linked monosaccharides and the oligosaccharide precursor used
CC for N-glycosylation (PubMed:20637498). Acts as a polyprenol reductase
CC that promotes the reduction of the alpha-isoprene unit of polyprenols
CC into dolichols in a NADP-dependent mechanism (PubMed:20637498). Also
CC able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT)
CC (By similarity). {ECO:0000250|UniProtKB:Q9H8P0,
CC ECO:0000269|PubMed:20637498}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=di-trans,poly-cis-dolichol + NADP(+) = di-trans,cis-polyprenol
CC + H(+) + NADPH; Xref=Rhea:RHEA:34279, Rhea:RHEA-COMP:9521, Rhea:RHEA-
CC COMP:9525, ChEBI:CHEBI:15378, ChEBI:CHEBI:16091, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:67132; EC=1.3.1.94;
CC Evidence={ECO:0000269|PubMed:20637498};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:34281;
CC Evidence={ECO:0000269|PubMed:20637498};
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:0000269|PubMed:20637498}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q5RJM1}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5RJM1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9WUP4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WUP4-2; Sequence=VSP_039779;
CC -!- DISRUPTION PHENOTYPE: Death by 12.5 dpc. At 10.5 dpc, embryos are
CC smaller and fail to undergo axial rotation observed at 8.5 dpc in wild-
CC types and present dilated hearts and open neural tubes.
CC {ECO:0000269|PubMed:20637498}.
CC -!- SIMILARITY: Belongs to the steroid 5-alpha reductase family. Polyprenol
CC reductase subfamily. {ECO:0000305}.
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DR EMBL; AF146793; AAD30567.1; -; Genomic_DNA.
DR EMBL; AK040198; BAC30537.1; -; mRNA.
DR EMBL; AK075635; BAC35871.1; -; mRNA.
DR EMBL; AK138681; BAE23745.1; -; mRNA.
DR EMBL; AK139290; BAE23944.1; -; mRNA.
DR EMBL; AK162527; BAE36955.1; -; mRNA.
DR EMBL; AC147239; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC145647; AAI45648.1; -; mRNA.
DR CCDS; CCDS19358.1; -. [Q9WUP4-1]
DR RefSeq; NP_065636.2; NM_020611.4. [Q9WUP4-1]
DR AlphaFoldDB; Q9WUP4; -.
DR SMR; Q9WUP4; -.
DR BioGRID; 208270; 2.
DR STRING; 10090.ENSMUSP00000031143; -.
DR iPTMnet; Q9WUP4; -.
DR PhosphoSitePlus; Q9WUP4; -.
DR SwissPalm; Q9WUP4; -.
DR EPD; Q9WUP4; -.
DR MaxQB; Q9WUP4; -.
DR PaxDb; Q9WUP4; -.
DR PeptideAtlas; Q9WUP4; -.
DR PRIDE; Q9WUP4; -.
DR ProteomicsDB; 289720; -. [Q9WUP4-1]
DR ProteomicsDB; 289721; -. [Q9WUP4-2]
DR DNASU; 57357; -.
DR Ensembl; ENSMUST00000031143; ENSMUSP00000031143; ENSMUSG00000029233. [Q9WUP4-1]
DR GeneID; 57357; -.
DR KEGG; mmu:57357; -.
DR UCSC; uc008xun.2; mouse. [Q9WUP4-2]
DR UCSC; uc008xuo.2; mouse. [Q9WUP4-1]
DR CTD; 79644; -.
DR MGI; MGI:1930252; Srd5a3.
DR VEuPathDB; HostDB:ENSMUSG00000029233; -.
DR eggNOG; KOG1640; Eukaryota.
DR GeneTree; ENSGT00500000044920; -.
DR HOGENOM; CLU_044409_2_1_1; -.
DR InParanoid; Q9WUP4; -.
DR OMA; SSPHMFF; -.
DR OrthoDB; 1574389at2759; -.
DR PhylomeDB; Q9WUP4; -.
DR TreeFam; TF315011; -.
DR BRENDA; 1.3.1.94; 3474.
DR Reactome; R-MMU-193048; Androgen biosynthesis.
DR Reactome; R-MMU-446199; Synthesis of Dolichyl-phosphate.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 57357; 9 hits in 73 CRISPR screens.
DR ChiTaRS; Srd5a3; mouse.
DR PRO; PR:Q9WUP4; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9WUP4; protein.
DR Bgee; ENSMUSG00000029233; Expressed in lumbar dorsal root ganglion and 232 other tissues.
DR ExpressionAtlas; Q9WUP4; baseline and differential.
DR Genevisible; Q9WUP4; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0003865; F:3-oxo-5-alpha-steroid 4-dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0047751; F:cholestenone 5-alpha-reductase activity; IEA:UniProtKB-EC.
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; IMP:UniProtKB.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0016095; P:polyprenol catabolic process; IMP:UniProtKB.
DR InterPro; IPR001104; 3-oxo-5_a-steroid_4-DH_C.
DR InterPro; IPR039698; Dfg10/SRD5A3.
DR PANTHER; PTHR14624; PTHR14624; 1.
DR Pfam; PF02544; Steroid_dh; 1.
DR PROSITE; PS50244; S5A_REDUCTASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..330
FT /note="Polyprenol reductase"
FT /id="PRO_0000317704"
FT TOPO_DOM 1..16
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..80
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 154..169
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..206
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 228..277
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VAR_SEQ 200..330
FT /note="VYVLGKNLLIQARWFHILGMVMFFWSSAHQYKCHVILSNLRRNKKGVVIHCQ
FT HRIPFGDWFEYVSSANYLAELMIYISMAVTFGLHNLTWWLVVTYVFSSQALSAFFNHKF
FT YRSTFVSYPKHRKAFLPFLF -> GKWPCQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_039779"
FT CONFLICT 109
FT /note="S -> G (in Ref. 1; AAD30567 and 4; AAI45648)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="S -> F (in Ref. 1; AAD30567 and 4; AAI45648)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 330 AA; 37936 MW; A26CAB23B295D75C CRC64;
MAGWAGFELS ALNPLRTLWL ALAAAFLFAL LLQLAPARLL PSCALFQDLL RYGKTKQSGS
RRPAVCRAFD VPKRYFSHFY VISVVWNGSL LWLLSQSLFL GAPFPNWLSA LLRTLGATQF
QALEMESKAS RMPAAELALS AFLVLVFLWV HSLRRLFECF YVSVFSNAAI HVVQYCFGLV
YYVLVGLTVL SQVPMDDKNV YVLGKNLLIQ ARWFHILGMV MFFWSSAHQY KCHVILSNLR
RNKKGVVIHC QHRIPFGDWF EYVSSANYLA ELMIYISMAV TFGLHNLTWW LVVTYVFSSQ
ALSAFFNHKF YRSTFVSYPK HRKAFLPFLF
