RETST_MOUSE
ID RETST_MOUSE Reviewed; 609 AA.
AC Q64FW2; Q149J8; Q3UNN9; Q78JX8; Q8VHE7; Q9CW85;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=All-trans-retinol 13,14-reductase;
DE EC=1.3.99.23 {ECO:0000269|PubMed:15358783, ECO:0000269|PubMed:17253779, ECO:0000269|PubMed:19139408};
DE AltName: Full=All-trans-13,14-dihydroretinol saturase;
DE Short=RetSat;
DE AltName: Full=PPAR-alpha-regulated and starvation-induced gene protein;
DE Flags: Precursor;
GN Name=Retsat; Synonyms=Ppsig;
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=A/J;
RX PubMed=11753649; DOI=10.1038/sj.onc.1204941;
RA Wang Y., Hu L., Yao R., Wang M., Crist K.A., Grubbs C.J., Johanning G.L.,
RA Lubet R.A., You M.;
RT "Altered gene expression profile in chemically induced rat mammary
RT adenocarcinomas and its modulation by an aromatase inhibitor.";
RL Oncogene 20:7710-7721(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=15358783; DOI=10.1074/jbc.m409130200;
RA Moise A.R., Kuksa V., Imanishi Y., Palczewski K.;
RT "Identification of all-trans-retinol: all-trans-13,14-dihydroretinol
RT saturase.";
RL J. Biol. Chem. 279:50230-50242(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND
RP INDUCTION.
RC STRAIN=129/Sv, and 129S6/SvEvTac; TISSUE=Liver, and Spleen;
RX PubMed=18289917; DOI=10.1016/j.biocel.2008.01.006;
RA Sun Y., Ng L., Lam W., Lo C.K., Chan P.T., Yuen Y.L., Wong P.F.,
RA Tsang D.S., Cheung W.T., Lee S.S.;
RT "Identification and characterization of a novel mouse peroxisome
RT proliferator-activated receptor alpha-regulated and starvation-induced
RT gene, Ppsig.";
RL Int. J. Biochem. Cell Biol. 40:1775-1791(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C3H/HeJ, and C57BL/6J; TISSUE=Brain, and Kidney;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17253779; DOI=10.1021/bi062147u;
RA Moise A.R., Isken A., Dominguez M., de Lera A.R., von Lintig J.,
RA Palczewski K.;
RT "Specificity of zebrafish retinol saturase: formation of all-trans-13,14-
RT dihydroretinol and all-trans-7,8-dihydroretinol.";
RL Biochemistry 46:1811-1820(2007).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, INDUCTION BY PPARG, AND MUTAGENESIS OF 1-MET--HIS-17;
RP 91-ARG--GLU-96 AND GLU-96.
RX PubMed=19139408; DOI=10.1073/pnas.0812065106;
RA Schupp M., Lefterova M.I., Janke J., Leitner K., Cristancho A.G.,
RA Mullican S.E., Qatanani M., Szwergold N., Steger D.J., Curtin J.C.,
RA Kim R.J., Suh M.J., Suh M., Albert M.R., Engeli S., Gudas L.J., Lazar M.A.;
RT "Retinol saturase promotes adipogenesis and is downregulated in obesity.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:1105-1110(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, and Liver;
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).
RN [11]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19940255; DOI=10.1096/fj.09-147207;
RA Moise A.R., Lobo G.P., Erokwu B., Wilson D.L., Peck D., Alvarez S.,
RA Dominguez M., Alvarez R., Flask C.A., de Lera A.R., von Lintig J.,
RA Palczewski K.;
RT "Increased adiposity in the retinol saturase-knockout mouse.";
RL FASEB J. 24:1261-1270(2010).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28855500; DOI=10.1038/s41467-017-00430-w;
RA Heidenreich S., Witte N., Weber P., Goehring I., Tolkachov A.,
RA von Loeffelholz C., Doecke S., Bauer M., Stockmann M., Pfeiffer A.F.H.,
RA Birkenfeld A.L., Pietzke M., Kempa S., Muenzner M., Schupp M.;
RT "Retinol saturase coordinates liver metabolism by regulating ChREBP
RT activity.";
RL Nat. Commun. 8:384-384(2017).
CC -!- FUNCTION: Catalyzes the saturation of all-trans-retinol to all-trans-
CC 13,14-dihydroretinol (PubMed:15358783, PubMed:17253779,
CC PubMed:19139408). Does not exhibit any activity toward all-trans-
CC retinoic acid, nor 9-cis, 11-cis or 13-cis-retinol isomers
CC (PubMed:15358783). May play a role in the metabolism of vitamin A
CC (PubMed:15358783, PubMed:17253779). Independently of retinol
CC conversion, may regulate liver metabolism upstream of MLXIPL/ChREBP
CC (PubMed:28855500). Required for adipocyte differentiation in a 3T3-L1
CC cell culture model (PubMed:19139408). This effect seems not to mimic
CC the in vivo situation in which animals show increased adiposity in the
CC absence of RETSAT (PubMed:19940255). {ECO:0000269|PubMed:15358783,
CC ECO:0000269|PubMed:17253779, ECO:0000269|PubMed:19139408,
CC ECO:0000269|PubMed:19940255, ECO:0000269|PubMed:28855500,
CC ECO:0000305|PubMed:19940255}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + all-trans-13,14-dihydroretinol = AH2 + all-trans-retinol;
CC Xref=Rhea:RHEA:19193, ChEBI:CHEBI:13193, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:52075; EC=1.3.99.23;
CC Evidence={ECO:0000269|PubMed:15358783, ECO:0000269|PubMed:17253779,
CC ECO:0000269|PubMed:19139408};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000250|UniProtKB:Q8S4R4};
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q8S4R4};
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q8S4R4};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15358783, ECO:0000269|PubMed:19139408}; Peripheral
CC membrane protein {ECO:0000269|PubMed:15358783}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the liver (at protein
CC level) (PubMed:19940255). Also expressed at high levels in kidney,
CC intestine, and white fat and brown fat (PubMed:15358783,
CC PubMed:18289917, PubMed:19139408, PubMed:28855500). Weakly expressed in
CC heart, skeletal muscle and testis and barely detected in the lung,
CC brain and spleen (PubMed:15358783, PubMed:18289917, PubMed:28855500).
CC Up-regulated in the liver of diet-induced obese mice, compared to lean
CC animals (PubMed:28855500). Down-regulated in adipose tissue of obese
CC mice; this decrease could be due to the impact of inflammatory cells on
CC adipocytes (PubMed:19139408). {ECO:0000269|PubMed:15358783,
CC ECO:0000269|PubMed:18289917, ECO:0000269|PubMed:19139408,
CC ECO:0000269|PubMed:19940255, ECO:0000269|PubMed:28855500}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during adipocyte differentiation in a
CC 3T3-L1 cell culture model (at protein level).
CC {ECO:0000269|PubMed:19139408, ECO:0000269|PubMed:19940255}.
CC -!- INDUCTION: Up-regulated during starvation (PubMed:18289917). Up-
CC regulated by PPARG (PubMed:19139408). {ECO:0000269|PubMed:18289917,
CC ECO:0000269|PubMed:19139408}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice fed either low-fat or high-fat
CC (HFD) diets gain weight at a similar rate as their wild-type
CC littermates and show normal insulin resistance and glucose tolerance.
CC However, they exhibit increased adiposity and increased expression of
CC key adipogenic markers, including PPAR-gamma and its target adipocyte
CC P2 (aP2/FABP4), while maintained on an HFD.
CC {ECO:0000269|PubMed:19940255}.
CC -!- SIMILARITY: Belongs to the carotenoid/retinoid oxidoreductase family.
CC CrtISO subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB22406.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF466400; AAL73986.1; -; Genomic_DNA.
DR EMBL; AY704159; AAU25836.1; -; mRNA.
DR EMBL; EF620363; ABS17600.1; -; mRNA.
DR EMBL; EF620364; ABS17601.1; -; mRNA.
DR EMBL; EF620365; ABS17602.1; -; mRNA.
DR EMBL; EF620366; ABS17603.1; -; Genomic_DNA.
DR EMBL; AK002851; BAB22406.2; ALT_INIT; mRNA.
DR EMBL; AK144115; BAE25708.1; -; mRNA.
DR EMBL; AC125039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466523; EDK98989.1; -; Genomic_DNA.
DR EMBL; BC011203; AAH11203.2; -; mRNA.
DR EMBL; BC117751; AAI17752.1; -; mRNA.
DR CCDS; CCDS20244.1; -.
DR RefSeq; NP_080435.3; NM_026159.4.
DR AlphaFoldDB; Q64FW2; -.
DR SMR; Q64FW2; -.
DR BioGRID; 212189; 1.
DR STRING; 10090.ENSMUSP00000068568; -.
DR iPTMnet; Q64FW2; -.
DR PhosphoSitePlus; Q64FW2; -.
DR jPOST; Q64FW2; -.
DR MaxQB; Q64FW2; -.
DR PaxDb; Q64FW2; -.
DR PRIDE; Q64FW2; -.
DR ProteomicsDB; 255237; -.
DR Antibodypedia; 2224; 18 antibodies from 9 providers.
DR DNASU; 67442; -.
DR Ensembl; ENSMUST00000070597; ENSMUSP00000068568; ENSMUSG00000056666.
DR GeneID; 67442; -.
DR KEGG; mmu:67442; -.
DR UCSC; uc009cix.1; mouse.
DR CTD; 54884; -.
DR MGI; MGI:1914692; Retsat.
DR VEuPathDB; HostDB:ENSMUSG00000056666; -.
DR eggNOG; KOG4254; Eukaryota.
DR GeneTree; ENSGT00390000017613; -.
DR HOGENOM; CLU_019722_1_0_1; -.
DR InParanoid; Q64FW2; -.
DR OMA; AFMFADW; -.
DR OrthoDB; 873686at2759; -.
DR PhylomeDB; Q64FW2; -.
DR TreeFam; TF328375; -.
DR BioCyc; MetaCyc:MON-16797; -.
DR BRENDA; 1.3.99.23; 3474.
DR BioGRID-ORCS; 67442; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Retsat; mouse.
DR PRO; PR:Q64FW2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q64FW2; protein.
DR Bgee; ENSMUSG00000056666; Expressed in left lobe of liver and 227 other tissues.
DR ExpressionAtlas; Q64FW2; baseline and differential.
DR Genevisible; Q64FW2; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:HGNC-UCL.
DR GO; GO:0031965; C:nuclear membrane; IDA:HGNC-UCL.
DR GO; GO:0005640; C:nuclear outer membrane; IDA:HGNC-UCL.
DR GO; GO:0051786; F:all-trans-retinol 13,14-reductase activity; IDA:HGNC-UCL.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042572; P:retinol metabolic process; IDA:HGNC-UCL.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Lipid metabolism; Membrane; NAD;
KW NADP; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..609
FT /note="All-trans-retinol 13,14-reductase"
FT /id="PRO_0000225667"
FT MUTAGEN 1..17
FT /note="Missing: Loss of localization to the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:19139408"
FT MUTAGEN 91..96
FT /note="Missing: Loss of catalytic activity, as measured by
FT the saturation of retinol to 13,14-dihydroretinol. Loss of
FT adipocyte differentiation in a 3T3-L1 cell culture model."
FT /evidence="ECO:0000269|PubMed:19139408"
FT MUTAGEN 96
FT /note="E->A: Loss of catalytic activity, as measured by the
FT saturation of retinol to 13,14-dihydroretinol. Loss of
FT adipocyte differentiation in a 3T3-L1 cell culture model."
FT /evidence="ECO:0000269|PubMed:19139408"
FT CONFLICT 273
FT /note="A -> T (in Ref. 1; AAL73986 and 4; BAE25708)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="G -> R (in Ref. 1; AAL73986 and 4; BAE25708)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="I -> V (in Ref. 7; AAH11203)"
FT /evidence="ECO:0000305"
FT CONFLICT 451
FT /note="E -> D (in Ref. 4; BAE25708)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="A -> V (in Ref. 4; BAB22406)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 609 AA; 67334 MW; 7BC21825B8A4ABD2 CRC64;
MWITALLLAV LLLVILHRVY VGLYAASSPN PFAEDVKRPP EPLVTDKEAR KKVLKQAFSV
SRVPEKLDAV VIGSGIGGLA SAAVLAKAGK RVLVLEQHTK AGGCCHTFGE NGLEFDTGIH
YIGRMREGNI GRFILDQITE GQLDWAPMAS PFDLMILEGP NGRKEFPMYS GRKEYIQGLK
KKFPKEEAVI DKYMELVKVV ARGVSHAVLL KFLPLPLTQL LSKFGLLTRF SPFCRASTQS
LAEVLQQLGA SRELQAVLSY IFPTYGVTPS HTAFSLHALL VDHYIQGAYY PRGGSSEIAF
HTIPLIQRAG GAVLTRATVQ SVLLDSAGRA CGVSVKKGQE LVNIYCPVVI SNAGMFNTYQ
HLLPETVRHL PDVKKQLAMV RPGLSMLSIF ICLKGTKEDL KLQSTNYYVY FDTDMDKAME
RYVSMPKEKA PEHIPLLFIA FPSSKDPTWE ERFPDRSTMT ALVPMAFEWF EEWQEEPKGK
RGVDYETLKN AFVEASMSVI MKLFPQLEGK VESVTGGSPL TNQYYLAAPR GATYGADHDL
ARLHPHAMAS IRAQTPIPNL YLTGQDIFTC GLMGALQGAL LCSSAILKRN LYSDLQALGS
KVKAQKKKM
