RETST_HUMAN
ID RETST_HUMAN Reviewed; 610 AA.
AC Q6NUM9; A6NIK3; Q53R95; Q53SA9; Q6UX05; Q8N2H5; Q96FA4; Q9NXE5;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=All-trans-retinol 13,14-reductase;
DE EC=1.3.99.23 {ECO:0000250|UniProtKB:Q64FW2};
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; ORFNames=UNQ439/PRO872;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 161-610 (ISOFORM 2).
RC TISSUE=Colon, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-610 (ISOFORM 1).
RC TISSUE=Hepatoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP TISSUE SPECIFICITY.
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP 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. Does not exhibit any activity toward all-trans-
CC retinoic acid, nor 9-cis, 11-cis or 13-cis-retinol isomers. May play a
CC role in the metabolism of vitamin A. Independently of retinol
CC conversion, may regulate liver metabolism upstream of MLXIPL/ChREBP.
CC May play a role in adipocyte differentiation.
CC {ECO:0000250|UniProtKB:Q64FW2}.
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:0000250|UniProtKB:Q64FW2};
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:0000250|UniProtKB:Q64FW2}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q64FW2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6NUM9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NUM9-2; Sequence=VSP_017410, VSP_017411;
CC -!- TISSUE SPECIFICITY: Expressed in liver; expression positively
CC correlates with obesity and liver steatosis (PubMed:28855500).
CC Expressed in adipose tissue; expression tends to be decreased in obese
CC versus lean individuals (PubMed:19139408).
CC {ECO:0000269|PubMed:19139408, ECO:0000269|PubMed:28855500}.
CC -!- SIMILARITY: Belongs to the carotenoid/retinoid oxidoreductase family.
CC CrtISO subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH11418.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91069.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY358568; AAQ88931.1; -; mRNA.
DR EMBL; AK075261; BAC11505.1; -; mRNA.
DR EMBL; AC062037; AAY24126.1; -; Genomic_DNA.
DR EMBL; AC093162; AAY24096.1; -; Genomic_DNA.
DR EMBL; BC068517; AAH68517.1; -; mRNA.
DR EMBL; BC011418; AAH11418.1; ALT_INIT; mRNA.
DR EMBL; AK000303; BAA91069.1; ALT_INIT; mRNA.
DR CCDS; CCDS1972.1; -. [Q6NUM9-1]
DR RefSeq; NP_060220.3; NM_017750.3. [Q6NUM9-1]
DR AlphaFoldDB; Q6NUM9; -.
DR SMR; Q6NUM9; -.
DR BioGRID; 120232; 126.
DR IntAct; Q6NUM9; 20.
DR MINT; Q6NUM9; -.
DR STRING; 9606.ENSP00000295802; -.
DR DrugBank; DB00162; Vitamin A.
DR iPTMnet; Q6NUM9; -.
DR PhosphoSitePlus; Q6NUM9; -.
DR SwissPalm; Q6NUM9; -.
DR BioMuta; RETSAT; -.
DR DMDM; 90108452; -.
DR EPD; Q6NUM9; -.
DR jPOST; Q6NUM9; -.
DR MassIVE; Q6NUM9; -.
DR MaxQB; Q6NUM9; -.
DR PaxDb; Q6NUM9; -.
DR PeptideAtlas; Q6NUM9; -.
DR PRIDE; Q6NUM9; -.
DR ProteomicsDB; 66690; -. [Q6NUM9-1]
DR ProteomicsDB; 66691; -. [Q6NUM9-2]
DR Antibodypedia; 2224; 18 antibodies from 9 providers.
DR DNASU; 54884; -.
DR Ensembl; ENST00000295802.9; ENSP00000295802.4; ENSG00000042445.14. [Q6NUM9-1]
DR GeneID; 54884; -.
DR KEGG; hsa:54884; -.
DR MANE-Select; ENST00000295802.9; ENSP00000295802.4; NM_017750.4; NP_060220.3.
DR UCSC; uc002spd.4; human. [Q6NUM9-1]
DR CTD; 54884; -.
DR DisGeNET; 54884; -.
DR GeneCards; RETSAT; -.
DR HGNC; HGNC:25991; RETSAT.
DR HPA; ENSG00000042445; Tissue enhanced (adipose).
DR MIM; 617597; gene.
DR neXtProt; NX_Q6NUM9; -.
DR OpenTargets; ENSG00000042445; -.
DR PharmGKB; PA145007867; -.
DR VEuPathDB; HostDB:ENSG00000042445; -.
DR eggNOG; KOG4254; Eukaryota.
DR GeneTree; ENSGT00390000017613; -.
DR HOGENOM; CLU_019722_1_0_1; -.
DR InParanoid; Q6NUM9; -.
DR OMA; AFMFADW; -.
DR OrthoDB; 873686at2759; -.
DR PhylomeDB; Q6NUM9; -.
DR TreeFam; TF328375; -.
DR PathwayCommons; Q6NUM9; -.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SignaLink; Q6NUM9; -.
DR BioGRID-ORCS; 54884; 14 hits in 1087 CRISPR screens.
DR ChiTaRS; RETSAT; human.
DR GeneWiki; RETSAT; -.
DR GenomeRNAi; 54884; -.
DR Pharos; Q6NUM9; Tdark.
DR PRO; PR:Q6NUM9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6NUM9; protein.
DR Bgee; ENSG00000042445; Expressed in mucosa of transverse colon and 194 other tissues.
DR ExpressionAtlas; Q6NUM9; baseline and differential.
DR Genevisible; Q6NUM9; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:HGNC-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; ISS:HGNC-UCL.
DR GO; GO:0005640; C:nuclear outer membrane; ISS:HGNC-UCL.
DR GO; GO:0051786; F:all-trans-retinol 13,14-reductase activity; ISS:HGNC-UCL.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042572; P:retinol metabolic process; ISS: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 Alternative splicing; Endoplasmic reticulum; FAD; Flavoprotein;
KW Lipid metabolism; Membrane; NAD; NADP; Oxidoreductase; Reference proteome;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..610
FT /note="All-trans-retinol 13,14-reductase"
FT /id="PRO_0000225665"
FT VAR_SEQ 457..481
FT /note="RSTMIMLIPTAYEWFEEWQAELKGK -> GECDCRIPTHQPVLSGCSPRCLL
FT RG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017410"
FT VAR_SEQ 482..610
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017411"
FT VARIANT 533
FT /note="A -> V (in dbSNP:rs4832169)"
FT /id="VAR_025473"
FT VARIANT 536
FT /note="G -> R (in dbSNP:rs4832168)"
FT /id="VAR_059243"
FT VARIANT 559
FT /note="P -> T (in dbSNP:rs13384912)"
FT /id="VAR_059244"
FT CONFLICT 140
FT /note="T -> S (in Ref. 4; AAH68517)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="E -> Q (in Ref. 4; AAH11418)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="N -> S (in Ref. 2; BAC11505)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 610 AA; 66820 MW; 06AE8EBC16BBA2EC CRC64;
MWLPLVLLLA VLLLAVLCKV YLGLFSGSSP NPFSEDVKRP PAPLVTDKEA RKKVLKQAFS
ANQVPEKLDV VVIGSGFGGL AAAAILAKAG KRVLVLEQHT KAGGCCHTFG KNGLEFDTGI
HYIGRMEEGS IGRFILDQIT EGQLDWAPLS SPFDIMVLEG PNGRKEYPMY SGEKAYIQGL
KEKFPQEEAI IDKYIKLVKV VSSGAPHAIL LKFLPLPVVQ LLDRCGLLTR FSPFLQASTQ
SLAEVLQQLG ASSELQAVLS YIFPTYGVTP NHSAFSMHAL LVNHYMKGGF YPRGGSSEIA
FHTIPVIQRA GGAVLTKATV QSVLLDSAGK ACGVSVKKGH ELVNIYCPIV VSNAGLFNTY
EHLLPGNARC LPGVKQQLGT VRPGLGMTSV FICLRGTKED LHLPSTNYYV YYDTDMDQAM
ERYVSMPREE AAEHIPLLFF AFPSAKDPTW EDRFPGRSTM IMLIPTAYEW FEEWQAELKG
KRGSDYETFK NSFVEASMSV VLKLFPQLEG KVESVTAGSP LTNQFYLAAP RGACYGADHD
LGRLHPCVMA SLRAQSPIPN LYLTGQDIFT CGLVGALQGA LLCSSAILKR NLYSDLKNLD
SRIRAQKKKN
