EST1_MOUSE
ID EST1_MOUSE Reviewed; 565 AA.
AC Q8VCC2; O55136;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Liver carboxylesterase 1 {ECO:0000305};
DE EC=3.1.1.1 {ECO:0000250|UniProtKB:P23141};
DE AltName: Full=Acyl-coenzyme A:cholesterol acyltransferase {ECO:0000250|UniProtKB:P23141};
DE AltName: Full=Carboxylesterase 1G;
DE AltName: Full=Cholesteryl ester hydrolase {ECO:0000250|UniProtKB:P23141};
DE Short=CEH {ECO:0000250|UniProtKB:P23141};
DE EC=3.1.1.13 {ECO:0000250|UniProtKB:P23141};
DE AltName: Full=ES-x {ECO:0000303|PubMed:9565681};
DE Flags: Precursor;
GN Name=Ces1 {ECO:0000312|MGI:MGI:88378}; Synonyms=Ces1g;
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 [MRNA], INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=9565681; DOI=10.1016/s0167-4781(98)00023-2;
RA Ellinghaus P., Seedorf U., Assmann G.;
RT "Cloning and sequencing of a novel murine liver carboxylesterase cDNA.";
RL Biochim. Biophys. Acta 1397:175-179(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
CC -!- FUNCTION: Involved in the detoxification of xenobiotics and in the
CC activation of ester and amide prodrugs. Hydrolyzes aromatic and
CC aliphatic esters, but has no catalytic activity toward amides or a
CC fatty acyl-CoA ester. Displays fatty acid ethyl ester synthase
CC activity, catalyzing the ethyl esterification of oleic acid to
CC ethyloleate. Converts monoacylglycerides to free fatty acids and
CC glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins.
CC Hydrolyzes cellular cholesteryl esters to free cholesterols and
CC promotes reverse cholesterol transport (RCT) by facilitating both the
CC initial and final steps in the process. First of all, allows free
CC cholesterol efflux from macrophages to extracellular cholesterol
CC acceptors and secondly, releases free cholesterol from lipoprotein-
CC delivered cholesteryl esters in the liver for bile acid synthesis or
CC direct secretion into the bile. {ECO:0000250|UniProtKB:P23141}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a carboxylic ester + H2O = a carboxylate + an alcohol + H(+);
CC Xref=Rhea:RHEA:21164, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29067, ChEBI:CHEBI:30879, ChEBI:CHEBI:33308; EC=3.1.1.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10039};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate +
CC cholesterol + H(+); Xref=Rhea:RHEA:33875, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:46898; Evidence={ECO:0000250|UniProtKB:P23141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + prostaglandin E2 1-glyceryl ester = glycerol + H(+) +
CC prostaglandin E2; Xref=Rhea:RHEA:48296, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:90230,
CC ChEBI:CHEBI:606564; Evidence={ECO:0000250|UniProtKB:P23141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48297;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cholesterol ester + H2O = a fatty acid + cholesterol + H(+);
CC Xref=Rhea:RHEA:36403, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17002, ChEBI:CHEBI:28868; EC=3.1.1.13;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36404;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + prostaglandin F2alpha 1-glyceryl ester = glycerol + H(+)
CC + prostaglandin F2alpha; Xref=Rhea:RHEA:48300, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57404,
CC ChEBI:CHEBI:90233; Evidence={ECO:0000250|UniProtKB:P23141};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48301;
CC Evidence={ECO:0000250|UniProtKB:P23141};
CC -!- SUBUNIT: Homotrimer and homohexamer. Binds to beta-glucuronidase (By
CC similarity). {ECO:0000250|UniProtKB:P23141}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P23141}. Cytoplasm
CC {ECO:0000250|UniProtKB:P23141}. Lipid droplet
CC {ECO:0000250|UniProtKB:P23141}. Note=Moves from cytoplasm to lipid
CC droplets upon lipid loading. Associates with lipid droplets
CC independently of triglycerides (TG) content of the droplets and
CC hydrolyzes cholesteryl esters more efficiently from mixed droplets.
CC {ECO:0000250|UniProtKB:P23141}.
CC -!- TISSUE SPECIFICITY: Detected in kidney, liver and lung.
CC {ECO:0000269|PubMed:9565681}.
CC -!- INDUCTION: Up-regulated in liver upon feeding a diet enriched in
CC cholestyramine or cholate. {ECO:0000269|PubMed:9565681}.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
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DR EMBL; Y12887; CAA73388.1; -; mRNA.
DR EMBL; BC021150; AAH21150.1; -; mRNA.
DR EMBL; BC026897; AAH26897.1; -; mRNA.
DR CCDS; CCDS22531.1; -.
DR RefSeq; NP_067431.2; NM_021456.4.
DR AlphaFoldDB; Q8VCC2; -.
DR SMR; Q8VCC2; -.
DR BioGRID; 198678; 6.
DR STRING; 10090.ENSMUSP00000037555; -.
DR ChEMBL; CHEMBL4105953; -.
DR ESTHER; mouse-Ces1g; Carb_B_Chordata.
DR MEROPS; S09.972; -.
DR GlyGen; Q8VCC2; 2 sites.
DR iPTMnet; Q8VCC2; -.
DR PhosphoSitePlus; Q8VCC2; -.
DR SwissPalm; Q8VCC2; -.
DR CPTAC; non-CPTAC-3464; -.
DR jPOST; Q8VCC2; -.
DR MaxQB; Q8VCC2; -.
DR PaxDb; Q8VCC2; -.
DR PeptideAtlas; Q8VCC2; -.
DR PRIDE; Q8VCC2; -.
DR ProteomicsDB; 275785; -.
DR DNASU; 12623; -.
DR Ensembl; ENSMUST00000044602; ENSMUSP00000037555; ENSMUSG00000057074.
DR GeneID; 12623; -.
DR KEGG; mmu:12623; -.
DR UCSC; uc009muq.2; mouse.
DR CTD; 12623; -.
DR MGI; MGI:88378; Ces1g.
DR VEuPathDB; HostDB:ENSMUSG00000057074; -.
DR eggNOG; KOG1516; Eukaryota.
DR GeneTree; ENSGT00940000154623; -.
DR HOGENOM; CLU_006586_13_0_1; -.
DR InParanoid; Q8VCC2; -.
DR OMA; ERNEKAW; -.
DR OrthoDB; 754103at2759; -.
DR PhylomeDB; Q8VCC2; -.
DR TreeFam; TF315470; -.
DR BRENDA; 3.1.1.1; 3474.
DR BioGRID-ORCS; 12623; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q8VCC2; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8VCC2; protein.
DR Bgee; ENSMUSG00000057074; Expressed in left lobe of liver and 41 other tissues.
DR ExpressionAtlas; Q8VCC2; baseline and differential.
DR Genevisible; Q8VCC2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; ISO:MGI.
DR GO; GO:0080030; F:methyl indole-3-acetate esterase activity; IEA:UniProtKB-EC.
DR GO; GO:0004771; F:sterol esterase activity; ISS:UniProtKB.
DR GO; GO:0071397; P:cellular response to cholesterol; ISO:MGI.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISO:MGI.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISO:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0034378; P:chylomicron assembly; IMP:MGI.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:MGI.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0051791; P:medium-chain fatty acid metabolic process; ISO:MGI.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0120188; P:regulation of bile acid secretion; ISS:UniProtKB.
DR GO; GO:0090320; P:regulation of chylomicron remnant clearance; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0090207; P:regulation of triglyceride metabolic process; IMP:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0043691; P:reverse cholesterol transport; ISS:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR002018; CarbesteraseB.
DR InterPro; IPR019826; Carboxylesterase_B_AS.
DR InterPro; IPR019819; Carboxylesterase_B_CS.
DR Pfam; PF00135; COesterase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1.
DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW Lipid droplet; Lipid metabolism; Phosphoprotein; Reference proteome;
KW Serine esterase; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..565
FT /note="Liver carboxylesterase 1"
FT /id="PRO_0000008571"
FT ACT_SITE 221
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039"
FT ACT_SITE 353
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT ACT_SITE 466
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..116
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT DISULFID 273..284
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT CONFLICT 100
FT /note="L -> R (in Ref. 1; CAA73388)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="D -> E (in Ref. 1; CAA73388)"
FT /evidence="ECO:0000305"
FT CONFLICT 492
FT /note="K -> N (in Ref. 1; CAA73388)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 565 AA; 62680 MW; 21F3BE0184C2EB81 CRC64;
MWLCALSLIS LTACLSLGHP SLPPVVHTVH GKVLGKYVTL EGFSQPVAVF LGVPFAKPPL
GSLRFAPPEP AEPWSFVKHT TSYPPLCYQN PEAALRLAEL FTNQRKIIPH KFSEDCLYLN
IYTPADLTQN SRLPVMVWIH GGGLVIDGAS TYDGVPLAVH ENVVVVVIQY RLGIWGFFST
EDEHSRGNWG HLDQVAALHW VQDNIANFGG NPGSVTIFGE SAGGESVSVL VLSPLAKNLF
HRAIAQSSVI FNPCLFGRAA RPLAKKIAAL AGCKTTTSAA MVHCLRQKTE DELLEVSLKM
KFGTVDFLGD PRESYPFLPT VIDGVLLPKA PEEILAEKSF NTVPYMVGIN KHEFGWIIPM
FLDFPLSERK LDQKTAASIL WQAYPILNIS EKLIPAAIEK YLGGTEDPAT MTDLFLDLIG
DIMFGVPSVI VSRSHRDAGA PTYMYEYQYR PSFVSDDRPQ ELLGDHADEL FSVWGAPFLK
EGASEEEINL SKMVMKFWAN FARNGNPNGE GLPHWPEYDQ KEGYLQIGVP AQAAHRLKDK
EVDFWTELRA KETAERSSHR EHVEL
