EST1_MACFA
ID EST1_MACFA Reviewed; 566 AA.
AC O46421;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Liver carboxylesterase 1 {ECO:0000250|UniProtKB:P23141};
DE EC=3.1.1.1 {ECO:0000250|UniProtKB:P23141};
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 Flags: Precursor;
GN Name=CES1 {ECO:0000250|UniProtKB:P23141};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Sone T., Takabatake E., Isobe M.;
RT "cDNA cloning and characterization of a monkey liver carboxylesterase.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
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 -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
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DR EMBL; AB010633; BAA24523.1; -; mRNA.
DR RefSeq; NP_001270223.1; NM_001283294.1.
DR AlphaFoldDB; O46421; -.
DR SMR; O46421; -.
DR STRING; 9541.XP_005592011.1; -.
DR ESTHER; macfa-cxest; Carb_B_Chordata.
DR MEROPS; S09.963; -.
DR PRIDE; O46421; -.
DR GeneID; 102129184; -.
DR eggNOG; KOG1516; Eukaryota.
DR OrthoDB; 754103at2759; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
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:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
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: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 2: Evidence at transcript 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:0000255"
FT CHAIN 19..566
FT /note="Liver carboxylesterase 1"
FT /id="PRO_0000008570"
FT ACT_SITE 221
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039"
FT ACT_SITE 354
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT ACT_SITE 467
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..116
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT DISULFID 274..285
FT /evidence="ECO:0000250|UniProtKB:P23141"
SQ SEQUENCE 566 AA; 62510 MW; 808040F1A4077297 CRC64;
MWLRALVLAT LAAFTAWGHP SSPPVVDTVH GKVLGKFVSL EGFTQPVAVF LGIPFAKPPL
GPLRFTPPQP AEPWSFVKNA TSYPPMCSQD AVAGQVLSEL FTNRKENTPL KLSEDCLYLN
IYTPADLTKK NRLPVMVWIH GGGLVVGAAS TYDGLALAAH ENVVVVTIQY RLGIWGFFST
GDEHSRGNWG HLDQLAALRW VQDNIASFGG NPGSVTIFGE SAGGESVSVL VLSPLAKNLF
HRAISESGVA LTAVLVKKGD VKPLAEQIAI AAGCQTTTSA VMVHCLRQKT EEELLETTLK
MKFFSLDLHG DPRESHPFLG TVIDGLLLPK TPEELQAERK FNTVPYMVGF NKQEFGWIIP
MLMGYPLSEG KLDQKTAMSL LWKSYPLVYI AKELIPEATE KYLGGTDDPV KKKDRFLDLL
ADVMFSVPSV IVARHHRDAG VPTYMYEFQY RPSFSSDMKP KTVIGDHGDE LFSVFGAPFL
KEGASEEEIR LSKMVMKFWA NFARNGNPNG EGLPRWPEYN QEEGYLQIGA NTQAAQKLKD
KEVAFWTTLF AKKAVEKPPQ TEHIEL
