EST1_HUMAN
ID EST1_HUMAN Reviewed; 567 AA.
AC P23141; A6NIM1; A8K3K8; A8K844; E9PAU8; P82127; Q00015; Q13657; Q14062;
AC Q16737; Q16788; Q549X7; Q549X8; Q86UK2; Q96EE8; Q9UC52; Q9UDG8; Q9UK77;
AC Q9ULY2;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 2.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Liver carboxylesterase 1 {ECO:0000305};
DE AltName: Full=Acyl-coenzyme A:cholesterol acyltransferase;
DE Short=ACAT;
DE AltName: Full=Brain carboxylesterase hBr1;
DE AltName: Full=Carboxylesterase 1;
DE Short=CE-1;
DE Short=hCE-1;
DE EC=3.1.1.1 {ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062};
DE AltName: Full=Cholesteryl ester hydrolase {ECO:0000303|PubMed:11015575};
DE Short=CEH {ECO:0000303|PubMed:11015575};
DE EC=3.1.1.13 {ECO:0000269|PubMed:11015575, ECO:0000269|PubMed:16024911, ECO:0000269|PubMed:16971496, ECO:0000269|PubMed:18762277};
DE AltName: Full=Cocaine carboxylesterase;
DE AltName: Full=Egasyn;
DE AltName: Full=HMSE;
DE AltName: Full=Methylumbelliferyl-acetate deacetylase 1;
DE EC=3.1.1.56 {ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:9169443};
DE AltName: Full=Monocyte/macrophage serine esterase;
DE AltName: Full=Retinyl ester hydrolase;
DE Short=REH;
DE AltName: Full=Serine esterase 1;
DE AltName: Full=Triacylglycerol hydrolase;
DE Short=TGH;
DE Flags: Precursor;
GN Name=CES1 {ECO:0000312|HGNC:HGNC:1863}; Synonyms=CES2, SES1;
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 [MRNA] (ISOFORM 1).
RX PubMed=1918003; DOI=10.1016/s0021-9258(18)55139-5;
RA Munger J.S., Shi G.P., Mark E.A., Chin D.T., Gerard C., Chapman H.A.;
RT "A serine esterase released by human alveolar macrophages is closely
RT related to liver microsomal carboxylesterases.";
RL J. Biol. Chem. 266:18832-18838(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Liver;
RX PubMed=8218228; DOI=10.1021/bi00094a018;
RA Kroetz D.L., McBride O.W., Gonzalez F.J.;
RT "Glycosylation-dependent activity of baculovirus-expressed human liver
RT carboxylesterases: cDNA cloning and characterization of two highly similar
RT enzyme forms.";
RL Biochemistry 32:11606-11617(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Peripheral blood, and Placenta;
RX PubMed=8406473; DOI=10.1006/geno.1993.1285;
RA Shibata F., Takagi Y., Kitajima M., Kuroda T., Omura T.;
RT "Molecular cloning and characterization of a human carboxylesterase gene.";
RL Genomics 17:76-82(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8049197; DOI=10.1161/01.atv.14.8.1346;
RA Becker A., Bottcher A., Lackner K.J., Fehringer P., Notka F., Aslanidis C.,
RA Schmitz G.;
RT "Purification, cloning, and expression of a human enzyme with acyl coenzyme
RT A: cholesterol acyltransferase activity, which is identical to liver
RT carboxylesterase.";
RL Arterioscler. Thromb. 14:1346-1355(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INTERACTION WITH BETA-GLUCURONIDASE.
RC TISSUE=Liver;
RX PubMed=10562416; DOI=10.1006/abbi.1999.1449;
RA Islam M.R., Waheed A., Shah G.N., Tomatsu S., Sly W.S.;
RT "Human egasyn binds beta-glucuronidase but neither the esterase active site
RT of egasyn nor the C-terminus of beta-glucuronidase is involved in their
RT interaction.";
RL Arch. Biochem. Biophys. 372:53-61(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Macrophage;
RX PubMed=11015575; DOI=10.1152/physiolgenomics.2000.2.1.1;
RA Ghosh S.;
RT "Cholesteryl ester hydrolase in human monocyte/macrophage: cloning,
RT sequencing, and expression of full-length cDNA.";
RL Physiol. Genomics 2:1-8(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 19-28.
RC TISSUE=Liver;
RX PubMed=11812220; DOI=10.1006/prep.2001.1553;
RA Alam M., Ho S., Vance D.E., Lehner R.;
RT "Heterologous expression, purification, and characterization of human
RT triacylglycerol hydrolase.";
RL Protein Expr. Purif. 24:33-42(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Hosokawa M., Yaginuma Y., Watanabe N., Yamamoto N., Tsukada E., Ohhata Y.,
RA Satoh T., Chiba K.;
RT "Inverted duplication of human carboxylesterase 1(CES1) genes, which are
RT difference in regulation at the transcriptional level.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Esophagus, and Heart;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Blood, and Lung;
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 [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-429 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10518925; DOI=10.1016/s0014-5793(99)01111-4;
RA Mori M., Hosokawa M., Ogasawara Y., Tsukada E., Chiba K.;
RT "cDNA cloning, characterization and stable expression of novel human brain
RT carboxylesterase.";
RL FEBS Lett. 458:17-22(1999).
RN [13]
RP PROTEIN SEQUENCE OF 18-27; 37-52; 65-75; 187-198; 258-273; 288-298;
RP 314-319; 340-352; 377-382; 439-461; 463-473; 499-504; 506-514 AND 539-557,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=7980644; DOI=10.1016/0006-2952(94)90461-8;
RA Brzezinski M.R., Abraham T.L., Stone C.L., Dean R.A., Bosron W.F.;
RT "Purification and characterization of a human liver cocaine
RT carboxylesterase that catalyzes the production of benzoylecgonine and the
RT formation of cocaethylene from alcohol and cocaine.";
RL Biochem. Pharmacol. 48:1747-1755(1994).
RN [14]
RP PROTEIN SEQUENCE OF 18-28; 65-78; 93-107; 243-255; 258-266; 297-313 AND
RP 341-346, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC TISSUE=Liver;
RX PubMed=9490062; DOI=10.1046/j.1432-1327.1998.2510863.x;
RA Schindler R., Mentlein R., Feldheim W.;
RT "Purification and characterization of retinyl ester hydrolase as a member
RT of the non-specific carboxylesterase supergene family.";
RL Eur. J. Biochem. 251:863-873(1998).
RN [15]
RP PROTEIN SEQUENCE OF 19-34, NUCLEOTIDE SEQUENCE [MRNA] OF 113-121; 138-149;
RP 216-224; 351-357 AND 466-471, AND SUBUNIT.
RC TISSUE=Liver;
RX PubMed=8597091; DOI=10.1016/0378-4274(95)03493-5;
RA Satoh T., Hosokawa M.;
RT "Molecular aspects of carboxylesterase isoforms in comparison with other
RT esterases.";
RL Toxicol. Lett. 82:439-445(1995).
RN [16]
RP PROTEIN SEQUENCE OF 19-28, ACTIVE SITES, GLYCOSYLATION AT ASN-79, AND
RP MUTAGENESIS OF ASN-79; SER-221; GLU-354; HIS-468 AND 564-HIS--LEU-567.
RX PubMed=12022871; DOI=10.1021/bi0255625;
RA Alam M., Vance D.E., Lehner R.;
RT "Structure-function analysis of human triacylglycerol hydrolase by site-
RT directed mutagenesis: identification of the catalytic triad and a
RT glycosylation site.";
RL Biochemistry 41:6679-6687(2002).
RN [17]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-567.
RC TISSUE=Liver;
RX PubMed=1997784; DOI=10.1016/0024-3205(91)90515-d;
RA Long R.M., Calabrese M.R., Martin B.M., Pohl L.R.;
RT "Cloning and sequencing of a human liver carboxylesterase isoenzyme.";
RL Life Sci. 48:PL43-PL49(1991).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 64-567, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2070086;
RA Zschunke F., Salmassi A., Kreipe H., Buck F., Parwaresch M.R., Radzun H.J.;
RT "cDNA cloning and characterization of human monocyte/macrophage serine
RT esterase-1.";
RL Blood 78:506-512(1991).
RN [19]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 114-567.
RC TISSUE=Liver;
RX PubMed=1748313; DOI=10.1016/0378-1119(91)90448-k;
RA Riddles P.W., Richards L.J., Bowles M.R., Pond S.M.;
RT "Cloning and analysis of a cDNA encoding a human liver carboxylesterase.";
RL Gene 108:289-292(1991).
RN [20]
RP FUNCTION AS METHYLUMBELLIFERYL-ACETATE DEACETYLASE, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9169443; DOI=10.1074/jbc.272.23.14769;
RA Pindel E.V., Kedishvili N.Y., Abraham T.L., Brzezinski M.R., Zhang J.,
RA Dean R.A., Bosron W.F.;
RT "Purification and cloning of a broad substrate specificity human liver
RT carboxylesterase that catalyzes the hydrolysis of cocaine and heroin.";
RL J. Biol. Chem. 272:14769-14775(1997).
RN [21]
RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16024911; DOI=10.1194/jlr.m500207-jlr200;
RA Zhao B., Fisher B.J., St Clair R.W., Rudel L.L., Ghosh S.;
RT "Redistribution of macrophage cholesteryl ester hydrolase from cytoplasm to
RT lipid droplets upon lipid loading.";
RL J. Lipid Res. 46:2114-2121(2005).
RN [22]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16971496; DOI=10.1152/ajpcell.00306.2006;
RA Zhao B., Song J., St Clair R.W., Ghosh S.;
RT "Stable overexpression of human macrophage cholesteryl ester hydrolase
RT results in enhanced free cholesterol efflux from human THP1 macrophages.";
RL Am. J. Physiol. 292:C405-C412(2007).
RN [23]
RP TISSUE SPECIFICITY, CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=18762277; DOI=10.1016/j.bbalip.2008.07.005;
RA Crow J.A., Middleton B.L., Borazjani A., Hatfield M.J., Potter P.M.,
RA Ross M.K.;
RT "Inhibition of carboxylesterase 1 is associated with cholesteryl ester
RT retention in human THP-1 monocyte/macrophages.";
RL Biochim. Biophys. Acta 1781:643-654(2008).
RN [24]
RP FUNCTION.
RX PubMed=18599737; DOI=10.1194/jlr.m800277-jlr200;
RA Zhao B., Song J., Ghosh S.;
RT "Hepatic overexpression of cholesteryl ester hydrolase enhances cholesterol
RT elimination and in vivo reverse cholesterol transport.";
RL J. Lipid Res. 49:2212-2217(2008).
RN [25]
RP POLYMORPHISM, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT GLU-143, AND
RP CHARACTERIZATION OF VARIANT GLU-143.
RX PubMed=18485328; DOI=10.1016/j.ajhg.2008.04.015;
RA Zhu H.-J., Patrick K.S., Yuan H.-J., Wang J.-S., Donovan J.L., DeVane C.L.,
RA Malcolm R., Johnson J.A., Youngblood G.L., Sweet D.H., Langaee T.Y.,
RA Markowitz J.S.;
RT "Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity
RT in man: clinical significance and molecular basis.";
RL Am. J. Hum. Genet. 82:1241-1248(2008).
RN [26]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=21049984; DOI=10.1021/tx1002194;
RA Xie S., Borazjani A., Hatfield M.J., Edwards C.C., Potter P.M., Ross M.K.;
RT "Inactivation of lipid glyceryl ester metabolism in human THP1
RT monocytes/macrophages by activated organophosphorus insecticides: role of
RT carboxylesterases 1 and 2.";
RL Chem. Res. Toxicol. 23:1890-1904(2010).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH SUBSTRATE.
RX PubMed=12725862; DOI=10.1016/s1074-5521(03)00071-1;
RA Bencharit S., Morton C.L., Hyatt J.L., Kuhn P., Danks M.K., Potter P.M.,
RA Redinbo M.R.;
RT "Crystal structure of human carboxylesterase 1 complexed with the
RT Alzheimer's drug tacrine. From binding promiscuity to selective
RT inhibition.";
RL Chem. Biol. 10:341-349(2003).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATES.
RX PubMed=12679808; DOI=10.1038/nsb919;
RA Bencharit S., Morton C.L., Xue Y., Potter P.M., Redinbo M.R.;
RT "Structural basis of heroin and cocaine metabolism by a promiscuous human
RT drug-processing enzyme.";
RL Nat. Struct. Biol. 10:349-356(2003).
CC -!- FUNCTION: Involved in the detoxification of xenobiotics and in the
CC activation of ester and amide prodrugs (PubMed:7980644, PubMed:9169443,
CC PubMed:9490062, PubMed:18762277). Hydrolyzes aromatic and aliphatic
CC esters, but has no catalytic activity toward amides or a fatty acyl-CoA
CC ester (PubMed:7980644, PubMed:9169443, PubMed:9490062,
CC PubMed:18762277). Hydrolyzes the methyl ester group of cocaine to form
CC benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of
CC cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid
CC ethyl ester synthase activity, catalyzing the ethyl esterification of
CC oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides
CC to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol
CC and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl
CC esters to free cholesterols and promotes reverse cholesterol transport
CC (RCT) by facilitating both the initial and final steps in the process
CC (PubMed:18762277, PubMed:16024911, PubMed:11015575, PubMed:16971496).
CC First of all, allows free cholesterol efflux from macrophages to
CC extracellular cholesterol acceptors and secondly, releases free
CC cholesterol from lipoprotein-delivered cholesteryl esters in the liver
CC for bile acid synthesis or direct secretion into the bile
CC (PubMed:18762277, PubMed:18599737, PubMed:16971496).
CC {ECO:0000269|PubMed:11015575, ECO:0000269|PubMed:16024911,
CC ECO:0000269|PubMed:16971496, ECO:0000269|PubMed:18599737,
CC ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:21049984,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062}.
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 ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone +
CC acetate + H(+); Xref=Rhea:RHEA:12208, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17224, ChEBI:CHEBI:17763,
CC ChEBI:CHEBI:30089; EC=3.1.1.56;
CC Evidence={ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:9169443};
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:0000269|PubMed:11015575, ECO:0000269|PubMed:16024911,
CC ECO:0000269|PubMed:16971496, ECO:0000269|PubMed:18762277};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36404;
CC Evidence={ECO:0000305|PubMed:18762277};
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:0000269|PubMed:11015575,
CC ECO:0000269|PubMed:16024911, ECO:0000269|PubMed:16971496,
CC ECO:0000269|PubMed:18762277};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000305|PubMed:11015575};
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:0000269|PubMed:21049984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000305|PubMed:21049984};
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:0000269|PubMed:21049984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48297;
CC Evidence={ECO:0000305|PubMed:21049984};
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:0000269|PubMed:21049984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48301;
CC Evidence={ECO:0000305|PubMed:21049984};
CC -!- ACTIVITY REGULATION: Activated by CHAPS (PubMed:9490062). Inhibited by
CC chlorpyrifos oxon (IC(50)=0.21 nM), paraoxon (IC(50)=0.29 nM), or
CC methyl paraoxon (IC(50)=49 nM) (PubMed:18762277).
CC {ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:9490062}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=106.6 uM for p-nitrophenyl acetate {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=775.7 uM for L-methylphenidate {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=663.5 uM for D-methylphenidate {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=116 uM for cocaine {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=43 mM for ethanol {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=0.8 mM for 4-methylumbelliferyl acetate
CC {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644,
CC ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062};
CC KM=6.3 mM for heroin {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=8.3 mM for 6-monoacetylmorphine {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC KM=49 uM for 2-arachidonoylglycerol {ECO:0000269|PubMed:21049984};
CC KM=250 uM for prostaglandin E2 1-glyceryl ester
CC {ECO:0000269|PubMed:21049984};
CC KM=93 uM for prostaglandin F2alpha 1-glyceryl ester
CC {ECO:0000269|PubMed:21049984};
CC Vmax=493.9 nmol/min/mg enzyme with p-nitrophenyl acetate as substrate
CC {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644,
CC ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062};
CC Vmax=1701.1 pmol/min/mg enzyme with L-methylphenidate as substrate
CC {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644,
CC ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062};
CC Vmax=177.2 pmol/min/mg enzyme with D-methylphenidate as substrate
CC {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644,
CC ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062};
CC Note=kcat is 59 min(-1), 29 min(-1), 90 min(-1) with 2-
CC arachidonoylglycerol, prostaglandin F2alpha 1-glyceryl ester and
CC prostaglandin E2 1-glyceryl ester as substrates, respectively.
CC {ECO:0000269|PubMed:21049984};
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:18485328,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443,
CC ECO:0000269|PubMed:9490062};
CC -!- SUBUNIT: Homotrimer and homohexamer. Binds to beta-glucuronidase.
CC {ECO:0000269|PubMed:12679808, ECO:0000269|PubMed:12725862,
CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:8597091}.
CC -!- INTERACTION:
CC P23141-3; Q8IVF2-3: AHNAK2; NbExp=3; IntAct=EBI-12360993, EBI-12078468;
CC P23141-3; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12360993, EBI-3867333;
CC P23141-3; Q15125: EBP; NbExp=3; IntAct=EBI-12360993, EBI-3915253;
CC P23141-3; Q5T7V8: GORAB; NbExp=3; IntAct=EBI-12360993, EBI-3917143;
CC P23141-3; Q5T749: KPRP; NbExp=3; IntAct=EBI-12360993, EBI-10981970;
CC P23141-3; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-12360993, EBI-716063;
CC P23141-3; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-12360993, EBI-769257;
CC P23141-3; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-12360993, EBI-3920694;
CC P23141-3; O95231: VENTX; NbExp=3; IntAct=EBI-12360993, EBI-10191303;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:10562416}. Cytoplasm {ECO:0000269|PubMed:16024911}.
CC Lipid droplet {ECO:0000269|PubMed:16024911}. Note=Moves from cytoplasm
CC to lipid 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:0000269|PubMed:16024911}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P23141-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23141-2; Sequence=VSP_021026;
CC Name=3;
CC IsoId=P23141-3; Sequence=VSP_047158;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in liver with lower levels
CC in heart and lung (PubMed:10562416). Expressed in macrophages
CC (PubMed:11015575, PubMed:21049984, PubMed:18762277).
CC {ECO:0000269|PubMed:10562416, ECO:0000269|PubMed:11015575,
CC ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:21049984}.
CC -!- PTM: Contains sialic acid.
CC -!- PTM: Cleavage of the signal sequence can occur at 2 positions, either
CC between Trp-17 and Gly-18 or between Gly-18 and His-19.
CC -!- POLYMORPHISM: Genetic variants in CES1 are associated with clinically
CC significant alterations in pharmacokinetics and drug response of
CC carboxylesterase 1 substrates [MIM:618057].
CC {ECO:0000269|PubMed:18485328}.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA83932.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; M73499; AAA35649.1; -; mRNA.
DR EMBL; L07764; AAA16036.1; -; mRNA.
DR EMBL; L07765; AAA35711.1; -; mRNA.
DR EMBL; D21088; BAA04650.1; -; Genomic_DNA.
DR EMBL; S73751; AAC60631.2; -; mRNA.
DR EMBL; AF177775; AAD53175.1; -; mRNA.
DR EMBL; AY268104; AAP20868.1; -; mRNA.
DR EMBL; AB119995; BAC87748.1; -; mRNA.
DR EMBL; AB119996; BAC87749.1; -; mRNA.
DR EMBL; AB119997; BAC87750.1; -; Genomic_DNA.
DR EMBL; AB119998; BAC87751.1; -; Genomic_DNA.
DR EMBL; AK290623; BAF83312.1; -; mRNA.
DR EMBL; AK292209; BAF84898.1; -; mRNA.
DR EMBL; AC147362; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012418; AAH12418.1; -; mRNA.
DR EMBL; BC110338; AAI10339.1; -; mRNA.
DR EMBL; AB025026; BAA84995.1; -; mRNA.
DR EMBL; M55509; AAA35650.1; -; mRNA.
DR EMBL; X52973; CAA37147.1; -; mRNA.
DR EMBL; M65261; AAA83932.1; ALT_FRAME; mRNA.
DR CCDS; CCDS32450.1; -. [P23141-2]
DR CCDS; CCDS45488.1; -. [P23141-1]
DR CCDS; CCDS45489.1; -. [P23141-3]
DR PIR; A41010; A41010.
DR RefSeq; NP_001020365.1; NM_001025194.1. [P23141-1]
DR RefSeq; NP_001020366.1; NM_001025195.1. [P23141-2]
DR RefSeq; NP_001257.4; NM_001266.4. [P23141-3]
DR PDB; 1MX1; X-ray; 2.40 A; A/B/C/D/E/F=19-567.
DR PDB; 1MX5; X-ray; 2.80 A; A/B/C/D/E/F=19-567.
DR PDB; 1MX9; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=19-567.
DR PDB; 1YA4; X-ray; 3.20 A; A/B/C=21-552.
DR PDB; 1YA8; X-ray; 3.00 A; A/B/C=21-552.
DR PDB; 1YAH; X-ray; 3.00 A; A/B/C=21-552.
DR PDB; 1YAJ; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=21-552.
DR PDB; 2DQY; X-ray; 3.00 A; A/B/C=19-561.
DR PDB; 2DQZ; X-ray; 2.80 A; A/B/C=19-561.
DR PDB; 2DR0; X-ray; 3.20 A; A/B/C=19-561.
DR PDB; 2H7C; X-ray; 2.00 A; A/B/C/D/E/F=19-561.
DR PDB; 2HRQ; X-ray; 2.70 A; A/B/C/D/E/F=21-553.
DR PDB; 2HRR; X-ray; 2.70 A; A/B/C=21-553.
DR PDB; 3K9B; X-ray; 3.10 A; A/B/C=24-553.
DR PDB; 4AB1; X-ray; 2.20 A; A=21-553.
DR PDB; 5A7F; X-ray; 1.86 A; A=21-553.
DR PDB; 5A7G; X-ray; 1.48 A; A=21-553.
DR PDB; 5A7H; X-ray; 2.01 A; A=22-553.
DR PDBsum; 1MX1; -.
DR PDBsum; 1MX5; -.
DR PDBsum; 1MX9; -.
DR PDBsum; 1YA4; -.
DR PDBsum; 1YA8; -.
DR PDBsum; 1YAH; -.
DR PDBsum; 1YAJ; -.
DR PDBsum; 2DQY; -.
DR PDBsum; 2DQZ; -.
DR PDBsum; 2DR0; -.
DR PDBsum; 2H7C; -.
DR PDBsum; 2HRQ; -.
DR PDBsum; 2HRR; -.
DR PDBsum; 3K9B; -.
DR PDBsum; 4AB1; -.
DR PDBsum; 5A7F; -.
DR PDBsum; 5A7G; -.
DR PDBsum; 5A7H; -.
DR AlphaFoldDB; P23141; -.
DR SMR; P23141; -.
DR BioGRID; 107494; 26.
DR IntAct; P23141; 13.
DR MINT; P23141; -.
DR STRING; 9606.ENSP00000353720; -.
DR BindingDB; P23141; -.
DR ChEMBL; CHEMBL2265; -.
DR DrugBank; DB07821; (1R)-1,2,2-trimethylpropyl (R)-methylphosphinate.
DR DrugBank; DB08224; (1S,7S,8S,8AR)-1,2,3,7,8,8A-HEXAHYDRO-7-METHYL-8-[2-[(2R,4R)-TETRAHYDRO-4-HY DROXY-6-OXO-2H-PYRAN-2-YL]ETHYL]-1-NAPHTHALENOL.
DR DrugBank; DB03056; 4-Piperidino-Piperidine.
DR DrugBank; DB06442; Avasimibe.
DR DrugBank; DB01086; Benzocaine.
DR DrugBank; DB01101; Capecitabine.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB01410; Ciclesonide.
DR DrugBank; DB00758; Clopidogrel.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB04838; Cyclandelate.
DR DrugBank; DB06695; Dabigatran etexilate.
DR DrugBank; DB00647; Dextropropoxyphene.
DR DrugBank; DB01452; Diamorphine.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB14845; Filgotinib.
DR DrugBank; DB00875; Flupentixol.
DR DrugBank; DB11181; Homatropine.
DR DrugBank; DB02161; Hydroxy-Phenyl-Acetic Acid 8-Methyl-8-Aza-Bicyclo[3.2.1]Oct-3-Yl Ester.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB00583; Levocarnitine.
DR DrugBank; DB00454; Meperidine.
DR DrugBank; DB06693; Mevastatin.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB03721; N-acetyl-alpha-neuraminic acid.
DR DrugBank; DB01183; Naloxone.
DR DrugBank; DB00198; Oseltamivir.
DR DrugBank; DB09269; Phenylacetic acid.
DR DrugBank; DB01599; Probucol.
DR DrugBank; DB09342; Propoxycaine.
DR DrugBank; DB00881; Quinapril.
DR DrugBank; DB14761; Remdesivir.
DR DrugBank; DB12404; Remimazolam.
DR DrugBank; DB06201; Rufinamide.
DR DrugBank; DB11362; Selexipag.
DR DrugBank; DB00382; Tacrine.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB09299; Tenofovir alafenamide.
DR DrugBank; DB04795; Thenoyltrifluoroacetone.
DR DrugBank; DB00519; Trandolapril.
DR DrugBank; DB16349; Vicagrel.
DR DrugCentral; P23141; -.
DR GuidetoPHARMACOLOGY; 2592; -.
DR SwissLipids; SLP:000001265; -.
DR ESTHER; human-CES1; Carb_B_Chordata.
DR MEROPS; S09.982; -.
DR GlyConnect; 1462; 3 N-Linked glycans (1 site).
DR GlyGen; P23141; 2 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P23141; -.
DR PhosphoSitePlus; P23141; -.
DR BioMuta; CES1; -.
DR DMDM; 119576; -.
DR EPD; P23141; -.
DR jPOST; P23141; -.
DR MassIVE; P23141; -.
DR MaxQB; P23141; -.
DR PaxDb; P23141; -.
DR PeptideAtlas; P23141; -.
DR PRIDE; P23141; -.
DR ProteomicsDB; 19083; -.
DR ProteomicsDB; 54055; -. [P23141-1]
DR ProteomicsDB; 54056; -. [P23141-2]
DR Antibodypedia; 28513; 325 antibodies from 37 providers.
DR DNASU; 1066; -.
DR Ensembl; ENST00000360526.8; ENSP00000353720.4; ENSG00000198848.13. [P23141-2]
DR Ensembl; ENST00000361503.8; ENSP00000355193.4; ENSG00000198848.13. [P23141-1]
DR Ensembl; ENST00000422046.6; ENSP00000390492.2; ENSG00000198848.13. [P23141-3]
DR Ensembl; ENST00000571922.5; ENSP00000460045.1; ENSG00000262243.5.
DR Ensembl; ENST00000574513.5; ENSP00000461208.1; ENSG00000262243.5.
DR Ensembl; ENST00000576783.5; ENSP00000458586.1; ENSG00000262243.5.
DR GeneID; 1066; -.
DR KEGG; hsa:1066; -.
DR MANE-Select; ENST00000360526.8; ENSP00000353720.4; NM_001025195.2; NP_001020366.1. [P23141-2]
DR UCSC; uc002eil.4; human. [P23141-1]
DR CTD; 1066; -.
DR DisGeNET; 1066; -.
DR GeneCards; CES1; -.
DR HGNC; HGNC:1863; CES1.
DR HPA; ENSG00000198848; Tissue enriched (liver).
DR MalaCards; CES1; -.
DR MIM; 114835; gene.
DR MIM; 618057; phenotype.
DR neXtProt; NX_P23141; -.
DR OpenTargets; ENSG00000198848; -.
DR PharmGKB; PA107; -.
DR VEuPathDB; HostDB:ENSG00000198848; -.
DR eggNOG; KOG1516; Eukaryota.
DR GeneTree; ENSGT00940000154623; -.
DR HOGENOM; CLU_006586_13_0_1; -.
DR InParanoid; P23141; -.
DR OMA; WYNGTDW; -.
DR OrthoDB; 754103at2759; -.
DR PhylomeDB; P23141; -.
DR TreeFam; TF315470; -.
DR BioCyc; MetaCyc:HS11616-MON; -.
DR BRENDA; 3.1.1.1; 2681.
DR PathwayCommons; P23141; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR SABIO-RK; P23141; -.
DR SignaLink; P23141; -.
DR BioGRID-ORCS; 1066; 16 hits in 1075 CRISPR screens.
DR ChiTaRS; CES1; human.
DR EvolutionaryTrace; P23141; -.
DR GeneWiki; Carboxylesterase_1; -.
DR GenomeRNAi; 1066; -.
DR Pharos; P23141; Tchem.
DR PRO; PR:P23141; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P23141; protein.
DR Bgee; ENSG00000198848; Expressed in right lobe of liver and 94 other tissues.
DR ExpressionAtlas; P23141; baseline and differential.
DR Genevisible; P23141; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IDA:ARUK-UCL.
DR GO; GO:0080030; F:methyl indole-3-acetate esterase activity; IEA:UniProtKB-EC.
DR GO; GO:0047374; F:methylumbelliferyl-acetate deacetylase activity; IEA:UniProtKB-EC.
DR GO; GO:0004771; F:sterol esterase activity; IDA:UniProtKB.
DR GO; GO:0071397; P:cellular response to cholesterol; IMP:ARUK-UCL.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IMP:ARUK-UCL.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0090122; P:cholesterol ester hydrolysis involved in cholesterol transport; TAS:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:ARUK-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0051791; P:medium-chain fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; IMP:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0120188; P:regulation of bile acid secretion; IMP:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; TAS:ProtInc.
DR GO; GO:0043691; P:reverse cholesterol transport; IMP: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 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW Lipid droplet; Lipid metabolism; Phosphoprotein; Reference proteome;
KW Serine esterase; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:7980644,
FT ECO:0000269|PubMed:9490062"
FT CHAIN 18..567
FT /note="Liver carboxylesterase 1"
FT /id="PRO_0000391359"
FT ACT_SITE 221
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039,
FT ECO:0000269|PubMed:12022871"
FT ACT_SITE 354
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:12022871"
FT ACT_SITE 468
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:12022871"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12022871"
FT DISULFID 87..116
FT DISULFID 274..285
FT VAR_SEQ 17
FT /note="W -> WA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:8218228"
FT /id="VSP_021026"
FT VAR_SEQ 362
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_047158"
FT VARIANT 18
FT /note="G -> GA"
FT /id="VAR_002357"
FT VARIANT 75
FT /note="S -> N (in dbSNP:rs2307240)"
FT /id="VAR_014314"
FT VARIANT 143
FT /note="G -> E (5.4-fold decrease in activity with p-
FT nitrophenyl acetate as substrate; no change in affinity for
FT p-nitrophenyl acetate; loss of activity with L- or D-
FT methylphenidate as substrate; dbSNP:rs71647871)"
FT /evidence="ECO:0000269|PubMed:18485328"
FT /id="VAR_046954"
FT VARIANT 199
FT /note="R -> H (in dbSNP:rs2307243)"
FT /id="VAR_014594"
FT VARIANT 203
FT /note="D -> E (in dbSNP:rs2307227)"
FT /id="VAR_014595"
FT MUTAGEN 79
FT /note="N->A: Abolishes glycosylation."
FT /evidence="ECO:0000269|PubMed:12022871"
FT MUTAGEN 221
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12022871"
FT MUTAGEN 354
FT /note="E->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12022871"
FT MUTAGEN 468
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12022871"
FT MUTAGEN 564..567
FT /note="Missing: Does not result in secretion."
FT /evidence="ECO:0000269|PubMed:12022871"
FT CONFLICT 2
FT /note="W -> L (in Ref. 5; AAD53175)"
FT /evidence="ECO:0000305"
FT CONFLICT 4..7
FT /note="RAFI -> PALV (in Ref. 3; BAA04650, 8; BAC87749/
FT BAC87751, 9; BAF83312/BAF84898 and 11; AAH12418)"
FT /evidence="ECO:0000305"
FT CONFLICT 12
FT /note="S -> A (in Ref. 3; BAA04650, 8; BAC87749/BAC87751,
FT 9; BAF83312/BAF84898 and 11; AAH12418)"
FT /evidence="ECO:0000305"
FT CONFLICT 19..21
FT /note="HPS -> GPP (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 19
FT /note="H -> N (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 21..24
FT /note="SSPP -> EAVV (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 27..28
FT /note="DT -> AK (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 28..29
FT /note="TV -> DT (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="A -> G (in Ref. 2; AAA16036/AAA35711)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="R -> G (in Ref. 18; CAA37147)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="F -> S (in Ref. 6; AAP20868)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="S -> A (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 78
FT /note="K -> I (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="Q -> R (in Ref. 6; AAP20868)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="S -> F (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 105..107
FT /note="KEN -> PAD (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="D -> H (in Ref. 19; AAA83932)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="R -> G (in Ref. 18; CAA37147)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="S -> I (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="L -> K (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="S -> G (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="L -> P (in Ref. 9; BAF83312)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="K -> Q (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="V -> A (in Ref. 19; AAA83932)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="T -> I (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="K -> A (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="S -> M (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="A -> R (in Ref. 19; AAA83932)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="F -> I (in Ref. 19; AAA83932)"
FT /evidence="ECO:0000305"
FT CONFLICT 512
FT /note="E -> K (in Ref. 19; AAA83932)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="A -> G (in Ref. 2; AAA16036/AAA35711)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="E -> D (in Ref. 19; AAA83932)"
FT /evidence="ECO:0000305"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 91..101
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:5A7G"
FT TURN 127..130
FT /evidence="ECO:0007829|PDB:4AB1"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:5A7G"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 155..161
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 173..177
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2HRQ"
FT HELIX 189..204
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 205..208
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 210..220
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 222..231
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:5A7G"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:1MX9"
FT STRAND 241..247
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 262..272
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 279..288
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 291..301
FT /evidence="ECO:0007829|PDB:5A7G"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:5A7F"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 332..338
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:2H7C"
FT STRAND 346..351
FT /evidence="ECO:0007829|PDB:5A7G"
FT TURN 352..355
FT /evidence="ECO:0007829|PDB:2HRQ"
FT HELIX 358..361
FT /evidence="ECO:0007829|PDB:5A7G"
FT TURN 363..365
FT /evidence="ECO:0007829|PDB:1MX9"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:1MX5"
FT HELIX 375..384
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 386..389
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 396..404
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 410..425
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 427..439
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 444..450
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:1MX5"
FT TURN 468..471
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 472..475
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 478..480
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 487..506
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:2DQZ"
FT STRAND 525..532
FT /evidence="ECO:0007829|PDB:5A7G"
FT STRAND 534..537
FT /evidence="ECO:0007829|PDB:5A7G"
FT HELIX 541..551
FT /evidence="ECO:0007829|PDB:5A7G"
SQ SEQUENCE 567 AA; 62521 MW; D3A00BDCDC7E5DFF CRC64;
MWLRAFILAT LSASAAWGHP SSPPVVDTVH GKVLGKFVSL EGFAQPVAIF LGIPFAKPPL
GPLRFTPPQP AEPWSFVKNA TSYPPMCTQD PKAGQLLSEL FTNRKENIPL KLSEDCLYLN
IYTPADLTKK NRLPVMVWIH GGGLMVGAAS TYDGLALAAH ENVVVVTIQY RLGIWGFFST
GDEHSRGNWG HLDQVAALRW VQDNIASFGG NPGSVTIFGE SAGGESVSVL VLSPLAKNLF
HRAISESGVA LTSVLVKKGD VKPLAEQIAI TAGCKTTTSA VMVHCLRQKT EEELLETTLK
MKFLSLDLQG DPRESQPLLG TVIDGMLLLK TPEELQAERN FHTVPYMVGI NKQEFGWLIP
MQLMSYPLSE GQLDQKTAMS LLWKSYPLVC IAKELIPEAT EKYLGGTDDT VKKKDLFLDL
IADVMFGVPS VIVARNHRDA GAPTYMYEFQ YRPSFSSDMK PKTVIGDHGD ELFSVFGAPF
LKEGASEEEI RLSKMVMKFW ANFARNGNPN GEGLPHWPEY NQKEGYLQIG ANTQAAQKLK
DKEVAFWTNL FAKKAVEKPP QTEHIEL
