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 27-MAR-2024, entry version 221. 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 CC 2-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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8EOR; EM; 2.67 A; A/B/C=1-567. 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 PDBsum; 8EOR; -. DR AlphaFoldDB; P23141; -. DR EMDB; EMD-28465; -. DR SMR; P23141; -. DR BioGRID; 107494; 30. 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; DB09061; Cannabidiol. DR DrugBank; DB14737; Cannabinol. 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; DB00470; Dronabinol. 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; DB14009; Medical Cannabis. 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; DB00641; Simvastatin. DR DrugBank; DB00382; Tacrine. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB12095; Telotristat ethyl. 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 GlyCosmos; P23141; 1 site, 2 glycans. 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; 9606-ENSP00000353720; -. DR PeptideAtlas; P23141; -. DR ProteomicsDB; 19083; -. DR ProteomicsDB; 54055; -. [P23141-1] DR ProteomicsDB; 54056; -. [P23141-2] DR Antibodypedia; 28513; 349 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 AGR; HGNC:1863; -. 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; WLTVNVW; -. DR OrthoDB; 4386at2759; -. DR PhylomeDB; P23141; -. DR TreeFam; TF315470; -. DR BioCyc; MetaCyc:HS11616-MONOMER; -. 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-5578768; Physiological factors. DR Reactome; R-HSA-9749641; Aspirin ADME. DR SABIO-RK; P23141; -. DR SignaLink; P23141; -. DR BioGRID-ORCS; 1066; 19 hits in 1163 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 95 other cell types or tissues. DR ExpressionAtlas; P23141; baseline and differential. 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:0106435; F:carboxylesterase activity; IDA:ARUK-UCL. DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IBA:GO_Central. 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 CDD; cd00312; Esterase_lipase; 1. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR002018; CarbesteraseB. DR InterPro; IPR019826; Carboxylesterase_B_AS. DR InterPro; IPR019819; Carboxylesterase_B_CS. DR PANTHER; PTHR11559; CARBOXYLESTERASE; 1. DR PANTHER; PTHR11559:SF179; LIVER CARBOXYLESTERASE 1-RELATED; 1. DR Pfam; PF00135; COesterase; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1. DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1. DR Genevisible; P23141; HS. 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 FT p-nitrophenyl acetate as substrate; no change in affinity FT for p-nitrophenyl acetate; loss of activity with L- or FT D-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; FT BAC87749/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:8EOR" FT HELIX 358..361 FT /evidence="ECO:0007829|PDB:5A7G" FT TURN 363..365 FT /evidence="ECO:0007829|PDB:1MX9" FT HELIX 368..370 FT /evidence="ECO:0007829|PDB:8EOR" 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 //