ID EST1_HUMAN Reviewed; 567 AA. AC P23141; A6NIM1; A8K3K8; A8K844; E9PAU8; P82127; Q00015; Q13657; AC Q14062; Q16737; Q16788; Q549X7; Q549X8; Q86UK2; Q96EE8; Q9UC52; AC Q9UDG8; Q9UK77; Q9ULY2; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 2. DT 09-DEC-2015, entry version 169. DE RecName: Full=Liver carboxylesterase 1; 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; 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; 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; Synonyms=CES2, SES1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1918003; 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 RT similar 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 RT gene."; RL Genomics 17:76-82(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=8049197; RA Becker A., Bottcher A., Lackner K.J., Fehringer P., Notka F., RA Aslanidis C., Schmitz G.; RT "Purification, cloning, and expression of a human enzyme with acyl RT coenzyme A: cholesterol acyltransferase activity, which is identical RT to liver 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 RT site of egasyn nor the C-terminus of beta-glucuronidase is involved in RT their interaction."; RL Arch. Biochem. Biophys. 372:53-61(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Macrophage; RX PubMed=11015575; 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., RA Ohhata Y., Satoh T., Chiba K.; RT "Inverted duplication of human carboxylesterase 1(CES1) genes, which RT are 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA 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., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA 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 RT project: 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 RT brain 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 RP 539-557, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP 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 RT the 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 RP AND 341-346, CATALYTIC ACTIVITY, ENZYME REGULATION, AND RP BIOPHYSICOCHEMICAL 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 RT member 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; RP 138-149; 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 RT other 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 RT site-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., RA 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 RT carboxylesterase."; RL Gene 108:289-292(1991). RN [20] RP FUNCTION AS METHYLUMBELLIFERYL-ACETATE DEACETYLASE, CATALYTIC RP ACTIVITY, AND 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 RT heroin."; RL J. Biol. Chem. 272:14769-14775(1997). RN [21] RP BIOPHYSICOCHEMICAL PROPERTIES, VARIANT GLU-143, AND CHARACTERIZATION RP 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., RA DeVane C.L., Malcolm R., Johnson J.A., Youngblood G.L., Sweet D.H., RA Langaee T.Y., Markowitz J.S.; RT "Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 RT activity in man: clinical significance and molecular basis."; RL Am. J. Hum. Genet. 82:1241-1248(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, AND IDENTIFICATION RP BY 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [23] 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., RA Ayoub D., 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 [24] 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., RA Potter P.M., 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 [25] 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 RT human 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. Hydrolyzes aromatic and CC aliphatic esters, but has no catalytic activity toward amides or a CC fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine CC to form benzoylecgonine. Catalyzes the transesterification of CC cocaine to form cocaethylene. Displays fatty acid ethyl ester CC synthase activity, catalyzing the ethyl esterification of oleic CC acid to ethyloleate. {ECO:0000269|PubMed:7980644, CC ECO:0000269|PubMed:9169443}. CC -!- CATALYTIC ACTIVITY: A carboxylic ester + H(2)O = an alcohol + a CC carboxylate. {ECO:0000255|PROSITE-ProRule:PRU10039}. CC -!- CATALYTIC ACTIVITY: 4-methylumbelliferyl acetate + H(2)O = 4- CC methylumbelliferone + acetate. CC -!- ENZYME REGULATION: Activated by CHAPS. CC {ECO:0000269|PubMed:9490062}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=106.6 uM for p-nitrophenyl acetate CC {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, CC ECO:0000269|PubMed:9169443, 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 Vmax=493.9 nmol/min/mg enzyme with p-nitrophenyl acetate as CC substrate {ECO:0000269|PubMed:18485328, CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, CC ECO:0000269|PubMed:9490062}; CC Vmax=1701.1 pmol/min/mg enzyme with L-methylphenidate as CC substrate {ECO:0000269|PubMed:18485328, CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, CC ECO:0000269|PubMed:9490062}; CC Vmax=177.2 pmol/min/mg enzyme with D-methylphenidate as CC substrate {ECO:0000269|PubMed:18485328, CC ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, CC ECO:0000269|PubMed:9490062}; 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 -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen CC {ECO:0000269|PubMed:10562416}. 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 CC levels in heart and lung. {ECO:0000269|PubMed:10562416}. CC -!- PTM: Contains sialic acid. CC -!- PTM: Cleavage of the signal sequence can occur at 2 positions, CC either between Trp-17 and Gly-18 or between Gly-18 and His-19. CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA83932.1; Type=Frameshift; Positions=301, 312, 318, 383, 391; 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 UniGene; Hs.558865; -. 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 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 ProteinModelPortal; P23141; -. DR SMR; P23141; 21-553. DR BioGrid; 107494; 2. DR IntAct; P23141; 1. DR MINT; MINT-5004142; -. DR STRING; 9606.ENSP00000353720; -. DR BindingDB; P23141; -. DR ChEMBL; CHEMBL2265; -. DR DrugBank; DB01086; Benzocaine. DR DrugBank; DB01101; Capecitabine. DR DrugBank; DB02659; Cholic Acid. DR DrugBank; DB01410; Ciclesonide. DR DrugBank; DB00758; Clopidogrel. DR DrugBank; DB04838; Cyclandelate. DR DrugBank; DB06695; Dabigatran etexilate. DR DrugBank; DB00328; Indomethacin. DR DrugBank; DB00762; Irinotecan. DR DrugBank; DB00583; L-Carnitine. DR DrugBank; DB00688; Mycophenolate mofetil. DR DrugBank; DB00198; Oseltamivir. DR DrugBank; DB01599; Probucol. DR DrugBank; DB06201; Rufinamide. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00519; Trandolapril. DR GuidetoPHARMACOLOGY; 2592; -. DR SwissLipids; SLP:000001265; -. DR ESTHER; human-CES1; Carb_B_Chordata. DR MEROPS; S09.982; -. DR PhosphoSite; P23141; -. DR BioMuta; CES1; -. DR DMDM; 119576; -. DR MaxQB; P23141; -. DR PaxDb; P23141; -. DR PRIDE; P23141; -. DR DNASU; 1066; -. DR Ensembl; ENST00000360526; ENSP00000353720; ENSG00000198848. [P23141-2] DR Ensembl; ENST00000361503; ENSP00000355193; ENSG00000198848. [P23141-1] DR Ensembl; ENST00000422046; ENSP00000390492; ENSG00000198848. [P23141-3] DR Ensembl; ENST00000571922; ENSP00000460045; ENSG00000262243. DR Ensembl; ENST00000574513; ENSP00000461208; ENSG00000262243. DR Ensembl; ENST00000576783; ENSP00000458586; ENSG00000262243. DR GeneID; 1066; -. DR KEGG; hsa:1066; -. DR UCSC; uc002eil.3; human. [P23141-2] DR UCSC; uc002eim.3; human. [P23141-1] DR CTD; 1066; -. DR GeneCards; CES1; -. DR HGNC; HGNC:1863; CES1. DR HPA; HPA012023; -. DR HPA; HPA046717; -. DR MIM; 114835; gene+phenotype. DR neXtProt; NX_P23141; -. DR PharmGKB; PA107; -. DR eggNOG; KOG1516; Eukaryota. DR eggNOG; COG2272; LUCA. DR GeneTree; ENSGT00760000118946; -. DR HOVERGEN; HBG008839; -. DR InParanoid; P23141; -. DR KO; K01044; -. DR OMA; DPRESHT; -. DR OrthoDB; EOG75XGKD; -. DR PhylomeDB; P23141; -. DR TreeFam; TF315470; -. DR BioCyc; MetaCyc:HS11616-MONOMER; -. DR BRENDA; 3.1.1.1; 2681. DR Reactome; R-HSA-211945; Phase 1 - Functionalization of compounds. DR SABIO-RK; P23141; -. DR ChiTaRS; CES1; human. DR EvolutionaryTrace; P23141; -. DR GeneWiki; Carboxylesterase_1; -. DR GenomeRNAi; 1066; -. DR NextBio; 4450; -. DR PRO; PR:P23141; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; P23141; -. DR CleanEx; HS_CES1; -. DR CleanEx; HS_CES2; -. DR ExpressionAtlas; P23141; baseline and differential. DR Genevisible; P23141; HS. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0052689; F:carboxylic ester hydrolase activity; TAS:ProtInc. DR GO; GO:0047374; F:methylumbelliferyl-acetate deacetylase activity; IEA:UniProtKB-EC. DR GO; GO:0004771; F:sterol esterase activity; IBA:GO_Central. DR GO; GO:0004806; F:triglyceride lipase activity; IBA:GO_Central. DR GO; GO:0030855; P:epithelial cell differentiation; IDA:UniProtKB. DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central. DR GO; GO:0008152; P:metabolic process; TAS:ProtInc. DR GO; GO:0009636; P:response to toxic substance; TAS:ProtInc. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome. 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; Complete proteome; KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; KW Glycoprotein; Hydrolase; Phosphoprotein; Polymorphism; KW Reference proteome; Serine esterase; Signal. FT SIGNAL 1 17 {ECO:0000269|PubMed:7980644, FT ECO:0000269|PubMed:9490062}. FT CHAIN 18 567 Liver carboxylesterase 1. FT /FTId=PRO_0000391359. FT ACT_SITE 221 221 Acyl-ester intermediate. FT {ECO:0000255|PROSITE-ProRule:PRU10039, FT ECO:0000269|PubMed:12022871}. FT ACT_SITE 354 354 Charge relay system. FT {ECO:0000269|PubMed:12022871}. FT ACT_SITE 468 468 Charge relay system. FT {ECO:0000269|PubMed:12022871}. FT MOD_RES 380 380 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT CARBOHYD 79 79 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12022871}. FT DISULFID 87 116 FT DISULFID 274 285 FT VAR_SEQ 17 17 W -> WA (in isoform 2). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:8218228}. FT /FTId=VSP_021026. FT VAR_SEQ 362 362 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_047158. FT VARIANT 18 18 G -> GA. FT /FTId=VAR_002357. FT VARIANT 75 75 S -> N (in dbSNP:rs2307240). FT /FTId=VAR_014314. FT VARIANT 143 143 G -> E (5.4-fold decrease in activity FT with p-nitrophenyl acetate as substrate; FT no change in affinity for p-nitrophenyl FT acetate; loss of activity with L- or D- FT methylphenidate as substrate; FT dbSNP:rs71647871). FT {ECO:0000269|PubMed:18485328}. FT /FTId=VAR_046954. FT VARIANT 199 199 R -> H (in dbSNP:rs2307243). FT /FTId=VAR_014594. FT VARIANT 203 203 D -> E (in dbSNP:rs2307227). FT /FTId=VAR_014595. FT MUTAGEN 79 79 N->A: Abolishes glycosylation. FT {ECO:0000269|PubMed:12022871}. FT MUTAGEN 221 221 S->A: Loss of activity. FT {ECO:0000269|PubMed:12022871}. FT MUTAGEN 354 354 E->A: Loss of activity. FT {ECO:0000269|PubMed:12022871}. FT MUTAGEN 468 468 H->A: Loss of activity. FT {ECO:0000269|PubMed:12022871}. FT MUTAGEN 564 567 Missing: Does not result in secretion. FT {ECO:0000269|PubMed:12022871}. FT CONFLICT 2 2 W -> L (in Ref. 5; AAD53175). FT {ECO:0000305}. FT CONFLICT 4 7 RAFI -> PALV (in Ref. 3; BAA04650, 8; FT BAC87749/BAC87751, 9; BAF83312/BAF84898 FT and 11; AAH12418). {ECO:0000305}. FT CONFLICT 12 12 S -> A (in Ref. 3; BAA04650, 8; BAC87749/ FT BAC87751, 9; BAF83312/BAF84898 and 11; FT AAH12418). {ECO:0000305}. FT CONFLICT 19 21 HPS -> GPP (in Ref. 15; AA sequence). FT {ECO:0000305}. FT CONFLICT 19 19 H -> N (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 21 24 SSPP -> EAVV (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 27 28 DT -> AK (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 28 29 TV -> DT (in Ref. 15; AA sequence). FT {ECO:0000305}. FT CONFLICT 56 56 A -> G (in Ref. 2; AAA16036/AAA35711). FT {ECO:0000305}. FT CONFLICT 64 64 R -> G (in Ref. 18; CAA37147). FT {ECO:0000305}. FT CONFLICT 65 65 F -> S (in Ref. 6; AAP20868). FT {ECO:0000305}. FT CONFLICT 75 75 S -> A (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 78 78 K -> I (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 89 89 Q -> R (in Ref. 6; AAP20868). FT {ECO:0000305}. FT CONFLICT 98 98 S -> F (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 105 107 KEN -> PAD (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 115 115 D -> H (in Ref. 19; AAA83932). FT {ECO:0000305}. FT CONFLICT 186 186 R -> G (in Ref. 18; CAA37147). FT {ECO:0000305}. FT CONFLICT 247 247 S -> I (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 251 251 L -> K (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 253 253 S -> G (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 255 255 L -> P (in Ref. 9; BAF83312). FT {ECO:0000305}. FT CONFLICT 258 258 K -> Q (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 281 281 V -> A (in Ref. 19; AAA83932). FT {ECO:0000305}. FT CONFLICT 298 298 T -> I (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 302 302 K -> A (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 305 305 S -> M (in Ref. 14; AA sequence). FT {ECO:0000305}. FT CONFLICT 337 337 A -> R (in Ref. 19; AAA83932). FT {ECO:0000305}. FT CONFLICT 417 417 F -> I (in Ref. 19; AAA83932). FT {ECO:0000305}. FT CONFLICT 512 512 E -> K (in Ref. 19; AAA83932). FT {ECO:0000305}. FT CONFLICT 536 536 A -> G (in Ref. 2; AAA16036/AAA35711). FT {ECO:0000305}. FT CONFLICT 563 563 E -> D (in Ref. 19; AAA83932). FT {ECO:0000305}. FT STRAND 25 28 {ECO:0000244|PDB:2H7C}. FT STRAND 31 34 {ECO:0000244|PDB:2H7C}. FT STRAND 36 38 {ECO:0000244|PDB:2H7C}. FT STRAND 47 54 {ECO:0000244|PDB:2H7C}. FT HELIX 61 63 {ECO:0000244|PDB:2H7C}. FT STRAND 75 79 {ECO:0000244|PDB:2H7C}. FT STRAND 86 88 {ECO:0000244|PDB:2H7C}. FT HELIX 91 101 {ECO:0000244|PDB:2H7C}. FT STRAND 104 106 {ECO:0000244|PDB:2H7C}. FT STRAND 112 114 {ECO:0000244|PDB:2H7C}. FT STRAND 118 123 {ECO:0000244|PDB:2H7C}. FT TURN 127 130 {ECO:0000244|PDB:4AB1}. FT STRAND 133 139 {ECO:0000244|PDB:2H7C}. FT TURN 143 145 {ECO:0000244|PDB:2H7C}. FT HELIX 149 151 {ECO:0000244|PDB:2HRR}. FT HELIX 155 161 {ECO:0000244|PDB:2H7C}. FT STRAND 164 168 {ECO:0000244|PDB:2H7C}. FT HELIX 173 177 {ECO:0000244|PDB:2H7C}. FT HELIX 183 185 {ECO:0000244|PDB:2HRQ}. FT HELIX 189 204 {ECO:0000244|PDB:2H7C}. FT HELIX 205 208 {ECO:0000244|PDB:2H7C}. FT STRAND 210 220 {ECO:0000244|PDB:2H7C}. FT HELIX 222 232 {ECO:0000244|PDB:2H7C}. FT HELIX 234 236 {ECO:0000244|PDB:2H7C}. FT TURN 237 239 {ECO:0000244|PDB:1MX9}. FT STRAND 241 247 {ECO:0000244|PDB:2H7C}. FT HELIX 253 255 {ECO:0000244|PDB:2H7C}. FT HELIX 262 271 {ECO:0000244|PDB:2H7C}. FT HELIX 279 288 {ECO:0000244|PDB:2H7C}. FT HELIX 291 301 {ECO:0000244|PDB:2H7C}. FT TURN 302 304 {ECO:0000244|PDB:2H7C}. FT STRAND 308 310 {ECO:0000244|PDB:2HRR}. FT HELIX 312 314 {ECO:0000244|PDB:2H7C}. FT STRAND 325 327 {ECO:0000244|PDB:2H7C}. FT HELIX 332 335 {ECO:0000244|PDB:2H7C}. FT STRAND 339 341 {ECO:0000244|PDB:2H7C}. FT STRAND 346 351 {ECO:0000244|PDB:2H7C}. FT TURN 352 355 {ECO:0000244|PDB:2HRQ}. FT HELIX 358 361 {ECO:0000244|PDB:2H7C}. FT TURN 363 365 {ECO:0000244|PDB:1MX9}. FT STRAND 369 371 {ECO:0000244|PDB:1MX5}. FT HELIX 375 384 {ECO:0000244|PDB:2H7C}. FT HELIX 386 389 {ECO:0000244|PDB:2H7C}. FT HELIX 393 395 {ECO:0000244|PDB:2H7C}. FT HELIX 396 404 {ECO:0000244|PDB:2H7C}. FT HELIX 410 425 {ECO:0000244|PDB:2H7C}. FT HELIX 427 439 {ECO:0000244|PDB:2H7C}. FT STRAND 444 450 {ECO:0000244|PDB:2H7C}. FT STRAND 458 460 {ECO:0000244|PDB:1MX5}. FT TURN 468 471 {ECO:0000244|PDB:2H7C}. FT HELIX 472 475 {ECO:0000244|PDB:2H7C}. FT HELIX 478 480 {ECO:0000244|PDB:2H7C}. FT HELIX 487 506 {ECO:0000244|PDB:2H7C}. FT STRAND 521 523 {ECO:0000244|PDB:2DQZ}. FT STRAND 525 532 {ECO:0000244|PDB:2H7C}. FT STRAND 534 537 {ECO:0000244|PDB:2H7C}. FT HELIX 541 552 {ECO:0000244|PDB:2H7C}. 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 //