Liver carboxylesterase 1

Details

Name
Liver carboxylesterase 1
Synonyms
  • ACAT
  • Acyl-coenzyme A:cholesterol acyltransferase
  • Brain carboxylesterase hBr1
  • Carboxylesterase 1
  • CE-1
  • CES2
  • Cocaine carboxylesterase
  • Egasyn
  • hCE-1
  • HMSE
  • Methylumbelliferyl-acetate deacetylase 1
  • Monocyte/macrophage serine esterase
  • REH
  • Retinyl ester hydrolase
  • Serine esterase 1
  • SES1
  • TGH
  • Triacylglycerol hydrolase
Gene Name
CES1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0005305|Liver carboxylesterase 1
MWLRAFILATLSASAAWGHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPL
GPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLN
IYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWGFFST
GDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLF
HRAISESGVALTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLK
MKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIP
MQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDL
IADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPF
LKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLK
DKEVAFWTNLFAKKAVEKPPQTEHIEL
Number of residues
567
Molecular Weight
62520.62
Theoretical pI
6.58
GO Classification
Functions
carboxylic ester hydrolase activity / methylumbelliferyl-acetate deacetylase activity / sterol esterase activity / triglyceride lipase activity
Processes
epithelial cell differentiation / lipid catabolic process / metabolic process / response to toxic substance / small molecule metabolic process / xenobiotic metabolic process
Components
endoplasmic reticulum lumen / extracellular space
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum lumen
Gene sequence
>lcl|BSEQ0021334|Liver carboxylesterase 1 (CES1)
ATGTGGCTCCGTGCCTTTATCCTGGCCACTCTCTCTGCTTCCGCGGCTTGGGGGCATCCG
TCCTCGCCACCTGTGGTGGACACCGTGCATGGCAAAGTGCTGGGGAAGTTCGTCAGCTTA
GAAGGATTTGCACAGCCTGTGGCCATTTTCCTGGGAATCCCTTTTGCCAAGCCGCCTCTT
GGACCCCTGAGGTTTACTCCACCGCAGCCTGCAGAACCATGGAGCTTTGTGAAGAATGCC
ACCTCGTACCCTCCTATGTGCACCCAAGATCCCAAGGCGGGGCAGTTACTCTCAGAGCTA
TTTACAAACCGAAAGGAGAACATTCCTCTCAAGCTTTCTGAAGACTGTCTTTACCTCAAT
ATTTACACTCCTGCTGACTTGACCAAGAAAAACAGGCTGCCGGTGATGGTGTGGATCCAC
GGAGGGGGGCTGATGGTGGGTGCGGCATCAACCTATGATGGGCTGGCCCTTGCTGCCCAT
GAAAACGTGGTGGTGGTGACCATTCAATATCGCCTGGGCATCTGGGGATTCTTCAGCACA
GGGGATGAACACAGCCGGGGGAACTGGGGTCACCTGGACCAGGTGGCTGCCCTGCGCTGG
GTCCAGGACAACATTGCCAGCTTTGGAGGGAACCCAGGCTCTGTGACCATCTTTGGAGAG
TCAGCGGGAGGAGAAAGTGTCTCTGTTCTTGTTTTGTCTCCATTGGCCAAGAACCTCTTC
CACCGGGCCATTTCTGAGAGTGGCGTGGCCCTCACTTCTGTTCTGGTGAAGAAAGGTGAT
GTCAAGCCCTTGGCTGAGCAAATTGCTATCACTGCTGGGTGCAAAACCACCACCTCTGCT
GTCATGGTTCACTGCCTGCGACAGAAGACGGAAGAGGAGCTCTTGGAGACGACATTGAAA
ATGAAATTCTTATCTCTGGACTTACAGGGAGACCCCAGAGAGAGTCAACCCCTTCTGGGC
ACTGTGATTGATGGGATGCTGCTGCTGAAAACACCTGAAGAGCTTCAAGCTGAAAGGAAT
TTCCACACTGTCCCCTACATGGTCGGAATTAACAAGCAGGAGTTTGGCTGGTTGATTCCA
ATGCAGTTGATGAGCTATCCACTCTCCGAAGGGCAACTGGACCAGAAGACAGCCATGTCA
CTCCTGTGGAAGTCCTATCCCCTTGTTTGCATTGCTAAGGAACTGATTCCAGAAGCCACT
GAGAAATACTTAGGAGGAACAGACGACACTGTCAAAAAGAAAGACCTGTTCCTGGACTTG
ATAGCAGATGTGATGTTTGGTGTCCCATCTGTGATTGTGGCCCGGAACCACAGAGATGCT
GGAGCACCCACCTACATGTATGAGTTTCAGTACCGTCCAAGCTTCTCATCAGACATGAAA
CCCAAGACGGTGATAGGAGACCACGGGGATGAGCTCTTCTCCGTCTTTGGGGCCCCATTT
TTAAAAGAGGGTGCCTCAGAAGAGGAGATCAGACTTAGCAAGATGGTGATGAAATTCTGG
GCCAACTTTGCTCGCAATGGAAACCCCAATGGGGAAGGGCTGCCCCACTGGCCAGAGTAC
AACCAGAAGGAAGGGTATCTGCAGATTGGTGCCAACACCCAGGCGGCCCAGAAGCTGAAG
GACAAAGAAGTAGCTTTCTGGACCAACCTCTTTGCCAAGAAGGCAGTGGAGAAGCCACCC
CAGACAGAACACATAGAGCTGTGA
Chromosome Location
16
Locus
16q13-q22.1
External Identifiers
ResourceLink
UniProtKB IDP23141
UniProtKB Entry NameEST1_HUMAN
GenBank Gene IDM73499
GenAtlas IDCES1
HGNC IDHGNC:1863
General References
  1. Munger JS, Shi GP, Mark EA, Chin DT, Gerard C, Chapman HA: A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. J Biol Chem. 1991 Oct 5;266(28):18832-8. [PubMed:1918003]
  2. Kroetz DL, McBride OW, Gonzalez FJ: Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms. Biochemistry. 1993 Nov 2;32(43):11606-17. [PubMed:8218228]
  3. Shibata F, Takagi Y, Kitajima M, Kuroda T, Omura T: Molecular cloning and characterization of a human carboxylesterase gene. Genomics. 1993 Jul;17(1):76-82. [PubMed:8406473]
  4. Becker A, Bottcher A, Lackner KJ, Fehringer P, Notka F, Aslanidis C, Schmitz G: Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase. Arterioscler Thromb. 1994 Aug;14(8):1346-55. [PubMed:8049197]
  5. Islam MR, Waheed A, Shah GN, Tomatsu S, Sly WS: Human egasyn binds beta-glucuronidase but neither the esterase active site of egasyn nor the C terminus of beta-glucuronidase is involved in their interaction. Arch Biochem Biophys. 1999 Dec 1;372(1):53-61. [PubMed:10562416]
  6. Ghosh S: Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA. Physiol Genomics. 2000 Jan 24;2(1):1-8. [PubMed:11015575]
  7. Alam M, Ho S, Vance DE, Lehner R: Heterologous expression, purification, and characterization of human triacylglycerol hydrolase. Protein Expr Purif. 2002 Feb;24(1):33-42. [PubMed:11812220]
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  9. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [PubMed:15616553]
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  11. Mori M, Hosokawa M, Ogasawara Y, Tsukada E, Chiba K: cDNA cloning, characterization and stable expression of novel human brain carboxylesterase. FEBS Lett. 1999 Sep 10;458(1):17-22. [PubMed:10518925]
  12. Brzezinski MR, Abraham TL, Stone CL, Dean RA, Bosron WF: Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. Biochem Pharmacol. 1994 Nov 1;48(9):1747-55. [PubMed:7980644]
  13. Schindler R, Mentlein R, Feldheim W: Purification and characterization of retinyl ester hydrolase as a member of the non-specific carboxylesterase supergene family. Eur J Biochem. 1998 Feb 1;251(3):863-73. [PubMed:9490062]
  14. Satoh T, Hosokawa M: Molecular aspects of carboxylesterase isoforms in comparison with other esterases. Toxicol Lett. 1995 Dec;82-83:439-45. [PubMed:8597091]
  15. Alam M, Vance DE, Lehner R: Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site. Biochemistry. 2002 May 28;41(21):6679-87. [PubMed:12022871]
  16. Long RM, Calabrese MR, Martin BM, Pohl LR: Cloning and sequencing of a human liver carboxylesterase isoenzyme. Life Sci. 1991;48(11):PL43-9. [PubMed:1997784]
  17. Zschunke F, Salmassi A, Kreipe H, Buck F, Parwaresch MR, Radzun HJ: cDNA cloning and characterization of human monocyte/macrophage serine esterase-1. Blood. 1991 Jul 15;78(2):506-12. [PubMed:2070086]
  18. Riddles PW, Richards LJ, Bowles MR, Pond SM: Cloning and analysis of a cDNA encoding a human liver carboxylesterase. Gene. 1991 Dec 15;108(2):289-92. [PubMed:1748313]
  19. Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF: Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. J Biol Chem. 1997 Jun 6;272(23):14769-75. [PubMed:9169443]
  20. Zhu HJ, Patrick KS, Yuan HJ, Wang JS, Donovan JL, DeVane CL, Malcolm R, Johnson JA, Youngblood GL, Sweet DH, Langaee TY, Markowitz JS: Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. Am J Hum Genet. 2008 Jun;82(6):1241-8. doi: 10.1016/j.ajhg.2008.04.015. Epub 2008 May 15. [PubMed:18485328]
  21. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
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  24. Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR: Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003 May;10(5):349-56. [PubMed:12679808]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04795ThenoyltrifluoroacetoneexperimentalunknownDetails
DB02161Hydroxy-Phenyl-Acetic Acid 8-Methyl-8-Aza-Bicyclo[3.2.1]Oct-3-Yl EsterexperimentalunknownDetails
DB03721N-acetyl-alpha-neuraminic acidexperimentalunknownDetails
DB04509N-MethylnaloxoniumexperimentalunknownDetails
DB06442AvasimibeinvestigationalunknownDetails
DB02161Hydroxy-Phenyl-Acetic Acid 8-Methyl-8-Aza-Bicyclo[3.2.1]Oct-3-Yl EsterexperimentalunknownDetails
DB03721N-acetyl-alpha-neuraminic acidexperimentalunknownDetails
DB04509N-MethylnaloxoniumexperimentalunknownDetails
DB01101Capecitabineapproved, investigationalunknownsubstrateDetails
DB00198OseltamivirapprovedyesotherDetails
DB00762Irinotecanapproved, investigationalunknownsubstrateDetails
DB00675TamoxifenapprovedunknowninhibitorDetails
DB00328Indometacinapproved, investigationalunknownsubstrateDetails
DB06693MevastatinexperimentalunknowninhibitorDetails
DB030564-Piperidino-PiperidineexperimentalunknownDetails
DB02659Cholic AcidapprovedunknownDetails
DB07821(1R)-1,2,2-trimethylpropyl (R)-methylphosphinateexperimentalunknownDetails
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-NAPHTHALENOLexperimentalunknownDetails
DB01410Ciclesonideapproved, investigationalunknownsubstrateDetails
DB00583Levocarnitineapproved, investigationalunknownDetails
DB04838CyclandelateapprovedunknownDetails
DB01599Probucolapproved, investigationalunknownDetails
DB01086Benzocaineapproved, investigationalunknowninhibitorDetails
DB00519TrandolaprilapprovedunknownsubstrateDetails
DB06201RufinamideapprovedunknownsubstrateDetails
DB06695Dabigatran etexilateapprovedunknownsubstrateDetails
DB00758ClopidogrelapprovedunknownsubstrateDetails
DB00688Mycophenolate mofetilapproved, investigationalunknownsubstrateDetails
DB11362SelexipagapprovednosubstrateDetails
DB09269Phenylacetic acidapprovedunknownsubstrateDetails
DB00454MeperidineapprovedunknownDetails
DB00647Dextropropoxypheneapproved, illicit, investigational, withdrawnunknownDetails
DB01183Naloxoneapproved, vet_approvedunknownDetails
DB00382Tacrineapproved, investigational, withdrawnunknownDetails
DB00907Cocaineapproved, illicitunknownDetails
DB01452Diamorphineapproved, illicit, investigationalunknownDetails
DB09342PropoxycaineapprovedunknownsubstrateDetails
DB11181HomatropineapprovedunknownsubstrateDetails
DB09299Tenofovir alafenamideapprovednosubstrateDetails