ID EST1_HUMAN STANDARD; PRT; 567 AA. AC P23141; Q00015; Q13657; Q14062; Q16737; Q16788; Q86UK2; Q96EE8; AC Q9UK77; Q9ULY2; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 2. DT 16-MAY-2006, entry version 66. DE Liver carboxylesterase 1 precursor (EC 3.1.1.1) (Acyl coenzyme DE A:cholesterol acyltransferase) (ACAT) (Monocyte/macrophage serine DE esterase) (HMSE) (Serine esterase 1) (Brain carboxylesterase hBr1) DE (Triacylglycerol hydrolase) (TGH) (Egasyn). 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. RX MEDLINE=92011649; 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. RC TISSUE=Liver; RX MEDLINE=94032283; PubMed=8218228; 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. RC TISSUE=Peripheral blood, and Placenta; RX MEDLINE=94010913; PubMed=8406473; 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. RC TISSUE=Liver; RX MEDLINE=94325258; 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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP 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. RC TISSUE=Macrophage; RX MEDLINE=20473717; 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, 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 [LARGE SCALE MRNA]. RC TISSUE=Lung; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [9] RP NUCLEOTIDE SEQUENCE OF 1-429. RC TISSUE=Brain; RX MEDLINE=99448370; 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 [10] RP NUCLEOTIDE SEQUENCE OF 61-567. RC TISSUE=Liver; RX MEDLINE=91148424; 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 [11] RP NUCLEOTIDE SEQUENCE OF 64-567, AND PARTIAL PROTEIN SEQUENCE. RX MEDLINE=91300111; 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 [12] RP NUCLEOTIDE SEQUENCE OF 114-567. RC TISSUE=Liver; RX MEDLINE=92084150; 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 [13] 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 [14] 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 [15] 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. CC -!- CATALYTIC ACTIVITY: A carboxylic ester + H(2)O = an alcohol + a CC carboxylate. CC -!- SUBUNIT: Homotrimer and homohexamer. Binds to beta-glucuronidase. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum; endoplasmic reticulum CC lumen. CC -!- TISSUE SPECIFICITY: Expressed predominantly in liver with lower CC levels in heart and lung. CC -!- PTM: Contains sialic acid. CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs 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; AB025026; BAA84995.1; -; mRNA. DR EMBL; S73751; AAC60631.2; -; mRNA. DR EMBL; AY268104; AAP20868.1; -; mRNA. DR EMBL; AF177775; AAD53175.1; -; mRNA. DR EMBL; BC012418; AAH12418.1; -; mRNA. DR EMBL; M55509; AAA35650.1; -; mRNA. DR EMBL; X52973; CAA37147.1; -; mRNA. DR EMBL; M65261; AAA83932.1; -; mRNA. DR PIR; A41010; A41010. DR UniGene; Hs.558865; -. DR PDB; 1MX1; X-ray; A/B/C/D/E/F=19-567. DR PDB; 1MX5; X-ray; A/B/C/D/E/F=19-567. DR PDB; 1MX9; X-ray; A/B/C/D/E/F/G/H/I/J/K/L=19-567. DR PDB; 1YA4; X-ray; A/B/C=21-553. DR PDB; 1YA8; X-ray; A/B/C=21-553. DR PDB; 1YAH; X-ray; A/B/C=21-553. DR PDB; 1YAJ; X-ray; A/B/C/D/E/F/G/H/I/J/K/L=21-553. DR MEROPS; S09.982; -. DR Ensembl; ENSG00000196959; Homo sapiens. DR HGNC; HGNC:1863; CES1. DR H-InvDB; HIX0013044; -. DR MIM; 114835; gene+phenotype. DR GO; GO:0004759; F:serine esterase activity; TAS. DR GO; GO:0008152; P:metabolism; TAS. DR GO; GO:0009636; P:response to toxin; TAS. DR InterPro; IPR002018; CarbesteraseB. DR InterPro; IPR000379; Ser_estrs. DR PANTHER; PTHR11559; CarbesteraseB; 1. DR Pfam; PF00135; COesterase; 1. DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1. DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1. KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum; KW Glycoprotein; Hydrolase; Polymorphism; Serine esterase; Signal. FT SIGNAL 1 18 FT CHAIN 19 567 Liver carboxylesterase 1. FT /FTId=PRO_0000008569. FT ACT_SITE 221 221 Acyl-ester intermediate. FT ACT_SITE 354 354 Charge relay system. FT ACT_SITE 468 468 Charge relay system. FT CARBOHYD 79 79 N-linked (GlcNAc...). FT DISULFID 87 116 FT DISULFID 274 285 FT VARIANT 18 18 G -> GA. FT /FTId=VAR_002357. FT VARIANT 75 75 S -> N (in dbSNP:2307240). FT /FTId=VAR_014314. FT VARIANT 199 199 R -> H (in dbSNP:2307243). FT /FTId=VAR_014594. FT VARIANT 203 203 D -> E (in dbSNP:2307227). FT /FTId=VAR_014595. FT VARIANT 362 362 Missing. FT /FTId=VAR_002358. FT MUTAGEN 79 79 N->A: Abolishes glycosylation. FT MUTAGEN 221 221 S->A: Loss of activity. FT MUTAGEN 354 354 E->A: Loss of activity. FT MUTAGEN 468 468 H->A: Loss of activity. FT MUTAGEN 564 567 Missing: Does not result in secretion. FT CONFLICT 2 2 W -> L (in Ref. 5). FT CONFLICT 4 7 RAFI -> PALV (in Ref. 3 and 8). FT CONFLICT 12 12 S -> A (in Ref. 3 and 8). FT CONFLICT 17 17 W -> WA (in Ref. 2; AAA16036). FT CONFLICT 56 56 A -> G (in Ref. 2). FT CONFLICT 64 64 R -> G (in Ref. 11). FT CONFLICT 65 65 F -> S (in Ref. 6). FT CONFLICT 89 89 Q -> R (in Ref. 6). FT CONFLICT 115 115 D -> H (in Ref. 12). FT CONFLICT 186 186 R -> G (in Ref. 11). FT CONFLICT 281 281 V -> A (in Ref. 12). FT CONFLICT 301 317 MKFLSLDLQGDPRESQP -> IGNSYLWTYRETQREST FT (in Ref. 12). FT CONFLICT 337 337 A -> R (in Ref. 12). FT CONFLICT 362 362 Missing (in Ref. 8). FT CONFLICT 383 390 WKSYPLVC -> GSPIPLFA (in Ref. 12). FT CONFLICT 417 417 F -> I (in Ref. 12). FT CONFLICT 512 512 E -> K (in Ref. 12). FT CONFLICT 536 536 A -> G (in Ref. 2). FT CONFLICT 563 563 E -> D (in Ref. 12). FT STRAND 25 28 FT TURN 29 30 FT STRAND 31 34 FT STRAND 36 38 FT TURN 41 42 FT STRAND 44 45 FT STRAND 47 54 FT STRAND 56 56 FT HELIX 61 63 FT TURN 64 65 FT STRAND 66 66 FT STRAND 77 79 FT STRAND 86 88 FT HELIX 91 97 FT STRAND 101 101 FT STRAND 104 106 FT STRAND 112 113 FT STRAND 118 123 FT STRAND 125 125 FT TURN 127 128 FT STRAND 129 129 FT STRAND 133 139 FT STRAND 142 142 FT TURN 143 145 FT STRAND 146 146 FT HELIX 155 161 FT TURN 162 162 FT STRAND 164 168 FT HELIX 173 177 FT STRAND 180 182 FT TURN 183 184 FT STRAND 185 186 FT HELIX 189 204 FT TURN 205 206 FT STRAND 210 219 FT TURN 223 225 FT HELIX 230 232 FT TURN 235 238 FT STRAND 239 239 FT STRAND 241 246 FT TURN 250 251 FT STRAND 256 257 FT STRAND 259 259 FT HELIX 262 271 FT TURN 272 273 FT STRAND 277 277 FT HELIX 281 288 FT STRAND 289 289 FT HELIX 291 301 FT TURN 302 302 FT STRAND 309 310 FT HELIX 312 314 FT STRAND 321 322 FT STRAND 325 327 FT STRAND 329 330 FT HELIX 332 337 FT TURN 338 339 FT STRAND 341 341 FT STRAND 346 351 FT TURN 352 352 FT STRAND 353 353 FT TURN 354 355 FT STRAND 356 357 FT HELIX 358 363 FT TURN 364 364 FT HELIX 375 379 FT TURN 382 384 FT TURN 387 389 FT TURN 393 395 FT HELIX 396 404 FT TURN 405 406 FT HELIX 410 425 FT TURN 426 429 FT HELIX 432 438 FT TURN 439 441 FT STRAND 444 450 FT STRAND 460 460 FT TURN 462 463 FT STRAND 466 467 FT TURN 468 469 FT HELIX 470 473 FT HELIX 478 480 FT TURN 481 481 FT STRAND 482 483 FT HELIX 488 492 FT HELIX 495 506 FT STRAND 507 508 FT TURN 512 513 FT STRAND 514 514 FT STRAND 521 521 FT TURN 522 523 FT STRAND 525 532 FT STRAND 534 537 FT TURN 539 540 FT HELIX 541 550 FT TURN 551 552 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 //