EST1_RABIT
ID EST1_RABIT Reviewed; 565 AA.
AC P12337; O77540;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 3.
DT 25-MAY-2022, entry version 133.
DE RecName: Full=Liver carboxylesterase 1;
DE EC=3.1.1.1;
DE AltName: Full=Acyl-coenzyme A:cholesterol acyltransferase;
DE Flags: Precursor;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-52, AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=9635592;
RA Potter P.M., Pawlik C.A., Morton C.L., Naeve C.W., Danks M.K.;
RT "Isolation and partial characterization of a cDNA encoding a rabbit liver
RT carboxylesterase that activates the prodrug irinotecan (CPT-11).";
RL Cancer Res. 58:2646-2651(1998).
RN [2]
RP PROTEIN SEQUENCE OF 19-557, AND ACTIVE SITES SER-221 AND HIS-467.
RX PubMed=3343253; DOI=10.1016/s0021-9258(18)69097-0;
RA Korza G., Ozols J.;
RT "Complete covalent structure of 60-kDa esterase isolated from 2,3,7,8-
RT tetrachlorodibenzo-p-dioxin-induced rabbit liver microsomes.";
RL J. Biol. Chem. 263:3486-3495(1988).
RN [3]
RP PROTEIN SEQUENCE OF 19-88 AND 558-565.
RX PubMed=3667634; DOI=10.1016/s0021-9258(18)48177-x;
RA Ozols J.;
RT "Isolation and characterization of a 60-kilodalton glycoprotein esterase
RT from liver microsomal membranes.";
RL J. Biol. Chem. 262:15316-15321(1987).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-565 IN COMPLEX WITH PRODUCT.
RX PubMed=11967565; DOI=10.1038/nsb790;
RA Bencharit S., Morton C.L., Howard-Williams E.L., Danks M.K., Potter P.M.,
RA Redinbo M.R.;
RT "Structural insights into CPT-11 activation by mammalian
RT carboxylesterases.";
RL Nat. Struct. Biol. 9:337-342(2002).
CC -!- FUNCTION: Involved in the detoxification of xenobiotics and in the
CC activation of ester and amide prodrugs. {ECO:0000269|PubMed:9635592}.
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 -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11967565}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Note=Microsomal
CC membrane, lumen of endoplasmic reticulum.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
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DR EMBL; AF036930; AAC39258.1; -; mRNA.
DR PIR; A29923; A29923.
DR RefSeq; NP_001076234.1; NM_001082765.2.
DR PDB; 1K4Y; X-ray; 2.50 A; A=23-556.
DR PDBsum; 1K4Y; -.
DR AlphaFoldDB; P12337; -.
DR SMR; P12337; -.
DR STRING; 9986.ENSOCUP00000005826; -.
DR BindingDB; P12337; -.
DR ChEMBL; CHEMBL2623; -.
DR ESTHER; rabit-1cxes; Carb_B_Chordata.
DR iPTMnet; P12337; -.
DR PRIDE; P12337; -.
DR GeneID; 100009551; -.
DR KEGG; ocu:100009551; -.
DR eggNOG; KOG1516; Eukaryota.
DR OrthoDB; 754103at2759; -.
DR BRENDA; 3.1.1.1; 1749.
DR SABIO-RK; P12337; -.
DR EvolutionaryTrace; P12337; -.
DR PRO; PR:P12337; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0080030; F:methyl indole-3-acetate esterase activity; IEA:UniProtKB-EC.
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; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Reference proteome;
KW Serine esterase; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:3343253,
FT ECO:0000269|PubMed:3667634, ECO:0000269|PubMed:9635592"
FT CHAIN 19..565
FT /note="Liver carboxylesterase 1"
FT /id="PRO_0000008578"
FT MOTIF 565
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255"
FT ACT_SITE 221
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10039"
FT ACT_SITE 353
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 467
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3343253"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:3343253"
FT DISULFID 87..116
FT /evidence="ECO:0000269|PubMed:11967565,
FT ECO:0007744|PDB:1K4Y"
FT DISULFID 273..284
FT /evidence="ECO:0000269|PubMed:11967565,
FT ECO:0007744|PDB:1K4Y"
FT CONFLICT 30
FT /note="H -> K (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="Q -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 175..198
FT /note="WGFFSTGDEHSRGNWGHLDQVAAL -> GGFGFNIDELFLVAVN (in
FT Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 335..336
FT /note="LA -> YE (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 47..56
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 91..101
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:1K4Y"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 155..161
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 173..177
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 189..204
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 205..208
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 210..220
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 222..232
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:1K4Y"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 241..247
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 261..271
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 278..287
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 290..300
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 331..337
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 345..351
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 376..383
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:1K4Y"
FT TURN 392..394
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 395..402
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 416..424
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 426..437
FT /evidence="ECO:0007829|PDB:1K4Y"
FT TURN 438..440
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 443..448
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 469..474
FT /evidence="ECO:0007829|PDB:1K4Y"
FT TURN 475..479
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 486..505
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 525..531
FT /evidence="ECO:0007829|PDB:1K4Y"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:1K4Y"
FT HELIX 540..552
FT /evidence="ECO:0007829|PDB:1K4Y"
SQ SEQUENCE 565 AA; 62292 MW; 0ACD61400CC81D2F CRC64;
MWLCALALAS LAACTAWGHP SAPPVVDTVH GKVLGKFVSL EGFAQPVAVF LGVPFAKPPL
GSLRFAPPQP AESWSHVKNT TSYPPMCSQD AVSGHMLSEL FTNRKENIPL KFSEDCLYLN
IYTPADLTKR GRLPVMVWIH GGGLMVGGAS TYDGLALSAH ENVVVVTIQY RLGIWGFFST
GDEHSRGNWG HLDQVAALRW VQDNIANFGG DPGSVTIFGE SAGGQSVSIL LLSPLTKNLF
HRAISESGVA LLSSLFRKNT KSLAEKIAIE AGCKTTTSAV MVHCLRQKTE EELMEVTLKM
KFMALDLVGD PKENTAFLTT VIDGVLLPKA PAEILAEKKY NMLPYMVGIN QQEFGWIIPM
QMLGYPLSEG KLDQKTATEL LWKSYPIVNV SKELTPVATE KYLGGTDDPV KKKDLFLDML
ADLLFGVPSV NVARHHRDAG APTYMYEYRY RPSFSSDMRP KTVIGDHGDE IFSVLGAPFL
KEGATEEEIK LSKMVMKYWA NFARNGNPNG EGLPQWPAYD YKEGYLQIGA TTQAAQKLKD
KEVAFWTELW AKEAARPRET EHIEL
