EST1D_RAT
ID EST1D_RAT Reviewed; 565 AA.
AC P16303; Q64574; Q6P785; Q91YG2; Q9QUX7; Q9R135;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Carboxylesterase 1D {ECO:0000305};
DE AltName: Full=Carboxyesterase ES-10 {ECO:0000303|PubMed:12230550};
DE AltName: Full=Carboxylesterase 3;
DE EC=3.1.1.1;
DE EC=3.1.1.67;
DE AltName: Full=ES-HVEL;
DE AltName: Full=Fatty acid ethyl ester synthase;
DE Short=FAEE synthase;
DE AltName: Full=Liver carboxylesterase 10;
DE AltName: Full=pI 6.1 esterase;
DE Flags: Precursor;
GN Name=Ces1d {ECO:0000312|RGD:70896}; Synonyms=Ces3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley, and Wistar; TISSUE=Liver;
RX PubMed=2386485; DOI=10.1042/bj2690451;
RA Robbi M., Beaufay H., Octave J.-N.;
RT "Nucleotide sequence of cDNA coding for rat liver pI 6.1 esterase (ES-10),
RT a carboxylesterase located in the lumen of the endoplasmic reticulum.";
RL Biochem. J. 269:451-458(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1606962; DOI=10.1111/j.1432-1033.1992.tb16987.x;
RA Medda S., Proia R.L.;
RT "The carboxylesterase family exhibits C-terminal sequence diversity
RT reflecting the presence or absence of endoplasmic-reticulum-retention
RT sequences.";
RL Eur. J. Biochem. 206:801-806(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8541339; DOI=10.1016/0005-2760(95)00184-0;
RA Ghosh S., Mallonee D.H., Hylemon P.B., Grogan W.M.;
RT "Molecular cloning and expression of rat hepatic neutral cholesteryl ester
RT hydrolase.";
RL Biochim. Biophys. Acta 1259:305-312(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF GLN-186; MET-423; SER-491;
RP LYS-492 AND ASN-506.
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=11429416; DOI=10.1074/jbc.m105644200;
RA Wallace T.J., Kodsi E.M., Langston T.B., Gergis M.R., Grogan W.M.;
RT "Mutation of residues 423 (Met/Ile), 444 (Thr/Met), and 506 (Asn/Ser)
RT confer cholesteryl esterase activity on rat lung carboxylesterase. Ser-506
RT is required for activation by cAMP-dependent protein kinase.";
RL J. Biol. Chem. 276:33165-33174(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Ryu J.W., Lee W., Jung C.Y.;
RT "Rattus norvegicus adipocyte carboxylesterase mRNA.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [7]
RP PROTEIN SEQUENCE OF 19-45, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Adipose tissue;
RX PubMed=1429692; DOI=10.1016/s0021-9258(18)35865-4;
RA Tsujita T., Okuda H.;
RT "Fatty acid ethyl ester synthase in rat adipose tissue and its relationship
RT to carboxylesterase.";
RL J. Biol. Chem. 267:23489-23494(1992).
RN [8]
RP PROTEIN SEQUENCE OF 19-38, NUCLEOTIDE SEQUENCE [MRNA] OF 113-121; 138-149;
RP 216-224; 350-356 AND 464-469, 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 [9]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12230550; DOI=10.1046/j.1432-1033.2002.03121.x;
RA Sanghani S.P., Davis W.I., Dumaual N.G., Mahrenholz A., Bosron W.F.;
RT "Identification of microsomal rat liver carboxylesterases and their
RT activity with retinyl palmitate.";
RL Eur. J. Biochem. 269:4387-4398(2002).
CC -!- FUNCTION: Major lipase in white adipose tissue (By similarity).
CC Involved in the metabolism of xenobiotics and of natural substrates.
CC Hydrolyzes triacylglycerols and monoacylglycerols, with a preference
CC for monoacylglycerols. The susceptibility of the substrate increases
CC with decreasing acyl chain length of the fatty acid moiety. Catalyzes
CC the synthesis of fatty acid ethyl esters (PubMed:1429692). Hydrolyzes
CC retinyl esters (PubMed:12230550). {ECO:0000250|UniProtKB:Q8VCT4,
CC ECO:0000269|PubMed:12230550, ECO:0000269|PubMed:1429692}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinyl hexadecanoate + H2O = all-trans-retinol +
CC H(+) + hexadecanoate; Xref=Rhea:RHEA:13933, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17616; Evidence={ECO:0000269|PubMed:12230550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC Evidence={ECO:0000305|PubMed:12230550};
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:1429692};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acyl ethyl ester + H2O = a long-chain fatty
CC acid + ethanol + H(+); Xref=Rhea:RHEA:16641, ChEBI:CHEBI:13209,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16236,
CC ChEBI:CHEBI:57560; EC=3.1.1.67;
CC Evidence={ECO:0000269|PubMed:1429692};
CC -!- ACTIVITY REGULATION: FAEE-synthesizing and PNPB-hydrolyzing activities
CC are both inhibited by DFP. {ECO:0000269|PubMed:1429692}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.71 M for oleic acid {ECO:0000269|PubMed:1429692};
CC KM=1.16 uM for retinyl palmitate {ECO:0000269|PubMed:12230550};
CC Vmax=1482 nmol/h/mg enzyme toward oleic acid
CC {ECO:0000269|PubMed:1429692};
CC Note=kcat is 0.22 min(-1) with retinyl palmitate as substrate.
CC {ECO:0000269|PubMed:12230550};
CC pH dependence:
CC Optimum pH for FAEE synthesis is 7.0. Optimum pH for PNPB-hydrolyzing
CC activity is 6-8. {ECO:0000269|PubMed:1429692};
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:8597091}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:Q8VCT4}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8VCT4}. Lipid droplet
CC {ECO:0000250|UniProtKB:Q8VCT4}. Microsome
CC {ECO:0000269|PubMed:12230550}.
CC -!- TISSUE SPECIFICITY: Detected in liver, lung and testis, but not in
CC kidney (at protein level). {ECO:0000269|PubMed:12230550,
CC ECO:0000269|PubMed:1429692}.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC {ECO:0000305}.
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DR EMBL; X51974; CAA36236.1; -; mRNA.
DR EMBL; X65296; CAA46391.1; -; mRNA.
DR EMBL; L46791; AAA88507.1; -; mRNA.
DR EMBL; L81144; AAL00849.1; -; mRNA.
DR EMBL; AF171640; AAD49369.1; -; mRNA.
DR EMBL; BC061789; AAH61789.1; -; mRNA.
DR PIR; A45140; A45140.
DR PIR; S10367; S10367.
DR RefSeq; NP_579829.3; NM_133295.3.
DR AlphaFoldDB; P16303; -.
DR SMR; P16303; -.
DR STRING; 10116.ENSRNOP00000021812; -.
DR SwissLipids; SLP:000001457; -.
DR ESTHER; ratno-Ces1d; Carb_B_Chordata.
DR CarbonylDB; P16303; -.
DR GlyGen; P16303; 2 sites.
DR iPTMnet; P16303; -.
DR PhosphoSitePlus; P16303; -.
DR PaxDb; P16303; -.
DR PRIDE; P16303; -.
DR GeneID; 113902; -.
DR KEGG; rno:113902; -.
DR CTD; 104158; -.
DR RGD; 70896; Ces1d.
DR eggNOG; KOG1516; Eukaryota.
DR InParanoid; P16303; -.
DR OrthoDB; 754103at2759; -.
DR PhylomeDB; P16303; -.
DR BRENDA; 3.1.1.1; 5301.
DR Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR Reactome; R-RNO-9749641; Aspirin ADME.
DR SABIO-RK; P16303; -.
DR PRO; PR:P16303; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0047376; F:all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity; IEA:RHEA.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0030339; F:fatty-acyl-ethyl-ester synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0080030; F:methyl indole-3-acetate esterase activity; IEA:UniProtKB-EC.
DR GO; GO:0004771; F:sterol esterase activity; ISS:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; ISS:UniProtKB.
DR GO; GO:0046464; P:acylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0071397; P:cellular response to cholesterol; ISO:RGD.
DR GO; GO:0070417; P:cellular response to cold; ISO:RGD.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISO:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
DR GO; GO:0060086; P:circadian temperature homeostasis; ISO:RGD.
DR GO; GO:0106106; P:cold-induced thermogenesis; ISO:RGD.
DR GO; GO:0061725; P:cytosolic lipolysis; ISO:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0016042; P:lipid catabolic process; ISO:RGD.
DR GO; GO:0051791; P:medium-chain fatty acid metabolic process; ISO:RGD.
DR GO; GO:0010887; P:negative regulation of cholesterol storage; ISO:RGD.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:RGD.
DR GO; GO:0090205; P:positive regulation of cholesterol metabolic process; ISO:RGD.
DR GO; GO:0061411; P:positive regulation of transcription from RNA polymerase II promoter in response to cold; ISO:RGD.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISO:RGD.
DR GO; GO:0120188; P:regulation of bile acid secretion; ISO:RGD.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:UniProtKB.
DR GO; GO:0043691; P:reverse cholesterol transport; ISO:RGD.
DR GO; GO:0019626; P:short-chain fatty acid catabolic process; ISO:RGD.
DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; ISO:RGD.
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 Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipid degradation;
KW Lipid droplet; Lipid metabolism; Microsome; Reference proteome;
KW Serine esterase; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:1429692,
FT ECO:0000269|PubMed:8597091"
FT CHAIN 19..565
FT /note="Carboxylesterase 1D"
FT /id="PRO_0000008584"
FT MOTIF 562..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|UniProtKB:P23141"
FT ACT_SITE 466
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT MOD_RES 382
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCT4"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 489
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..116
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT DISULFID 273..284
FT /evidence="ECO:0000250|UniProtKB:P23141"
FT MUTAGEN 186
FT /note="Q->R: No effect on the hydrolysis of PNPC or PNPA,
FT no activity on cholesteryl oleate. No effect on the
FT hydrolysis of PNPC or PNPA, no activity on cholesteryl
FT oleate; when associated with E-492; or with T-491 and E-
FT 492. Increases activity on PNPC compared to activity on
FT PNPA; when associated with I-423; T-491 and E-492."
FT /evidence="ECO:0000269|PubMed:11429416"
FT MUTAGEN 423
FT /note="M->I: Increases specific activity against PNPC by 8-
FT fold, does not increase activity against PNPA, no activity
FT on cholesteryl oleate. Increases activity on PNPC compared
FT to activity on PNPA; when associated with R-186; T-491 and
FT E-492. Increases specific activity against PNPC by 7.5-fold
FT and against PNPA by 3.6-fold, and increases cholesteryl
FT esterase activity by 2.7 fold; when associated with S-506."
FT /evidence="ECO:0000269|PubMed:11429416"
FT MUTAGEN 491
FT /note="S->T: No effect on the hydrolysis of PNPC or PNPA,
FT no activity on cholesteryl oleate; when associated with R-
FT 186 and E-492. Increases activity on PNPC compared to
FT activity on PNPA; when associated with R-186; I-423 and E-
FT 492."
FT /evidence="ECO:0000269|PubMed:11429416"
FT MUTAGEN 492
FT /note="K->E: No effect on the hydrolysis of PNPC or PNPA,
FT no activity on cholesteryl oleate; when associated with R-
FT 186; or with R-186 and T-491. Increases activity on PNPC
FT compared to activity on PNPA; when associated with R-186;
FT I-423 and T-491."
FT /evidence="ECO:0000269|PubMed:11429416"
FT MUTAGEN 506
FT /note="N->S: Increases specific activity against PNPC by 6-
FT fold and against PNPA by 8.7-fold, no activity on
FT cholesteryl oleate. Increases specific activity against
FT PNPC by 7.5-fold and against PNPA by 3.6-fold, and
FT increases cholesteryl esterase activity by 2.7 fold; when
FT associated with I-423."
FT /evidence="ECO:0000269|PubMed:11429416"
FT CONFLICT 186
FT /note="Q -> R (in Ref. 1; CAA36236, 3; AAA88507 and 5;
FT AAD49369)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="N -> K (in Ref. 1; CAA36236)"
FT /evidence="ECO:0000305"
FT CONFLICT 420
FT /note="A -> E (in Ref. 3; AAA88507)"
FT /evidence="ECO:0000305"
FT CONFLICT 423
FT /note="M -> I (in Ref. 1; CAA36236, 3; AAA88507 and 5;
FT AAD49369)"
FT /evidence="ECO:0000305"
FT CONFLICT 444
FT /note="M -> T (in Ref. 4; AAL00849)"
FT /evidence="ECO:0000305"
FT CONFLICT 491..492
FT /note="SK -> TQ (in Ref. 3; AAA88507)"
FT /evidence="ECO:0000305"
FT CONFLICT 506
FT /note="N -> S (in Ref. 1; CAA36236, 3; AAA88507 and 5;
FT AAD49369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 565 AA; 62147 MW; F3277B7FAD2141A4 CRC64;
MRLYPLVWLF LAACTAWGYP SSPPVVNTVK GKVLGKYVNL EGFAQPVAVF LGIPFAKPPL
GSLRFAPPQP AEPWNFVKNT TSYPPMCSQD AVGGQVLSEL FTNRKENIPL QFSEDCLYLN
VYTPADLTKN SRLPVMVWIH GGGLVVGGAS TYDGQVLSAH ENVVVVTIQY RLGIWGFFST
GDEHSQGNWG HLDQVAALHW VQDNIANFGG NPGSVTIFGE SAGGFSVSAL VLSPLAKNLF
HRAISESGVV LTSALITTDS KPIANLIATL SGCKTTTSAV MVHCLRQKTE DELLETSLKL
NLFKLDLLGN PKESYPFLPT VIDGVVLPKT PEEILAEKSF NTVPYIVGIN KQEFGWIIPT
LMGYPLSEGK LDQKTAKSLL WKSYPTLKIS EKMIPVVAEK YFGGTDDPAK RKDLFQDLVA
DVMFGVPSVM VSRSHRDAGA PTFMYEFEYR PSFVSAMRPK TVIGDHGDEL FSVFGSPFLK
DGASEEETNL SKMVMKYWAN FARNGNPNGG GLPHWPEYDQ KEGYLKIGAS TQAAQRLKDK
EVAFWSELRA KEAAEEPSHW KHVEL
