LOCUS EST1D_RAT 565 aa linear ROD 27-NOV-2024
DEFINITION RecName: Full=Carboxylesterase 1D; AltName: Full=Carboxyesterase
ES-10; AltName: Full=Carboxylesterase 3; AltName: Full=ES-HVEL;
AltName: Full=Fatty acid ethyl ester synthase; Short=FAEE synthase;
AltName: Full=Liver carboxylesterase 10; AltName: Full=pI 6.1
esterase; Flags: Precursor.
ACCESSION P16303
VERSION P16303.2
DBSOURCE UniProtKB: locus EST1D_RAT, accession P16303;
class: standard.
extra accessions:Q64574,Q6P785,Q91YG2,Q9QUX7,Q9R135
created: Aug 1, 1990.
sequence updated: Oct 25, 2004.
annotation updated: Nov 27, 2024.
xrefs: X51974.1, CAA36236.1, X65296.1, CAA46391.1, L46791.1,
AAA88507.1, L81144.1, AAL00849.1, AF171640.1, AAD49369.1,
BC061789.1, AAH61789.1, A45140, S10367, NP_579829.3
xrefs (non-sequence databases): AlphaFoldDB:P16303, SMR:P16303,
STRING:10116.ENSRNOP00000021812, SwissLipids:SLP:000001457,
ESTHER:ratno-Ces1d, CarbonylDB:P16303, GlyCosmos:P16303,
GlyGen:P16303, iPTMnet:P16303, PhosphoSitePlus:P16303,
PaxDb:10116-ENSRNOP00000021812, GeneID:113902, KEGG:rno:113902,
AGR:RGD:1359640, AGR:RGD:70896, CTD:104158, RGD:70896,
eggNOG:KOG1516, InParanoid:P16303, OrthoDB:4386at2759,
PhylomeDB:P16303, BRENDA:3.1.1.1, Reactome:R-RNO-2022377,
Reactome:R-RNO-211945, Reactome:R-RNO-5578768,
Reactome:R-RNO-9749641, SABIO-RK:P16303, PRO:PR:P16303,
Proteomes:UP000002494, GO:0005737, GO:0005829, GO:0005783,
GO:0005788, GO:0043231, GO:0005811, GO:0047376, GO:0106435,
GO:0052689, GO:0030339, GO:0050253, GO:0004771, GO:0004806,
GO:0046464, GO:0071397, GO:0070417, GO:0071404, GO:0006695,
GO:0042632, GO:0008203, GO:0060086, GO:0106106, GO:0061725,
GO:0030855, GO:0016042, GO:0051791, GO:0010887, GO:0010875,
GO:0090205, GO:0045944, GO:0070857, GO:0120188, GO:0001523,
GO:0043691, GO:0019626, GO:0034379, CDD:cd00312,
FunFam:3.40.50.1820:FF:000011, Gene3D:3.40.50.1820,
InterPro:IPR029058, InterPro:IPR002018, InterPro:IPR019826,
InterPro:IPR019819, InterPro:IPR050309, PANTHER:PTHR11559,
PANTHER:PTHR11559:SF179, Pfam:PF00135, SUPFAM:SSF53474,
PROSITE:PS00122, PROSITE:PS00941
KEYWORDS Cytoplasm; Direct protein sequencing; Disulfide bond; Endoplasmic
reticulum; Glycoprotein; Hydrolase; Lipid degradation; Lipid
droplet; Lipid metabolism; Microsome; Reference proteome; Serine
esterase; Signal.
SOURCE Rattus norvegicus (Norway rat)
ORGANISM Rattus norvegicus
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
REFERENCE 1 (residues 1 to 565)
AUTHORS Robbi,M., Beaufay,H. and Octave,J.N.
TITLE Nucleotide sequence of cDNA coding for rat liver pI 6.1 esterase
(ES-10), a carboxylesterase located in the lumen of the endoplasmic
reticulum
JOURNAL Biochem J 269 (2), 451-458 (1990)
PUBMED 2386485
REMARK NUCLEOTIDE SEQUENCE [MRNA].;
STRAIN=Sprague-Dawley, and Wistar; TISSUE=Liver
REFERENCE 2 (residues 1 to 565)
AUTHORS Medda,S. and Proia,R.L.
TITLE The carboxylesterase family exhibits C-terminal sequence diversity
reflecting the presence or absence of
endoplasmic-reticulum-retention sequences
JOURNAL Eur J Biochem 206 (3), 801-806 (1992)
PUBMED 1606962
REMARK NUCLEOTIDE SEQUENCE [MRNA].;
STRAIN=Sprague-Dawley; TISSUE=Liver
REFERENCE 3 (residues 1 to 565)
AUTHORS Ghosh,S., Mallonee,D.H., Hylemon,P.B. and Grogan,W.M.
TITLE Molecular cloning and expression of rat hepatic neutral cholesteryl
ester hydrolase
JOURNAL Biochim Biophys Acta 1259 (3), 305-312 (1995)
PUBMED 8541339
REMARK NUCLEOTIDE SEQUENCE [MRNA].;
STRAIN=Sprague-Dawley; TISSUE=Liver
REFERENCE 4 (residues 1 to 565)
AUTHORS Wallace,T.J., Kodsi,E.M., Langston,T.B., Gergis,M.R. and
Grogan,W.M.
TITLE Mutation of residues 423 (Met/Ile), 444 (Thr/Met), and 506
(Asn/Ser) confer cholesteryl esterase activity on rat lung
carboxylesterase. Ser-506 is required for activation by
cAMP-dependent protein kinase
JOURNAL J Biol Chem 276 (35), 33165-33174 (2001)
PUBMED 11429416
REMARK NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF GLN-186; MET-423;
SER-491; LYS-492 AND ASN-506.;
STRAIN=Sprague-Dawley; TISSUE=Lung
REFERENCE 5 (residues 1 to 565)
AUTHORS Ryu,J.W., Lee,W. and Jung,C.Y.
TITLE Direct Submission
JOURNAL Submitted (??-JUL-1999) to the EMBL/GenBank/DDBJ databases
REMARK NUCLEOTIDE SEQUENCE [MRNA].;
STRAIN=Sprague-Dawley
REFERENCE 6 (residues 1 to 565)
AUTHORS Gerhard,D.S., Wagner,L., Feingold,E.A., Shenmen,C.M., Grouse,L.H.,
Schuler,G., Klein,S.L., Old,S., Rasooly,R., Good,P., Guyer,M.,
Peck,A.M., Derge,J.G., Lipman,D., Collins,F.S., Jang,W., Sherry,S.,
Feolo,M., Misquitta,L., Lee,E., Rotmistrovsky,K., Greenhut,S.F.,
Schaefer,C.F., Buetow,K., Bonner,T.I., Haussler,D., Kent,J.,
Kiekhaus,M., Furey,T., Brent,M., Prange,C., Schreiber,K.,
Shapiro,N., Bhat,N.K., Hopkins,R.F., Hsie,F., Driscoll,T.,
Soares,M.B., Casavant,T.L., Scheetz,T.E., Brown-stein,M.J.,
Usdin,T.B., Toshiyuki,S., Carninci,P., Piao,Y., Dudekula,D.B.,
Ko,M.S., Kawakami,K., Suzuki,Y., Sugano,S., Gruber,C.E.,
Smith,M.R., Simmons,B., Moore,T., Waterman,R., Johnson,S.L.,
Ruan,Y., Wei,C.L., Mathavan,S., Gunaratne,P.H., Wu,J., Garcia,A.M.,
Hulyk,S.W., Fuh,E., Yuan,Y., Sneed,A., Kowis,C., Hodgson,A.,
Muzny,D.M., McPherson,J., Gibbs,R.A., Fahey,J., Helton,E.,
Ketteman,M., Madan,A., Rodrigues,S., Sanchez,A., Whiting,M.,
Madari,A., Young,A.C., Wetherby,K.D., Granite,S.J., Kwong,P.N.,
Brinkley,C.P., Pearson,R.L., Bouffard,G.G., Blakesly,R.W.,
Green,E.D., Dickson,M.C., Rodriguez,A.C., Grimwood,J., Schmutz,J.,
Myers,R.M., Butterfield,Y.S., Griffith,M., Griffith,O.L.,
Krzywinski,M.I., Liao,N., Morin,R., Palmquist,D., Petrescu,A.S.,
Skalska,U., Smailus,D.E., Stott,J.M., Schnerch,A., Schein,J.E.,
Jones,S.J., Holt,R.A., Baross,A., Marra,M.A., Clifton,S.,
Makowski,K.A., Bosak,S. and Malek,J.
CONSRTM MGC Project Team
TITLE The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC)
JOURNAL Genome Res 14 (10B), 2121-2127 (2004)
PUBMED 15489334
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].;
TISSUE=Prostate
Erratum:[Genome Res. 2006 Jun;16(6):804. Morrin, Ryan [corrected to
Morin, Ryan]]
REFERENCE 7 (residues 1 to 565)
AUTHORS Tsujita,T. and Okuda,H.
TITLE Fatty acid ethyl ester synthase in rat adipose tissue and its
relationship to carboxylesterase
JOURNAL J Biol Chem 267 (33), 23489-23494 (1992)
PUBMED 1429692
REMARK PROTEIN SEQUENCE OF 19-45, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.;
STRAIN=Wistar; TISSUE=Adipose tissue
REFERENCE 8 (residues 1 to 565)
AUTHORS Satoh,T. and Hosokawa,M.
TITLE Molecular aspects of carboxylesterase isoforms in comparison with
other esterases
JOURNAL Toxicol Lett 82-83, 439-445 (1995)
PUBMED 8597091
REMARK PROTEIN SEQUENCE OF 19-38, NUCLEOTIDE SEQUENCE [MRNA] OF 113-121;
138-149; 216-224; 350-356 AND 464-469, AND SUBUNIT.;
TISSUE=Liver
REFERENCE 9 (residues 1 to 565)
AUTHORS Sanghani,S.P., Davis,W.I., Dumaual,N.G., Mahrenholz,A. and
Bosron,W.F.
TITLE Identification of microsomal rat liver carboxylesterases and their
activity with retinyl palmitate
JOURNAL Eur J Biochem 269 (18), 4387-4398 (2002)
PUBMED 12230550
REMARK CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, TISSUE
SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
COMMENT On or before Sep 26, 2008 this sequence version replaced
gi:81916247, gi:81868876, gi:92053, gi:119596.
[FUNCTION] Major lipase in white adipose tissue (By similarity).
Involved in the metabolism of xenobiotics and of natural
substrates. Hydrolyzes triacylglycerols and monoacylglycerols, with
a preference for monoacylglycerols. The susceptibility of the
substrate increases with decreasing acyl chain length of the fatty
acid moiety. Catalyzes the synthesis of fatty acid ethyl esters
(PubMed:1429692). Hydrolyzes retinyl esters (PubMed:12230550).
{ECO:0000250|UniProtKB:Q8VCT4, ECO:0000269|PubMed:12230550,
ECO:0000269|PubMed:1429692}.
[CATALYTIC ACTIVITY] Reaction=all-trans-retinyl hexadecanoate + H2O
= all-trans-retinol + hexadecanoate + H(+); Xref=Rhea:RHEA:13933,
ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
ChEBI:CHEBI:17336, ChEBI:CHEBI:17616;
Evidence={ECO:0000269|PubMed:12230550};
PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
Evidence={ECO:0000305|PubMed:12230550}.
[CATALYTIC ACTIVITY] Reaction=a carboxylic ester + H2O = an alcohol
+ a carboxylate + H(+); Xref=Rhea:RHEA:21164, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:29067, ChEBI:CHEBI:30879,
ChEBI:CHEBI:33308; EC=3.1.1.1;
Evidence={ECO:0000255|PROSITE-ProRule:PRU10039,
ECO:0000269|PubMed:1429692}.
[CATALYTIC ACTIVITY] Reaction=a long-chain fatty acyl ethyl ester +
H2O = a long-chain fatty acid + ethanol + H(+);
Xref=Rhea:RHEA:16641, ChEBI:CHEBI:13209, ChEBI:CHEBI:15377,
ChEBI:CHEBI:15378, ChEBI:CHEBI:16236, ChEBI:CHEBI:57560;
EC=3.1.1.67; Evidence={ECO:0000269|PubMed:1429692}.
ACTIVITY REGULATION: FAEE-synthesizing and PNPB-hydrolyzing
activities are both inhibited by DFP. {ECO:0000269|PubMed:1429692}.
[BIOPHYSICOCHEMICAL PROPERTIES] Kinetic parameters: KM=0.71 M for
oleic acid {ECO:0000269|PubMed:1429692}; KM=1.16 uM for retinyl
palmitate {ECO:0000269|PubMed:12230550}; Vmax=1482 nmol/h/mg enzyme
toward oleic acid {ECO:0000269|PubMed:1429692}; Note=kcat is 0.22
min(-1) with retinyl palmitate as substrate.
{ECO:0000269|PubMed:12230550}; pH dependence: Optimum pH for FAEE
synthesis is 7.0. Optimum pH for PNPB-hydrolyzing activity is 6-8.
{ECO:0000269|PubMed:1429692}.
[SUBUNIT] Homotrimer. {ECO:0000269|PubMed:8597091}.
[SUBCELLULAR LOCATION] Endoplasmic reticulum lumen
{ECO:0000250|UniProtKB:Q8VCT4}. Cytoplasm, cytosol
{ECO:0000250|UniProtKB:Q8VCT4}. Lipid droplet
{ECO:0000250|UniProtKB:Q8VCT4}. Microsome
{ECO:0000269|PubMed:12230550}.
[TISSUE SPECIFICITY] Detected in liver, lung and testis, but not in
kidney (at protein level). {ECO:0000269|PubMed:12230550,
ECO:0000269|PubMed:1429692}.
[SIMILARITY] Belongs to the type-B carboxylesterase/lipase family.
{ECO:0000305}.
FEATURES Location/Qualifiers
source 1..565
/organism="Rattus norvegicus"
/db_xref="taxon:10116"
gene 1..565
/gene="Ces1d"
/gene_synonym="Ces3"
Protein 1..565
/product="Carboxylesterase 1D"
/EC_number="3.1.1.1"
/EC_number="3.1.1.67"
/note="Carboxyesterase ES-10; Carboxylesterase 3; ES-HVEL;
Fatty acid ethyl ester synthase; Liver carboxylesterase
10; pI 6.1 esterase; FAEE synthase"
/UniProtKB_evidence="Evidence at protein level"
Region 1..18
/region_name="Signal"
/note="/evidence=ECO:0000269|PubMed:1429692,
ECO:0000269|PubMed:8597091."
Region 19..565
/region_name="Mature chain"
/note="Carboxylesterase 1D. /id=PRO_0000008584."
Region 22..545
/region_name="COesterase"
/note="Carboxylesterase family; pfam00135"
/db_xref="CDD:395084"
Site 79
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000250."
Bond bond(87,116)
/bond_type="disulfide"
/note="/evidence=ECO:0000250|UniProtKB:P23141."
Site order(141..143,220..222,225,382,386..387,419,467,470)
/site_type="other"
/note="substrate binding pocket [chemical binding]"
/db_xref="CDD:238191"
Region 186
/region_name="Conflict"
/note="Q -> R (in Ref. 1; CAA36236, 3; AAA88507 and 5;
AAD49369). /evidence=ECO:0000305."
Site 186
/site_type="mutagenized"
/note="Q->R: No effect on the hydrolysis of PNPC or PNPA,
no activity on cholesteryl oleate. No effect on the
hydrolysis of PNPC or PNPA, no activity on cholesteryl
oleate; when associated with E-492; or with T-491 and
E-492. Increases activity on PNPC compared to activity on
PNPA; when associated with I-423; T-491 and E-492.
/evidence=ECO:0000269|PubMed:11429416."
Site order(221,353,466)
/site_type="active"
/note="catalytic triad [active]"
/db_xref="CDD:238191"
Site 221
/site_type="active"
/note="Acyl-ester intermediate.
/evidence=ECO:0000255|PROSITE-ProRule:PRU10039."
Region 265
/region_name="Conflict"
/note="N -> K (in Ref. 1; CAA36236).
/evidence=ECO:0000305."
Bond bond(273,284)
/bond_type="disulfide"
/note="/evidence=ECO:0000250|UniProtKB:P23141."
Site 353
/site_type="active"
/note="Charge relay system.
/evidence=ECO:0000250|UniProtKB:P23141."
Site 382
/site_type="modified"
/note="N6-succinyllysine.
/evidence=ECO:0000250|UniProtKB:Q8VCT4."
Region 420
/region_name="Conflict"
/note="A -> E (in Ref. 3; AAA88507).
/evidence=ECO:0000305."
Region 423
/region_name="Conflict"
/note="M -> I (in Ref. 1; CAA36236, 3; AAA88507 and 5;
AAD49369). /evidence=ECO:0000305."
Site 423
/site_type="mutagenized"
/note="M->I: Increases specific activity against PNPC by
8-fold, does not increase activity against PNPA, no
activity on cholesteryl oleate. Increases activity on PNPC
compared to activity on PNPA; when associated with R-186;
T-491 and E-492. Increases specific activity against PNPC
by 7.5-fold and against PNPA by 3.6-fold, and increases
cholesteryl esterase activity by 2.7 fold; when associated
with S-506. /evidence=ECO:0000269|PubMed:11429416."
Region 444
/region_name="Conflict"
/note="M -> T (in Ref. 4; AAL00849).
/evidence=ECO:0000305."
Site 466
/site_type="active"
/note="Charge relay system.
/evidence=ECO:0000250|UniProtKB:P23141."
Site 489
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255."
Region 491..492
/region_name="Conflict"
/note="SK -> TQ (in Ref. 3; AAA88507).
/evidence=ECO:0000305."
Site 491
/site_type="mutagenized"
/note="S->T: No effect on the hydrolysis of PNPC or PNPA,
no activity on cholesteryl oleate; when associated with
R-186 and E-492. Increases activity on PNPC compared to
activity on PNPA; when associated with R-186; I-423 and
E-492. /evidence=ECO:0000269|PubMed:11429416."
Site 492
/site_type="mutagenized"
/note="K->E: No effect on the hydrolysis of PNPC or PNPA,
no activity on cholesteryl oleate; when associated with
R-186; or with R-186 and T-491. Increases activity on PNPC
compared to activity on PNPA; when associated with R-186;
I-423 and T-491. /evidence=ECO:0000269|PubMed:11429416."
Region 506
/region_name="Conflict"
/note="N -> S (in Ref. 1; CAA36236, 3; AAA88507 and 5;
AAD49369). /evidence=ECO:0000305."
Site 506
/site_type="mutagenized"
/note="N->S: Increases specific activity against PNPC by
6-fold and against PNPA by 8.7-fold, no activity on
cholesteryl oleate. Increases specific activity against
PNPC by 7.5-fold and against PNPA by 3.6-fold, and
increases cholesteryl esterase activity by 2.7 fold; when
associated with I-423.
/evidence=ECO:0000269|PubMed:11429416."
Region 562..565
/region_name="Short sequence motif of biological interest"
/note="Prevents secretion from ER. /evidence=ECO:0000255."
ORIGIN
1 mrlyplvwlf laactawgyp ssppvvntvk gkvlgkyvnl egfaqpvavf lgipfakppl
61 gslrfappqp aepwnfvknt tsyppmcsqd avggqvlsel ftnrkenipl qfsedclyln
121 vytpadltkn srlpvmvwih ggglvvggas tydgqvlsah envvvvtiqy rlgiwgffst
181 gdehsqgnwg hldqvaalhw vqdnianfgg npgsvtifge saggfsvsal vlsplaknlf
241 hraisesgvv ltsalittds kpianliatl sgcktttsav mvhclrqkte delletslkl
301 nlfkldllgn pkesypflpt vidgvvlpkt peeilaeksf ntvpyivgin kqefgwiipt
361 lmgyplsegk ldqktaksll wksyptlkis ekmipvvaek yfggtddpak rkdlfqdlva
421 dvmfgvpsvm vsrshrdaga ptfmyefeyr psfvsamrpk tvigdhgdel fsvfgspflk
481 dgaseeetnl skmvmkywan farngnpngg glphwpeydq kegylkigas tqaaqrlkdk
541 evafwselra keaaeepshw khvel
//