ID EST3_HUMAN Reviewed; 571 AA.
AC Q6UWW8; B2Z3W9; F5H242; Q7Z6J1; Q9H6X7;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 29-MAY-2013, entry version 83.
DE RecName: Full=Carboxylesterase 3;
DE EC=3.1.1.1;
DE AltName: Full=Liver carboxylesterase 31 homolog;
DE Flags: Precursor;
GN Name=CES3; ORFNames=UNQ869/PRO1887;
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 [MRNA] (ISOFORM 1), GLYCOSYLATION, TISSUE
RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Liver;
RX PubMed=15100172; DOI=10.1124/dmd.32.5.505;
RA Sanghani S.P., Quinney S.K., Fredenburg T.B., Davis W.I., Murry D.J.,
RA Bosron W.F.;
RT "Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-
RT [4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and
RT 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by
RT human carboxylesterases CES1A1, CES2, and a newly expressed
RT carboxylesterase isoenzyme, CES3.";
RL Drug Metab. Dispos. 32:505-511(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-129; THR-151;
RP HIS-160; LYS-191; ASN-213; TRP-367; VAL-523 AND VAL-555.
RG NIEHS SNPs program;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=14581373;
RA Sanghani S.P., Quinney S.K., Fredenburg T.B., Sun Z., Davis W.I.,
RA Murry D.J., Cummings O.W., Seitz D.E., Bosron W.F.;
RT "Carboxylesterases expressed in human colon tumor tissue and their
RT role in CPT-11 hydrolysis.";
RL Clin. Cancer Res. 9:4983-4991(2003).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=15687373; DOI=10.1124/jpet.104.081265;
RA Quinney S.K., Sanghani S.P., Davis W.I., Hurley T.D., Sun Z.,
RA Murry D.J., Bosron W.F.;
RT "Hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine by human
RT carboxylesterases and inhibition by loperamide.";
RL J. Pharmacol. Exp. Ther. 313:1011-1016(2005).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
CC -!- FUNCTION: Involved in the detoxification of xenobiotics and in the
CC activation of ester and amide prodrugs. Shows low catalytic
CC efficiency for hydrolysis of CPT-11 (7-ethyl-10-[4-(1-piperidino)-
CC 1-piperidino]-carbonyloxycamptothecin), a prodrug for camptothecin
CC used in cancer therapeutics.
CC -!- CATALYTIC ACTIVITY: A carboxylic ester + H(2)O = an alcohol + a
CC carboxylate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=137 uM for 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-
CC carbonyloxycamptothecin;
CC KM=460 uM for 7-ethyl-10-[4-(1-piperidino)-1-amino]-
CC carbonyloxycamptothecin;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UWW8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UWW8-2; Sequence=VSP_044994;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in liver, colon and small intestine.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ces3/";
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DR EMBL; AY358609; AAQ88972.1; -; mRNA.
DR EMBL; AK025389; BAB15123.1; -; mRNA.
DR EMBL; EU595874; ACD11491.1; -; Genomic_DNA.
DR EMBL; AC009084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83060.1; -; Genomic_DNA.
DR EMBL; BC053670; AAH53670.1; -; mRNA.
DR IPI; IPI00374310; -.
DR IPI; IPI00977205; -.
DR RefSeq; NP_001172105.1; NM_001185176.1.
DR RefSeq; NP_001172106.1; NM_001185177.1.
DR RefSeq; NP_079198.2; NM_024922.5.
DR UniGene; Hs.268700; -.
DR ProteinModelPortal; Q6UWW8; -.
DR IntAct; Q6UWW8; 1.
DR STRING; 9606.ENSP00000304782; -.
DR MEROPS; S09.958; -.
DR PhosphoSite; Q6UWW8; -.
DR DMDM; 74758561; -.
DR PaxDb; Q6UWW8; -.
DR PRIDE; Q6UWW8; -.
DR Ensembl; ENST00000303334; ENSP00000304782; ENSG00000172828.
DR Ensembl; ENST00000394037; ENSP00000377602; ENSG00000172828.
DR Ensembl; ENST00000543856; ENSP00000445559; ENSG00000172828.
DR GeneID; 23491; -.
DR KEGG; hsa:23491; -.
DR UCSC; uc002eqt.3; human.
DR UCSC; uc010viw.2; human.
DR CTD; 23491; -.
DR GeneCards; GC16P066995; -.
DR HGNC; HGNC:1865; CES3.
DR HPA; HPA041008; -.
DR HPA; HPA041307; -.
DR MIM; 605279; gene.
DR neXtProt; NX_Q6UWW8; -.
DR PharmGKB; PA26418; -.
DR eggNOG; COG2272; -.
DR HOGENOM; HOG000091866; -.
DR HOVERGEN; HBG008839; -.
DR InParanoid; Q6UWW8; -.
DR KO; K15743; -.
DR OMA; QFWSETL; -.
DR OrthoDB; EOG466VM9; -.
DR PhylomeDB; Q6UWW8; -.
DR BioCyc; MetaCyc:HS10576-MONOMER; -.
DR GenomeRNAi; 23491; -.
DR NextBio; 45851; -.
DR ArrayExpress; Q6UWW8; -.
DR Bgee; Q6UWW8; -.
DR CleanEx; HS_CES3; -.
DR Genevestigator; Q6UWW8; -.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0004091; F:carboxylesterase activity; IBA:RefGenome.
DR GO; GO:0080030; F:methyl indole-3-acetate esterase activity; IEA:EC.
DR GO; GO:0080032; F:methyl jasmonate esterase activity; IEA:EC.
DR GO; GO:0080031; F:methyl salicylate esterase activity; IEA:EC.
DR GO; GO:0050253; F:retinyl-palmitate esterase activity; IEA:EC.
DR InterPro; IPR002018; CarbesteraseB.
DR InterPro; IPR019826; Carboxylesterase_B_AS.
DR Pfam; PF00135; COesterase; 1.
DR PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1.
DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; FALSE_NEG.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Polymorphism;
KW Reference proteome; Serine esterase; Signal.
FT SIGNAL 1 26 Potential.
FT CHAIN 27 571 Carboxylesterase 3.
FT /FTId=PRO_0000305191.
FT MOTIF 568 571 Prevents secretion from ER (Potential).
FT ACT_SITE 229 229 Acyl-ester intermediate (By similarity).
FT ACT_SITE 347 347 Charge relay system (By similarity).
FT ACT_SITE 460 460 Charge relay system (By similarity).
FT CARBOHYD 105 105 N-linked (GlcNAc...).
FT DISULFID 97 124 By similarity.
FT DISULFID 281 292 By similarity.
FT VAR_SEQ 1 361 Missing (in isoform 2).
FT /FTId=VSP_044994.
FT VARIANT 129 129 V -> I.
FT /FTId=VAR_060699.
FT VARIANT 151 151 A -> T.
FT /FTId=VAR_060700.
FT VARIANT 160 160 Y -> H.
FT /FTId=VAR_060701.
FT VARIANT 191 191 E -> K.
FT /FTId=VAR_060702.
FT VARIANT 213 213 I -> N.
FT /FTId=VAR_060703.
FT VARIANT 367 367 R -> W.
FT /FTId=VAR_060704.
FT VARIANT 523 523 A -> V.
FT /FTId=VAR_060705.
FT VARIANT 555 555 I -> V.
FT /FTId=VAR_060706.
FT CONFLICT 372 372 A -> S (in Ref. 3; BAB15123).
FT CONFLICT 481 483 Missing (in Ref. 7; AAH53670).
SQ SEQUENCE 571 AA; 62282 MW; F2200968FDE072D2 CRC64;
MERAVRVESG VLVGVVCLLL ACPATATGPE VAQPEVDTTL GRVRGRQVGV KGTDRLVNVF
LGIPFAQPPL GPDRFSAPHP AQPWEGVRDA STAPPMCLQD VESMNSSRFV LNGKQQIFSV
SEDCLVLNVY SPAEVPAGSG RPVMVWVHGG ALITGAATSY DGSALAAYGD VVVVTVQYRL
GVLGFFSTGD EHAPGNQGFL DVVAALRWVQ ENIAPFGGDL NCVTVFGGSA GGSIISGLVL
SPVAAGLFHR AITQSGVITT PGIIDSHPWP LAQKIANTLA CSSSSPAEMV QCLQQKEGEE
LVLSKKLKNT IYPLTVDGTV FPKSPKELLK EKPFHSVPFL MGVNNHEFSW LIPRGWGLLD
TMEQMSREDM LAISTPVLTS LDVPPEMMPT VIDEYLGSNS DAQAKCQAFQ EFMGDVFINV
PTVSFSRYLR DSGSPVFFYE FQHRPSSFAK IKPAWVKADH GAEGAFVFGG PFLMDESSRL
AFPEATEEEK QLSLTMMAQW THFARTGDPN SKALPPWPQF NQAEQYLEIN PVPRAGQKFR
EAWMQFWSET LPSKIQQWHQ KQKNRKAQED L
//
