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Database: UniProt
Entry: Q6UWW8
LinkDB: Q6UWW8
Original site: Q6UWW8 
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   01-OCT-2014, entry version 96.
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.
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. {ECO:0000255|PROSITE-ProRule:PRU10039}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=137 uM for 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-
CC         carbonyloxycamptothecin {ECO:0000269|PubMed:15100172};
CC         KM=460 uM for 7-ethyl-10-[4-(1-piperidino)-1-amino]-
CC         carbonyloxycamptothecin {ECO:0000269|PubMed:15100172};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000250}.
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       {ECO:0000269|PubMed:14581373, ECO:0000269|PubMed:15100172,
CC       ECO:0000269|PubMed:15687373}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15100172,
CC       ECO:0000269|PubMed:19159218}.
CC   -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family.
CC       {ECO:0000305}.
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   CCDS; CCDS10826.1; -. [Q6UWW8-1]
DR   CCDS; CCDS54023.1; -. [Q6UWW8-2]
DR   RefSeq; NP_001172105.1; NM_001185176.1. [Q6UWW8-2]
DR   RefSeq; NP_001172106.1; NM_001185177.1.
DR   RefSeq; NP_079198.2; NM_024922.5. [Q6UWW8-1]
DR   UniGene; Hs.268700; -.
DR   ProteinModelPortal; Q6UWW8; -.
DR   SMR; Q6UWW8; 34-548.
DR   BioGrid; 117043; 1.
DR   IntAct; Q6UWW8; 1.
DR   STRING; 9606.ENSP00000304782; -.
DR   MEROPS; S09.958; -.
DR   PhosphoSite; Q6UWW8; -.
DR   DMDM; 74758561; -.
DR   MaxQB; Q6UWW8; -.
DR   PaxDb; Q6UWW8; -.
DR   PRIDE; Q6UWW8; -.
DR   Ensembl; ENST00000303334; ENSP00000304782; ENSG00000172828. [Q6UWW8-1]
DR   Ensembl; ENST00000394037; ENSP00000377602; ENSG00000172828.
DR   Ensembl; ENST00000543856; ENSP00000445559; ENSG00000172828. [Q6UWW8-2]
DR   GeneID; 23491; -.
DR   KEGG; hsa:23491; -.
DR   UCSC; uc002eqt.3; human. [Q6UWW8-1]
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; EOG7RBZ7R; -.
DR   PhylomeDB; Q6UWW8; -.
DR   TreeFam; TF315470; -.
DR   BioCyc; MetaCyc:HS10576-MONOMER; -.
DR   SABIO-RK; Q6UWW8; -.
DR   GeneWiki; Carboxylesterase_3; -.
DR   GenomeRNAi; 23491; -.
DR   NextBio; 45851; -.
DR   PRO; PR:Q6UWW8; -.
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:0070062; C:extracellular vesicular exosome; IDA:UniProt.
DR   GO; GO:0052689; F:carboxylic ester hydrolase 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   Pfam; PF00135; COesterase; 1.
DR   SUPFAM; SSF53474; SSF53474; 2.
DR   PROSITE; PS00122; CARBOXYLESTERASE_B_1; 1.
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       {ECO:0000255}.
FT   CHAIN        27    571       Carboxylesterase 3.
FT                                /FTId=PRO_0000305191.
FT   MOTIF       568    571       Prevents secretion from ER.
FT                                {ECO:0000255}.
FT   ACT_SITE    229    229       Acyl-ester intermediate.
FT                                {ECO:0000255|PROSITE-ProRule:PRU10039}.
FT   ACT_SITE    347    347       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    460    460       Charge relay system. {ECO:0000250}.
FT   CARBOHYD    105    105       N-linked (GlcNAc...).
FT                                {ECO:0000269|PubMed:15100172,
FT                                ECO:0000269|PubMed:19159218}.
FT   DISULFID     97    124       {ECO:0000250}.
FT   DISULFID    281    292       {ECO:0000250}.
FT   VAR_SEQ       1    361       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_044994.
FT   VARIANT     129    129       V -> I (in dbSNP:rs61745806).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060699.
FT   VARIANT     151    151       A -> T (in dbSNP:rs71647891).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060700.
FT   VARIANT     160    160       Y -> H (in dbSNP:rs71647892).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060701.
FT   VARIANT     191    191       E -> K (in dbSNP:rs61742964).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060702.
FT   VARIANT     213    213       I -> N (in dbSNP:rs71647894).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060703.
FT   VARIANT     367    367       R -> W (in dbSNP:rs61743167).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060704.
FT   VARIANT     523    523       A -> V. {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060705.
FT   VARIANT     555    555       I -> V (in dbSNP:rs8059252).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_060706.
FT   CONFLICT    372    372       A -> S (in Ref. 3; BAB15123).
FT                                {ECO:0000305}.
FT   CONFLICT    481    483       Missing (in Ref. 7; AAH53670).
FT                                {ECO:0000305}.
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
//
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