Q6UWW8 (EST3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxylesterase 3
EC=3.1.1.1

Alternative name(s):
Liver carboxylesterase 31 homolog

Gene names

Name:	CES3
ORF Names:	UNQ869/PRO1887

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	571 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows low catalytic efficiency for hydrolysis of CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin), a prodrug for camptothecin used in cancer therapeutics.
Catalytic activity	A carboxylic ester + H2O = an alcohol + a carboxylate.
Subcellular location	Endoplasmic reticulum lumen By similarity.
Tissue specificity	Expressed in liver, colon and small intestine. Ref.1 Ref.8 Ref.9
Post-translational modification	N-glycosylated. Ref.1
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.
Biophysicochemical properties	Kinetic parameters: KM=137 µM for 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin Ref.1 KM=460 µM for 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hydrolase Serine esterase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carboxylesterase activity Inferred from Biological aspect of Ancestor. Source: RefGenome methyl indole-3-acetate esterase activity Inferred from electronic annotation. Source: EC methyl jasmonate esterase activity Inferred from electronic annotation. Source: EC methyl salicylate esterase activity Inferred from electronic annotation. Source: EC retinyl-palmitate esterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6UWW8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6UWW8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-361: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 571	545	Carboxylesterase 3		PRO_0000305191
Regions
	Motif	568 – 571	4	Prevents secretion from ER Potential
Sites
	Active site	229	1	Acyl-ester intermediate By similarity
	Active site	347	1	Charge relay system By similarity
	Active site	460	1	Charge relay system By similarity
Amino acid modifications
	Glycosylation	105	1	N-linked (GlcNAc...) Ref.10
	Disulfide bond	97 ↔ 124		By similarity
	Disulfide bond	281 ↔ 292		By similarity
Natural variations
	Alternative sequence	1 – 361	361	Missing in isoform 2.		VSP_044994
	Natural variant	129	1	V → I. Ref.4		VAR_060699
	Natural variant	151	1	A → T. Ref.4		VAR_060700
	Natural variant	160	1	Y → H. Ref.4		VAR_060701
	Natural variant	191	1	E → K. Ref.4		VAR_060702
	Natural variant	213	1	I → N. Ref.4		VAR_060703
	Natural variant	367	1	R → W. Ref.4		VAR_060704
	Natural variant	523	1	A → V. Ref.4		VAR_060705
	Natural variant	555	1	I → V. Ref.4		VAR_060706
Experimental info
	Sequence conflict	372	1	A → S in BAB15123. Ref.3
	Sequence conflict	481 – 483	3	Missing in AAH53670. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: F2200968FDE072D2	FASTA	571	62,282
	10 20 30 40 50 60 MERAVRVESG VLVGVVCLLL ACPATATGPE VAQPEVDTTL GRVRGRQVGV KGTDRLVNVF 70 80 90 100 110 120 LGIPFAQPPL GPDRFSAPHP AQPWEGVRDA STAPPMCLQD VESMNSSRFV LNGKQQIFSV 130 140 150 160 170 180 SEDCLVLNVY SPAEVPAGSG RPVMVWVHGG ALITGAATSY DGSALAAYGD VVVVTVQYRL 190 200 210 220 230 240 GVLGFFSTGD EHAPGNQGFL DVVAALRWVQ ENIAPFGGDL NCVTVFGGSA GGSIISGLVL 250 260 270 280 290 300 SPVAAGLFHR AITQSGVITT PGIIDSHPWP LAQKIANTLA CSSSSPAEMV QCLQQKEGEE 310 320 330 340 350 360 LVLSKKLKNT IYPLTVDGTV FPKSPKELLK EKPFHSVPFL MGVNNHEFSW LIPRGWGLLD 370 380 390 400 410 420 TMEQMSREDM LAISTPVLTS LDVPPEMMPT VIDEYLGSNS DAQAKCQAFQ EFMGDVFINV 430 440 450 460 470 480 PTVSFSRYLR DSGSPVFFYE FQHRPSSFAK IKPAWVKADH GAEGAFVFGG PFLMDESSRL 490 500 510 520 530 540 AFPEATEEEK QLSLTMMAQW THFARTGDPN SKALPPWPQF NQAEQYLEIN PVPRAGQKFR 550 560 570 EAWMQFWSET LPSKIQQWHQ KQKNRKAQED L
	Isoform 2 [UniParc]. Checksum: 875CDDA899639F65	FASTA	210	24,106
	10 20 30 40 50 60 MEQMSREDML AISTPVLTSL DVPPEMMPTV IDEYLGSNSD AQAKCQAFQE FMGDVFINVP 70 80 90 100 110 120 TVSFSRYLRD SGSPVFFYEF QHRPSSFAKI KPAWVKADHG AEGAFVFGGP FLMDESSRLA 130 140 150 160 170 180 FPEATEEEKQ LSLTMMAQWT HFARTGDPNS KALPPWPQFN QAEQYLEINP VPRAGQKFRE 190 200 210 AWMQFWSETL PSKIQQWHQK QKNRKAQEDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3." Sanghani S.P., Quinney S.K., Fredenburg T.B., Davis W.I., Murry D.J., Bosron W.F. Drug Metab. Dispos. 32:505-511(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Liver.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Colon mucosa.
[4]	NIEHS SNPs program Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-129; THR-151; HIS-160; LYS-191; ASN-213; TRP-367; VAL-523 AND VAL-555.
[5]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Eye.
[8]	"Carboxylesterases expressed in human colon tumor tissue and their role in CPT-11 hydrolysis." Sanghani S.P., Quinney S.K., Fredenburg T.B., Sun Z., Davis W.I., Murry D.J., Cummings O.W., Seitz D.E., Bosron W.F. Clin. Cancer Res. 9:4983-4991(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamide." Quinney S.K., Sanghani S.P., Davis W.I., Hurley T.D., Sun Z., Murry D.J., Bosron W.F. J. Pharmacol. Exp. Ther. 313:1011-1016(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-105, MASS SPECTROMETRY. Tissue: Liver.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY358609 mRNA. Translation: AAQ88972.1. AK025389 mRNA. Translation: BAB15123.1. EU595874 Genomic DNA. Translation: ACD11491.1. AC009084 Genomic DNA. No translation available. CH471092 Genomic DNA. Translation: EAW83060.1. BC053670 mRNA. Translation: AAH53670.1.
IPI	IPI00374310. IPI00977205.
RefSeq	NP_001172105.1. NM_001185176.1. NP_001172106.1. NM_001185177.1. NP_079198.2. NM_024922.5.
UniGene	Hs.268700.
3D structure databases
HSSP	HSSP built from PDB template 1K4Y based on UniProtKB P12337.
ProteinModelPortal	Q6UWW8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6UWW8. 1 interaction.
STRING	9606.ENSP00000304782.
Protein family/group databases
MEROPS	S09.958.
PTM databases
PhosphoSite	Q6UWW8.
Polymorphism databases
DMDM	74758561.
Proteomic databases
PaxDb	Q6UWW8.
PRIDE	Q6UWW8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303334; ENSP00000304782; ENSG00000172828. ENST00000394037; ENSP00000377602; ENSG00000172828. ENST00000543856; ENSP00000445559; ENSG00000172828.
GeneID	23491.
KEGG	hsa:23491.
UCSC	uc002eqt.3. human.
Organism-specific databases
CTD	23491.
GeneCards	GC16P066995.
HGNC	HGNC:1865. CES3.
HPA	HPA041008. HPA041307.
MIM	605279. gene.
neXtProt	NX_Q6UWW8.
PharmGKB	PA26418.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2272.
HOGENOM	HOG000091866.
HOVERGEN	HBG008839.
InParanoid	Q6UWW8.
KO	K15743.
OMA	QFWSETL.
OrthoDB	EOG466VM9.
PhylomeDB	Q6UWW8.
Enzyme and pathway databases
BioCyc	MetaCyc:HS10576-MONOMER.
Gene expression databases
ArrayExpress	Q6UWW8.
Bgee	Q6UWW8.
CleanEx	HS_CES3.
Genevestigator	Q6UWW8.
Family and domain databases
InterPro	IPR002018. CarbesteraseB. IPR019826. Carboxylesterase_B_AS. [Graphical view]
Pfam	PF00135. COesterase. 1 hit. [Graphical view]
PROSITE	PS00122. CARBOXYLESTERASE_B_1. 1 hit. PS00941. CARBOXYLESTERASE_B_2. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	23491.
NextBio	45851.
SOURCE	Search...

Entry information

Entry name

EST3_HUMAN

Accession

Primary (citable) accession number: Q6UWW8
Secondary accession number(s): B2Z3W9 , F5H242, Q7Z6J1, Q9H6X7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.