P16422 (EPCAM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Epithelial cell adhesion molecule
Short name=Ep-CAM

Alternative name(s):
Adenocarcinoma-associated antigen
Cell surface glycoprotein Trop-1
Epithelial cell surface antigen
Epithelial glycoprotein
Short name=EGP
Epithelial glycoprotein 314
Short name=EGP314
Short name=hEGP314
KS 1/4 antigen
KSA
Major gastrointestinal tumor-associated protein GA733-2
Tumor-associated calcium signal transducer 1
CD_antigen=CD326

Gene names

Name:	EPCAM
Synonyms:	GA733-2, M1S2, M4S1, MIC18, TACSTD1, TROP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	314 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	May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E. Ref.13 Ref.14 Ref.19 Ref.20
Subunit structure	Monomer. Interacts with phosphorylated CLDN7. Ref.11 Ref.15
Subcellular location	Lateral cell membrane; Single-pass type I membrane protein. Cell junction › tight junction. Note: Co-localizes with CLDN7 at the lateral cell membrane and tight junction. Ref.13 Ref.15 Ref.20
Tissue specificity	Highly and selectively expressed by undifferentiated rather than differentiated embryonic stem cells (ESC). Levels rapidly diminish as soon as ESC's differentiate (at protein levels). Expressed in almost all epithelial cell membranes but not on mesodermal or neural cell membranes. Found on the surface of adenocarcinoma. Ref.19
Post-translational modification	Hyperglycosylated in carcinoma tissue as compared with autologous normal epithelia. Glycosylation at Asn-198 is crucial for protein stability. Ref.12 Ref.16 Ref.17
Involvement in disease	Defects in EPCAM are the cause of diarrhea type 5 (DIAR5) [MIM:613217]. It is an intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum. Ref.21 Defects in EPCAM are a cause of hereditary non-polyposis colorectal cancer type 8 (HNPCC8) [MIM:613244]. HNPCC is a disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. Note=HNPCC8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM. Ref.18
Sequence similarities	Belongs to the EPCAM family. Contains 1 thyroglobulin type-1 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Tight junction
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary nonpolyposis colorectal cancer
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Tumor antigen
PTM	Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of cell proliferation Inferred from direct assay Ref.13. Source: UniProtKB
Cellular component	apical plasma membrane Inferred from direct assay. Source: MGI basolateral plasma membrane Inferred from direct assay. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lateral plasma membrane Inferred from direct assay Ref.15. Source: UniProtKB tight junction Inferred from direct assay Ref.15. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.15. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 314	291	Epithelial cell adhesion molecule		PRO_0000022467
Regions
	Topological domain	24 – 265	242	Extracellular Potential
	Transmembrane	266 – 288	23	Helical; Potential
	Topological domain	289 – 314	26	Cytoplasmic Potential
	Domain	63 – 135	73	Thyroglobulin type-1
Amino acid modifications
	Modified residue	24	1	Pyrrolidone carboxylic acid Probable
	Glycosylation	74	1	N-linked (GlcNAc...); partial Ref.12 Ref.16
	Glycosylation	111	1	N-linked (GlcNAc...) Ref.12 Ref.16
	Glycosylation	198	1	N-linked (GlcNAc...) Ref.16 Ref.17
	Disulfide bond	27 ↔ 46		Ref.12
	Disulfide bond	29 ↔ 59		Ref.12
	Disulfide bond	38 ↔ 48		Ref.12
	Disulfide bond	66 ↔ 99		Ref.12
	Disulfide bond	110 ↔ 116		Ref.12
	Disulfide bond	118 ↔ 135		Ref.12
Natural variations
	Natural variant	66	1	C → Y in DIAR5. Ref.21		VAR_063829
	Natural variant	115	1	M → T. Ref.1 Ref.2 Ref.3 Ref.9 Corresponds to variant rs1126497 [ dbSNP | Ensembl ].		VAR_018329
Experimental info
	Mutagenesis	74	1	N → A: Changed glycosylation pattern. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-111 and A-198. Ref.16
	Mutagenesis	111	1	N → A: Changed glycosylation pattern. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-74 and A-198. Ref.16
	Mutagenesis	198	1	N → A: Decreased glycosyation, reduced protein stability and significant decrease in protein expression. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-74 and A-111. Ref.16
	Sequence conflict	277	1	I → M in AAA36151. Ref.1
	Sequence conflict	277	1	I → M in CAA32870. Ref.1
	Sequence conflict	277	1	I → M in AAA59543. Ref.2
	Sequence conflict	303	1	K → R in CAG47055. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P16422 [UniParc]. Last modified November 13, 2007. Version 2. Checksum: 023FCE418B2F1079	FASTA	314	34,932
	10 20 30 40 50 60 MAPPQVLAFG LLLAAATATF AAAQEECVCE NYKLAVNCFV NNNRQCQCTS VGAQNTVICS 70 80 90 100 110 120 KLAAKCLVMK AEMNGSKLGR RAKPEGALQN NDGLYDPDCD ESGLFKAKQC NGTSMCWCVN 130 140 150 160 170 180 TAGVRRTDKD TEITCSERVR TYWIIIELKH KAREKPYDSK SLRTALQKEI TTRYQLDPKF 190 200 210 220 230 240 ITSILYENNV ITIDLVQNSS QKTQNDVDIA DVAYYFEKDV KGESLFHSKK MDLTVNGEQL 250 260 270 280 290 300 DLDPGQTLIY YVDEKAPEFS MQGLKAGVIA VIVVVVIAVV AGIVVLVISR KKRMAKYEKA 310 EIKEMGEMHR ELNA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA." Strnad J., Hamilton A.E., Beavers L.S., Gamboa G.C., Apelgren L.D., Taber L.D., Sportsman J.R., Bumol T.F., Sharp J.D., Gadski R.A. Cancer Res. 49:314-317(1989) [PubMed: 2463074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-115. Tissue: Lung adenocarcinoma.
[2]	"Isolation and characterization of a cDNA encoding the KS1/4 epithelial carcinoma marker." Perez M.S., Walker L.E. J. Immunol. 142:3662-3667(1989) [PubMed: 2469722] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-115.
[3]	"Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein." Simon B., Podolsky D.K., Moldenhauer G., Isselbacher K.J., Gattoni-Celli S., Brand S.J. Proc. Natl. Acad. Sci. U.S.A. 87:2755-2759(1990) [PubMed: 2108441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-115.
[4]	"Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2." Szala S., Froehlich M., Scollon M., Kasai Y., Steplewski Z., Koprowski H., Linnenbach A.J. Proc. Natl. Acad. Sci. U.S.A. 87:3542-3546(1990) [PubMed: 2333300] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Colon carcinoma.
[5]	"Retroposition in a family of carcinoma-associated antigen genes." Linnenbach A.J., Seng B.A., Wu S., Robbins S., Scollon M., Pyrc J.J., Druck T., Huebner K. Mol. Cell. Biol. 13:1507-1515(1993) [PubMed: 8382772] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lymphoma.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-115. Tissue: Ovary.
[10]	"Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733." Linnenbach A.J., Wojcierowski J., Wu S., Pyrc J.J., Ross A.H., Dietzschold B., Speicher D., Koprowski H. Proc. Natl. Acad. Sci. U.S.A. 86:27-31(1989) [PubMed: 2911574] [Abstract] Cited for: PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 81-126. Tissue: Placenta.
[11]	"Isolation, partial characterization, and molecular cloning of a human colon adenocarcinoma cell-surface glycoprotein recognized by the C215 mouse monoclonal antibody." Bjoerk P., Joensson U., Svedberg H., Larsson K., Lind P., Dillner J., Hedlund G., Dohlsten M., Kalland T. J. Biol. Chem. 268:24232-24241(1993) [PubMed: 7693697] [Abstract] Cited for: PROTEIN SEQUENCE OF 82-100, SUBUNIT.
[12]	"Determination of disulfide bond assignments and N-glycosylation sites of the human gastrointestinal carcinoma antigen GA733-2 (CO17-1A, EGP, KS1-4, KSA, and Ep-CAM)." Chong J.M., Speicher D.W. J. Biol. Chem. 276:5804-5813(2001) [PubMed: 11080501] [Abstract] Cited for: DISULFIDE BONDS, GLYCOSYLATION AT ASN-74 AND ASN-111.
[13]	"The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation." Muenz M., Kieu C., Mack B., Schmitt B., Zeidler R., Gires O. Oncogene 23:5748-5758(2004) [PubMed: 15195135] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]	"The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP." Muenz M., Zeidler R., Gires O. Cancer Lett. 225:151-157(2005) [PubMed: 15922867] [Abstract] Cited for: FUNCTION.
[15]	"The cell-cell adhesion molecule EpCAM interacts directly with the tight junction protein claudin-7." Ladwein M., Pape U.F., Schmidt D.S., Schnoelzer M., Fiedler S., Langbein L., Franke W.W., Moldenhauer G., Zoeller M. Exp. Cell Res. 309:345-357(2005) [PubMed: 16054130] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CLDN7.
[16]	"Glycosylation is crucial for stability of tumour and cancer stem cell antigen EpCAM." Munz M., Fellinger K., Hofmann T., Schmitt B., Gires O. Front. Biosci. 13:5195-5201(2008) [PubMed: 18508581] [Abstract] Cited for: GLYCOSYLATION AT ASN-74; ASN-111 AND ASN-198, MUTAGENESIS OF ASN-74; ASN-111 AND ASN-198.
[17]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-198, MASS SPECTROMETRY. Tissue: Liver.
[18]	"Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1." Ligtenberg M.J., Kuiper R.P., Chan T.L., Goossens M., Hebeda K.M., Voorendt M., Lee T.Y., Bodmer D., Hoenselaar E., Hendriks-Cornelissen S.J., Tsui W.Y., Kong C.K., Brunner H.G., van Kessel A.G., Yuen S.T., van Krieken J.H., Leung S.Y., Hoogerbrugge N. Nat. Genet. 41:112-117(2009) [PubMed: 19098912] [Abstract] Cited for: INVOLVEMENT IN HNPCC8.
[19]	"Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells." Lu T.Y., Lu R.M., Liao M.Y., Yu J., Chung C.H., Kao C.F., Wu H.C. J. Biol. Chem. 285:8719-8732(2010) [PubMed: 20064925] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[20]	"Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells." Ng V.Y., Ang S.N., Chan J.X., Choo A.B. Stem Cells 28:29-35(2010) [PubMed: 19785009] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[21]	"Identification of EpCAM as the gene for congenital tufting enteropathy." Sivagnanam M., Mueller J.L., Lee H., Chen Z., Nelson S.F., Turner D., Zlotkin S.H., Pencharz P.B., Ngan B.Y., Libiger O., Schork N.J., Lavine J.E., Taylor S., Newbury R.O., Kolodner R.D., Hoffman H.M. Gastroenterology 135:429-437(2008) [PubMed: 18572020] [Abstract] Cited for: VARIANT DIAR5 TYR-66.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	M32325 mRNA. Translation: AAA36151.1. X14758 mRNA. Translation: CAA32870.1. M26481 mRNA. Translation: AAA59543.1. M32306 mRNA. Translation: AAA35723.1. M33011 mRNA. Translation: AAA35861.1. M93036 , M93029, M93030, M93031, M93032, M93033, M93034, M93035 Genomic DNA. Translation: AAB00775.1. CR542259 mRNA. Translation: CAG47055.1. CR542283 mRNA. Translation: CAG47078.1. AC079775 Genomic DNA. Translation: AAY15095.1. CH471053 Genomic DNA. Translation: EAX00218.1. BC014785 mRNA. Translation: AAH14785.1.
IPI	IPI00296215.
PIR	B48149.
RefSeq	NP_002345.2. NM_002354.2.
UniGene	Hs.542050.
3D structure databases
ProteinModelPortal	P16422.
SMR	P16422. Positions 92-137.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16422. 1 interaction.
STRING	P16422.
Polymorphism databases
DMDM	160266056.
Proteomic databases
PRIDE	P16422.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263735; ENSP00000263735; ENSG00000119888.
GeneID	4072.
KEGG	hsa:4072.
Organism-specific databases
CTD	4072.
GeneCards	GC02P047572.
H-InvDB	HIX0002040.
HGNC	HGNC:11529. EPCAM.
HPA	CAB003809. CAB030012. HPA026761.
MIM	185535. gene. 613217. phenotype. 613244. phenotype.
neXtProt	NX_P16422.
Orphanet	144. Hereditary nonpolyposis colon cancer. 92050. Intestinal epithelial dysplasia.
PharmGKB	PA164719165. PA35493.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14941.
GeneTree	ENSGT00390000018245.
PhylomeDB	P16422.
Gene expression databases
ArrayExpress	P16422.
Bgee	P16422.
CleanEx	HS_EPCAM.
Genevestigator	P16422.
GermOnline	ENSG00000119888. Homo sapiens.
Family and domain databases
InterPro	IPR000716. Thyroglobulin_1. [Graphical view]
Gene3D	G3DSA:4.10.800.10. Thyroglobulin_1. 1 hit.
KO	K06737.
Pfam	PF00086. Thyroglobulin_1. 1 hit. [Graphical view]
SMART	SM00211. TY. 1 hit. [Graphical view]
SUPFAM	SSF57610. Thyroglobulin_1. 1 hit.
PROSITE	PS00484. THYROGLOBULIN_1_1. 1 hit. PS51162. THYROGLOBULIN_1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

EPCAM_HUMAN

Accession

Primary (citable) accession number: P16422
Secondary accession number(s): P18180 , Q6FG26, Q6FG49, Q96C47, Q9UCD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	November 13, 2007
Last modified:	January 25, 2012
This is version 119 of the entry and version 2 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.