Skip Header

Contribute Send feedback
Read comments (?) or add your own

P16422 (EPCAM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length314 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 junctiontight 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 314291Epithelial cell adhesion molecule
PRO_0000022467

Regions

Topological domain24 – 265242Extracellular Potential
Transmembrane266 – 28823Helical; Potential
Topological domain289 – 31426Cytoplasmic Potential
Domain63 – 13573Thyroglobulin type-1

Amino acid modifications

Modified residue241Pyrrolidone carboxylic acid Probable
Glycosylation741N-linked (GlcNAc...); partial Ref.12 Ref.16
Glycosylation1111N-linked (GlcNAc...) Ref.12 Ref.16
Glycosylation1981N-linked (GlcNAc...) Ref.16 Ref.17
Disulfide bond27 ↔ 46 Ref.12
Disulfide bond29 ↔ 59 Ref.12
Disulfide bond38 ↔ 48 Ref.12
Disulfide bond66 ↔ 99 Ref.12
Disulfide bond110 ↔ 116 Ref.12
Disulfide bond118 ↔ 135 Ref.12

Natural variations

Natural variant661C → Y in DIAR5. Ref.21
VAR_063829
Natural variant1151M → T. Ref.1 Ref.2 Ref.3 Ref.9
Corresponds to variant rs1126497 [ dbSNP | Ensembl ].
VAR_018329

Experimental info

Mutagenesis741N → A: Changed glycosylation pattern. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-111 and A-198. Ref.16
Mutagenesis1111N → A: Changed glycosylation pattern. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-74 and A-198. Ref.16
Mutagenesis1981N → 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 conflict2771I → M in AAA36151. Ref.1
Sequence conflict2771I → M in CAA32870. Ref.1
Sequence conflict2771I → M in AAA59543. Ref.2
Sequence conflict3031K → R in CAG47055. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P16422 [UniParc].

Last modified November 13, 2007. Version 2.
Checksum: 023FCE418B2F1079

FASTA31434,932
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.

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 expand/collapse EMBL AC list , 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.
IPIIPI00296215.
PIRB48149.
RefSeqNP_002345.2. NM_002354.2.
UniGeneHs.542050.

3D structure databases

ProteinModelPortalP16422.
SMRP16422. Positions 92-137.
ModBaseSearch...

Protein-protein interaction databases

IntActP16422. 1 interaction.
STRINGP16422.

Polymorphism databases

DMDM160266056.

Proteomic databases

PRIDEP16422.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263735; ENSP00000263735; ENSG00000119888.
GeneID4072.
KEGGhsa:4072.

Organism-specific databases

CTD4072.
GeneCardsGC02P047572.
H-InvDBHIX0002040.
HGNCHGNC:11529. EPCAM.
HPACAB003809.
CAB030012.
HPA026761.
MIM185535. gene.
613217. phenotype.
613244. phenotype.
neXtProtNX_P16422.
Orphanet144. Hereditary nonpolyposis colon cancer.
92050. Intestinal epithelial dysplasia.
PharmGKBPA164719165.
PA35493.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14941.
GeneTreeENSGT00390000018245.
PhylomeDBP16422.

Gene expression databases

ArrayExpressP16422.
BgeeP16422.
CleanExHS_EPCAM.
GenevestigatorP16422.
GermOnlineENSG00000119888. Homo sapiens.

Family and domain databases

InterProIPR000716. Thyroglobulin_1.
[Graphical view]
Gene3DG3DSA:4.10.800.10. Thyroglobulin_1. 1 hit.
KOK06737.
PfamPF00086. Thyroglobulin_1. 1 hit.
[Graphical view]
SMARTSM00211. TY. 1 hit.
[Graphical view]
SUPFAMSSF57610. Thyroglobulin_1. 1 hit.
PROSITEPS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

SOURCESearch...

Entry information

Entry nameEPCAM_HUMAN
AccessionPrimary (citable) accession number: P16422
Secondary accession number(s): P18180 expand/collapse secondary AC list , 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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families