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Protein

Epithelial cell adhesion molecule

Gene

EPCAM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: GO_Central
  • protein complex binding Source: UniProtKB

GO - Biological processi

  • cell-cell adhesion via plasma-membrane adhesion molecules Source: Ensembl
  • leukocyte migration Source: Reactome
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of cell-cell adhesion mediated by cadherin Source: UniProtKB
  • positive regulation of cell motility Source: Ensembl
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of stem cell proliferation Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • signal transduction involved in regulation of gene expression Source: UniProtKB
  • stem cell differentiation Source: UniProtKB
  • ureteric bud development Source: Ensembl

Keywordsi

Molecular functionTumor antigen

Enzyme and pathway databases

ReactomeiR-HSA-202733. Cell surface interactions at the vascular wall.

Names & Taxonomyi

Protein namesi
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 namesi
Name:EPCAM
Synonyms:GA733-2, M1S2, M4S1, MIC18, TACSTD1, TROP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000119888.10.
HGNCiHGNC:11529. EPCAM.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 265ExtracellularSequence analysisAdd BLAST242
Transmembranei266 – 288HelicalSequence analysisAdd BLAST23
Topological domaini289 – 314CytoplasmicSequence analysisAdd BLAST26

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

Diarrhea 5, with tufting enteropathy, congenital (DIAR5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:613217
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06382966C → Y in DIAR5. 1 PublicationCorresponds to variant dbSNP:rs267606785Ensembl.1
Hereditary non-polyposis colorectal cancer 8 (HNPCC8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. 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.
Disease descriptionAn autosomal dominant 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.
See also OMIM:613244

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi74N → A: Changed glycosylation pattern. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-111 and A-198. 1 Publication1
Mutagenesisi111N → A: Changed glycosylation pattern. Complete loss of glycosylation and substantial decrease in protein expression; when associated with A-74 and A-198. 1 Publication1
Mutagenesisi198N → 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. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer

Organism-specific databases

DisGeNETi4072.
GeneReviewsiEPCAM.
MalaCardsiEPCAM.
MIMi613217. phenotype.
613244. phenotype.
OpenTargetsiENSG00000119888.
Orphaneti144. Hereditary nonpolyposis colon cancer.
92050. Intestinal epithelial dysplasia.
PharmGKBiPA35493.

Chemistry databases

ChEMBLiCHEMBL3580493.
DrugBankiDB05831. ING-1.
DB05319. oportuzumab monatox.

Polymorphism and mutation databases

BioMutaiEPCAM.
DMDMi160266056.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000002246724 – 314Epithelial cell adhesion moleculeAdd BLAST291

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24Pyrrolidone carboxylic acidCurated1
Disulfide bondi27 ↔ 46PROSITE-ProRule annotation1 Publication
Disulfide bondi29 ↔ 59PROSITE-ProRule annotation1 Publication
Disulfide bondi38 ↔ 48PROSITE-ProRule annotation1 Publication
Disulfide bondi66 ↔ 99PROSITE-ProRule annotation1 Publication
Glycosylationi74N-linked (GlcNAc...) asparagine; partial2 Publications1
Disulfide bondi110 ↔ 116PROSITE-ProRule annotation1 Publication
Glycosylationi111N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi118 ↔ 135PROSITE-ProRule annotation1 Publication
Glycosylationi198N-linked (GlcNAc...) asparagine2 Publications1

Post-translational modificationi

Hyperglycosylated in carcinoma tissue as compared with autologous normal epithelia. Glycosylation at Asn-198 is crucial for protein stability.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

EPDiP16422.
MaxQBiP16422.
PaxDbiP16422.
PeptideAtlasiP16422.
PRIDEiP16422.

PTM databases

iPTMnetiP16422.
PhosphoSitePlusiP16422.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000119888.
CleanExiHS_EPCAM.
ExpressionAtlasiP16422. baseline and differential.
GenevisibleiP16422. HS.

Organism-specific databases

HPAiCAB003809.
CAB030012.
CAB055098.
HPA026761.
HPA067463.

Interactioni

Subunit structurei

Monomer. Interacts with phosphorylated CLDN7.2 Publications

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: GO_Central
  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110250. 5 interactors.
IntActiP16422. 1 interactor.
MINTiMINT-4999389.
STRINGi9606.ENSP00000263735.

Structurei

Secondary structure

1314
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 40Combined sources6
Beta strandi46 – 50Combined sources5
Beta strandi56 – 58Combined sources3
Helixi65 – 72Combined sources8
Turni73 – 75Combined sources3
Beta strandi107 – 111Combined sources5
Turni112 – 114Combined sources3
Beta strandi115 – 120Combined sources6
Beta strandi130 – 132Combined sources3
Beta strandi141 – 150Combined sources10
Helixi159 – 173Combined sources15
Helixi178 – 180Combined sources3
Beta strandi181 – 187Combined sources7
Beta strandi190 – 196Combined sources7
Turni199 – 201Combined sources3
Helixi209 – 220Combined sources12
Beta strandi226 – 228Combined sources3
Helixi244 – 246Combined sources3
Beta strandi248 – 255Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4MZVX-ray1.86A24-265[»]
ProteinModelPortaliP16422.
SMRiP16422.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 135Thyroglobulin type-1PROSITE-ProRule annotationAdd BLAST73

Sequence similaritiesi

Belongs to the EPCAM family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFI6. Eukaryota.
ENOG4111M3B. LUCA.
GeneTreeiENSGT00390000018245.
HOGENOMiHOG000074086.
InParanoidiP16422.
KOiK06737.
PhylomeDBiP16422.
TreeFamiTF332767.

Family and domain databases

Gene3Di4.10.800.10. 1 hit.
InterProiView protein in InterPro
IPR000716. Thyroglobulin_1.
PfamiView protein in Pfam
PF00086. Thyroglobulin_1. 1 hit.
SMARTiView protein in SMART
SM00211. TY. 1 hit.
SUPFAMiSSF57610. SSF57610. 1 hit.
PROSITEiView protein in PROSITE
PS00484. THYROGLOBULIN_1_1. 1 hit.
PS51162. THYROGLOBULIN_1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P16422-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPPQVLAFG LLLAAATATF AAAQEECVCE NYKLAVNCFV NNNRQCQCTS
60 70 80 90 100
VGAQNTVICS KLAAKCLVMK AEMNGSKLGR RAKPEGALQN NDGLYDPDCD
110 120 130 140 150
ESGLFKAKQC NGTSMCWCVN TAGVRRTDKD TEITCSERVR TYWIIIELKH
160 170 180 190 200
KAREKPYDSK SLRTALQKEI TTRYQLDPKF ITSILYENNV ITIDLVQNSS
210 220 230 240 250
QKTQNDVDIA DVAYYFEKDV KGESLFHSKK MDLTVNGEQL DLDPGQTLIY
260 270 280 290 300
YVDEKAPEFS MQGLKAGVIA VIVVVVIAVV AGIVVLVISR KKRMAKYEKA
310
EIKEMGEMHR ELNA
Length:314
Mass (Da):34,932
Last modified:November 13, 2007 - v2
Checksum:i023FCE418B2F1079
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti277I → M in AAA36151 (PubMed:2463074).Curated1
Sequence conflicti277I → M in CAA32870 (PubMed:2463074).Curated1
Sequence conflicti277I → M in AAA59543 (PubMed:2469722).Curated1
Sequence conflicti303K → R in CAG47055 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06382966C → Y in DIAR5. 1 PublicationCorresponds to variant dbSNP:rs267606785Ensembl.1
Natural variantiVAR_018329115M → T4 PublicationsCorresponds to variant dbSNP:rs1126497Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1833.1.
PIRiB48149.
RefSeqiNP_002345.2. NM_002354.2.
UniGeneiHs.542050.

Genome annotation databases

EnsembliENST00000263735; ENSP00000263735; ENSG00000119888.
GeneIDi4072.
KEGGihsa:4072.
UCSCiuc002rvx.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEPCAM_HUMAN
AccessioniPrimary (citable) accession number: P16422
Secondary accession number(s): P18180
, Q6FG26, Q6FG49, Q96C47, Q9UCD0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 13, 2007
Last modified: September 27, 2017
This is version 172 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families