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CD324; E-cadherin; cadherin-1; epithelial cadherin; uvomorulin; CAM 120/80 (CDH1, CDHE, UVO)
Function:
- cadherin
- role in regulating cell-cell adhesions, mobility & proliferation of epithelial cells
- potent invasive suppressor role
- ligand for integrin alpha-E/beta-7
- promotes non-amyloidogenic degradation of Abeta precursors
- strong inhibitory effect on APP-C99 & APP-C83 production
- during apoptosis or with Ca+2 influx, cleaved by
a) a membrane-bound metalloproteinase (ADAM10)
1] forms 38 kD (E-CAD/CTF1)
2] processing by ADAM10, induced by Ca+2 influx, causes disruption of cell-cell adhesion & subsequent release of beta-catenin into the cytoplasm
3] residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway
b) PS1/gamma-secretase
1] forms 33 kD (E-CAD/CTF2)
2] cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system
c) caspase-3
1] 29 kD (E-CAD/CTF3)
2] gamma-secretase-mediated cleavage promotes disassembly of adherens junctions
- interacts directly, via the cytoplasmic domain, with CTNNB1 or JUP to form the PSEN1/cadherin/catenin adhesion complex which connects to the actin skeleton through actin binding of alpha-catenin
- interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions
- interacts with AJAP1, CTNND1 & DLGAP5
Structure:
- homodimer, disulfide-linked.
- contains 5 cadherin domains
Compartment:
- cell junction, cell membrane
- colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells
- anchored to actin microfilaments through association with alpha-catenin, beta-catenin & gamma-catenin
- sequential proteolysis induced by apoptosis or Ca+2 influx, results in translocation from sites of cell-cell contact to the cytoplasm
Expression: non-neural epithelial tissues
Pathology:
- defects in CDH1 are involved in dysfunction of the cell-cell adhesion system, triggering cancer invasion (gastric cancer, breast cancer, ovarian cancer, endometrial cancer & thyroid cancer) & metastasis
- defects in CDH1 are a cause of:
a) hereditary diffuse gastric cancer
b) susceptibility to endometrial cancer
Interactions
molecular events
Related
CDH1 (E-cadherin) gene
E-cadherin Ag in tissue
General
cadherin
glycoprotein
phosphoprotein
Properties
SIZE: entity length = 882 aa
MW = 97 kD
COMPARTMENT: cytoplasm
cellular membrane
MOTIF: signal sequence {1-22}
cadherin domain {155-262}
MOTIF: cysteine residue {C163}
MODIFICATION: cysteine residue {C-INTERCHAIN}
cadherin domain {263-375}
cadherin domain {376-486}
cadherin domain {487-593}
MOTIF: N-glycosylation site {N558}
cadherin domain {594-697}
MOTIF: N-glycosylation site {N637}
peptide motif {700-701}
transmembrane domain {710-730}
peptide motif {731-732}
peptide motif {750-751}
binding site
SITE: 758-769
FOR-BINDING-OF: catenin delta-1
presenilin-1
binding site
SITE: 811-882
FOR-BINDING-OF: catenin
MOTIF: serine-rich region {838-851}
MOTIF: serine residue (SEVERAL)
Ser phosphorylation site {S838}
Ser phosphorylation site {S840}
Ser phosphorylation site {S846}
References
- UniProt :accession P12830
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDH1
- Wikipedia; Note: E-cadherin entry
http://en.wikipedia.org/wiki/E-cadherin
- Takeichi M.
Cadherin cell adhesion receptors as a morphogenetic regulator.
Science. 1991 Mar 22;251(5000):1451-5. Review.
PMID: 2006419
- Walsh FS et al
N-cadherin gene maps to human chromosome 18 and is not linked
to the E-cadherin gene.
J Neurochem. 1990 Sep;55(3):805-12.
PMID: 2384753
Component-of
molecular complex
Databases & Figures
OMIM correlations
MORBIDMAP 192090
UniProt P12830
PFAM correlations
Entrez Gene 999
Kegg hsa:999
E-cadherin/CD31 ... F-actin