CD324; E-cadherin; cadherin-1; epithelial cadherin; uvomorulin; CAM 120/80 (CDH1, CDHE, UVO)
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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 membrane-bound metalloproteinase (ADAM10)
- forms 38 kD (E-CAD/CTF1)
- processing by ADAM10, induced by Ca+2 influx, causes disruption of cell-cell adhesion & subsequent release of beta-catenin into the cytoplasm
- residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway
- PS1/gamma-secretase
- forms 33 kD (E-CAD/CTF2)
- cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system
- caspase-3
- 29 kD (E-CAD/CTF3)
- gamma-secretase-mediated cleavage promotes disassembly of adherens junctions
- a membrane-bound metalloproteinase (ADAM10)
- 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:
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P12830.html
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/2384753
Database
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:999
- OMIM: https://mirror.omim.org/entry/137215
- OMIM: https://mirror.omim.org/entry/192090
- OMIM: https://mirror.omim.org/entry/608089
- UniProt: http://www.uniprot.org/uniprot/P12830.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=999