CDH1

disease:Defects in CDH1 are a cause of gastric cancer [MIM:137215]; also known as hereditary familial diffuse gastric cancer (HDGC).,disease:Defects in CDH1 are a cause of susceptibility to endometrial cancer [MIM:608089].,disease:Defects in CDH1 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome.,disease:Defects in CDH1 are involved in dysfunction of the cell-cell adhesion system, triggering cancer invasion (gastric, breast, ovary, endometrium and thyroid) and metastasis.,function:Cadherins are calcium dependent cell adhesion proteins.,function:Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.,function:E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.,online information:E-cadherin entry,PTM:During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 to produce fragments of about 38 kDa (E-CAD/CTF1), 33 kDa (E-CAD/CTF2) and 29 kDa (E-CAD/CTF3), respectively. Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm. The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway. Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system. The gamma-secretase-mediated cleavage promotes disaaaembly of adherens junctions.,similarity:Contains 5 cadherin domains.,subcellular location:Colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells. Anchored to actin microfilaments through association with alpha-, beta- and gamma-catenin. Sequential proteolysis induced by apoptosis or calcium influx, results in translocation from sites of cell-cell contact to the cytoplasm.,subunit:Homodimer; disulfide-linked. 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 the actin binding of alpha-catenin. Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs). Interacts with AJAP1, CTNND1 and DLGAP5.,tissue specificity:Non-neural epithelial tissues.,

in utero embryonic development, blastocyst development, blastocyst formation, trophectodermal cell differentiation,protein complex assembly, cell adhesion, homophilic cell adhesion, synaptogenesis, response to toxin, embryonic development ending in birth or egg hatching, response to organic substance, regulation of cell death, cell-cell adhesion, diencephalon development, pituitary gland development, biological adhesion, cell projection organization,neuron differentiation, forebrain development, neuron projection development, regulation of intracellular transport,positive regulation of intracellular transport, regulation of protein localization, regulation of intracellular protein transport, endocrine system development, regulation of protein import into nucleus, positive regulation of protein import into nucleus, response to drug, regulation of apoptosis, regulation of transcription factor import into nucleus,positive regulation of transcription factor import into nucleus, chordate embryonic development, extracellular structure organization, regulation of programmed cell death, regulation of caspase activity, macromolecular complex subunit organization, regulation of nucleocytoplasmic transport, positive regulation of nucleocytoplasmic transport, neuron development, gland development, synapse organization, positive regulation of transport, positive regulation of protein transport, regulation of protein transport, protein oligomerization, protein homooligomerization, regulation of hydrolase activity, regulation of peptidase activity, regulation of endopeptidase activity, regulation of cellular localization, macromolecular complex assembly, regulation of establishment of protein localization, protein complex biogenesis,

Cell junction, adherens junction . Cell membrane ; Single-pass type I membrane protein. Endosome. Golgi apparatus, trans-Golgi network. Colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells. Anchored to actin microfilaments through association with alpha-, beta- and gamma-catenin. Sequential proteolysis induced by apoptosis or calcium influx, results in translocation from sites of cell-cell contact to the cytoplasm. Colocalizes with RAB11A endosomes during its transport from the Golgi apparatus to the plasma membrane.

Non-neural epithelial tissues.