CDH1
Cadherin-1 also known as CAM 120/80 or epithelial cadherin (E-cadherin) or uvomorulin is a protein that in humans is encoded by the CDH1 gene.
Function
Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333).
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 (PubMed:11976333).
Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.
E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.
(Microbial infection) Serves as a receptor for Listeria monocytogenes; internalin A (InlA) binds to this protein and promotes uptake of the bacteria.
Biological Process
Adherens junction organization Source: UniProtKB
Cell-cell adhesion Source: BHF-UCL
Cell-cell adhesion via plasma-membrane adhesion molecules Source: GO_Central
Cellular response to indole-3-methanol Source: UniProtKB
Cellular response to lithium ion Source: UniProtKB
Entry of bacterium into host cell Source: Reactome
Extracellular matrix organization Source: Reactome
Homophilic cell adhesion via plasma membrane adhesion molecules Source: UniProtKB
Negative regulation of cell-cell adhesion Source: UniProtKB
Negative regulation of cell migration Source: ARUK-UCL
Neuron projection development Source: Ensembl
Pituitary gland development Source: Ensembl
Positive regulation of protein import into nucleus Source: BHF-UCL
Positive regulation of transcription, DNA-templated Source: BHF-UCL
Protein localization to plasma membrane Source: BHF-UCL
Regulation of gene expression Source: UniProtKB
Regulation of protein catabolic process at postsynapse, modulating synaptic transmission Source: Ensembl
Response to drug Source: Ensembl
Response to toxic substance Source: Ensembl
Synapse assembly Source: GO_Central
Cellular Location
Endosome; Trans-Golgi network; Cell membrane; Adherens junction. 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.
Involvement in disease
Hereditary diffuse gastric cancer (HDGC): Disease susceptibility is associated with variants affecting the gene represented in this entry. Heterozygous CDH1 germline mutations are responsible for familial cases of diffuse gastric cancer. Somatic mutations has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer. A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body.
Endometrial cancer (ENDMC): A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids.
Ovarian cancer (OC): The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
Breast cancer, lobular (LBC): A type of breast cancer that begins in the milk-producing glands (lobules) of the breast.
Blepharocheilodontic syndrome 1 (BCDS1): A form of blepharocheilodontic syndrome, a rare autosomal dominant disorder. It is characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and features of ectodermal dysplasia, including hair anomalies, conical teeth and tooth agenesis. An additional rare manifestation is imperforate anus. There is considerable phenotypic variability among affected individuals.
Topology
Extracellular: 155-709
Helical: 710-730
Cytoplasmic: 731-882
PTM
During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 (PubMed:11076937, PubMed:11953314, PubMed:10597309). Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm (PubMed:10597309). The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway (PubMed:10597309). Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system (PubMed:11076937). The gamma-secretase-mediated cleavage promotes disassembly of adherens junctions (PubMed:11953314). During development of the cochlear organ of Corti, cleavage by ADAM10 at adherens junctions promotes pillar cell separation (By similarity).
N-glycosylation at Asn-637 is essential for expression, folding and trafficking. Addition of bisecting N-acetylglucosamine by MGAT3 modulates its cell membrane location (PubMed:19403558).
Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, requires prior phosphorylation at Tyr-754.
O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4. Thr-285 and Thr-509 are O-mannosylated by TMTC2 or TMTC4 but not TMTC1 or TMTC3.
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Datasheet