Cdh1

SECTIONS

1 - Domain
2 - Function
3 - Involvement in disease
4 - Post-translational modifications
5 - Tissue specificity
6 - Cellular localization
7 - Alternative names
8 - Database links
9 - Target type
10 - Primary research area
11 - Other research areas
12 - Molecular weight

Domain

Three calcium ions are usually bound at the interface of each cadherin domain and strengthen the connections, imparting a strong curvature to the full-length ectodomain.

Function

CDH1 encodes a protein that is a calcium-dependent cell adhesion molecule, playing a role in cell-cell adhesion, mobility, and proliferation in epithelial cells. It acts as a potent invasive suppressor and serves as a ligand for integrin alpha-E/beta-7. The protein contributes to the sorting of heterogeneous cell types due to its homophilic interactions. E-Cad/CTF2, a product of CDH1, promotes the non-amyloidogenic degradation of Abeta precursors and strongly inhibits the production of APP C99 and C83. Additionally, in the context of microbial infection, it functions as a receptor for Listeria monocytogenes, with internalin A binding to it to promote bacterial uptake. This supplementary information is collated from multiple sources and compiled automatically.

Involvement in disease

Diffuse gastric and lobular breast cancer syndrome

DGLBC

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. In addition to gastric cancer, most female mutation carriers develop lobular carcinoma of the breast.

None

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.

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.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Ovarian cancer

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.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Breast cancer, lobular

LBC

A type of breast cancer that begins in the milk-producing glands (lobules) of the breast.

None

The gene represented in this entry may be involved in disease pathogenesis.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 (PubMed:10597309, PubMed:11076937, PubMed:11953314). 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.

(Microbial infection) Cleaved by S.pyogenes SpeB protease; leading to its degradation (PubMed:23532847). Degradation by SpeB promotes bacterial translocation across the host epithelial barrier (PubMed:23532847).

Tissue specificity

Expressed in granuloma macrophages (at protein level) (PubMed:27760340). Expressed in the skin (at protein level) (PubMed:22294297). Expressed in the liver (PubMed:3263290).

Cellular localization

Cell junction
Adherens junction
Cell membrane
Single-pass type I membrane protein
Endosome
Golgi apparatus
trans-Golgi network
Cytoplasm
Cell junction
Desmosome
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. Recruited to desmosomes at the initial assembly phase and also accumulates progressively at mature desmosome cell-cell junctions (PubMed:25208567). Localizes to cell-cell contacts as keratinocyte differentiation progresses (By similarity).