Background: 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. E-cadherin is a Ca2+-dependent epithelial cell-cell adhesion molecule. Downregulation of E-cadherin expression often correlates with strong invasive potential and poor prognosis of human carcinomas. It has 16 exons spanning approximately 100 kb of genomic DNA. The gene structure is similar to that of other cadherins. E-cadherin plays a central part in the process of epithelial morphogenesis. Expression of this protein is downregulated during the acquisition of metastatic potential at late stages of epithelial tumour progression.
NCBI and Uniprot Product Information
NCBI Description
This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. Identified transcript variants arise from mutation at consensus splice sites. [provided by RefSeq, Jul 2008]
Uniprot Description
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. Ref.25E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production. Ref.25
Subunit structure: Homodimer; disulfide-linked. Component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and potentially alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs). Interacts with AJAP1, CTNND1 and DLGAP5
By similarity. Interacts with TBC1D2. Interacts with LIMA1. Interacts with CAV1. Interacts with the TRPV4 and CTNNB1 complex
By similarity. Interacts with PIP5K1C. Interacts with RAB8B
By similarity. Interacts with DDR1; this stabilizes CDH1 at the cell surface and inhibits its internalization. Ref.10 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.28 Ref.30 Ref.31
Subcellular location: Cell junction. Cell membrane; Single-pass type I membrane protein. Endosome. Golgi apparatus › trans-Golgi network. Note: 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. Ref.4 Ref.21 Ref.24 Ref.31
Tissue specificity: Non-neural epithelial tissues.
Induction: Expression is repressed by MACROD1. Ref.26
Domain: Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Ref.16
Post-translational modification: 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 disassembly of adherens junctions. Ref.4 Ref.15 Ref.18N-glycosylation at Asn-637 is essential for expression, folding and trafficking.Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, requires prior phosphorylation at Tyr-754. Ref.33 Ref.34
Involvement in disease: Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Heterozygous germline mutations CDH1 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. Ref.46 Ref.51Endometrial cancer (ENDMC) [MIM:608089]: 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.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.Ovarian cancer (OC) [MIM:167000]: 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.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Sequence similarities: Contains 5 cadherin domains.
Sequence caution: The sequence AAA61259.1 differs from that shown. Reason: Frameshift at positions 16, 22, 25, 28, 31, 34, 52, 67, 73, 76, 94, 102, 633 and 636.
Research Articles on CDH1
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Product Notes
The Mouse CDH1 cdh1 (Catalog #AAA355433) is an ELISA Kit and is intended for research purposes only. The product is available for immediate purchase. The AAA355433 ELISA Kit recognizes Mouse CDH1. AAA Biotech's E-Cadherin can be used in a range of immunoassay formats including, but not limited to, Quantitative sELISA (EIA). For quantitative detection of E-Cadherin in mouse serum, plasma, body fluids, tissue lysates or cell culture supernatants. Researchers should empirically determine the suitability of the CDH1 cdh1 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "E-Cadherin, ELISA Kit" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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