ID:CADH1_HUMAN DESCRIPTION: RecName: Full=Cadherin-1; AltName: Full=CAM 120/80; AltName: Full=Epithelial cadherin; Short=E-cadherin; AltName: Full=Uvomorulin; AltName: CD_antigen=CD324; Contains: RecName: Full=E-Cad/CTF1; Contains: RecName: Full=E-Cad/CTF2; Contains: RecName: Full=E-Cad/CTF3; Flags: Precursor; 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. SUBUNIT: 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. INTERACTION: P30260:CDC27; NbExp=2; IntAct=EBI-727477, EBI-994813; P35222:CTNNB1; NbExp=6; IntAct=EBI-727477, EBI-491549; P11362:FGFR1; NbExp=2; IntAct=EBI-727477, EBI-1028277; P62136:PPP1CA; NbExp=2; IntAct=EBI-727477, EBI-357253; Q15139:PRKD1; NbExp=7; IntAct=EBI-727477, EBI-1181072; P12931:SRC; NbExp=2; IntAct=EBI-727477, EBI-621482; Q68CZ2:TNS3; NbExp=2; IntAct=EBI-727477, EBI-1220488; 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. TISSUE SPECIFICITY: Non-neural epithelial tissues. INDUCTION: Expression is repressed by MACROD1. 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 disassembly of adherens junctions. PTM: N-glycosylation at Asn-637 is essential for expression, folding and trafficking. PTM: Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. DISEASE: Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [MIM:137215]. An autosomal dominant 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=Heterozygous germline mutations CDH1 are responsible for familial cases of diffuse gastric cancer. Somatic mutations in the has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer. DISEASE: Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089]. DISEASE: Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [MIM:167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms 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. SIMILARITY: Contains 5 cadherin domains. SEQUENCE CAUTION: Sequence=AAA61259.1; Type=Frameshift; Positions=16, 22, 25, 28, 31, 34, 52, 67, 73, 76, 94, 102, 633, 636; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDH1ID166ch16q22.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CDH1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdh1/"; WEB RESOURCE: Name=Wikipedia; Note=E-cadherin entry; URL="http://en.wikipedia.org/wiki/E-cadherin";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P12830
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0007155 cell adhesion GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007416 synapse assembly GO:0009636 response to toxic substance GO:0010033 response to organic substance GO:0021983 pituitary gland development GO:0022408 negative regulation of cell-cell adhesion GO:0030198 extracellular matrix organization GO:0031175 neuron projection development GO:0034332 adherens junction organization GO:0035635 entry of bacterium into host cell GO:0042307 positive regulation of protein import into nucleus GO:0042493 response to drug GO:0045893 positive regulation of transcription, DNA-templated GO:0071285 cellular response to lithium ion GO:0071681 cellular response to indole-3-methanol GO:0072659 protein localization to plasma membrane GO:0098609 cell-cell adhesion
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
