E-Cadherin Rabbit Polyclonal Antibody

Function

Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the CDH1 gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. CDH1 has also been designated as CD324 (cluster of differentiation 324). It is a tumor suppressor gene. Cadherin-1 is a classical member of the cadherin superfamily. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed 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 cancers. 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. E-cadherin (epithelial) is the most well-studied member of the cadherin family. It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin. The intracellular domain contains a highly-phosphorylated region vital to beta-catenin binding and, therefore, to E-cadherin function.

Background References

1. Meigs T.E et al. Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin. J Biol Chem 277:24594-24600 (2002).

2. Agiostratidou G et al. The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors. J Neurochem 96:1182-1188 (2006).

Tissue Specificity

Non-neural epithelial tissues.

Post-translational Modification

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

Subcellular Location

Cell membrane.

UNIPROT

SwissProt: P12830 Human

SwissProt: P09803 Mouse

Synonyms