Cdh1

Developmental stage

In the testis, expression is highest in fetal gonad, then decreases 5-fold in newborn. Detectable in 7-day-old but not in 21-day-old or adult.

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

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). Promotes organization of radial actin fiber structure and cellular response to contractile forces, via its interaction with AMOTL2 which facilitates anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane (By similarity). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7 (By similarity).

E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production (By similarity).

(Microbial infection) Does not function as a receptor for L.monocytogenes internalin A (InlA); mutating a single surface-exposed residue confers receptor activity to this protein and promotes uptake of the bacteria.

Post-translational modifications

During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 (By similarity). Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm (By similarity). The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway (By similarity). Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system (By similarity). The gamma-secretase-mediated cleavage promotes disassembly of adherens junctions (By similarity). During development of the cochlear organ of Corti, cleavage by ADAM10 at adherens junctions promotes pillar cell separation (PubMed:30639848).

O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4. Ser-287 and Thr-511 are O-manosylated by TMTC2 or TMTC4 but not TMTC1 or TMTC3.

N-glycosylation at Asn-639 is essential for expression, folding and trafficking. Addition of bisecting N-acetylglucosamine by MGAT3 modulates its cell membrane location (By similarity).

Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, requires prior phosphorylation at Tyr-756 (By similarity).

Tissue Specificity

Expressed in inner and outer pillar cells of the organ of Corti (at protein level) (PubMed:30639848). Expressed in granuloma macrophages (at protein level) (PubMed:27760340). Expressed in the epidermal keratinocytes of the skin from birth (at protein level) (PubMed:18079750, PubMed:27375112). Expressed in non-neural epithelial tissues.

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 (By similarity). Recruited to desmosomes at the initial assembly phase and also accumulates progressively at mature desmosome cell-cell junctions (By similarity). Localizes to cell-cell contacts as keratinocyte differentiation progresses (PubMed:27375112).

Alternative names

CD324, Cadherin-1, ARC-1, Epithelial cadherin, Uvomorulin, E-cadherin, Cdh1

Database links

swissprot:P09803 entrezGene:12550

Other research areas

• Neuroscience