| Category | Evidence-backed summary |
|---|---|
| Identity/aliases | Human **CDH1** encodes **E-cadherin**, a ~120 kDa calcium-dependent cell-cell adhesion glycoprotein also known as epithelial cadherin; this matches the canonical epithelial adherens-junction cadherin described for CDH1 at chromosome 16q22.1 (pqac-00000003, pqac-00000006). |
| Structure/domains | E-cadherin is a **single-pass transmembrane** protein with extracellular, transmembrane, and intracellular regions; the ectodomain contains **five cadherin repeats (EC1-EC5)** with calcium-binding sites, consistent with cadherin-family domain architecture (pqac-00000003). |
| Adhesion mechanism | Adhesion is mediated by **homophilic trans-interactions** between EC1 domains, proceeding through an **X-dimer intermediate** to a stable **strand-swapped dimer** in which a tryptophan side chain inserts into the partner EC1 hydrophobic pocket; calcium stabilizes the ectodomain for adhesion (pqac-00000003). |
| Localization | E-cadherin localizes mainly at the **plasma membrane of epithelial cells**, concentrated at **adherens junctions**, where it maintains epithelial sheet cohesion, polarity, and barrier/tissue architecture (pqac-00000003, pqac-00000004). |
| Key binding partners | Its cytoplasmic tail links to the actin cytoskeleton through **catenins**, especially **β-catenin**, **α-catenin**, and **p120-catenin**; this coupling is central to junction stability and force transmission (pqac-00000003, pqac-00000005). |
| Signaling/pathways | Beyond adhesion, CDH1/E-cadherin participates in **mechanotransduction** and constrains oncogenic signaling; loss of E-cadherin can permit **β-catenin nuclear translocation/Wnt signaling**, alter **RhoA/Rac1** activity via p120-catenin, and is tightly linked to **EMT** and tumor progression (pqac-00000002, pqac-00000005). |
| Proteolytic processing/soluble fragments | E-cadherin can undergo **proteolytic cleavage/shedding**, generating **soluble E-cadherin fragments**; cleavage releases junctional restraint and can free β-catenin, with reported detection of soluble E-cadherin in cancer-associated biofluids such as urine (pqac-00000005). |
| Disease relevance/clinical | Germline **CDH1 pathogenic variants** cause **hereditary diffuse gastric cancer (HDGC)** and increase risk of **lobular breast cancer**. Recent reviews report lower modern estimates for **advanced diffuse gastric cancer risk (~13-19%)** than historic estimates, while **~30% to one third** of carriers decline prophylactic total gastrectomy because of major long-term consequences, motivating expert-center endoscopic surveillance in selected patients (pqac-00000009, pqac-00000011). |


*Table: This table summarizes core functional-annotation facts for human CDH1/E-cadherin (UniProt P12830), including structure, mechanism, localization, partners, pathways, and clinical relevance. It is useful as a compact, evidence-backed reference for the final research report.*