|CD324||CDH1 (cadherin 1), CDHE, UVO(uvomorulin), ECAD, Arc1, E-cadherin|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|120 / 120|
|CD324 is expressed on non-neural epithelial tissues, stem cells, erythroblasts, keratinocytes, trophoblasts, and platelets.|
|MOLECULAR FAMILY NAME: Belongs to the cadherin superfamily.|
CD324 is a single-pass type-1 728 aa glycoprotein. It contains a 23 aa signal sequence, an 131 aa propeptide, a 553 aa extracellular domain which contains 5 cadherin domains, 2 potential N-linked glycosylation sites and binds a Ca2+ ion, a 24 aa transmembrane domain and a highly conserved 151 aa cytoplasmic domain which has a 14 aa stretch which is serine rich. Some studies have identified the cadherin domains as essential for homophilic binding, whereas other studies indicate all five domains are required. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein.
The extracellular domain 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.
CD324 has 2 potential N-linked glycosylation domains.
|LIGANDS AND MOLECULE ASSOCIATED WITH CD324|
CD324 is associated with CD103, E-cadherin, PS1, catenins and internalin. CD324 displays homophilic binding but has also been found to bind integrin αEβ7 and integrin α2β1.
|CD324, E-Cadherin, functions as a cell-cell adhesion molecule via calcium-dependent homophilic binding and plays an important role in the intracellular adhesion of epithelial cells. Classical type 1 cadherins are mostly found in tissues where a high level of cell cohesiveness is required to maintain tissue integrity. The cadherins and catenins, being the prime mediators of the cell-cell adhesion, are intimately involved in the control of morphological differentiation and cellular proliferation. Loss or abnormal function of CD324 has been implicated in the development and progression of a wide range of tumors. This loss of their intercellular function allows malignant cells to escape from their site of origin, degrade the extracellular matrix, acquire a more motile and invasive phenotype, and finally, invade and matastasize. The E-cadherin-catenin complex is fundamental for the establishment and maintenance of multicellular organism and regulates or significantly contributes to a variety of functions, including signal transduction, cell growth, differentiation, site-specific gene expression, morphogenesis, immunological function, cell motility, wound healing and inflammation. CD324 contributes to cell differentiation and polarity. It is localized principally in the adherens junctions. The cytoplasmic domain binds β-catenin, which via association with α-catenin and other structural proteins is connected to the aactin cytoskeleton. The connection of CD324 with the actin cytoskeleton is required for normal cell-cell adhesion as mutant CD324 molecules lacking the cytoplasmic domain display weak binding to substrate compared with the wild-type molecule. |
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD324 IN INTACT ANIMAL
CD324 has a potent invasive suppressor role in tumor suppression and cell growth and differentiation. CD324 is a suppressor of tumor development and progression, as loss of abnormal function is associated with several tumors, including gastric, breast, ovarian, endometrial and thyroid carcinomas. Loss of function is thought to contribute to progression in gastric and endometrial cancer by increasing proliferation, invasion, and/or metastasis.
CD324 expression is downregulated in several carcinomas and this usually correlates with high grade tumor progression and a poor prognosis. CD324 knockout mice embryros die at pre-implantation stage, indicating expression of the cadherin is critical during embryonic development.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD324: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD324: No information.
For further information see Harrington , K. J. et al (2000) Ann. Surg. Oncol. 7: 783-788.
Database accession numbers
Revised June 25, 2008