PECAM1

Description

The PECAM1 (platelet and endothelial cell adhesion molecule 1) is a protein-coding gene located on chromosome 17.

Platelet endothelial cell adhesion molecule (PECAM-1), also known as cluster of differentiation 31 (CD31), is a protein encoded by the PECAM1 gene on chromosome 17q23.3. PECAM-1 plays a critical role in removing aged neutrophils from the body. PECAM-1 is a highly glycosylated protein with a molecular weight of approximately 130 kDa. Its structure was determined by molecular cloning in 1990. PECAM-1 has an N-terminal domain with 574 amino acids, a transmembrane domain with 19 amino acids, and a C-terminal cytoplasmic domain with 118 amino acids. The N-terminal domain consists of six extracellular Ig-like domains. PECAM-1 is a cell-cell adhesion protein that interacts with other PECAM-1 molecules (homophilic interactions) or with non-PECAM-1 molecules (heterophilic interactions). Homophilic interactions between PECAM-1 molecules are mediated by antiparallel interactions between extracellular Ig-like domain 1 and Ig-like domain 2. These interactions are regulated by the level of PECAM-1 expression. Homophilic interactions occur only when the surface expression of PECAM-1 is high. Otherwise, when expression is low, heterophilic interactions occur.

PECAM1 is a cell adhesion molecule essential for leukocyte migration across endothelial barriers (transendothelial migration, TEM) under inflammatory conditions. The tyrosine residue at position 690 (Tyr-690) is crucial for TEM by controlling PECAM1 trafficking between the lateral border recycling compartment (LBRC) and the cell membrane, and by facilitating LBRC membrane movement around migrating leukocytes. PECAM1 interacts with itself (homophilically) to contribute to cell-cell adhesion within endothelial junctions. PECAM1 also interacts with CD177 (heterophilically), playing a role in neutrophil TEM. Interestingly, PECAM1 ligation prevents macrophages from engulfing neighboring healthy leukocytes by sending a detachment signal. Conversely, PECAM1 promotes the engulfment of apoptotic leukocytes by tethering them to macrophages, as the detachment signal seems to be disabled in apoptotic cells. PECAM1 modulates bradykinin receptor activation and regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in endothelial cells. It has been linked to increased susceptibility to atherosclerosis. PECAM1 does not protect cells from apoptosis. It forms trans-homodimers through its Ig-like C2-type 1 and 2 domains, a process vital for cell-cell interactions. PECAM1 associates with BDKRB2 and GNAQ. Additionally, it interacts with PTPN11, with Tyr-713 being essential for PTPN11 recruitment. PECAM1 also interacts with FER. PECAM1 binds to CD177 through its Ig-like C2-type domain 6, in a calcium-dependent and direct manner.

PECAM1 is also known as CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing