ITGA2

ITGA2, officially known as integrin subunit alpha 2, is a protein-encoding gene located on the short arm of chromosome 5 (5p13.1). It belongs to the integrin family, which are transmembrane receptors involved in cell adhesion and signal transduction. Integrins play critical roles in various cellular processes, including migration, differentiation, and survival.

The integrin alpha-2 subunit pairs primarily with the integrin beta-1 subunit (ITGB1) to form the α2β1 integrin receptor, also referred to as very late antigen-2 (VLA-2). This heterodimeric receptor is expressed on the surface of many cell types, including platelets, leukocytes, and endothelial cells. Its primary ligand is collagen, a major structural protein in the extracellular matrix, which enables α2β1 to mediate cell adhesion to collagen fibers.

Mutations in ITGA2 have been linked to several human disorders. The most well-characterized condition associated with ITGA2 dysfunction is Glanzmann thrombasthenia-like syndrome, though this is more commonly caused by defects in other integrin subunits. More specifically, rare mutations in ITGA2 can lead to a bleeding disorder known as platelet-type von Willebrand disease (PT-vWD), where impaired α2β1 function results in defective platelet adhesion to collagen. This can cause prolonged bleeding times and increased susceptibility to hemorrhage.

In addition to its role in hemostasis, α2β1 integrin is involved in immune responses, wound healing, and cancer progression. Research suggests that α2β1 may influence tumor metastasis by modulating cell adhesion and migration in the tumor microenvironment. Further studies are ongoing to elucidate its precise mechanisms in disease pathology and potential therapeutic targets.

The structure of the α2 integrin subunit includes a large extracellular domain, a single transmembrane region, and a short cytoplasmic tail. Its extracellular domain contains multiple binding sites for collagen and other ligands, facilitating its adhesive functions. The gene itself spans approximately 100 kilobases and consists of 20 exons, encoding a protein of around 1,100 amino acids.