PROSITE documentation PDOC00215

Integrins alpha chain signature

Integrins [1,2] are a large family of cell surface receptors that mediate cell to cell as well as cell to matrix adhesion. Some integrins recognize the R-G-D sequence in their extracellular matrix protein ligand. Structurally, integrins consist of a dimer of an α and a β chain. Each subunit has a large N-terminal extracellular domain followed by a transmembrane domain and a short C-terminal cytoplasmic region. Some α subunits are cleaved post-translationally to produce a heavy and a light chain linked by a disulfide bond. The sequence of a number of α chains has been obtained and are listed below:

• The α-1 chain (VLA-1) (CD49a) which, with the β-1 chain, acts as a receptor for laminin and collagen.
• The α-2 chain (VLA-2) (CD49b) which, with the β-1 chain, acts as a receptor that binds collagen.
• The α-3 chain (VLA-3) (Galactoprotein B3).
• The α-4 chain (VLA-4) (CD49d) which, with the β-1 chain, interacts with vascular cell adhesion protein 1 (VCAM-1).
• The α-5 chain (VLA-5) (CD49e) which, with the β-1 chain, forms a receptor specific to fibronectin.
• The α-6 chain (VLA-6) which, with the β-1 chain, forms a platelet laminin receptor.
• The α-7 chain which, with the β-1 chain, forms a skeletal myoblast laminin receptor.
• The α-8 chain which, with the β-1 chain plays a possible role in cell-cell interactions during axon-growth and fasciculation.
• The α-L chain (LFA-1) (CD11a) which, with the β-2 chain, interacts with intercellular adhesion molecule 1 (ICAM-1).
• The α-M chain (MAC-1) (CD11b) which, with the β-2 chain, forms the receptor for the iC3b fragment of the third complement component.
• The α-X chain (p150,95) (CD11c) which, with the β-2 chain, probably forms a receptor for the iC3b fragment of the third complement component.
• The α-V chain (CD51) which, with the β-3 chain, forms a receptor that binds vitronectin.
• The α-IIB chain (CD41) (also known as platelet glycoprotein IIb) which, with the β-3 chain, forms a receptor which binds VWF, fibrinogen, fibronectin, and vitronectin.
• The Drosophila position-specific antigen 2 α chain (PS2).
• Caenorhabditis elegans hypothetical proteins F54F2.1 and F54G8.3.

All these integrin α chains share a conserved sequence which is found at the beginning of the cytoplasmic domain, just after the end of the transmembrane region. This motif is probably involved in heterodimer association and may lock the heterodimer into a low affinity conformation in the abscence of activating signals. We have used this conserved region as a signature pattern.