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Beschreibung

Integrin alpha-M (UniProt: P11215, also known as CD11 antigen-like family member B, CR-3 alpha chain, Cell surface glycoprotein MAC-1 subunit alpha, Leukocyte adhesion receptor MO1, Neutrophil adherence receptor, CD11b) is encoded by the ITGAM (also known as CD11B, CR3A) gene (Gene ID: 3684) in human. Integrins are alpha/beta heterodimeric adhesion receptors that couple the extracellular matrix on other cells with the contractile cytoskeleton to transduce mechanochemical signals across the plasma membrane. CD11b is a single-pass type I membrane protein that is synthesized with a signal peptide (aa 1-16), which is cleaved off in the mature form. It is predominantly expressed in monocytes and granulocytes and some expression is also observed in neutrophils. It is usually found as a heterodimer of alpha and beta subunits and associates with Integrin beta-2 (ITGB2). Two isoforms of CD11b have been reported that are produced by alternative splicing. CD11b contains a large extracellular domain (aa 17-1104), a short transmembrane domain (aa 1105-1128), and a cytoplasmic domain (aa 1129-1152). It has been implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It contains a metal ion-dependent adhesion site (MIDAS) in the integrin A domain, which is essential for stabilization of domain A in high affinity state. The major ligand recognition site of CD11b/CD18 has been mapped to the A-domain in the CD11b subunit (CD11bA). Both magnesium and calcium ions exhibit equal affinities for the inactive CD11bA, however, upon activation there is a 10-fold increase in the binding affinity of magnesium ions without affecting affinity of calcium ions. Mutations in ITGAM gene are known to cause Systemic lupus erythematosus 6, which is characterized by wide range of system dysfunctions, principally involving skin, joints, kidneys and serosal membranes. (Ref.: Zerria, K., et al. (2006). Immunology 119(4), 431-440, Mahalingam, B., et al., (2011). J. Immunol. 187 (12), 6393-6401, Li, R., et al. (2002). J. Immunol. 168 (3), 1219-1225.).