Integrin alpha X beta 2, also called CD11c/CD18, p150/95 or complement receptor type 4 (CR4), is one of four beta 2 integrins. The non-covalent heterodimer of 150 kDa alpha X/CD11c and 95 kDa beta 2/CD18 integrin subunits is expressed on macrophages, dendritic cells and hairy cell leukemias, with lower amounts on other myeloid cells and activated B, NK and some cytotoxic T cells (1‑7). Like other integrins, alpha X beta 2 has multiple activation states (3). In the presence of divalent cations and "inside-out" signaling, alpha X beta 2 is fully active and extended. The alpha X vWFA or I-domain, which contains the adhesion sites, forms the N-terminal head region with the alpha X beta-propeller and the beta 2 vWFA domain (1, 8). In the inactive state, the heterodimer flexes in the center at the alpha X thigh and calf domains and beta 2 I-EGF domains, impeding access to adhesion sites (1). The 1088 aa human alpha X/CD11c ECD shares 70‑76% aa sequence identity with mouse, rat and canine alpha X while the 678 aa human beta 2/CD18 ECD shares 81‑83% aa sequence identity with mouse, rat, cow, dog, goat, sheep, and pig beta 2. Potential alpha X isoforms containing 719 and 725 aa (as compared to full-length 1163 aa alpha X) lack the vWFA domain and the N-terminus. Active alpha X beta 2 shares some adhesion partners with alpha M beta 2/CD11b/CD18, including complement opsonin fragment iC3b, ICAMs, vWF and fibrinogen, and is expressed on many of the same cells (4‑11). However, alpha M beta 2 activity is often constitutive, while alpha X beta 2 activity requires cell activation (4‑7). alpha X beta 2 also binds osteopontin, Thy-1, plasminogen, heparin, and proteins with abnormally exposed acidic residues (11‑16). The adhesion events are important for proliferation, degranulation, chemotactic migration, and phagocytosis of complement-opsonized particles (5, 6, 9, 11, 12, 16). Mutations of beta 2, especially in the vWFA domain, cause leukocyte adhesion deficiency (LAD-1) and susceptibility to bacterial infections (17).
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| Product By Gene ID | 3687 |
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