ITGB2 Gene

Last updated on: 30.06.2022

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DefinitionThis section has been translated automatically.

The ITGB2 gene (ITGB2 stands for "Integrin Subunit Beta 2") is a protein-coding gene located on chromosome 21q22.3. Alternative splicing results in multiple transcript variants.

General informationThis section has been translated automatically.

The ITGB2 gene encodes an integrin beta chain that combines with several different alpha chains to form different integrin heterodimers (ITGAL/ITGB2). Integrins are integral cell surface proteins involved in both cell adhesion and cell surface-mediated signal transduction. The encoded protein plays an important role in the immune response. Defects in this gene lead to a deficiency in leukocyte adhesion, resulting in essential leukocyte dysfunction.

The integrin heterodimer ITGAL/ITGB2 is a receptor for ICAMs (ICAM1, ICAM2, ICAM3, ICAM4). Furthermore, this protein complex also functions as a receptor for the secreted form of the ubiquitin-like protein ISG15; the interaction is mediated by ITGAL (Swaim CD et al. 2017).

The complexed integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and further for fibrinogen. The integrin ITGAX/ITGB2 receptor recognizes the sequence G-P-R in the alpha chain of fibrinogen. The integrin ITGAM/ITGB2 receptor recognizes the P1 and P2 peptides of the fibrinogen gamma chain. Furthermore, the integrin ITGAM/ITGB2 complex also functions as a receptor for factor X.

The integrin ITGAD/ITGB2 -heterodimer is a receptor for ICAM3 and VCAM1. This receptor contributes to the cytotoxicity of natural killer cells. It further participates in leukocyte adhesion and transmigration of leukocytes, including T cells and neutrophils (Ostermann G et. al. 2002) and triggers transmigration of neutrophils in lung injury through PTK2B/PYK2-mediated activation. The integrin ITGAL/ITGB2 receptor complex, in conjunction with ICAM3, contributes to phagocytosis of apoptotic neutrophil granulocytes by macrophages (Kristóf E et al. (2013).

Adhesion of tumor cells to the vascular endothelium also proceeds via a cascade, the first molecules of which are E- and P-selectins on the endothelial side. This binding causes circulating tumor cells to slow down and allows loose attachment to the endothelium. Downstream of the selectins are the integrins. They trigger an integrin/receptor (e.g. ITGB1/VCAM-1 or ITGB2/ICAM-1)-mediated cascade that leads to consolidation of adhesion and opening of cell-cell contacts between endothelial cells. These opened contacts allow tumor cells to migrate through the endothelium (Orr et al. 2000).

Clinical pictureThis section has been translated automatically.

Diseases associated with ITGB2 include:

  • Leukocyte adhesion deficiency, type I (LAD1)

and

LiteratureThis section has been translated automatically.

  1. Kristóf E et al. (2013) Novel role of ICAM3 and LFA-1 in the clearance of apoptotic neutrophils by human macrophages. Apoptosis 18:1235-1251.
  2. Orr FW et al (2000) Interactions between cancer cells and the endothelium in metastasis. J Pathol 190: 310-329.
  3. Ostermann G et al (2002) JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol 3:151-158.
  4. Swaim CD et al (2017) Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor. Mol Cell 68: 581-590.e5.

Last updated on: 30.06.2022