Integrin beta-2

Function

Integrin ITGAL:ITGB2 is a receptor for ICAM1, ICAM2 and ICAM3. Integrin ITGAL:ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Integrins ITGAM:ITGB2 and ITGAX:ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX:ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM:ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM:ITGB2 is also a receptor for factor X. Integrin ITGAD:ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation. Integrin ITGAL:ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils. Integrins ITGAX:ITGB2 functions as a receptor of the erythrocyte-specific adhesion molecule ICAM4 and mediates erythrophagocytosis. Integrins ITGAX:ITGB2 functions as a receptor of the neuron-specific adhesion molecule ICAM5 ensuring neuron cell-leukocyte adhesion. Integrin ITGAL:ITGB2 functions as a receptor of ICAM1 by acting as a platform at the immunological synapse to translate TCR engagement and density of the ITGAL ligand ICAM1 into graded adhesion. Integrin ITGAM:ITGB2/MAC-1 complex functions as a signaling receptor for the ligand receptor ICAM1, ensuring adhesion between stimulated neutrophils and stimulated endothelial cells. Integrin ITGAL/ITGB2 that functions as a signaling receptor of ICAM2, ensuring leukocyte cell-cell adhesion on resting cells.

Classification

Family (Pfam)

PF23105 EGF_integrin, PF08725 Integrin_b_cyt, PF07965 Integrin_B_tail, PF00362 Integrin_beta, PF17205 PSI_integrin

InterPro

EGF_integrin_2, Integrin_b-2_sf, Integrin_beta_N, Integrin_bsu, Integrin_bsu_cyt_dom, Integrin_bsu_tail, Integrin_bsu_tail_dom_sf, Integrin_bsu_VWA, Integrin_dom_sf, Integrin_I-EGF_CS, PSI, vWFA_dom_sf

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 24

• 1L3Y NMR
• 1YUK X-ray 1.80A
• 2JF1 X-ray 2.20A
• 2P26 X-ray 1.75A
• 2P28 X-ray 2.20A
• 2V7D X-ray 2.50A
• 3K6S X-ray 3.50A
• 3K71 X-ray 3.95A
• 3K72 X-ray 3.70A
• 4NEH X-ray 2.75A
• 4NEN X-ray 2.90A
• 5E6R X-ray 2.90A
• … and 12 more

A predicted model is available from AlphaFold.

Gene Ontology · 61

• GO:0009986 cell surface
• GO:0009897 external side of plasma membrane
• GO:0070062 extracellular exosome
• GO:1903561 extracellular vesicle
• GO:0101003 ficolin-1-rich granule membrane
• GO:0005925 focal adhesion
• GO:0034690 integrin alphaD-beta2 complex
• GO:0034687 integrin alphaL-beta2 complex
• GO:0034688 integrin alphaM-beta2 complex
• GO:0034689 integrin alphaX-beta2 complex
• GO:0008305 integrin complex
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0044853 plasma membrane raft
• GO:0043235 receptor complex
• GO:0035579 specific granule membrane
• GO:0070821 tertiary granule membrane
• GO:0001540 amyloid-beta binding
• GO:0050839 cell adhesion molecule binding
• GO:0001851 complement component C3b binding
• GO:0031072 heat shock protein binding
• GO:0030369 ICAM-3 receptor activity
• GO:0005178 integrin binding
• GO:0046872 metal ion binding
• GO:0019901 protein kinase binding
• GO:0097242 amyloid-beta clearance
• GO:0006915 apoptotic process
• GO:0007155 cell adhesion
• GO:0033627 cell adhesion mediated by integrin
• GO:0098609 cell-cell adhesion
• GO:0033631 cell-cell adhesion mediated by integrin
• GO:0007267 cell-cell signaling
• GO:0007160 cell-matrix adhesion
• GO:0045123 cellular extravasation
• GO:0071404 cellular response to low-density lipoprotein particle stimulus
• GO:0035987 endodermal cell differentiation
• GO:0043542 endothelial cell migration
• GO:0034113 heterotypic cell-cell adhesion
• GO:0006954 inflammatory response
• GO:0007229 integrin-mediated signaling pathway
• GO:0061756 leukocyte adhesion to vascular endothelial cell
• GO:0007159 leukocyte cell-cell adhesion
• GO:0002523 leukocyte migration involved in inflammatory response
• GO:0001774 microglial cell activation
• GO:0045963 negative regulation of dopamine metabolic process
• GO:0007158 neuron cell-cell adhesion
• GO:0030593 neutrophil chemotaxis
• GO:1990266 neutrophil migration
• GO:0006909 phagocytosis
• GO:0006911 phagocytosis, engulfment
• GO:0045766 positive regulation of angiogenesis
• GO:1904996 positive regulation of leukocyte adhesion to vascular endothelial cell
• GO:0043315 positive regulation of neutrophil degranulation
• GO:0045429 positive regulation of nitric oxide biosynthetic process
• GO:0090314 positive regulation of protein targeting to membrane
• GO:0032930 positive regulation of superoxide anion generation
• GO:0043113 receptor clustering
• GO:0031623 receptor internalization
• GO:0006898 receptor-mediated endocytosis
• GO:0008360 regulation of cell shape
• GO:0050730 regulation of peptidyl-tyrosine phosphorylation

Disease associations

• leukocyte adhesion deficiency 1 MONDO:0007293

Drugs targeting this protein · 1

• LIFITEGRAST antagonist

Related proteins · sequence + function similarity

• Integrin beta-2 0.98
• Integrin beta-2 0.98
• Integrin beta-2 0.98
• Integrin beta-2 0.98
• Integrin beta-2 0.98
• Integrin beta-2 0.98
• Integrin beta-1 0.91
• Integrin beta-1-B 0.90
• Integrin beta-1 0.89
• Integrin beta-1-A 0.89
• Integrin beta-6 0.88
• Integrin beta-1 0.88

Co-cited proteins · studied together in the literature

• Integrin alpha-L 10 shared papers
• Integrin alpha-D 3 shared papers
• Integrin alpha-X 2 shared papers
• Integrin alpha-M 4 shared papers
• Intercellular adhesion molecule 3 2 shared papers
• Intercellular adhesion molecule 5 1 shared papers
• CD177 antigen 2 shared papers
• Intercellular adhesion molecule 4 1 shared papers
• Intercellular adhesion molecule 2 1 shared papers
• Intercellular adhesion molecule 1 2 shared papers
• Integrin alpha-L 1 shared papers
• COP9 signalosome complex subunit 5 1 shared papers

Literature · 46 cited papers

• LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity. Nat. Commun. · 2024
• Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor. Mol. Cell · 2017
• CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation. Blood · 2017
• LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin. Biochem. Biophys. Res. Commun. · 2016
• Leukocyte integrin alphaLbeta2 headpiece structures: The alphaI domain, the pocket for the internal ligand, and concerted movements of its loops. Proc. Natl. Acad. Sci. U.S.A. · 2016
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An internal ligand-bound, metastable state of a leukocyte integrin, alphaXbeta2. J. Cell Biol. · 2013
• Novel role of ICAM3 and LFA-1 in the clearance of apoptotic neutrophils by human macrophages. Apoptosis · 2013
• Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA neutrophil activation. J. Biol. Chem. · 2011
• Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene. J. Clin. Immunol. · 2010
• A novel point mutation in CD18 causing leukocyte adhesion deficiency in a Chinese patient. Chin. Med. J. · 2010
• Structure of an integrin with an alphaI domain, complement receptor type 4. EMBO J. · 2010
• … and 34 more in the literature graph