Integrin beta 2

In molecular biology, CD18 (Integrin beta chain-2) is an integrin beta chain protein that is encoded by the ITGB2 gene in humans. Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple heterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses. CD18 also exists in soluble, ligand binding forms. Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans, reducing the immune system's ability to fight off foreign invaders.

ITGB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1L3Y, 1YUK, 2JF1, 2P26, 2P28, 3K6S, 3K71, 3K72, 2V7D, 4NEH, 4NEN, 5E6X, 5E6V, 5E6S, 5E6R, 5E6W, 5ES4, 5E6U
Identifiers
Aliases	ITGB2, CD18, LAD, LCAMB, LFA-1, MAC-1, MF17, MFI7, integrin subunit beta 2
External IDs	OMIM: 600065; MGI: 96611; HomoloGene: 20092; GeneCards: ITGB2; OMA:ITGB2 - orthologs
Gene location (Human) Chr. Chromosome 21 (human) Band 21q22.3 Start 44,885,953 bp End 44,931,989 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10 C1|10 39.72 cM Start 77,366,086 bp End 77,401,542 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte monocyte blood spleen bone marrow cells appendix trabecular bone lymph node right lung upper lobe of left lung Top expressed in granulocyte stroma of bone marrow tibiofemoral joint spleen thymus mesenteric lymph nodes blood right lung lobe ankle joint subcutaneous adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-containing complex binding metal ion binding protein binding protein heterodimerization activity ICAM-3 receptor activity protein kinase binding cell adhesion molecule binding heat shock protein binding amyloid-beta binding complement component C3b binding integrin binding signaling receptor activity cargo receptor activity Cellular component integral component of membrane extracellular vesicle integrin alphaL-beta2 complex membrane plasma membrane receptor complex cell surface integrin complex extracellular exosome specific granule membrane tertiary granule membrane ficolin-1-rich granule membrane focal adhesion external side of plasma membrane integrin alphaM-beta2 complex plasma membrane raft membrane raft cytoplasmic region protein-containing complex Biological process leukocyte cell-cell adhesion endodermal cell differentiation toll-like receptor 4 signaling pathway positive regulation of nitric oxide biosynthetic process heterotypic cell-cell adhesion cell-cell signaling ageing receptor internalization leukocyte migration involved in inflammatory response natural killer cell activation cellular response to low-density lipoprotein particle stimulus extracellular matrix organization receptor clustering positive regulation of angiogenesis neutrophil chemotaxis cell adhesion positive regulation of NF-kappaB transcription factor activity regulation of cell shape regulation of immune response cellular extravasation integrin-mediated signaling pathway cell-matrix adhesion inflammatory response endothelial cell migration leukocyte migration regulation of peptidyl-tyrosine phosphorylation apoptotic process phagocytosis neutrophil degranulation microglial cell activation receptor-mediated endocytosis phagocytosis, engulfment cell migration cytokine-mediated signaling pathway positive regulation of superoxide anion generation cell adhesion mediated by integrin positive regulation of neutrophil degranulation negative regulation of dopamine metabolic process positive regulation of protein _targeting to membrane amyloid-beta clearance cell-cell adhesion cell-cell adhesion via plasma-membrane adhesion molecules positive regulation of neuron death positive regulation of microglial cell activation neutrophil migration positive regulation of prostaglandin-E synthase activity positive regulation of leukocyte adhesion to vascular endothelial cell Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3689 16414 Ensembl ENSG00000160255 ENSMUSG00000000290 UniProt P05107 P11835 RefSeq (mRNA) NM_000211 NM_001127491 NM_001303238 NM_008404 RefSeq (protein) NP_000202 NP_001120963 NP_001290167 NP_032430 Location (UCSC) Chr 21: 44.89 – 44.93 Mb Chr 10: 77.37 – 77.4 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Structure and function

The ITGB2 protein product is CD18. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain, and are crucial for cells to be able to efficiently bind to the extracellular matrix. This is especially important for neutrophils, as cellular adhesion plays a large role in extravasation from the blood vessels. A given chain may combine with multiple partners resulting in different integrins.

The known binding partners of CD18 are CD11a, CD11b, CD11c and CD11d. Binding of CD18 and CD11a results in the formation of lymphocyte function-associated antigen-1 (LFA-1), a protein found on B cells, all T cells, monocytes, neutrophils and NK cells. LFA-1 is involved in adhesion and binding to antigen presenting cells through interactions with the surface protein ICAM-1.

Binding of CD18 and CD11b-d results in the formation of complement receptors (e.g. Macrophage-1 antigen receptor, Mac-1, when bound to CD11b), which are proteins found largely on neutrophils, macrophages and NK cells. These complement receptors participate in the innate immune response by recognizing foreign antigen peptides and phagocytizing them, thus destroying the antigen.

Clinical significance

In humans, lack of functional CD18 causes leukocyte adhesion deficiency, a disease defined by a lack of leukocyte extravasation from blood into tissues, which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue. This subsequently reduces the ability of the individual's immune system to fight off infection, making them more susceptible to foreign infection than those with functional CD18 proteins. The beta 2 integrins have also been found in a soluble form, meaning they are not anchored into the plasma membrane of the cell, but rather exist outside of the cell in the plasma, and are capable of ligand binding. The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.

Interactions

CD18 has been shown to interact with:

• FHL2,
• GNB2L1,
• ICAM-1, and
• PSCD1.

See also

• leukocyte adhesion deficiency
• integrin

Further reading

• Bunting M, Harris ES, McIntyre TM, Prescott SM, Zimmerman GA (January 2002). "Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands". Current Opinion in Hematology. 9 (1): 30–5. doi:10.1097/00062752-200201000-00006. PMID 11753075.
• Roos D, Law SK (2003). "Hematologically important mutations: leukocyte adhesion deficiency". Blood Cells, Molecules & Diseases. 27 (6): 1000–4. doi:10.1006/bcmd.2001.0473. PMID 11831866.
• Gahmberg CG, Fagerholm S (August 2002). "Activation of leukocyte beta2-integrins". Vox Sanguinis. 83 (Suppl 1): 355–8. doi:10.1111/j.1423-0410.2002.tb05333.x. PMID 12617168. S2CID 84695792.
• Schymeinsky J, Mócsai A, Walzog B (August 2007). "Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications". Thrombosis and Haemostasis. 98 (2): 262–73. doi:10.1160/th07-02-0156. PMID 17721605. S2CID 41094726.

External links

• CD18+antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• ITGB2 Info with links in the Cell Migration Gateway Archived 11 December 2014 at the Wayback Machine
• Human ITGB2 genome location and ITGB2 gene details page in the UCSC Genome Browser.