Integrin alpha M

Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (α_Mβ₂) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3 (CR3).[5] ITGAM is also known as CR3A, and cluster of differentiation molecule 11B (CD11B). The second chain of α_Mβ₂ is the common integrin β₂ subunit known as CD18, and integrin α_Mβ₂ thus belongs to the β₂ subfamily (or leukocyte) integrins.[6]

ITGAM
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BHO, 1BHQ, 1IDN, 1IDO, 1JLM, 1M1U, 1MF7, 1N9Z, 1NA5, 2LKE, 2LKJ, 3Q3G, 3QA3, 4M76, 4XW2
Identifiers
Aliases	ITGAM, CD11B, CR3A, MAC-1, MAC1A, MO1A, SLEB6, integrin subunit alpha M
External IDs	OMIM: 120980 MGI: 96607 HomoloGene: 526 GeneCards: ITGAM
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p11.2 Start 31,259,967 bp[1] End 31,332,892 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F3 Start 128,062,640 bp[2] End 128,118,491 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • metal ion binding • GO:0001948 protein binding • protein heterodimerization activity • heat shock protein binding • amyloid-beta binding • complement component C3b binding • cargo receptor activity Cellular component • extracellular exosome • cell membrane • cell surface • membrane • integral component of membrane • integrin complex • extracellular • specific granule membrane • tertiary granule membrane • external side of plasma membrane • integrin alphaM-beta2 complex • plasma membrane raft • membrane raft Biological process • ectodermal cell differentiation • toll-like receptor 4 signaling pathway • integrin-mediated signaling pathway • leukocyte migration • extracellular matrix organization • cell adhesion • neutrophil degranulation • microglial cell activation • immune system process • receptor-mediated endocytosis • phagocytosis, engulfment • cytokine-mediated signaling pathway • positive regulation of superoxide anion generation • positive regulation of neutrophil degranulation • innate immune system • negative regulation of dopamine metabolic process • positive regulation of protein targeting to membrane • amyloid-beta clearance • cell-cell adhesion via plasma-membrane adhesion molecules • complement-mediated synapse pruning • vertebrate eye-specific patterning • positive regulation of neuron death • positive regulation of microglial cell activation • positive regulation of microglial cell mediated cytotoxicity • cell surface receptor signaling pathway involved in cell-cell signaling • positive regulation of prostaglandin-E synthase activity • forebrain development • apoptotic signaling pathway • positive regulation of hippocampal neuron apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3684	16409
Ensembl	ENSG00000169896	ENSMUSG00000030786
UniProt	P11215	P05555
RefSeq (mRNA)	NM_000632 NM_001145808	NM_001082960 NM_008401
RefSeq (protein)	NP_000623 NP_001139280	n/a
Location (UCSC)	Chr 16: 31.26 – 31.33 Mb	Chr 7: 128.06 – 128.12 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

α_Mβ₂ is expressed on the surface of many leukocytes involved in the innate immune system, including monocytes, granulocytes, macrophages, and natural killer cells.[5] It mediates inflammation by regulating leukocyte adhesion and migration and has been implicated in several immune processes such as phagocytosis, cell-mediated cytotoxicity, chemotaxis and cellular activation.[5] It is involved in the complement system due to its capacity to bind inactivated complement component 3b (iC3b).[7] The ITGAM (alpha) subunit of integrin α_Mβ₂ is directly involved in causing the adhesion and spreading of cells but cannot mediate cellular migration without the presence of the β2 (CD18) subunit.[5]

In genomewide association studies, single nucleotide polymorphisms in ITGAM had the strongest association with systemic lupus erythematosus, with an odds ratio of 1.65 for the T allele of rs9888739 and lupus.[8][9]

In histopathology, immunohistochemistry with antibodies against CD11B is frequently used to identify macrophages and microglia.

See also

• integrin

References

1. GRCh38: Ensembl release 89: ENSG00000169896 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030786 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Solovjov DA, Pluskota E, Plow EF (January 2005). "Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2". The Journal of Biological Chemistry. 280 (2): 1336–45. doi:10.1074/jbc.M406968200. PMID 15485828.
6. Larson RS, Springer TA (April 1990). "Structure and function of leukocyte integrins". Immunological Reviews. 114: 181–217. doi:10.1111/j.1600-065X.1990.tb00565.x. PMID 2196220.
7. Arnaout MA, Todd RF, Dana N, Melamed J, Schlossman SF, Colten HR (July 1983). "Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mol)". The Journal of Clinical Investigation. 72 (1): 171–9. doi:10.1172/JCI110955. PMC 1129172. PMID 6874946.
8. Crow MK (February 2008). "Collaboration, genetic associations, and lupus erythematosus". The New England Journal of Medicine. 358 (9): 956–61. doi:10.1056/NEJMe0800096. PMID 18204099.
9. Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, Lee AT, Chung SA, Ferreira RC, Pant PV, Ballinger DG, Kosoy R, Demirci FY, Kamboh MI, Kao AH, Tian C, Gunnarsson I, Bengtsson AA, Rantapää-Dahlqvist S, Petri M, Manzi S, Seldin MF, Rönnblom L, Syvänen AC, Criswell LA, Gregersen PK, Behrens TW (February 2008). "Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX". The New England Journal of Medicine. 358 (9): 900–9. doi:10.1056/NEJMoa0707865. PMID 18204098.

Further reading

• Stewart M, Thiel M, Hogg N (October 1995). "Leukocyte integrins". Current Opinion in Cell Biology. 7 (5): 690–6. doi:10.1016/0955-0674(95)80111-1. PMID 8573344.
• Todd RF, Petty HR (May 1997). "Beta 2 (CD11/CD18) integrins can serve as signaling partners for other leukocyte receptors". The Journal of Laboratory and Clinical Medicine. 129 (5): 492–8. doi:10.1016/S0022-2143(97)90003-2. PMID 9142045.
• 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.

External links

• Integrin+alphaM at the US National Library of Medicine Medical Subject Headings (MeSH)
• Mouse CD Antigen Chart
• Human CD Antigen Chart
• ITGAM Info with links in the Cell Migration Gateway