HGNC Approved Gene Symbol: ITGB5
Cytogenetic location: 3q21.2 Genomic coordinates (GRCh38): 3:124,761,948-124,901,418 (from NCBI)
Integrins are a family of heterodimeric glycoproteins that mediate cell-to-cell and cell-to-extracellular matrix interactions. Each integrin consists of an alpha subunit (e.g., ITGAV; 193210) and a beta subunit, such as ITGB5, that are noncovalently linked (summary by Busk et al., 1992).
McLean et al. (1990) isolated cDNA clones coding for the beta-5 subunit of the novel integrin receptor involved in cell adhesion to the matrix protein vitronectin which had been found in a human lung epithelial-derived cell line. This receptor had an alpha subunit that appeared to be identical to that in another vitronectin receptor, but the beta subunit was distinctive. McLean et al. (1990) demonstrated that the 3.3-kb mRNA coded for a mature protein of 775 amino acid residues with a hydrophobic leader sequence of 24 amino acids. A 56% identity was found between the beta-5 and beta-3 (173470) protein sequences, making them the most closely related of the integrin beta subunits. Studies of different cell lines indicated that the integrin receptor comprising the beta-5 subunit may be widely distributed.
Gross (2014) mapped the ITGB5 gene to chromosome 3q21.2 based on an alignment of the ITGB5 sequence (GenBank BC006541) with the genomic sequence (GRCh37).
Using coimmunoprecipitation and Western blot analysis, Busk et al. (1992) identified heterodimers of alpha-V (ITGAV)/beta-6 (ITGB6; 147558) integrins and alpha-V/beta-5 on the surface of UCLA-P3 and FG-2 human carcinoma cell lines. Affinity chromatography of lysates from FG-2 cells revealed that alpha-V/beta-6 bound to immobilized fibronectin (FN1; 135600), whereas alpha-V/beta-5 bound to vitronectin (VTN; 193190). Neither alpha-V/beta-6 nor alpha-V/beta-5 bound to immobilized collagen I (see COL1A1, 120150). The heterodimers were eluted from their respective columns by a peptide containing the sequence arg-gly-asp (RGD) in the presence of Ca2(+), with weaker release in the presence of Mg2(+). Busk et al. (1992) concluded that alpha-V/beta-6 functions as an RGD- and calcium-dependent fibronectin receptor, whereas alpha-V/beta-5 functions as an RGD- and calcium-dependent vitronectin receptor.
Reynolds et al. (2002) reported that mice lacking beta-3 integrins or both beta-3 and beta-5 integrins not only support tumorigenesis but have enhanced tumor growth as well. The tumors in these integrin-deficient mice display enhanced angiogenesis, strongly suggesting that neither beta-3 nor beta-5 integrins are essential for neovascularization. Reynolds et al. (2002) also observed that angiogenic responses to hypoxia and vascular endothelial growth factor (VEGF; 192240) are augmented significantly in the absence of beta-3 integrins. Reynolds et al. (2002) found no evidence that the expression or functions of other integrins were altered as a consequence of the beta-3 deficiency, but did observe elevated levels of VEGF receptor-2 (191306) in beta-3-null endothelial cells. Reynolds et al. (2002) concluded that alpha-5-beta-3 and alpha-5-beta-5 integrins are not essential for vascular development or pathologic angiogenesis.
Busk, M., Pytela, R., Sheppard, D. Characterization of the integrin alpha-v-beta-6 as a fibronectin-binding protein. J. Biol. Chem. 267: 5790-5796, 1992. [PubMed: 1532572]
Gross, M. B. Personal Communication. Baltimore, Md. 5/21/2014.
McLean, J. W., Vestal, D. J., Cheresh, D. A., Bodary, S. C. cDNA sequence of the human integrin beta 5 subunit. J. Biol. Chem. 265: 17126-17131, 1990. [PubMed: 2211615]
Reynolds, L. E., Wyder, L., Lively, J. C., Taverna, D., Robinson, S. D., Huang, X., Sheppard, D., Hynes, R. O., Hodivala-Dilke, K. M. Enhanced pathological angiogenesis in mice lacking beta-3 integrin or beta-3 and beta-5 integrins. Nature Med. 8: 27-34, 2002. [PubMed: 11786903] [Full Text: https://doi.org/10.1038/nm0102-27]