Integrin alpha V

Integrin alpha-V is a protein that in humans is encoded by the ITGAV gene.^[5]

ITGAV
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JV2, 1L5G, 1M1X, 1U8C, 3IJE, 4G1E, 4G1M, 4MMX, 4MMY, 4MMZ, 4O02, 4UM8, 4UM9
Identifiers
Aliases	ITGAV, CD51, MSK8, VNRA, VTNR, integrin subunit alpha V
External IDs	OMIM: 193210; MGI: 96608; HomoloGene: 20510; GeneCards: ITGAV; OMA:ITGAV - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q32.1 Start 186,590,056 bp[1] End 186,680,901 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 D|2 49.33 cM Start 83,554,741 bp[2] End 83,637,260 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium Epithelium of choroid plexus germinal epithelium tibia right ventricle skin of hip visceral pleura glomerulus metanephric glomerulus parietal pleura Top expressed in cumulus cell retinal pigment epithelium renal corpuscle conjunctival fornix decidua calvaria epithelium of lens body of femur gastrula external carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transforming growth factor beta binding metal ion binding voltage-gated calcium channel activity virus receptor activity protein kinase C binding protease binding extracellular matrix protein binding extracellular matrix binding fibronectin binding opsonin binding insulin-like growth factor I binding protein binding fibroblast growth factor binding neuregulin binding coreceptor activity C-X3-C chemokine binding signaling receptor binding peptide binding integrin binding Cellular component lamellipodium membrane integrin alphav-beta3 complex extracellular exosome alphav-beta3 integrin-IGF-1-IGF1R complex integral component of membrane integrin alphav-beta5 complex membrane integrin alphav-beta8 complex ruffle membrane integrin complex microvillus membrane filopodium membrane external side of plasma membrane phagocytic vesicle plasma membrane integral component of plasma membrane cell surface cytosol focal adhesion cell junction specific granule membrane integrin alphav-beta6 complex alphav-beta3 integrin-PKCalpha complex alphav-beta3 integrin-HMGB1 complex Biological process regulation of phagocytosis apoptotic cell clearance endodermal cell differentiation apolipoprotein A-I-mediated signaling pathway negative chemotaxis negative regulation of lipid storage extracellular matrix organization heterotypic cell-cell adhesion positive regulation of cell migration regulation of apoptotic cell clearance substrate adhesion-dependent cell spreading vascular endothelial growth factor receptor signaling pathway cell-matrix adhesion viral process antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent blood vessel development negative regulation of entry of bacterium into host cell integrin-mediated signaling pathway calcium ion transmembrane transport negative regulation of macrophage derived foam cell differentiation negative regulation of extrinsic apoptotic signaling pathway leukocyte migration cell-substrate adhesion negative regulation of lipoprotein metabolic process negative regulation of lipid transport extrinsic apoptotic signaling pathway in absence of ligand positive regulation of cell adhesion ERK1 and ERK2 cascade cell growth positive regulation of osteoblast proliferation cell adhesion angiogenesis vasculogenesis cellular calcium ion homeostasis positive regulation of cytosolic calcium ion concentration positive regulation of cell population proliferation cell migration neutrophil degranulation positive regulation of MAPK cascade cell adhesion mediated by integrin viral entry into host cell regulation of transforming growth factor beta activation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3685 16410 Ensembl ENSG00000138448 ENSMUSG00000027087 UniProt P06756 P43406 RefSeq (mRNA) NM_001144999 NM_001145000 NM_002210 NM_008402 NM_001398691 RefSeq (protein) NP_001138471 NP_001138472 NP_002201 NP_032428 NP_001385620 Location (UCSC) Chr 2: 186.59 – 186.68 Mb Chr 2: 83.55 – 83.64 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

ITGAV encodes integrin alpha chain V. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha V undergoes post-translational cleavage to yield disulfide-linked heavy and light chains, that combine with multiple integrin beta chains to form different integrins. Among the known associating beta chains (beta chains 1,3,5,6, and 8; ITGB1, ITGB3, ITGB5, ITGB6, and ITGB8), each can interact with extracellular matrix ligands; the alpha V beta 3 integrin, perhaps the most studied of these, is referred to as the Vitronectin receptor (VNR). In addition to adhesion, many integrins are known to facilitate signal transduction.^[6]

Alpha V class integrins

In mammals the integrins that include alpha-V are :

Name	Synonyms	Distribution	Ligands
αVβ1		neurological tumors	vitronectin; fibrinogen
αVβ3	vitronectin receptor[7]	activated endothelial cells, melanoma, glioblastoma	vitronectin,[7] fibronectin, fibrinogen, osteopontin, Cyr61, thyroxine[8][9]
αVβ5		widespread, esp. fibroblasts, epithelial cells	vitronectin and adenovirus
αVβ6		proliferating epithelia, esp. lung and mammary gland	fibronectin; TGFβ1+3
αVβ8		neural tissue; peripheral nerve	fibronectin; TGFβ1+3

Clinical significance

Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer,^[10] and prostate cancer.^[11]

As a drug target

The mAbs intetumumab, and abituzumab target this protein which is found on some tumour cells.^[12]

See also

• Cluster of differentiation

References

1. GRCh38: Ensembl release 89: ENSG00000138448 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027087 – 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. Sosnoski DM, Emanuel BS, Hawkins AL, van Tuinen P, Ledbetter DH, Nussbaum RL, et al. (June 1988). "Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa". The Journal of Clinical Investigation. 81 (6): 1993–1998. doi:10.1172/JCI113548. PMC 442653. PMID 2454952.
6. "Entrez Gene: ITGAV integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51)".
7. Hermann P, Armant M, Brown E, Rubio M, Ishihara H, Ulrich D, et al. (February 1999). "The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23". The Journal of Cell Biology. 144 (4): 767–775. doi:10.1083/jcb.144.4.767. PMC 2132927. PMID 10037797.
8. Bergh JJ, Lin HY, Lansing L, Mohamed SN, Davis FB, Mousa S, et al. (July 2005). "Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis". Endocrinology. 146 (7): 2864–2871. doi:10.1210/en.2005-0102. PMID 15802494.
9. Schmohl KA, Han Y, Tutter M, Schwenk N, Sarker RS, Steiger K, et al. (December 2020). "Integrin αvβ3-dependent thyroid hormone effects on tumour proliferation and vascularisation". Endocrine-Related Cancer. 27 (12): 685–697. doi:10.1530/ERC-20-0353. PMID 33112795.
10. Waisberg J, De Souza Viana L, Affonso Junior RJ, Silva SR, Denadai MV, Margeotto FB, et al. (October 2014). "Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer". Anticancer Research. 34 (10): 5599–5607. PMID 25275062.
11. Cooper CR, Chay CH, Pienta KJ (2002). "The role of alpha(v)beta(3) in prostate cancer progression". Neoplasia. 4 (3): 191–194. doi:10.1038/sj.neo.7900224. PMC 1531692. PMID 11988838.
12. Élez E, Kocáková I, Höhler T, Martens UM, Bokemeyer C, Van Cutsem E, et al. (January 2015). "Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial". Annals of Oncology. 26 (1): 132–140. doi:10.1093/annonc/mdu474. PMID 25319061.

Further reading

• Horton MA (May 1997). "The alpha v beta 3 integrin "vitronectin receptor"". The International Journal of Biochemistry & Cell Biology. 29 (5): 721–725. doi:10.1016/S1357-2725(96)00155-0. PMID 9251239.
• Porter JC, Hogg N (October 1998). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends in Cell Biology. 8 (10): 390–396. doi:10.1016/S0962-8924(98)01344-0. PMID 9789327.
• Sajid M, Stouffer GA (February 2002). "The role of alpha(v)beta3 integrins in vascular healing". Thrombosis and Haemostasis. 87 (2): 187–193. doi:10.1055/s-0037-1612971. PMID 11858476. S2CID 76995133.
• Cooper CR, Chay CH, Pienta KJ (2002). "The role of alpha(v)beta(3) in prostate cancer progression". Neoplasia. 4 (3): 191–194. doi:10.1038/sj.neo.7900224. PMC 1531692. PMID 11988838.
• Cacciari B, Spalluto G (2005). "Non peptidic alphavbeta3 antagonists: recent developments". Current Medicinal Chemistry. 12 (1): 51–70. doi:10.2174/0929867053363522. PMID 15638730.
• University of Edinburgh (2013). "Hope for transplant patients as study finds key to organ scarring". ScienceDaily. Retrieved December 2, 2014.

External links

• CD51+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• ITGAV Info with links in the Cell Migration Gateway Archived 2014-12-11 at the Wayback Machine