Integrin alpha-V
Also known as: ITGAV, MSK8, VNRA, VTNR
Function
The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 and ITGAV:ITGB6 act as receptors for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1. Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation. ITGAV:ITGB3 acts as a receptor for CD40LG. ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP.
Classification
- Family (Pfam)
- PF01839 FG-GAP, PF08441 Integrin_A_Ig_1, PF20805 Integrin_A_Ig_2, PF20806 Integrin_A_Ig_3, PF00357 Integrin_alpha
- InterPro
- FG-GAP, Int_alpha_beta-p, Integrin_alpha, Integrin_alpha_C_CS, Integrin_alpha_Ig-like_1, Integrin_alpha_Ig-like_2, Integrin_alpha_Ig-like_3, Integrin_alpha_N, Integrin_dom_sf
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 57
- 1JV2 X-ray 3.10A
- 1L5G X-ray 3.20A
- 1M1X X-ray 3.30A
- 1U8C X-ray 3.10A
- 3IJE X-ray 2.90A
- 4G1E X-ray 3.00A
- 4G1M X-ray 2.90A
- 4MMX X-ray 3.32A
- 4MMY X-ray 3.18A
- 4MMZ X-ray 3.10A
- 4O02 X-ray 3.60A
- 4UM8 X-ray 2.85A
- … and 45 more
A predicted model is available from AlphaFold.
Gene Ontology · 70
- GO:0035868 alphav-beta3 integrin-HMGB1 complex
- GO:0035867 alphav-beta3 integrin-IGF-1-IGF1R complex
- GO:0035866 alphav-beta3 integrin-PKCalpha complex
- GO:0009986 cell surface
- GO:0009897 external side of plasma membrane
- GO:0070062 extracellular exosome
- GO:0031527 filopodium membrane
- GO:0005925 focal adhesion
- GO:0034682 integrin alphav-beta1 complex
- GO:0034683 integrin alphav-beta3 complex
- GO:0034684 integrin alphav-beta5 complex
- GO:0034685 integrin alphav-beta6 complex
- GO:0034686 integrin alphav-beta8 complex
- GO:0008305 integrin complex
- GO:0031258 lamellipodium membrane
- GO:0016020 membrane
- GO:0031528 microvillus membrane
- GO:0045335 phagocytic vesicle
- GO:0005886 plasma membrane
- GO:0032587 ruffle membrane
- GO:0035579 specific granule membrane
- GO:0015026 coreceptor activity
- GO:0050840 extracellular matrix binding
- GO:1990430 extracellular matrix protein binding
- GO:0001968 fibronectin binding
- GO:0005178 integrin binding
- GO:0046872 metal ion binding
- GO:0001846 opsonin binding
- GO:0002020 protease binding
- GO:0005080 protein kinase C binding
- GO:0038023 signaling receptor activity
- GO:0050431 transforming growth factor beta binding
- GO:0001618 virus receptor activity
- GO:0001525 angiogenesis
- GO:0038027 apolipoprotein A-I-mediated signaling pathway
- GO:0043277 apoptotic cell clearance
- GO:0070588 calcium ion transmembrane transport
- GO:0007155 cell adhesion
- GO:0033627 cell adhesion mediated by integrin
- GO:0016477 cell migration
- GO:0098609 cell-cell adhesion
- GO:0007160 cell-matrix adhesion
- GO:0031589 cell-substrate adhesion
- GO:0035987 endodermal cell differentiation
- GO:0085017 entry into host cell by a symbiont-containing vacuole
- GO:0070371 ERK1 and ERK2 cascade
- GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
- GO:0034113 heterotypic cell-cell adhesion
- GO:0007229 integrin-mediated signaling pathway
- GO:0050919 negative chemotaxis
- GO:2000536 negative regulation of entry of bacterium into host cell
- GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
- GO:0010888 negative regulation of lipid storage
- GO:0032369 negative regulation of lipid transport
- GO:0050748 negative regulation of lipoprotein metabolic process
- GO:0010989 negative regulation of low-density lipoprotein particle clearance
- GO:0010745 negative regulation of macrophage derived foam cell differentiation
- GO:0045785 positive regulation of cell adhesion
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:1902533 positive regulation of intracellular signal transduction
- GO:0033690 positive regulation of osteoblast proliferation
- GO:0051057 positive regulation of small GTPase mediated signal transduction
- GO:0050764 regulation of phagocytosis
- GO:0034446 substrate adhesion-dependent cell spreading
- GO:0046718 symbiont entry into host cell
- GO:0071604 transforming growth factor beta production
- GO:0001570 vasculogenesis
- GO:0035313 wound healing, spreading of epidermal cells
Disease associations
Drugs targeting this protein · 2
- ATN-161 antagonist
- CILENGITIDE antagonist
Related proteins · sequence + function similarity
- Integrin alpha-V 1.00
- Integrin alpha-V 0.99
- Integrin alpha-V 0.98
- Integrin alpha-8 0.95
- Integrin alpha-5 0.94
- Integrin alpha-8 0.94
- Integrin alpha-8 0.91
- Integrin alpha-6 0.91
- Integrin alpha-6 0.90
- Integrin alpha-6 0.90
- Integrin alpha-4 0.88
- Integrin alpha-11 0.86
Co-cited proteins · studied together in the literature
- Integrin beta-3 26 shared papers
- Integrin beta-6 7 shared papers
- Envelope glycoprotein H 1 shared papers
- Integrin alpha-5 11 shared papers
- Genome polyprotein 1 shared papers
- Disintegrin Moojecin 1 shared papers
- Integrin beta-1 11 shared papers
- Envelope glycoprotein B 1 shared papers
- Genome polyprotein 1 shared papers
- Ras-related protein Rab-25 1 shared papers
- Integrin-binding sialoprotein 1 shared papers
- Integrin alpha-4 4 shared papers
Literature · 53 cited papers
- Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis. J. Exp. Med. · 2024
- Moojecin: The first disintegrin from Bothrops moojeni venom and its antitumor activity in acute myeloid leukemia. Int. J. Biol. Macromol. · 2024
- Tm4sf19 deficiency inhibits osteoclast multinucleation and prevents bone loss. Metabolism · 2024
- The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand. Life. Sci Alliance · 2023
- Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling. J. Immunol. · 2019
- Direct binding to integrins and loss of disulfide linkage in interleukin-1beta (IL-1beta) are involved in the agonistic action of IL-1beta. J. Biol. Chem. · 2017
- Direct integrin binding to insulin-like growth factor-2 through the C-domain is required for insulin-like growth factor receptor type 1 (IGF1R) signaling. PLoS ONE · 2017
- The integrin-binding defective FGF2 mutants potently suppress FGF2 signalling and angiogenesis. Biosci. Rep. · 2017
- Force interacts with macromolecular structure in activation of TGF-beta. Nature · 2017
- The CD9, CD81, and CD151 EC2 domains bind to the classical RGD-binding site of integrin alphavbeta3. Biochem. J. · 2017
- Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a newly identified binding site (site 2) in integrins alphavbeta3, alpha4beta1, and alpha5beta1. J. Biol. Chem. · 2015
- Herpes simplex virus type 2 glycoprotein H interacts with integrin alphavbeta3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells. J. Virol. · 2014
- … and 41 more in the literature graph