Integrin beta-3
Also known as: GP3A, ITGB3
Function
Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain (By similarity). Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts 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 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. In brain, plays a role in synaptic transmission and plasticity. Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin. Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition (By similarity). ITGAV:ITGB3 act as a receptor for CD40LG. ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP. Integrin ITGA2B:ITGB3 is also the receptor of the erythrocyte-specific ICAM4 ligand involved in heterotypic cell-cell adhesion between erythrocytes and activated platelets.
Classification
- Family (Pfam)
- PF07974 EGF_2, PF23105 EGF_integrin, PF18372 I-EGF_1, PF08725 Integrin_b_cyt, PF07965 Integrin_B_tail, PF00362 Integrin_beta, PF17205 PSI_integrin
- InterPro
- EGF_extracell, EGF_integrin_1, EGF_integrin_2, Integrin_beta_N, Integrin_bsu, Integrin_bsu_cyt_dom, Integrin_bsu_tail, Integrin_bsu_tail_dom_sf, Integrin_bsu_VWA, Integrin_dom_sf, Integrin_I-EGF_CS, PSI, vWFA_dom_sf
- Functional cluster
- Venom Serine Proteases & Phospholipase A2
Experimental structures · PDB · 116
- 1JV2 X-ray 3.10A
- 1KUP NMR
- 1KUZ NMR
- 1L5G X-ray 3.20A
- 1M1X X-ray 3.30A
- 1M8O NMR
- 1MIZ X-ray 1.90A
- 1MK7 X-ray 2.20A
- 1MK9 X-ray 2.80A
- 1S4X NMR
- 1TYE X-ray 2.90A
- 1U8C X-ray 3.10A
- … and 104 more
A predicted model is available from AlphaFold.
Gene Ontology · 101
- GO:0071133 alpha9-beta1 integrin-ADAM8 complex
- GO:0035868 alphav-beta3 integrin-HMGB1 complex
- GO:0035867 alphav-beta3 integrin-IGF-1-IGF1R complex
- GO:0035866 alphav-beta3 integrin-PKCalpha complex
- GO:0071062 alphav-beta3 integrin-vitronectin complex
- GO:0016324 apical plasma membrane
- GO:0009986 cell surface
- GO:0005911 cell-cell junction
- GO:0009897 external side of plasma membrane
- GO:0070062 extracellular exosome
- GO:0031527 filopodium membrane
- GO:0005925 focal adhesion
- GO:0098978 glutamatergic synapse
- GO:0098690 glycinergic synapse
- GO:0070442 integrin alphaIIb-beta3 complex
- GO:0034683 integrin alphav-beta3 complex
- GO:0008305 integrin complex
- GO:0031258 lamellipodium membrane
- GO:0042470 melanosome
- GO:0031528 microvillus membrane
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0031092 platelet alpha granule membrane
- GO:0045211 postsynaptic membrane
- GO:0032991 protein-containing complex
- GO:0043235 receptor complex
- GO:0032587 ruffle membrane
- GO:0045202 synapse
- GO:0050839 cell adhesion molecule binding
- GO:0015026 coreceptor activity
- GO:0019899 enzyme binding
- GO:0050840 extracellular matrix binding
- GO:0070051 fibrinogen binding
- GO:0001968 fibronectin binding
- GO:0042802 identical protein binding
- GO:0005178 integrin binding
- GO:0046872 metal ion binding
- GO:0005161 platelet-derived growth factor receptor binding
- GO:0002020 protease binding
- GO:0003756 protein disulfide isomerase activity
- GO:0005080 protein kinase C binding
- GO:0043184 vascular endothelial growth factor receptor 2 binding
- GO:0001618 virus receptor activity
- GO:0060055 angiogenesis involved in wound healing
- GO:0038027 apolipoprotein A-I-mediated signaling pathway
- GO:0043277 apoptotic cell clearance
- GO:0007596 blood coagulation
- GO:0007155 cell adhesion
- GO:0033627 cell adhesion mediated by integrin
- GO:0016477 cell migration
- GO:0033631 cell-cell adhesion mediated by integrin
- GO:0007160 cell-matrix adhesion
- GO:0031589 cell-substrate adhesion
- GO:1990314 cellular response to insulin-like growth factor stimulus
- GO:0071260 cellular response to mechanical stimulus
- GO:0071466 cellular response to xenobiotic stimulus
- GO:0007566 embryo implantation
- GO:0034113 heterotypic cell-cell adhesion
- GO:0007229 integrin-mediated signaling pathway
- GO:0098880 maintenance of postsynaptic specialization structure
- GO:0048333 mesodermal cell differentiation
- GO:0050919 negative chemotaxis
- GO:2000352 negative regulation of endothelial cell apoptotic process
- 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:0030168 platelet activation
- GO:0070527 platelet aggregation
- GO:1900731 positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway
- GO:0045766 positive regulation of angiogenesis
- GO:0045780 positive regulation of bone resorption
- GO:0033630 positive regulation of cell adhesion mediated by integrin
- GO:0010595 positive regulation of endothelial cell migration
- GO:0001938 positive regulation of endothelial cell proliferation
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:0010763 positive regulation of fibroblast migration
- GO:0010628 positive regulation of gene expression
- GO:0072126 positive regulation of glomerular mesangial cell proliferation
- GO:0033690 positive regulation of osteoblast proliferation
- GO:0014911 positive regulation of smooth muscle cell migration
- GO:0048661 positive regulation of smooth muscle cell proliferation
- GO:2000406 positive regulation of T cell migration
- GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway
- GO:1900748 positive regulation of vascular endothelial growth factor signaling pathway
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0045124 regulation of bone resorption
- GO:0150054 regulation of postsynaptic neurotransmitter receptor diffusion trapping
- GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization
- GO:0032880 regulation of protein localization
- GO:0051279 regulation of release of sequestered calcium ion into cytosol
- GO:0051611 regulation of serotonin uptake
- GO:0014823 response to activity
- GO:0036119 response to platelet-derived growth factor
- GO:0014909 smooth muscle cell migration
- GO:0034446 substrate adhesion-dependent cell spreading
- GO:0046718 symbiont entry into host cell
- GO:0035295 tube development
- GO:0042060 wound healing
- GO:0035313 wound healing, spreading of epidermal cells
Disease associations
- Glanzmann thrombasthenia 2 MONDO:0031009
- bleeding disorder, platelet-type, 24 MONDO:0030996
- fetomaternal alloimmune thrombocytopenia 1 MONDO:0980723
Drugs targeting this protein · 5
- EPTIFIBATIDE inhibitor
- ZALUNFIBAN inhibitor
- TIROFIBAN HYDROCHLORIDE inhibitor
- ATN-161 antagonist
- CILENGITIDE antagonist
Related proteins · sequence + function similarity
- Integrin beta-3 0.99
- Integrin beta-3 0.98
- Integrin beta-5 0.96
- Integrin beta-5 0.96
- Integrin beta-5 0.94
- Integrin beta-5 0.94
- Integrin beta-6 0.90
- Integrin beta-6 0.89
- Integrin beta-6 0.89
- Integrin beta-6 0.89
- Integrin beta-6 0.89
- Integrin beta-6 0.89
Co-cited proteins · studied together in the literature
- Integrin alpha-IIb 13 shared papers
- Integrin alpha-V 26 shared papers
- Integrin alpha-5 10 shared papers
- Disintegrin Moojecin 1 shared papers
- Integrin beta-1 13 shared papers
- Protein disulfide-isomerase A6 1 shared papers
- HLA class II histocompatibility antigen, DR beta 3 chain 2 shared papers
- Envelope glycoprotein B 1 shared papers
- Integrin beta-3 2 shared papers
- Intercellular adhesion molecule 4 1 shared papers
- Genome polyprotein 1 shared papers
- Stromal cell-derived factor 1 1 shared papers
Literature · 108 cited papers
- 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
- PEAK1 Y635 phosphorylation regulates cell migration through association with Tensin3 and integrins. J. Cell Biol. · 2022
- A nait-associated and previously unreported mutation in the ITGB3 gene with a low frequency in the local population. Transfus. Med. · 2021
- Cytoplasmic short linear motifs in ACE2 and integrin beta3 link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy. Sci. Signal. · 2021
- Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications. Sci. Signal. · 2021
- A point mutation c.473A > G of ITGB3 is responsible for the formation of the Woa human platelet alloantigen. Transfusion · 2020
- Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling. J. Immunol. · 2019
- A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin alphaIIbbeta3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction. Ann. Hematol. · 2018
- Stromal cell-derived factor-1 (CXCL12) activates integrins by direct binding to an allosteric ligand-binding site (site 2) of integrins without CXCR4. Biochem. J. · 2018
- Molecular characterization of Glanzmann's thrombasthenia in Iran: identification of three novel mutations. Blood Coagul. Fibrinolysis · 2017
- … and 96 more in the literature graph