ITGB3

The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]

Integrin Subunit Beta 3

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. 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 (PubMed:23125415, PubMed:24789099).
ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778).
ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324).
ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677).
ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119).
ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464).
ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430).
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 (PubMed:18635536, PubMed:25398877).
ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887).
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 (PubMed:31331973).
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8.
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Coxsackievirus A9.
(Microbial infection) Acts as a receptor for Hantaan virus.
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Cytomegalovirus/HHV-5.
(Microbial infection) Integrin ITGA5:ITGB3 acts as a receptor for Human metapneumovirus.
(Microbial infection) Integrin ITGAV:ITGB3 acts aP05556s a receptor for Human parechovirus 1.
(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus.
(Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

Activation of protein kinase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Angiogenesis involved in wound healingManual Assertion Based On ExperimentTAS:BHF-UCL
Apolipoprotein A-I-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Apoptotic cell clearanceManual Assertion Based On ExperimentIGI:BHF-UCL
Blood coagulationManual Assertion Based On ExperimentTAS:ProtInc
Cell adhesionManual Assertion Based On ExperimentTAS:ProtInc
Cell adhesion mediated by integrinManual Assertion Based On ExperimentIDA:UniProtKB
Cell migrationManual Assertion Based On ExperimentIBA:GO_Central
Cell-matrix adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Cell-substrate adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Heterotypic cell-cell adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentHDA:UniProtKB
Mesodermal cell differentiationManual Assertion Based On ExperimentIEP:UniProtKB
Negative chemotaxisManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of lipid storageManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of lipid transportManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of lipoprotein metabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of low-density lipoprotein receptor activityManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of macrophage derived foam cell differentiationManual Assertion Based On ExperimentIMP:BHF-UCL
Platelet activationManual Assertion Based On ExperimentIMP:UniProtKB
Platelet aggregationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of endothelial cell proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein phosphorylationManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of vascular endothelial growth factor receptor signaling pathwayManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of bone resorptionManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of postsynaptic neurotransmitter receptor internalizationManual Assertion Based On ExperimentIDA:SynGO
Regulation of protein localizationISS:UniProtKB
Regulation of serotonin uptakeISS:UniProtKB
Smooth muscle cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Substrate adhesion-dependent cell spreadingManual Assertion Based On ExperimentIDA:UniProtKB
Tube developmentManual Assertion Based On ExperimentTAS:BHF-UCL
Viral entry into host cellManual Assertion Based On ExperimentIMP:UniProtKB
Wound healing1 PublicationIC:BHF-UCL

Cell membrane; Cell projection, lamellipodium membrane; Cell junction, focal adhesion; Cell junction, synapse, postsynaptic cell membrane; Cell junction, synapse

Glanzmann thrombasthenia 2 (GT2):
A form of Glanzmann thrombasthenia, a disorder characterized by failure of platelet aggregation, absent or diminished clot retraction, and mucocutaneous bleeding of mild-to-moderate severity. Glanzmann thrombasthenia has been classified into clinical types I and II. In type I, platelets show absence of glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express glycoprotein IIb-IIIa complexes at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability.
Bleeding disorder, platelet-type, 24 (BDPLT24):
An autosomal dominant disorder of platelet production characterized by congenital macrothrombocytopenia and platelet anisocytosis. Affected individuals may have no or only mildly increased bleeding tendency.

Extracellular: 27-718
Helical: 719-741
Cytoplasmic: 742-788

Phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation. Probably involved in outside-in signaling. A peptide (AA 740-762) is capable of binding GRB2 only when both Tyr-773 and Tyr-785 are phosphorylated. Phosphorylation of Thr-779 inhibits SHC binding.