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Integrin beta-3

Domain

The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site.

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 (PubMed:9111081). 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). ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP (PubMed:10640428).

(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.

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence similarities

Belongs to the integrin beta chain family.

Tissue specificity

Isoform beta-3A and isoform beta-3C are widely expressed. Isoform beta-3A is specifically expressed in osteoblast cells; isoform beta-3C is specifically expressed in prostate and testis.

Cellular localization

  • Cell membrane
  • Single-pass type I membrane protein
  • Cell projection
  • Lamellipodium membrane
  • Cell junction
  • Focal adhesion
  • Postsynaptic cell membrane
  • Single-pass type I membrane protein
  • Synapse

Alternative names

CD61, GP3A, ITGB3, Integrin beta-3, Platelet membrane glycoprotein IIIa, GPIIIa

Target type

Proteins

Primary research area

Oncology

Molecular weight

87058Da

We found 3 products in 1 category

Primary Antibodies

Application

Reactive species