ITGB3 : integrin subunit beta 3

Description

The ITGB3 (integrin subunit beta 3) is a protein-coding gene located on chromosome 17.

The ITGB3 gene provides instructions for making the beta3 subunit of a receptor protein called integrin alphaIIb/beta3 (αIIbβ3), which is found on the surface of small cells called platelets. Platelets circulate in blood and are an essential component of blood clots. The beta3 subunit attaches (binds) to the alphaIIb subunit, which is produced from the ITGA2B gene, to form integrin αIIbβ3. It is estimated that 80,000 to 100,000 copies of integrin αIIbβ3 are present on the surface of each platelet.During clot formation, integrin αIIbβ3 binds to a protein called fibrinogen. Attachment of integrin αIIbβ3 from adjacent platelets to the same fibrinogen protein helps platelets cluster together (platelet cohesion) to form a blood clot. Blood clots protect the body after injury by sealing off damaged blood vessels and preventing further blood loss. Integrin αIIbβ3 can also bind other proteins on platelets and in the blood as well as proteins within the intricate lattice that forms in the space between cells (extracellular matrix) to ensure proper clot formation and promote wound healing.

The ITGB3 gene encodes the beta-3 subunit of integrin, also known as Platelet membrane glycoprotein IIIa. It forms heterodimers with either alpha-IIb (ITGA2B) or alpha-V (ITGAV). ITGAV:ITGB3 acts as a receptor for various ligands, including cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin, and von Willebrand factor. ITGA2B:ITGB3 binds to fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin, and vitronectin. Both ITGA2B:ITGB3 and ITGAV:ITGB3 recognize the R-G-D sequence in various ligands. ITGA2B:ITGB3 also specifically recognizes the H-H-L-G-G-G-A-K-Q-A-G-D-V sequence in the fibrinogen gamma chain. Following activation, ITGA2B:ITGB3 promotes platelet aggregation by binding soluble fibrinogen, physically plugging ruptured endothelial surfaces. This binding also enhances SELP expression in activated platelets. ITGAV:ITGB3 interacts with fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. It also binds to NRG1 (via the EGF domain), FGF1, FGF2, IGF1, IGF2, IL1B, and PLA2G2A. These interactions are essential for the corresponding signaling pathways. ITGAV:ITGB3 binds to fibrillin-1 (FBN1), mediating R-G-D-dependent cell adhesion. In the brain, it plays a role in synaptic transmission and plasticity, regulating serotonin neurotransmission, localizing the serotonin receptor SLC6A4, and facilitating serotonin reuptake. It also regulates excitatory synaptic strength by controlling GRIA2-containing AMPAR endocytosis. ITGAV:ITGB3 serves as a receptor for CD40LG and IBSP, promoting cell adhesion and migration to IBSP. It also acts as a receptor for various microbial pathogens, including Herpes virus 8/HHV-8, Coxsackievirus A9, Hantaan virus, Cytomegalovirus/HHV-5, Human metapneumovirus, Human parechovirus 1, and West Nile virus. In cases of HIV-1 infection, its interaction with viral Tat protein may enhance angiogenesis in Kaposi's sarcoma lesions. ITGB3 interacts with various proteins, including FLNB, COMP, PDIA6, SYK, MYO10, DAB2, FERMT2, EMP2, FBLN5, CCN3, SELP, CX3CR1, CX3CL1, NRG1, ERBB3, FGF1, FGFR1, FGF2, IL1B, IGF1, IGF1R, IGF2, FBN1, CD9, CD81, CD151, CXCL12, MXRA8/DICAM, PTN, SLC6A4, PPIA/CYPA, TNS3, herpes virus 8/HHV-8 glycoprotein B, coxsackievirus A9 capsid proteins, Hantaan virus glycoprotein G, cytomegalovirus/HHV-5 gH:gL proteins, human metapneumovirus fusion protein, human parechovirus 1 capsid proteins, west nile virus envelope protein E, and HIV-1 Tat. These interactions contribute to its diverse functions.

ITGB3 is also known as BDPLT16, BDPLT2, BDPLT24, CD61, GP3A, GPIIIa, GT, GT2.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing