Function: Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 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. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
Subunit structure: Heterodimer of an alpha and a beta subunit. Beta-3 associates with either alpha-IIb or alpha-V. Isoform Beta-3C interacts with FLNB. Interacts with COMP. Interacts with HIV-1 Tat. Interacts with PDIA6 following platelet stimulation. Interacts with SYK; upon activation by ITGB3 promotes platelet adhesion. Interacts with MYO10. Interacts with DAB2. Interacts with FERMT2. Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.31
Subcellular location: Cell membrane; Single-pass type I membrane protein. Cell projection › lamellipodium membrane. Cell junction › focal adhesion Ref.31.
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.
Post-translational modification: 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. Ref.18 Ref.20
Polymorphism: Position 59 is associated with platelet-specific alloantigen HPA-1 (ZW or PL(A)). HPA-1A/ZW(A)/PL(A1) has Leu-59 and HPA-1B/ZW(B)/PL(A2) has Pro-59. HPA-1A is involved in fetal-maternal alloimmune thromobocytopenia (FMAIT) as well as in neonatal alloimmune thrombocytopenia (NAIT).Position 169 is associated with platelet-specific alloantigen HPA-4 (PEN or YUK). HPA-4A/PEN(A)/YUK(A) has Arg-169 and HPA-4B/PEN(B)/YUK(B) has Gln-169. HPA-4B is involved in neonatal alloimmune thrombocytopenia (NAIT or NATP).Position 433 is associated with platelet-specific alloantigen MO. MO- has Pro-433 and MO+ has Ala-433. MO+ is involved in NAIT.Position 515 is associated with platelet-specific alloantigen CA/TU. CA-/TU- has Arg-515 and CA+/TU+ has Gln-515. CA+ is involved in NAIT.Position 662 is associated with platelet-specific alloantigen SR(A). SR(A)- has Arg-662 and SR(A)+ has Cys-662.
Involvement in disease: Glanzmann thrombasthenia (GT) [MIM:273800]: A common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.52 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59
Sequence similarities: Belongs to the integrin beta chain family.Contains 1 VWFA domain.
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