The Function of ITGA2B
Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It 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 cell surface.
Protein names
Recommended name:
Integrin alpha-IIbAlternative name(s):
GPalpha IIbGPIIb
Platelet membrane glycoprotein IIb
CD antigen CD41
- RS5911 (ITGA2B) ??
- RS708382 (ITGA2B) ??
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Top Gene-Substance Interactions
ITGA2B Interacts with These Diseases
Disease | Score |
Substances That Increase ITGA2B
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Substances That Decrease ITGA2B
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Advanced Summary
Glanzmann thrombasthenia At least 200 mutations in the ITGA2B gene have been found to cause Glanzmann thrombasthenia, which is a rare bleeding disorder. The mutations that cause this disorder occur in both copies of the gene in each cell and impair the production or activity of the alphaIIb subunit, which disrupts the formation of functional integrin αIIbβ3. A shortage (deficiency) of functional integrin αIIbβ3 prevents sufficient binding of fibrinogen or other proteins, impairing the formation of blood clots. A lack of platelet cohesion leads to prolonged or spontaneous bleeding episodes experienced by people with Glanzmann thrombasthenia. other disorders Mutations in the ITGA2B gene can also cause another rare bleeding disorder called platelet-type bleeding disorder 16. People with this disorder have signs and symptoms similar to Glanzmann thrombasthenia (described above), including frequent nosebleeds (epistaxis), bleeding from the gums, or red or purple spots on the skin caused by bleeding underneath the skin (petechiae), but the episodes are typically milder. Unlike Glanzmann thrombasthenia, this disorder results from a mutation in only one copy of the ITGA2B gene in each cell, and the mutations result in the formation of some integrin αIIbβ3 that is abnormally turned on (active), even when no clot is being formed. This abnormally active protein is unable to reach the surface of the platelet where it is needed to bind to other platelets during clot formation. The overactive integrin αIIbβ3 binds inappropriately to clotting proteins within the cell during the formation of platelets, causing the platelets to become misshapen and large. The abnormally shaped platelets have a shortened lifespan, so platelet numbers are often reduced, which impairs clot formation. (The combination of reduced numbers of enlarged platelets is referred to as macrothrombocytopenia.) Because the mutation that causes this disorder affects only one copy of the ITGA2B gene, some normal integrin is formed and normal platelets produced, which accounts for the mild signs and symptoms in affected individuals.
The ITGA2B gene provides instructions for making one part, the alphaIIb subunit, of a receptor complex called integrin alphaIIb/beta3 (αIIbβ3), which is found on the surface of small cell fragments called platelets. Platelets circulate in blood and are an essential component of blood clots. The alphaIIb subunit attaches (binds) to the beta3 subunit, which is produced from the ITGB3 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 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.
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Isoform 1 and isoform 2 were identified in platelets and megakaryocytes, but not in reticulocytes or in Jurkat and U-937 white blood cell line. Isoform 3 is expressed by leukemia, prostate adenocarcinoma and melanoma cells but not by platelets or normal prostate or breast epithelial cells.
Gene Pathways:
Molecular Function:
Biological Processes:
- Cell Adhesion
- Cell-Matrix Adhesion
- Extracellular Matrix Organization
- Integrin-Mediated Signaling Pathway
- Platelet Aggregation
- Platelet Degranulation
- Positive Regulation Of Leukocyte Migration
Drug Bank:
- Abciximab
- Tirofiban