Integrin alpha-IIb

UniProt P08514 Organism Homo sapiens Gene GP2B, ITGA2B, ITGAB

Also known as: GP2B, ITGA2B, ITGAB

Function

Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) 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 (By similarity). 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 (By similarity). Integrin ITGA2B:ITGB3 is also the receptor of erythrocyte-specific ICAM4 ligand involved in heterotypic cell-cell adhesion between erythrocytes and activated platelets.

Classification

Family (Pfam): PF01839 FG-GAP, PF08441 Integrin_A_Ig_1, PF20805 Integrin_A_Ig_2, PF20806 Integrin_A_Ig_3, PF00357 Integrin_alpha
InterPro: FG-GAP, Int_alpha_beta-p, Integrin_alpha, Integrin_alpha_C_CS, Integrin_alpha_Ig-like_1, Integrin_alpha_Ig-like_2, Integrin_alpha_Ig-like_3, Integrin_alpha_N, Integrin_dom_sf
Functional cluster: Secreted Growth Factors & Cytokines

Experimental structures · PDB · 78

1DPK NMR
1DPQ NMR
1KUP NMR
1KUZ NMR
1M8O NMR
1S4W NMR
1TYE X-ray 2.90A
2K1A NMR
2K9J NMR
2KNC NMR
2MTP NMR
2N9Y NMR
… and 66 more

A predicted model is available from AlphaFold.

Gene Ontology · 21

Disease associations

platelet-type bleeding disorder 16 MONDO:0008552
Glanzmann thrombasthenia 1 MONDO:0031332
fetomaternal alloimmune thrombocytopenia 2 MONDO:0980724

Drugs targeting this protein · 3

EPTIFIBATIDE inhibitor
ZALUNFIBAN inhibitor
TIROFIBAN HYDROCHLORIDE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Integrin beta-3 13 shared papers
Calcium and integrin-binding protein 1 5 shared papers
E3 ubiquitin-protein ligase RNF181 1 shared papers
Intercellular adhesion molecule 4 1 shared papers
Calcium and integrin-binding family member 4 1 shared papers
Calcium and integrin-binding family member 3 1 shared papers
Integrin alpha-6 1 shared papers
Integrin alpha-7 1 shared papers
Neutrophil elastase 1 shared papers
Calcium and integrin-binding family member 2 1 shared papers
Cathepsin G 1 shared papers
P-selectin 1 shared papers

Literature · 63 cited papers

The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand. Life. Sci Alliance · 2023
A V740L mutation in glycoprotein IIb defines a novel epitope (War) associated with fetomaternal alloimmune thrombocytopenia. Transfusion · 2013
Biophysical and structural studies of the human calcium- and integrin-binding protein family: understanding their functional similarities and differences. Biochem. Cell Biol. · 2012
Structural basis for the activation of platelet integrin alphaIIbbeta3 by calcium- and integrin-binding protein 1. J. Am. Chem. Soc. · 2012
Heterozygous ITGA2B R995W mutation inducing constitutive activation of the alphaIIbbeta3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia. Blood · 2011
Solution structures of Ca2+-CIB1 and Mg2+-CIB1 and their interactions with the platelet integrin alphaIIb cytoplasmic domain. J. Biol. Chem. · 2011
AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function. Hum. Mutat. · 2010
New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia. Transfusion · 2010
Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol. Cell · 2008
RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3. Biochem. Biophys. Res. Commun. · 2008
Type II Glanzmann thrombasthenia in a compound heterozygote for the alpha IIb gene. A novel missense mutation in exon 27. Haematologica · 2006
DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
… and 51 more in the literature graph

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