GP1BA

Fig1. Domain structure of VWF and the main interaction sites. (Frederik Denorme, 2019)

What is GP1BA protein?

GP1BA gene (glycoprotein Ib platelet subunit alpha) is a protein coding gene which situated on the short arm of chromosome 17 at locus 17p13. Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein composed of a heterodimer, an alpha chain and a beta chain, that is linked by disulfide bonds. The Gp Ib functions as a receptor for von Willebrand factor (VWF). The binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. This gene encodes the alpha subunit. The GP1BA protein is consisted of 652 amino acids and GP1BA molecular weight is approximately 71.5 kDa.

What is the function of GP1BA protein?

GP1BA protein is an important membrane protein on the surface of platelets, and it is a key component of the platelet glycoprotein Ib-IX-V complex. The primary function of the GP1BA protein is to act as a receptor for the von Willebrand factor (vWF), which is involved in the adhesion and activation of platelets, a key step in the blood clotting and hemostasis process. GP1BA helps stop bleeding by interacting with vWF, allowing platelets to adhere to the damaged blood vessels and form clots. Mutations in the GP1BA gene may lead to abnormalities in the GPIbα subunit, affecting its expression or function on the surface of platelets, which in turn affects the blood clotting process.

GP1BA related signaling pathway

Gp1ba-related signaling pathways are mainly involved in platelet function and hemostasis. GP1BA is an important receptor on the surface of platelets that binds to the von Willebrand Factor (vWF) in plasma, an interaction that plays a key role in how platelets adhere to damaged blood vessel walls. When blood vessels are injured, vWF binds to exposed collagen fibers, and then GP1BA receptors initiate platelet activation and aggregation by interacting with vWF. This process involves several signaling molecules, including G proteins, tyrosine kinases, and phosphatidylinositol-3-kinases, which together promote platelet activation, particle secretion, aggregation, and ultimately thrombosis.

GP1BA related diseases

The GP1BA protein is associated with several important blood diseases. It encodes the platelet membrane glycoprotein Ibα subunit, which is part of the platelet membrane glycoprotein Ib-IX-V complex and is essential for platelet function. Mutations or abnormal expression of the GP1BA gene are associated with Bernard-Soulier syndrome (BSS), a hemorrhagic disorder that results from abnormal platelet function and is characterized by reduced platelet count and increased platelet volume. In addition, polymorphism of GP1BA gene is also associated with platelet sensitivity to aspirin, which may affect the effect of aspirin in the prevention of cardiovascular and cerebrovascular diseases. Variations in the GP1BA gene have also been associated with other diseases such as myocardial infarction, non-arteriosclerotic anterior optic nerve ischemia, and platelet-type bleeding disorders.

Bioapplications of GP1BA

The biological applications of rhGP1BA are mainly focused on the study of hemostasis and thrombosis and the treatment of platelet dysfunction. As an important receptor on platelets, rhGP1BA can be used to diagnose and study related diseases, such as inherited platelet dysfunction such as Bernard-Soulier syndrome. In addition, rhGP1BA has potential value in the development of novel antithrombotic drugs and drugs that promote hemostasis, which can mimic or modulate the adhesion and aggregation process of platelets. In clinical treatment, the use of rhGP1BA or its derivatives may help restore or replace platelet function, thereby controlling bleeding or promoting wound healing. However, its specific application needs to be validated in clinical trials to ensure safety and efficacy.

Case Study 1: Jing Li, 2019

This research showed that platelet protein disulfide isomerase (PDI) boosts the activity of glycoprotein Ibα (GPIbα), a receptor involved in platelet-neutrophil interactions during thromboinflammation. PDI directly interacts with GPIbα, enhancing its ligand binding by reducing specific disulfide bonds. Experiments with PDI-null platelets and a GPIbα inhibitor confirmed PDI's role in these interactions and vascular occlusion. This interaction was also crucial for tissue damage in a mouse model of stroke.

Fig1. Wild-type (WT) and hIL4R/glycoprotein Ibα (GPIbα) platelets were used.

Fig2. Proteins were electrophoresed under reduced conditions and blotted with peroxidase-conjugated avidin.

Case Study 2: Rashi Singhal, 2015

This study uncovers a new mechanism where extracellular hemoglobin (Hb) influences platelet activation in hemolytic disorders, increasing the risk of hypercoagulation and thrombosis. Low Hb levels enhance platelet signaling and aggregation, while higher levels trigger pro-apoptotic pathways and clot formation. In paroxysmal nocturnal hemoglobinuria patients, elevated plasma or platelet-bound Hb correlates with platelet activation, suggesting a key role in disease pathogenesis.

Fig3. Hb binding to platelet GP1bα.

Fig4. Thrombin generation by platelets treated with Hb.

GP1BA has several biochemical functions, for example, protein binding,thrombin receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by GP1BA itself. We selected most functions GP1BA had, and list some proteins which have the same functions with GP1BA. You can find most of the proteins on our site.

GP1BA has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with GP1BA here. Most of them are supplied by our site. Hope this information will be useful for your research of GP1BA.

VWF;GP9;YWHAZ;F2;F12;GP1BB;FLNA;YWHAQ;YWHAB;YWHAG;YWHAE;YWHAH