F2
GeneName
F2
Summary
F2, commonly known as thrombin or prothrombin, is a 70kDa serine-type endopeptidase that plays a central role in the blood coagulation cascade. It is primarily expressed in the liver and circulates in the bloodstream as an inactive precursor. Upon activation, prothrombin is converted to thrombin, which not only catalyses the conversion of fibrinogen to fibrin, forming a blood clot, but also has numerous regulatory functions in various biological processes. Thrombin interacts with various receptors, modulating cell signalling pathways and influencing processes such as inflammation, cell growth, and tissue repair. It is found in multiple subcellular locations including the extracellular space, plasma membrane, and within blood microparticles, highlighting its diverse roles in both coagulation and cellular signalling.
Importance
F2 is relevant to: - Haemostasis and thrombosis, as it is a key enzyme in blood coagulation, influencing clot formation and stability. - Cardiovascular diseases, where dysregulation of thrombin activity can lead to conditions such as thrombosis or bleeding disorders. - Inflammatory responses, given its role in mediating interactions between platelets and other immune cells. - Cancer progression, as thrombin can promote tumour growth and metastasis through its effects on cell signalling and the extracellular matrix.
Top Products
For researchers investigating the F2 gene, we recommend two primary antibodies that stand out for their performance and reliability. The first is the well-cited polyclonal antibody, Anti-Thrombin antibody (ab92621), which has garnered 17 citations and is particularly effective for Western blotting (WB). This product is a trusted choice for those looking to study thrombin in various experimental contexts. Additionally, we offer the recombinant antibody, Anti-Prothrombin antibody [EPR20159] (ab208589), which has been validated for multiple applications, including WB, immunocytochemistry (ICC), flow cytometry (FC), and immunoprecipitation (IP). With 3 citations, this monoclonal antibody provides the batch-to-batch consistency that researchers often seek in their experiments. Together, these antibodies provide a robust toolkit for studying the F2 gene and its associated pathways. "The Mouse Thrombin ELISA Kit (ab230933), supported by 3 citations, is an excellent option for researchers looking to accurately measure thrombin levels in mouse samples."
Abcam Product Citation Summary
The data indicates that F2 antibodies are being utilised in various applications, including western blotting and immunohistochemistry, across different species, primarily focusing on human and mouse models. The studies highlight the role of F2 in thrombin interactions, atherosclerosis, and macrophage functions, suggesting its significance in coagulation and inflammatory processes.
Abcam Product Citation Table
Function
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. Activates coagulation factor XI (F11); activation is promoted by the contact with negatively charged surfaces (PubMed:2019570, PubMed:21976677). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL8/CXCL8, in endothelial cells (PubMed:30568593, PubMed:9780208).
Involvement in disease
Factor II deficiency
FA2D
A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.
None
The disease is caused by variants affecting the gene represented in this entry.
Ischemic stroke
ISCHSTR
A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Thrombophilia due to thrombin defect
THPH1
A multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation.
None
The disease is caused by variants affecting the gene represented in this entry. A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.
Pregnancy loss, recurrent, 2
RPRGL2
A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin.
N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major).
In the penultimate step of the coagulation cascade, prothrombin is converted to thrombin by the prothrombinase complex composed of factor Xa (F10), cofactor Va (F5), and phospholipids. This activation requires factor Xa-catalyzed sequential cleavage at 2 sites, Arg-314 and Arg-363, along 2 possible pathways. In the first pathway, the first cleavage occurs at Arg-314, leading to the formation of the inactive intermediate prethrombin-2. This pathway preferentially occurs on platelets and in the absence of cofactor Va. In the second pathway, the first cleavage occurs at Arg-363, which separates protease domain into 2 chains that remain connected through a disulfide bond and generates the active intermediate meizothrombin. The presence of cofactor Va directs activation along the meizothrombin pathway and greatly accelerates the rate of cleavage at Arg-363, but has a smaller effect on the cleavage of meizothrombin at Arg-314. Meizothrombin accumulates as an intermediate when prothrombinase is assembled on the membrane of red blood cells.
Sequence Similarities
Belongs to the peptidase S1 family.
Tissue Specificity
Expressed by the liver and secreted in plasma.
Cellular localization
- Secreted
- Extracellular space
Alternative names
Prothrombin, Coagulation factor II, F2