F11

Official Full Name

coagulation factor XI

Organism

Homo sapiens

GeneID

2160

Background

This gene encodes coagulation factor XI of the blood coagulation cascade. This protein is present in plasma as a zymogen, which is a unique plasma coagulation enzyme because it exists as a homodimer consisting of two identical polypeptide chains linked by disulfide bonds. During activation of the plasma factor XI, an internal peptide bond is cleaved by factor XIIa (or XII) in each of the two chains, resulting in activated factor XIa, a serine protease composed of two heavy and two light chains held together by disulfide bonds. This activated plasma factor XI triggers the middle phase of the intrisic pathway of blood coagulation by activating factor IX. Defects in this factor lead to Rosenthal syndrome, a blood coagulation abnormality. [provided by RefSeq, Jul 2008]

Synonyms

FXI; PTA;

Bio Chemical Class

mRNA target

Protein Sequence

MIFLYQVVHFILFTSVSGECVTQLLKDTCFEGGDITTVFTPSAKYCQVVCTYHPRCLLFTFTAESPSEDPTRWFTCVLKDSVTETLPRVNRTAAISGYSFKQCSHQISACNKDIYVDLDMKGINYNSSVAKSAQECQERCTDDVHCHFFTYATRQFPSLEHRNICLLKHTQTGTPTRITKLDKVVSGFSLKSCALSNLACIRDIFPNTVFADSNIDSVMAPDAFVCGRICTHHPGCLFFTFFSQEWPKESQRNLCLLKTSESGLPSTRIKKSKALSGFSLQSCRHSIPVFCHSSFYHDTDFLGEELDIVAAKSHEACQKLCTNAVRCQFFTYTPAQASCNEGKGKCYLKLSSNGSPTKILHGRGGISGYTLRLCKMDNECTTKIKPRIVGGTASVRGEWPWQVTLHTTSPTQRHLCGGSIIGNQWILTAAHCFYGVESPKILRVYSGILNQSEIKEDTSFFGVQEIIIHDQYKMAESGYDIALLKLETTVNYTDSQRPICLPSKGDRNVIYTDCWVTGWGYRKLRDKIQNTLQKAKIPLVTNEECQKRYRGHKITHKMICAGYREGGKDACKGDSGGPLSCKHNEVWHLVGITSWGEGCAQRERPGVYTNVVEYVDWILEKTQAV

Open

Disease

Alzheimer disease, Cerebral ischaemic stroke, Coagulation defect, Thrombosis

Approved Drug

Clinical Trial Drug

10 +

Discontinued Drug

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Detailed Information

Functions & Recent Research Progress

Coagulation factors are various protein components involved in the blood coagulation process. Its physiological role is to activate when blood vessels bleed, stick to platelets and fill the leaks on the blood vessels. Factor XI (F11) is essential for the normal function of the intrinsic pathway of blood coagulation. Factor XI is a key player in blood coagulation and therefore represents a potential target for antisense therapy. Moreover, F11 is required for the maintenance of endogenous pathways and plays a key role in the amplification of the coagulation cascade.

Figure 1. Coagulation cascade (Yahui Chen,2015)

The role of F11 in the coagulation cascade and thrombosis.

The coagulation cascade is a process in which a series of coagulation factors are sequentially activated to form fibrin. The coagulation cascade is initiated by the endogenous pathway (also known as the contact activation pathway) and the exogenous pathway (also known as the tissue factor pathway) to produce FXa, which is then produced by a common pathway to form thrombin (FIla), which ultimately forms fibrin. F11 is required for the maintenance of endogenous pathways and plays a key role in the amplification of the coagulation cascade. In the coagulation cascade, thrombin can feedbackly activate F11, which in turn promotes the production of thrombin. Thereby, the coagulation cascade is amplified. Therefore, a drug against the F11 target can block the endogenous pathway and inhibit the amplification of the coagulation cascade, thereby having an antithrombotic effect. Meanwhile, a large amount of thrombin dependent on F11a can be activated. The thrombin-activated fibrinolysis inhibitor (TAFI) down-regulates the fibrinolytic system.

F11 is essential for the normal function of the intrinsic pathway of blood coagulation. Nucleotide variants (rs3756008) in the promoter region of the F11 gene have recently been reported to be associated with venous thromboembolism. Scientists believe that the minor allele of rs3756008 in the F11 gene promoter can reduce its expression in the kidney.

F11 is a key player in blood clotting and therefore represents a potential target for antisense therapy. Although current treatment devices for venous thrombosis include the use of vitamin K antagonists, heparin and direct oral anticoagulants, these drugs have several important drawbacks. Antisense oligonucleotides are relatively short single-stranded nucleic acid sequences that hybridize to target messenger RNA (mRNA) and inhibit protein synthesis. The study found that Factor XI antisense oligonucleotides may be more effective at preventing the development and proliferation of thrombosis than conventional anticoagulants, and do not require factor measurement because the reduction in mRNA synthesis is dose dependent.

References:

Yahui Chen, et al.Research progress of coagulation factor XI as a new target for antithrombotic prevention.Chinese Pharmacological Bulletin,2015, 10.3969/j.issn.1001-1078.
Giuseppe Lippi, et al. Next Generation Antithrombotic Therapy: Focus on Antisense Therapy against Coagulation Factor XI. Semin Thromb Hemost, 2015, 255-262.
Minyoung Kong, et al. Functional investigation of a venous thromboembolism GWAS signal in a promoter region of coagulation factor XI gene. Molecular Biology Reports, 2014.

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