FGG

The protein encoded by this gene is the gamma component of fibrinogen, a blood-borne glycoprotein comprised of three pairs of nonidentical polypeptide chains. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots. In addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this gene lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia and thrombophilia. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

Fibrinogen Gamma Chain

Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways.

Blood coagulation, fibrin clot formation Source: UniProtKB
Cell-matrix adhesion Source: BHF-UCL
Cellular protein-containing complex assembly Source: BHF-UCL
Cellular response to interleukin-1 Source: Ensembl
Cellular response to interleukin-6 Source: Ensembl
Fibrinolysis Source: UniProtKB
Negative regulation of endothelial cell apoptotic process Source: BHF-UCL
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
Negative regulation of platelet aggregation Source: Ensembl
Plasminogen activation Source: UniProtKB
Platelet aggregation Source: BHF-UCL
Platelet maturation Source: Ensembl
Positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
Positive regulation of exocytosis Source: BHF-UCL
Positive regulation of heterotypic cell-cell adhesion Source: BHF-UCL
Positive regulation of peptide hormone secretion Source: BHF-UCL
Positive regulation of protein secretion Source: BHF-UCL
Positive regulation of substrate adhesion-dependent cell spreading Source: BHF-UCL
Positive regulation of vasoconstriction Source: BHF-UCL
Protein polymerization Source: BHF-UCL
Protein secretion Source: UniProtKB
Response to calcium ion Source: BHF-UCL

Secreted

Congenital afibrinogenemia (CAFBN):
The disease is caused by variants affecting the gene represented in this entry. Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding. Rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen.
Dysfibrinogenemia, congenital (DYSFIBRIN):
A disorder characterized by qualitative abnormalities (dysfibrinogenemia) of the circulating fibrinogen. Affected individuals are frequently asymptomatic, but some patients have bleeding diathesis, thromboembolic complications, or both. In some cases, dysfibrinogenemia is associated with low circulating fibrinogen levels (hypodysfibrinogenemia).

Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers.
Sulfation of C-terminal tyrosines increases affinity for thrombin.