UniProt functional annotation for P02679



	UniProt functional annotation for P02679

UniProt code: P02679.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000250|UniProtKB:E9PV24}.

Subunit: Heterohexamer; disulfide linked. Contains 2 sets of 3 non- identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain. {ECO:0000269|PubMed:10074346, ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:6860649, ECO:0000269|PubMed:9016719, ECO:0000269|PubMed:9207064, ECO:0000269|PubMed:9333233, ECO:0000269|PubMed:9628725}.

Subcellular location: Secreted {ECO:0000269|PubMed:10074346, ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725}.

Tissue specificity: Detected in blood plasma (at protein level). {ECO:0000269|PubMed:10074346, ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725}.

Domain: A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure. {ECO:0000269|PubMed:19296670, ECO:0000269|PubMed:9628725}.

Ptm: 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. {ECO:0000269|PubMed:2143188}.

Ptm: Sulfation of C-terminal tyrosines increases affinity for thrombin. {ECO:0000269|PubMed:11307817, ECO:0000269|PubMed:1892842}.

Disease: Congenital afibrinogenemia (CAFBN) [MIM:202400]: 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. {ECO:0000269|PubMed:25427968}. Note=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.

Disease: Dysfibrinogenemia, congenital (DYSFIBRIN) [MIM:616004]: 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). {ECO:0000269|PubMed:15632207, ECO:0000269|PubMed:2257302, ECO:0000269|PubMed:2976995, ECO:0000269|PubMed:3708159}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: The gamma-chain carries the main binding site for the platelet receptor.

Miscellaneous: [Isoform Gamma-B]: Present in about 10% of the fibrinogen molecules in plasma but absent from those in the platelets.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000250\|UniProtKB:E9PV24}.


Subunit:		Heterohexamer; disulfide linked. Contains 2 sets of 3 non- identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain. {ECO:0000269\|PubMed:10074346, ECO:0000269\|PubMed:19296670, ECO:0000269\|PubMed:6860649, ECO:0000269\|PubMed:9016719, ECO:0000269\|PubMed:9207064, ECO:0000269\|PubMed:9333233, ECO:0000269\|PubMed:9628725}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:10074346, ECO:0000269\|PubMed:19296670, ECO:0000269\|PubMed:9628725}.
Tissue specificity:		Detected in blood plasma (at protein level). {ECO:0000269\|PubMed:10074346, ECO:0000269\|PubMed:19296670, ECO:0000269\|PubMed:9628725}.
Domain:		A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure. {ECO:0000269\|PubMed:19296670, ECO:0000269\|PubMed:9628725}.
Ptm:		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. {ECO:0000269\|PubMed:2143188}.
Ptm:		Sulfation of C-terminal tyrosines increases affinity for thrombin. {ECO:0000269\|PubMed:11307817, ECO:0000269\|PubMed:1892842}.
Disease:		Congenital afibrinogenemia (CAFBN) [MIM:202400]: 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. {ECO:0000269\|PubMed:25427968}. Note=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.
Disease:		Dysfibrinogenemia, congenital (DYSFIBRIN) [MIM:616004]: 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). {ECO:0000269\|PubMed:15632207, ECO:0000269\|PubMed:2257302, ECO:0000269\|PubMed:2976995, ECO:0000269\|PubMed:3708159}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		The gamma-chain carries the main binding site for the platelet receptor.
Miscellaneous:		[Isoform Gamma-B]: Present in about 10% of the fibrinogen molecules in plasma but absent from those in the platelets.