UniProt functional annotation for P02675



	UniProt functional annotation for P02675

UniProt code: P02675.

Organism: Homo sapiens (Human).

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

Function: Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin 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. 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: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:10074346, 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}.

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:10666208, ECO:0000269|PubMed:11468164, ECO:0000269|PubMed:15070683, 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:1634610}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAH07030.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

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:		Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin 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. 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: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:10074346, 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}.
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:10666208, ECO:0000269\|PubMed:11468164, ECO:0000269\|PubMed:15070683, 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:1634610}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAH07030.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};