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MGP001062

UniProt Annotations

Entry Information
Gene Namefibrinogen alpha chain
Protein EntryFIBA_HUMAN
UniProt IDP02671
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; Synonyms=Alpha-E; IsoId=P02671-1; Sequence=Displayed; Name=2; Synonyms=Alpha; IsoId=P02671-2; Sequence=VSP_001531, VSP_001532; Note=Ref.3 (AAK31372) sequence is in conflict in positions: 640:PSLSP->LPCPPRLS. {ECO:0000305};
DiseaseAmyloidosis 8 (AMYL8) [MIM:105200]: A hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. {ECO:0000269|PubMed:8097946}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseCongenital 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. Note=The disease is caused by mutations affecting the gene represented in this entry. The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias.
DomainA 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.
FunctionCleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) 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 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 immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}.
InteractionP02647:APOA1; NbExp=2; IntAct=EBI-348571, EBI-701692;
PtmAbout one-third of the alpha chains in the molecules in blood were found to be phosphorylated.
PtmConversion 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}.
PtmForms F13A-mediated cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming fibronectin- fibrinogen heteropolymers.
PtmO-glycosylated. {ECO:0000269|PubMed:23050552}.
PtmPhosphorylation sites are present in the extracellular medium.
PtmThe alpha chain is normally not N-glycosylated (PubMed:23151259), even though glycosylation at Asn-686 was observed when a fragment of the protein was expressed in insect cells (PubMed:9689040). It is well known that heterologous expression of isolated domains can lead to adventitious protein modifications. Besides, glycosylation at Asn-686 is supported by large-scale glycoproteomics studies (PubMed:16335952 and PubMed:19159218), but the evidence is still quite tenuous. Most likely, Asn-686 is not glycosylated in the healthy human body, or only with low efficiency. {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23151259, ECO:0000269|PubMed:9689040, ECO:0000305}.
SimilarityContains 1 fibrinogen C-terminal domain. {ECO:0000255|PROSITE-ProRule:PRU00739}.
Subcellular LocationSecreted.
SubunitHeterohexamer; 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.
Tissue SpecificityPlasma.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/fga/";
Web ResourceName=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=FGA";
Web ResourceName=Wikipedia; Note=Fibrinogen entry; URL="http://en.wikipedia.org/wiki/Fibrinogen";
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