Fibrinogen beta chain (FGB)
The protein contains 491 amino acids for an estimated molecular weight of 55928 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Adaptive immune response
Blood coagulation
Blood coagulation, fibrin clot formation
Cell adhesion
Cell-matrix adhesion
Cellular protein complex assembly
Cellular protein-containing complex assembly
Cellular response to interleukin-1
Cellular response to leptin stimulus
Extracellular matrix organization
Fibrinolysis
Induction of bacterial agglutination
Innate immune response
Negative regulation of endothelial cell apoptotic process
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Plasminogen activation
Platelet activation
Platelet aggregation
Platelet degranulation
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of exocytosis
Positive regulation of heterotypic cell-cell adhesion
Positive regulation of peptide hormone secretion
Positive regulation of protein secretion
Positive regulation of substrate adhesion-dependent cell spreading
Positive regulation of vasoconstriction
Protein polymerization
Response to calcium ion
Signal transduction
Toll-like receptor signaling pathway
Cellular Component
Blood microparticle
Cell cortex
Cell surface
Collagen-containing extracellular matrix
Endoplasmic reticulum
External side of plasma membrane
Extracellular exosome
Extracellular region
Extracellular space
Extracellular vesicle
Fibrinogen complex
Plasma membrane
Platelet alpha granule
Platelet alpha granule lumen
Synapse
Vesicle
The reference OMIM entry for this protein is 134830
Fibrinogen, b beta polypeptide; fgb
Fibrinogen--beta polypeptide chain
DESCRIPTION
Fibrinogen, the soluble precursor of fibrin, is a plasma glycoprotein synthesized in the liver. It is composed of 3 structurally different subunits: alpha (FGA; 134820), beta, and gamma (FGG; 134850). Thrombin (176930) causes a limited proteolysis of the fibrinogen molecule, during which fibrinopeptides A and B are released from the N-terminal regions of the alpha and beta chains, respectively. The enzyme cleaves arginine-glycine linkages so that glycine is left as the N-terminal amino acid on both chains. Thrombin also activates fibrin-stabilizing factor (factor XIII; see 134570 and 134580), which in its activated form is a transpeptidase catalyzing the formation of epsilon-(gamma-glutamyl)-lysine crosslinks in fibrin. Fibrinopeptides, which have been sequenced in many species, may have a physiologic role as vasoconstrictors and may aid in local hemostasis during blood clotting (summary by Dayhoff, 1972).MAPPING
Divelbiss et al. (1989) studied a balanced de novo translocation between chromosomes 2 and 4 with a breakpoint at 4q31.1. Using RFLPs for both GYPA (111300) and GYPB (111740), they found that a paternal allele from the chromosomally normal father had not been inherited. This result was interpreted as indicating loss of genetic material at the site of the GYPA and GYPB genes presumably related to the de novo translocation. No evidence was found for rearrangement of gamma or beta fibrinogen. By in situ hybridization using probes for GYPA and for FGB, no hybridization was found on the derived chromosome 2, which contained most of 4q31. These data were interpreted as indicating that the fibrinogen locus is proximal to the GYPA/GYPB loci.GENE FUNCTION
Petzelbauer et al. (2005) demonstrated that the FGB(15-42) peptide fragment competes with the fibrin fragment N-terminal disulfide knot-II for binding to vascular endothelial cadherin (CDH5; 601120) and thus prevents transmigration of leukocytes across endothelial cell monolayers. In acute and chronic rat models of myocardial ischemia-reperfusion injury, FGB(15-42) substantially reduced leukocyte infiltration, infarct size, and subsequent scar formation. Petzelbauer et al. (2005) concluded that the interplay of fibrin fragments, leukocytes, and CDH5 contributes to the pathogenesis of myocardial damage and reperfusion injury.MOLECULAR GENETICS
Meyer et al. (1988) incidentally discovered an abnormality of the beta chain in the course of electrophoretic protein studies of normal blood samples. The 29-year-old blood donor had no symptoms of bleeding tendency or thrombosis. A sister was similarly affected. The mother, who may have had the variant, called Erfurt I, was deceased. Humphries et al. (1987) used RFLPs of fibrinogen genes to demonstrate a strong association between polymorphism detected with a beta-fibrinogen probe and the enzyme BclI (134830.0008). Genetic variation at the fibrinogen locus accounted for 15% of the total variance in fibrinogen level. In a large study in Copenhagen, Tybjaerg-Hansen et al. (1997) found that the -455G-A polymorphism in the FGB promoter (134830.0008) is associated with an increase in plasma fibrinogen in both genders, but does not appear to cause ischemic heart disease. Fowkes et al. (1992) concluded that there is an association between peripheral atherosclerosis and the presence in homozygous or heterozygous state of an allele at the FGB locus, the 4.2-kb allele with BclI digestion. The allel ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for FGB
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 134830 was added.