Fibrinogen alpha chain (FGA)
The protein contains 866 amino acids for an estimated molecular weight of 94973 Da.
Cleaved 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. (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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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
Amyloid fibril formation
Blood coagulation
Blood coagulation, common pathway
Blood coagulation, fibrin clot formation
Cell-matrix adhesion
Cellular protein complex assembly
Cellular protein metabolic process
Cellular protein-containing complex assembly
Extracellular matrix organization
Fibrinolysis
Induction of bacterial agglutination
Innate immune response
Negative regulation of blood coagulation, common pathway
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
Post-translational protein modification
Protein complex assembly
Protein polymerization
Protein-containing complex assembly
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 lumen
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 105200
Amyloidosis, familial visceral
Amyloidosis viii
Ostertag type amyloidosis
German type amyloidosis
Amyloidosis, familial renal
Amyloidosis, systemic nonneuropathic
A number sign (#) is used with this entry because of the evidence that systemic nonneuropathic amyloidosis is the result of mutation in the apolipoprotein A1 gene (APOA1; 107680), the fibrinogen alpha-chain gene (FGA; 134820), the lysozyme gene (LYZ; 153450), or the gene encoding beta-2-microglobulin (B2M; 109700).
CLINICAL FEATURES
Ostertag (1932, 1950) reported on a family with visceral amyloidosis. A woman, 3 of her children, and 1 of her grandchildren were affected with chronic nephropathy, arterial hypertension, and hepatosplenomegaly. Albuminuria, hematuria and pitting edema were early signs. The age of onset was variable. Death occurred about 10 years after onset. The visceral involvement by amyloid was found to be extensive. Maxwell and Kimbell (1936) described 3 brothers who died of visceral, especially renal, amyloidosis in their 40s. Chronic weakness, edema, proteinuria, and hepatosplenomegaly were features. McKusick (1974) followed up on the family reported by Maxwell and Kimbell (1936). The father of the 3 affected brothers died at age 72 after an automobile accident and their mother died suddenly at age 87 after being in apparent good health. A son of one of the brothers had frequent bouts of unexplained fever in childhood (as did his father and 2 uncles), accompanied at times by nonspecific rash. At the age of 35, proteinuria was discovered and renal amyloidosis was diagnosed by renal biopsy. For 2 years thereafter he displayed the nephrotic syndrome, followed in the next 2 years by uremia from which he died at age 39. Autopsy revealed amyloidosis, most striking in the kidneys but also involving the adrenal glands and spleen. Although some features of the family of Maxwell and Kimbell (1936) are similar to those of urticaria, deafness and amyloidosis (191900), no deafness was present in their family. Weiss and Page (1974) reported a family with 2 definite and 4 probable cases in 3 generations. Mornaghi et al. (1981, 1982) reported rapidly progressive biopsy-proved renal amyloidosis in 3 brothers, aged 49, 52 and 55, of Irish-American origin. None had evidence of a plasma cell dyscrasia, a monoclonal serum or urine protein, or any underlying chronic disease. Immunoperoxidase staining of 1 pulmonary and 1 renal biopsy specimen was negative for amyloid A (AA), amyloid L (AL) and prealbumin. The authors concluded that the disorder in the 3 brothers closely resembled that described by Ostertag (1932). Studying the proband of a kindred with the familial amyloidosis of Ostertag, Lanham et al. (1982) demonstrated permanganate-sensitive congophilia of the amyloid but found no immunofluorescent staining for amyloid A or prealbumin. They concluded that this amyloid may be chemically distinct from previously characterized forms. Libbey and Talbert (1987) described a case of nephropathic amyloidosis, presumably of the Ostertag type. In their case, the amyloid showed no staining for light chains or prealbumin. Involvement of the liver was associated with cholestasis. In the kindred reported by Lanham et al. (1982), 6 members in 2 generations showed the onset of renal disease between ages 23 and 45 years. The deposition of amyloid is characteristically interstitial rather than glomerular as seen in other forms of amyloidosis. The proband had the sicca syndrome. The details of their patient's family history were not given by Libbey and Talbert (1987). Zalin et al. (1991) described yet another family with the Ostertag type of f ... More on the omim web site
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
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for FGA
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 105200 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed