Fibrinogen gamma chain (FGG)

The protein contains 453 amino acids for an estimated molecular weight of 51512 Da.

 

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. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 98%
Model score: 100

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VariantDescription
dbSNP:rs11551835
dbSNP:rs2066870
Milano-12
Tochigi/Osaka-2/Milano-5/Villajoyosa
DYSFIBRIN
DYSFIBRIN
Baltimore-3
Kyoto-1; causes accelerated cleavage by plasmin
Hillsborough; prolonged thrombin clotting time
Asahi
Nagoya-1
DYSFIBRIN
Kyoto-3
Bern-1; impaired polymerization
Milano-7; impaired polymerization
Osaka-5
DYSFIBRIN
dbSNP:rs6061
CAFBN; hypofibrinogenemia; heterozygous; no effect on fibrinogen complex assembly; impaired fibrinogen complex secretion
CAFBN; hypofibrinogenemia; heterozygous; no effect on fibrinogen complex assembly; no effect on fibrinogen complex secretion
CAFBN; hypofibrinogenemia; heterozygous; no effect on fibrinogen complex assembly; decreased fibrinogen complex secretion
CAFBN

The reference OMIM entry for this protein is 134850

Fibrinogen, g gamma polypeptide; fgg
Fibrinogen--gamma 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), beta (FGB; 134830), 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 (summary by Dayhoff, 1972). In its essential role in the adhesion and aggregation of platelets, fibrinogen binds to specific receptor sites on platelets. Hawiger et al. (1982) showed that the gamma and to a lesser extent the alpha chains carry the main sites for interaction with the platelet receptor.

CLONING

In a variety of species, including rodents and man, the fibrinogen gamma chain occurs in 2 forms, called gamma-A and gamma-B, or gamma and gamma-prime. In the rat, these 2 fibrinogen gamma chains arise by translation of 2 mRNAs of 1,700 and 2,200 nucleotides, which are produced from a single gene by alternative splice patterns (Crabtree and Kant, 1982). The more abundant gamma-A mRNA encodes a protein that is 83% homologous with the human gamma-A chain. The gamma-B mRNA is identical with the gamma-A sequence with the exception of a 53-bp insert located 202 bp from the poly(A) extension. This 53-bp insert is identical to the seventh and final intron of the gamma-A gene and is located 4 codons before the termination codon for the gamma-A chain. Translocation into the inserted sequence produces a unique 12-amino acid C terminus in the rat gamma-B polypeptide that is homologous with the known C terminus of the human gamma-B chain. Olaisen et al. (1982) assigned the FGG locus to chromosome 4 by linkage to MN (111300). Using separate DNA clones for each in hybrid cell studies, Henry et al. (1984) found that all 3 fibrinogen genes map to chromosome 4.

GENE FUNCTION

Liu et al. (2006) studied the mechanical properties of single fibrin fibers using an atomic force-fluorescence microscopy technique. They determined the extensibility and elastic limit of fibers formed in the presence and absence of factor XIIIa (134570). Factor XIIIa induces covalent crosslinks between gamma chains (along the fiber axis) and between the alpha (134820) chains. Samples without factor XIIIa showed no crosslinking. Uncrosslinked fibers extended 226 +/- 52%, and crosslinked fibers extended 332 +/- 71%, or 4.32 times their original length. The most extreme fibers could be extended over 6 times their length. These extensibilities are the largest of any protein fiber. Liu et al. (2006) tested the elastic limit by stretching fibers to a certain strain and releasing the applied force. Uncrosslinked fibers could be stretched 2.2 times their length and recover elastically. Crosslinked fibers could be stretched over 2.8 times their length (180% strain) and still recover without permanent damage. Liu et al. (2006) concluded that the effect of crosslinking is unusual in fibrin. In collagen, spider silk, and keratin fibers, crosslinking makes fibers stiffer and less extensible. The increased extensibility and e ... More on the omim web site

Subscribe to this protein entry history

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 FGG

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 134850 was added.