FGL1 explained

Fibrinogen-like protein 1 (FGL-1) is a protein that is structurally related to fibrinogen. In humans, FGL-1 is encoded by the FGL1 gene.^{[1] [2]} It is classified as a hepatokine. Four splice variants exist for this gene.

Function

Fibrinogen-like protein 1 is a member of the fibrinogen family of proteins, which also includes fibrinogen, fibrinogen-like protein 2, and clotting factors V, VIII, and XIII. FGL-1 is homologous to the carboxy terminus of the fibrinogen beta- and gamma- subunits which contains the four conserved cysteines of that are common to all members of the fibrinogen family. However, FGL-1 lacks the platelet-binding site, cross-linking region, and thrombin-sensitive site which allow the other members of the fibrinogen family to aid in fibrin clot formation.

FGL-1 has also been observed to strongly bind to and activate LAG-3, a regulatory protein expressed on T cells. As LAG-3 has an important role in controlling activated T cells, manipulating FGL-1 binding to T cells has been proposed for both cancer immunotherapy and anti-inflammatory treatments.^[3]

Clinical significance

FGL-1 may play a role in the development of hepatocellular carcinomas.

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Hara H, Yoshimura H, Uchida S . Molecular cloning and functional expression analysis of a cDNA for human hepassocin, a liver-specific protein with hepatocyte mitogenic activity. . Biochim. Biophys. Acta . 1520 . 1 . 45–53 . 2001 . 11470158 . 10.1016/s0167-4781(01)00249-4. etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Zeng L, Dai J, Ying K . Identification of a novel human angiopoietin-like gene expressed mainly in heart. . J. Hum. Genet. . 48 . 3 . 159–62 . 2003 . 12624729 . 10.1007/s100380300025 . etal. free .
• Yan J, Yu Y, Wang N . LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma. . Oncogene . 23 . 10 . 1939–49 . 2004 . 14981537 . 10.1038/sj.onc.1207306 . etal. 9243597 .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Rual JF, Venkatesan K, Hao T . 4427026 . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . etal.
• Rijken DC, Dirkx SP, Luider TM, Leebeek FW . Hepatocyte-derived fibrinogen-related protein-1 is associated with the fibrin matrix of a plasma clot. . Biochem. Biophys. Res. Commun. . 350 . 1 . 191–4 . 2006 . 16996032 . 10.1016/j.bbrc.2006.09.018 .
• Liu Z, Ukomadu C . Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant. . Biochem. Biophys. Res. Commun. . 365 . 4 . 729–34 . 2008 . 18039467 . 10.1016/j.bbrc.2007.11.069 . 2288651 .

Notes and References

1. Yamamoto T, Gotoh M, Sasaki H, Terada M, Kitajima M, Hirohashi S . Molecular cloning and initial characterization of a novel fibrinogen-related gene, HFREP-1 . Biochem Biophys Res Commun . 193 . 2 . 681–7 . Jul 1993 . 8390249 . 10.1006/bbrc.1993.1678 .
2. Web site: Entrez Gene: FGL1 fibrinogen-like 1.
3. Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, Zheng L, Zhou T, Badri T, Yao S, Zhu S, Boto A, Sznol M, Melero I, Vignali DA, Schalper K, Chen L. 6 . Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3 . Cell . 176 . 1–2 . 334–347.e12 . January 2019 . 30580966 . 6365968 . 10.1016/j.cell.2018.11.010 .