Alternative titles; symbols
HGNC Approved Gene Symbol: FGL2
Cytogenetic location: 7q11.23 Genomic coordinates (GRCh38) : 7:77,193,369-77,199,819 (from NCBI)
For general information on fibrinogen, see FGA (134820), FGB (134830), and FGG (134850).
By screening a human small intestine cDNA library with a mouse Fgl2 cDNA as probe, Ruegg and Pytela (1995) isolated a cDNA encoding FGL2, which they called T49. The full-length cDNA encodes a deduced 439-amino acid polypeptide that shares approximately 25% identity with human FGB and FGG and 80% identity with mouse Fgl2. The protein contains a 15-amino acid signal peptide, conserved cysteines important for interactions between the chains in fibrinogen, coiled-coil regions, 5 potential N-glycosylation sites, and a C-terminal fibrinogen-related domain (FRED) similar to those in several extracellular proteins. Northern blot analysis detected expression of a major 4.5- and a minor 1.5-kb transcript that was strongest in peripheral blood T lymphocytes. RT-PCR revealed expression in 2 major subpopulations of peripheral blood T lymphocytes: the CD3+/CD4+ and CD3+/CD8+ subsets. Lack of expression in other lymphoid- and nonlymphoid-derived cell lines suggested that expression of FGL2 may be restricted to lymphocytes.
Marazzi et al. (1998) generated antibodies that specifically recognized FGL2, which they termed fibroleukin, as a 70-kD protein. Additional 65- and 62-kD products were observed in peripheral blood mononuclear cell (PBMC) lysates and were thought to correspond to nonsialylated and incompletely glycosylated precursors. Immunoprecipitation of PBMC supernatant showed that FGL2 is secreted as a disulfide-bonded complex. In immunoprecipitation studies, Marazzi et al. (1998) confirmed expression of FGL2 in CD3+/CD4+ and CD3+/CD8+ T lymphocytes. By RT-PCR, they demonstrated that FGL2 is preferentially expressed in memory T lymphocytes and at low levels or not at all in naive T lymphocytes. FGL2 expression was significantly reduced in PBMC cultures within 2 days and could not be recovered by T-cell activation. Immunohistologic study of colon mucosa revealed expression of FGL2 in the extracellular matrix of the T lymphocyte-rich upper portion of the lamina propria mucosa.
By Northern blot analysis, Hancock et al. (2004) confirmed that Ifng (147570), but not Il12 (see 161560) or Il4 (147780), upregulated Fgl2 expression in mouse macrophages and lymphocytes. Il2 (147680) and T-cell receptor (see 186740) stimulation or Th1-promoting conditions also enhanced Fgl2 expression in T cells. Infection of mice with Toxoplasma gondii increased Fgl2 expression in an Ifng-dependent manner. Hancock et al. (2004) concluded that FGL2 is induced via a mechanism involving IFNG and components of the IFNG signaling pathway, including STAT1 (600555) and IRF1 (147575).
The International Radiation Hybrid Mapping Consortium mapped the FGL2 gene to chromosome 7.
Hancock et al. (2004) generated healthy Fgl2-deficient mice with normal numbers of lymphoid cells. These mice survived infection with T. gondii, Listeria monocytogenes, Yersinia enterocolitica, and Mycobacterium tuberculosis, indicating that FGL2 is dispensable for IFNG-dependent protection against these pathogens. All immune mechanisms for resistance to these organisms, as well as for resistance to viruses and for allograft rejection, were intact. Hancock et al. (2004) concluded that FGL2 is dispensable for IFNG-dependent immunity, suggesting that other molecules compensate for FGL2 deficiency or that FGL2 functions during novel responses.
Hancock, W. W., Szaba, F. M., Berggren, K. N., Parent, M. A., Mullarky, I. K., Pearl, J., Cooper, A. M., Ely, K. H., Woodland, D. L., Kim, I.-J., Blackman, M. A., Johnson, L. L., Smiley, S. T. Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFN-gamma-inducible fibrinogen-like protein 2. Proc. Nat. Acad. Sci. 101: 3005-3010, 2004. [PubMed: 14976252] [Full Text: https://doi.org/10.1073/pnas.0308369101]
Marazzi, S., Blum, S., Hartmann, R., Gundersen, D., Schreyer, M., Argraves, S., von Fliedner, V., Pytela, R., Ruegg, C. Characterization of human fibroleukin, a fibrinogen-like protein secreted by T lymphocytes. J. Immun. 161: 138-147, 1998. [PubMed: 9647217]
Ruegg, C., Pytela, R. Sequence of a human transcript expressed in T-lymphocytes and encoding a fibrinogen-like protein. Gene 160: 257-262, 1995. [PubMed: 7642106] [Full Text: https://doi.org/10.1016/0378-1119(95)00240-7]