Nuclear factor of activated T-cells (NFAT) is a transcription factor required for T-cell expression of interleukin 2. NFAT binds to a sequence in the IL2 enhancer known as the antigen receptor response element 2. In addition, NFAT can bind RNA and is an essential component for encapsidation and protein priming of hepatitis B viral polymerase. NFAT is a heterodimer of 45 kDa and 90 kDa proteins, the larger of which is the product of this gene. The encoded protein, which is primarily localized to ribosomes, probably regulates transcription at the level of mRNA elongation. At least three transcript variants encoding three different isoforms have been found for this gene.[3]
Small NF90/ILF3-associated RNAs (snaR) (~120 nucleotides long) and are known to interact with ILF3 double-stranded RNA-binding motifs.[13] snaR-A is abundant in human testis and has been shown to associate with ribosomes in HeLa cells. snaR-A is present in human and gorilla but not in chimpanzee. Other snaR RNAs are found in African Great Apes (including chimpanzee and bonobo).[14]
ILF2 and ILF3 have been identified as autoantigens in mice with induced lupus,[15][16] in canine systemic rheumatic autoimmune disease,[17] and as a rare finding in humans with autoimmune disease.[18]
References
↑Kao PN, Chen L, Brock G, Ng J, Kenny J, Smith AJ, Corthésy B (August 1994). "Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90". The Journal of Biological Chemistry. 269 (32): 20691–9. PMID7519613.
↑Ting NS, Kao PN, Chan DW, Lintott LG, Lees-Miller SP (January 1998). "DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45". The Journal of Biological Chemistry. 273 (4): 2136–45. doi:10.1074/jbc.273.4.2136. PMID9442054.
↑ 5.05.1Saunders LR, Perkins DJ, Balachandran S, Michaels R, Ford R, Mayeda A, Barber GN (August 2001). "Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR". The Journal of Biological Chemistry. 276 (34): 32300–12. doi:10.1074/jbc.M104207200. PMID11438536.
↑Tang J, Kao PN, Herschman HR (June 2000). "Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3". The Journal of Biological Chemistry. 275 (26): 19866–76. doi:10.1074/jbc.M000023200. PMID10749851.
↑Langland JO, Kao PN, Jacobs BL (May 1999). "Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR". Biochemistry. 38 (19): 6361–8. doi:10.1021/bi982410u. PMID10320367.
↑Parker LM, Fierro-Monti I, Mathews MB (August 2001). "Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase". The Journal of Biological Chemistry. 276 (35): 32522–30. doi:10.1074/jbc.M104408200. PMID11438540.
↑Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo W, Erme SM, Williams BR, Sen GC (July 1999). "DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR". The Journal of Biological Chemistry. 274 (29): 20432–7. doi:10.1074/jbc.274.29.20432. PMID10400669.
↑Satoh M, Shaheen VM, Kao PN, Okano T, Shaw M, Yoshida H, Richards HB, Reeves WH (December 1999). "Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity". The Journal of Biological Chemistry. 274 (49): 34598–604. PMID10574923.
↑Kuroda Y, Ono N, Akaogi J, Nacionales DC, Yamasaki Y, Barker TT, Reeves WH, Satoh M (February 2006). "Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice". Toxicology. 218 (2–3): 186–96. doi:10.1016/j.tox.2005.10.011. PMID16309812.
↑Bremer HD, Landegren N, Sjöberg R, Hallgren Å, Renneker S, Lattwein E, Leonard D, Eloranta ML, Rönnblom L, Nordmark G, Nilsson P, Andersson G, Lilliehöök I, Lindblad-Toh K, Kämpe O, Hansson-Hamlin H (March 2018). "ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease". Scientific Reports. 8 (1): 4852. doi:10.1038/s41598-018-23034-w. PMID29556082.
↑Satoh M, Shaheen VM, Kao PN, Okano T, Shaw M, Yoshida H, Richards HB, Reeves WH (December 1999). "Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity". The Journal of Biological Chemistry. 274 (49): 34598–604. PMID10574923.
Ting NS, Kao PN, Chan DW, Lintott LG, Lees-Miller SP (January 1998). "DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45". The Journal of Biological Chemistry. 273 (4): 2136–45. doi:10.1074/jbc.273.4.2136. PMID9442054.
Marcoulatos P, Avgerinos E, Tsantzalos DV, Vamvakopoulos NC (May 1998). "Mapping interleukin enhancer binding factor 3 gene (ILF3) to human chromosome 19 (19q11-qter and 19p11-p13.1) by polymerase chain reaction amplification of human-rodent somatic cell hybrid DNA templates". Journal of Interferon & Cytokine Research. 18 (5): 351–5. doi:10.1089/jir.1998.18.351. PMID9620363.
Aoki Y, Zhao G, Qiu D, Shi L, Kao PN (December 1998). "CsA-sensitive purine-box transcriptional regulator in bronchial epithelial cells contains NF45, NF90, and Ku". The American Journal of Physiology. 275 (6 Pt 1): L1164–72. PMID9843854.
Langland JO, Kao PN, Jacobs BL (May 1999). "Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR". Biochemistry. 38 (19): 6361–8. doi:10.1021/bi982410u. PMID10320367.
Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo W, Erme SM, Williams BR, Sen GC (July 1999). "DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR". The Journal of Biological Chemistry. 274 (29): 20432–7. doi:10.1074/jbc.274.29.20432. PMID10400669.
Satoh M, Shaheen VM, Kao PN, Okano T, Shaw M, Yoshida H, Richards HB, Reeves WH (December 1999). "Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity". The Journal of Biological Chemistry. 274 (49): 34598–604. doi:10.1074/jbc.274.49.34598. PMID10574923.
Xu YH, Grabowski GA (December 1999). "Molecular cloning and characterization of a translational inhibitory protein that binds to coding sequences of human acid beta-glucosidase and other mRNAs". Molecular Genetics and Metabolism. 68 (4): 441–54. doi:10.1006/mgme.1999.2934. PMID10607473.
Tang J, Kao PN, Herschman HR (June 2000). "Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3". The Journal of Biological Chemistry. 275 (26): 19866–76. doi:10.1074/jbc.M000023200. PMID10749851.
Saunders LR, Jurecic V, Barber GN (January 2001). "The 90- and 110-kDa human NFAR proteins are translated from two differentially spliced mRNAs encoded on chromosome 19p13". Genomics. 71 (2): 256–9. doi:10.1006/geno.2000.6423. PMID11161820.
Duchange N, Pidoux J, Camus E, Sauvaget D (December 2000). "Alternative splicing in the human interleukin enhancer binding factor 3 (ILF3) gene". Gene. 261 (2): 345–53. doi:10.1016/S0378-1119(00)00495-9. PMID11167023.
Saunders LR, Perkins DJ, Balachandran S, Michaels R, Ford R, Mayeda A, Barber GN (August 2001). "Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR". The Journal of Biological Chemistry. 276 (34): 32300–12. doi:10.1074/jbc.M104207200. PMID11438536.
Parker LM, Fierro-Monti I, Mathews MB (August 2001). "Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase". The Journal of Biological Chemistry. 276 (35): 32522–30. doi:10.1074/jbc.M104408200. PMID11438540.