Alternative titles; symbols
HGNC Approved Gene Symbol: ZNF268
Cytogenetic location: 12q24.33 Genomic coordinates (GRCh38) : 12:133,181,495-133,214,832 (from NCBI)
Zinc finger proteins interact with nucleic acids and have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. ZNF268 belongs to the Kruppel-related family of zinc finger proteins (summary by Abrink et al., 1995).
See ZFP93 (604749) for additional information on zinc finger proteins.
By screening a human monoblast cell line (U-937) cDNA library with a degenerate oligonucleotide based on a conserved region of Kruppel-related zinc finger proteins that encompasses the H/C link, Abrink et al. (1995) isolated cDNAs encoding 42 distinct Kruppel-related zinc finger proteins, including ZNF268, which they called HZF3. Northern blot analysis detected a major 5.0-kb ZNF268 transcript in HeLa cells, U-937 cells, and PMA-induced U-937 cells.
Using a differential hybridization strategy, Gou et al. (2001) isolated a cDNA corresponding to a novel zinc finger gene, designated ZNF268, from a 3-week-old human embryo cDNA library. The full-length cDNA encodes a 947-amino acid protein with an N-terminal Kruppel-associated box (KRAB) domain and 24 C-terminal zinc fingers. Northern blot analysis detected high expression of a ZNF268 transcript in 3- to 5-week-old human embryos and lower expression in colon, heart, and 2-month-old fetuses. No signal was detected in other tissues tested.
By knockout analysis in HEK293T cells, Liu et al. (2023) demonstrated that ZNF268 isoform A (ZNF268a), which contains the KRAB and zinc finger domains, was required for the interferon response to RNA and DNA viruses. ZNF268a deficiency impaired virus-induced IRF3 (603734) signaling, a pathway essential to establish an antiviral state of host cells and further promote induction of adaptive immunity. ZNF268a interacted with TBK1 (604834) to facilitate IRF3 activation during viral infection. Viral infection did not change ZNF268a expression at the transcriptional level, but it prevented lysosomal degradation of ZNF268a in a TBK1-dependent manner, as TBK1 phosphorylated ZNF268a at ser178 to stabilize ZNF268a. Mass spectrometry analysis identified SETD4 (620995) as an interacting partner of ZNF268a during viral infection. By interacting with SETD4, ZNF268a recruited SETD4 to TBK1 and associated complexes upon viral infection. SETD4 knockdown confirmed that SETD4 methyltransferase activity was essential for antiviral innate immunity, as SETD4 catalyzed TBK1 monomethylation at lys607, which was critical for the interferon response. SETD4 regulation of TBK1 monomethylation at lys607 appeared to be human specific, as mice and rats do not appear to have a direct ortholog of human ZNF268, and an arginine has replaced lysine at position 607 in mouse and rat Tbk1.
Gou et al. (2001) determined that the ZNF268 gene contains 6 exons spanning about 22 kb of genomic DNA.
Gou et al. (2001) identified the ZNF268 sequence within a cosmid that maps to chromosome 5 (GenBank AC026786). However, Gross (2021) mapped the ZNF268 gene to chromosome 12q24.33 based on an alignment of the ZNF268 sequence (GenBank AF385187) with the genomic sequence (GRCh38).
Abrink, M., Aveskogh, M., Hellman, L. Isolation of cDNA clones for 42 different Kruppel-related zinc finger proteins expressed in the human monoblast cell line U-937. DNA Cell Biol. 14: 125-136, 1995. [PubMed: 7865130] [Full Text: https://doi.org/10.1089/dna.1995.14.125]
Gou, D. M., Sun, Y., Gao, L., Chow, L. M. C., Huang, J., Feng, Y. D., Jiang, D. H., Li, W. X. Cloning and characterization of a novel Kruppel-like zinc finger gene, ZNF268, expressed in early human embryo. Biochim. Biophys. Acta 1518: 306-310, 2001. [PubMed: 11311945] [Full Text: https://doi.org/10.1016/s0167-4781(01)00194-4]
Gross, M. B. Personal Communication. Baltimore, Md. 7/15/2021.
Liu, Y., Yin, W., Zeng, X., Fan, J., Liu, C., Gao, M., Huang, Z., Sun, G., Guo, M. TBK1-stabilized ZNF268a recruits SETD4 to methylate TBK1 for efficient interferon signaling. J. Biol. Chem. 299: 105428, 2023. [PubMed: 37926288] [Full Text: https://doi.org/10.1016/j.jbc.2023.105428]