IFI16

Interferon, gamma-inducible protein 16
PDB rendering based on 2oq0.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2OQ0​, 3B6Y​, 3RLN​, 3RLO​, 3RNU​
Identifiers
Symbols	IFI16 ; IFNGIP1; PYHIN2
External IDs	OMIM: 147586 MGI: 96429 HomoloGene: 115929 GeneCards: IFI16 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • core promoter binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • double-stranded DNA binding • protein binding • transcription factor binding • identical protein binding • poly(A) RNA binding Cellular component • nucleus • nucleoplasm • nucleolus • cytoplasm • cytosol • membrane • nuclear speck Biological process • negative regulation of transcription from RNA polymerase II promoter • positive regulation of cytokine production • activation of innate immune response • transcription, DNA-templated • autophagy • inflammatory response • cell proliferation • regulation of autophagy • hemopoiesis • myeloid cell differentiation • monocyte differentiation • positive regulation of type I interferon production • positive regulation of interleukin-1 beta production • regulation of gene expression, epigenetic • cellular response to glucose starvation • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • negative regulation of DNA binding • negative regulation of viral genome replication • innate immune response • negative regulation of innate immune response • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • defense response to virus • cellular response to ionizing radiation • intrinsic apoptotic signaling pathway by p53 class mediator • activation of cysteine-type endopeptidase activity • negative regulation of cysteine-type endopeptidase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3428	15950
Ensembl	ENSG00000163565	ENSMUSG00000039997
UniProt	Q16666	O35368
RefSeq (mRNA)	NM_001206567	NM_001045481
RefSeq (protein)	NP_001193496	NP_001289578
Location (UCSC)	Chr 1: 159 – 159.06 Mb	Chr 1: 173.92 – 173.94 Mb
PubMed search

Gamma-interferon-inducible protein Ifi-16 (Ifi-16) also known as interferon-inducible myeloid differentiation transcriptional activator is a protein that in humans is encoded by the IFI16 gene.^[1][2][3]

Function

This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway.^[3] IFI16 has been shown to play a role in the sensing of intracellular DNA^[4] - a hallmark of virally infected cells - and has also been linked to HIV-infected helper T-cell pyroptosis.^[5][6]

References

1. Trapani JA, Browne KA, Dawson MJ, Ramsay RG, Eddy RL, Show TB, White PC, Dupont B (Oct 1992). "A novel gene constitutively expressed in human lymphoid cells is inducible with interferon-gamma in myeloid cells". Immunogenetics 36 (6): 369–76. doi:10.1007/bf00218044. PMID 1526658.
2. Trapani JA, Dawson M, Apostolidis VA, Browne KA (Dec 1994). "Genomic organization of IFI16, an interferon-inducible gene whose expression is associated with human myeloid cell differentiation: correlation of predicted protein domains with exon organization". Immunogenetics 40 (6): 415–24. doi:10.1007/bf00177824. PMID 7959953.
3. "Entrez Gene: IFI16 interferon, gamma-inducible protein 16".
4. Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, Sirois CM, Jin T, Latz E, Xiao TS, Fitzgerald KA, Paludan SR, Bowie AG (2010). "IFI16 is an innate immune sensor for intracellular DNA". Nat. Immunol. 11 (11): 997–1004. doi:10.1038/ni.1932. PMC 3142795. PMID 20890285.
5. Monroe KM, Yang Z, Johnson JR, Geng X, Doitsh G, Krogan NJ, Greene WC (2014). "IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV". Science 343 (6169): 428–32. doi:10.1126/science.1243640. PMC 3976200. PMID 24356113.
6. Doitsh G, Galloway NL, Geng X, Yang Z, Monroe KM, Zepeda O, Hunt PW, Hatano H, Sowinski S, Muñoz-Arias I, Greene WC (2014). "Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection". Nature 505 (7484): 509–14. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.

Further reading

• Dawson MJ, Trapani JA (1995). "IFI 16 gene encodes a nuclear protein whose expression is induced by interferons in human myeloid leukaemia cell lines.". J. Cell. Biochem. 57 (1): 39–51. doi:10.1002/jcb.240570106. PMID 7536752.
• Dawson MJ, Trapani JA, Briggs RC, et al. (1995). "The closely linked genes encoding the myeloid nuclear differentiation antigen (MNDA) and IFI16 exhibit contrasting haemopoietic expression.". Immunogenetics 41 (1): 40–3. doi:10.1007/BF00188431. PMID 7806273.
• Johnstone RW, Kerry JA, Trapani JA (1998). "The human interferon-inducible protein, IFI 16, is a repressor of transcription.". J. Biol. Chem. 273 (27): 17172–7. doi:10.1074/jbc.273.27.17172. PMID 9642285.
• Johnstone RW, Kershaw MH, Trapani JA (1998). "Isotypic variants of the interferon-inducible transcriptional repressor IFI 16 arise through differential mRNA splicing.". Biochemistry 37 (34): 11924–31. doi:10.1021/bi981069a. PMID 9718316.
• Dawson MJ, Elwood NJ, Johnstone RW, Trapani JA (1998). "The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations.". J. Leukoc. Biol. 64 (4): 546–54. PMID 9766636.
• Briggs LJ, Johnstone RW, Elliot RM, et al. (2001). "Novel properties of the protein kinase CK2-site-regulated nuclear- localization sequence of the interferon-induced nuclear factor IFI 16.". Biochem. J. 353 (Pt 1): 69–77. doi:10.1042/0264-6021:3530069. PMC 1221544. PMID 11115400.
• Johnstone RW, Wei W, Greenway A, Trapani JA (2001). "Functional interaction between p53 and the interferon-inducible nucleoprotein IFI 16.". Oncogene 19 (52): 6033–42. doi:10.1038/sj.onc.1204005. PMID 11146555.
• Gariglio M, Azzimonti B, Pagano M, et al. (2003). "Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells.". J. Interferon Cytokine Res. 22 (7): 815–21. doi:10.1089/107999002320271413. PMID 12184920.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Izmailova E, Bertley FM, Huang Q, et al. (2003). "HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages.". Nat. Med. 9 (2): 191–7. doi:10.1038/nm822. PMID 12539042.
• Clarke CJ, Apostolidis V, Hii LL, et al. (2003). "Critical role of the transcription factor AP-1 for the constitutive and interferon-induced expression of IFI 16.". J. Cell. Biochem. 89 (1): 80–93. doi:10.1002/jcb.10475. PMID 12682910.
• Xin H, Curry J, Johnstone RW, et al. (2003). "Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence.". Oncogene 22 (31): 4831–40. doi:10.1038/sj.onc.1206754. PMID 12894224.
• Kwak JC, Ongusaha PP, Ouchi T, Lee SW (2003). "IFI16 as a negative regulator in the regulation of p53 and p21(Waf1).". J. Biol. Chem. 278 (42): 40899–904. doi:10.1074/jbc.M308012200. PMID 12925527.
• Aglipay JA, Lee SW, Okada S, et al. (2004). "A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway.". Oncogene 22 (55): 8931–8. doi:10.1038/sj.onc.1207057. PMID 14654789.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Raffaella R, Gioia D, De Andrea M, et al. (2004). "The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells.". Exp. Cell Res. 293 (2): 331–45. doi:10.1016/j.yexcr.2003.10.014. PMID 14729471.
• Fujiuchi N, Aglipay JA, Ohtsuka T, et al. (2004). "Requirement of IFI16 for the maximal activation of p53 induced by ionizing radiation.". J. Biol. Chem. 279 (19): 20339–44. doi:10.1074/jbc.M400344200. PMID 14990579.
• Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins.". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.

External links

• IFI16 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.