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IFI16

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IFI16
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesIFI16, IFNGIP1, PYHIN2, interferon gamma inducible protein 16
External IDsOMIM: 147586; MGI: 3695276; HomoloGene: 115929; GeneCards: IFI16; OMA:IFI16 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001033384
NM_001177349
NM_001177350
NM_001368798
NM_001368799

RefSeq (protein)

n/a

Location (UCSC)Chr 1: 159 – 159.06 MbChr 1: 173.39 – 173.43 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6][7]

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,[8] retinoblastoma-1 and BRCA1.[9] It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway.[7] IFI16 has been shown to play a role in the sensing of intracellular DNA[10] - a hallmark of virally infected cells - and has also been linked to the death of HIV-infected helper CD4 T cells by pyroptosis, a highly inflammatory form of programmed cell death.[11][12] Recently, it has been shown how IFI16, once extracellularly released, can induce inflammation upon TLR4 binding, acting as a DAMP.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000163565Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000073491Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. S2CID 1196925.
  6. ^ 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. S2CID 2602156.
  7. ^ a b "Entrez Gene: IFI16 interferon, gamma-inducible protein 16".
  8. ^ Ouchi, Mutsuko; Ouchi, Toru (2008-01-01). "Role of IFI16 in DNA damage and checkpoint". Frontiers in Bioscience. 13 (13): 236–239. doi:10.2741/2673. ISSN 1093-9946. PMID 17981541.
  9. ^ Dutta, Dipanjan; Dutta, Sujoy; Veettil, Mohanan Valiya; Roy, Arunava; Ansari, Mairaj Ahmed; Iqbal, Jawed; Chikoti, Leela; Kumar, Binod; Johnson, Karen E. (2015-06-01). "BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses". PLOS Pathogens. 11 (6): e1005030. doi:10.1371/journal.ppat.1005030. ISSN 1553-7374. PMC 4487893. PMID 26121674.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ 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.
  11. ^ 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. Bibcode:2014Sci...343..428M. doi:10.1126/science.1243640. PMC 3976200. PMID 24356113.
  12. ^ 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. Bibcode:2014Natur.505..509D. doi:10.1038/nature12940. PMC 4047036. PMID 24356306.
  13. ^ Iannucci A, Caneparo V, Raviola S, Debernardi I, Colangelo D, et al. (2020) Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding. PLOS Pathogens 16(9): e1008811. https://doi.org/10.1371/journal.ppat.1008811

Further reading

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