Homo sapiens Protein: IFI16
InnateDB Protein IDBP-103858.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IFI16
Protein Name interferon, gamma-inducible protein 16
Synonyms IFNGIP1; PYHIN2;
Species Homo sapiens
Ensembl Protein ENSP00000357113
InnateDB Gene IDBG-103852 (IFI16)
Protein Structure
UniProt Annotation
Function Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA binding and modulating TP53 phosphorylation status. Seems to be involved in energy-level-dependent activation of the ATM/ AMPK/TP53 pathway coupled to regulation of autophagy. May be involved in regulation of TP53-mediated cell death also involving BRCA1. May be involved in the senescence of prostate epithelial cells. Involved in innate immune response by recognizing viral dsDNA in the cytosol and probably in the nucleus. After binding to viral DNA in the cytoplasm recruits TMEM173/STING and mediates the induction of IFN-beta. Has anti-inflammatory activity and inhibits the activation of the AIM2 inflammasome, probably via association with AIM2. Proposed to bind viral DNA in the nucleus, such as of Kaposi's sarcoma-associated herpesvirus, and to induce the formation of nuclear caspase-1-activating inflammasome formation via association with PYCARD. Inhibits replication of herpesviruses such as human cytomegalovirus (HCMV) probably by interfering with promoter recruitment of members of the Sp1 family of transcription factors. Necessary to activate the IRF3 signaling cascade during human herpes simplex virus 1 (HHV-1) infection and promotes the assembly of heterochromatin on herpesviral DNA and inhibition of viral immediate-early gene expression and replication. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269PubMed:11146555, ECO:0000269PubMed:12894224, ECO:0000269PubMed:14654789, ECO:0000269PubMed:20890285, ECO:0000269PubMed:21573174, ECO:0000269PubMed:21575908, ECO:0000269PubMed:22046441, ECO:0000269PubMed:22291595, ECO:0000269PubMed:23027953, ECO:0000269PubMed:24198334, ECO:0000269PubMed:24413532, ECO:0000269PubMed:9642285}.
Subcellular Localization Nucleus. Cytoplasm. Note=Cellular distribution is dependent on the acetylation status of the multipartite nuclear localization signal (NLS); NLS acetylation promotes cytoplasmic localization. Localizes in the nucleus during human herpes simplex virus 1 (HHV-1) infection.
Disease Associations
Tissue Specificity Expressed in peripheral blood leukocytes, fibroblasts and lymphoid cells. Present in myeloid precursors (CD34+) and throughout monocyte development, but its expression is down-regulated in erythroid and polymorphonuclear precursor cells. Present in prostate, ovary and breast (at protein level). {ECO:0000269PubMed:12894224}.
Number of Interactions This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.
Experimentally validated
Total 23 [view]
Protein-Protein 20 [view]
Protein-DNA 3 [view]
Protein-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0003690 double-stranded DNA binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0044822 poly(A) RNA binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001819 positive regulation of cytokine production
GO:0002218 activation of innate immune response
GO:0006351 transcription, DNA-templated
GO:0006914 autophagy
GO:0006954 inflammatory response
GO:0008283 cell proliferation
GO:0010506 regulation of autophagy
GO:0030097 hemopoiesis
GO:0030099 myeloid cell differentiation
GO:0030224 monocyte differentiation
GO:0032481 positive regulation of type I interferon production
GO:0032731 positive regulation of interleukin-1 beta production
GO:0042149 cellular response to glucose starvation
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043392 negative regulation of DNA binding
GO:0045071 negative regulation of viral genome replication
GO:0045087 innate immune response (InnateDB)
GO:0045824 negative regulation of innate immune response
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051607 defense response to virus
GO:0071479 cellular response to ionizing radiation
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
GO:0097202 activation of cysteine-type endopeptidase activity
GO:2000117 negative regulation of cysteine-type endopeptidase activity
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0016607 nuclear speck
Protein Structure and Domains
InterPro IPR004020 DAPIN domain
IPR004021 HIN-200/IF120x
IPR011029 Death-like domain
PFAM PF02758
Post-translational Modifications
SwissProt Q16666
PhosphoSite PhosphoSite-Q16666
UniProt Splice Variant
Entrez Gene 3428
UniGene Hs.629190
RefSeq NP_005522
OMIM 147586
HPRD 00969
EMBL AB208989 AF208043 AK094968 AK296228 AL359753 AY138863 BC017059 M63838 S75417 S75419 S75421 S75423 S75424 S75426 S75429 S75431 S75433
GenPept AAA58683 AAB32519 AAF20997 AAH17059 AAM96005 BAC04462 BAD92226 BAG58950 CAI15081 CAI15082 CAI15083 CAI15084 CAI15085 CAI15086