IFI16

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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

Interferon Gamma Inducible Protein 16

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.

Activation of cysteine-type endopeptidase activity Source: UniProtKB
Activation of innate immune response Source: UniProtKB
Autophagy Source: UniProtKB-KW
Cellular response to glucose starvation Source: UniProtKB
Cellular response to interferon-beta Source: GO_Central
Cellular response to ionizing radiation Source: UniProtKB
Defense response to virus Source: UniProtKB
Inflammatory response Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
Monocyte differentiation Source: UniProtKB
Myeloid cell differentiation Source: UniProtKB
Negative regulation of cysteine-type endopeptidase activity Source: UniProtKB
Negative regulation of DNA binding Source: UniProtKB
Negative regulation of innate immune response Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Negative regulation of viral genome replication Source: UniProtKB
Positive regulation of cytokine production Source: UniProtKB
Positive regulation of interleukin-1 beta production Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Regulation of autophagy Source: UniProtKB
Regulation of gene expression, epigenetic Source: UniProtKB

Nucleus; Cytoplasm. 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.

Ubiquitinated by human herpes simplex virus 1 (HHV-1) ICP0 protein; leading to degradation by the proteasome.
Lysine acetylation in the multipartite nuclear localization signal (NLS) regulates the subcellular location. In vitro can be acetylated by p300/EP300 coupled to cytoplasmic localization.
Phosphorylated on Ser and Thr.
Isoform 3 seems to show a minor degree of complex carbohydrate addition.