ID:IF16_HUMAN DESCRIPTION: RecName: Full=Gamma-interferon-inducible protein 16; Short=Ifi-16; AltName: Full=Interferon-inducible myeloid differentiation transcriptional activator; 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. SUBUNIT: Forms homooligomers; isoform 2 can self-associate or associate with isoform 1 or isoform 3. Interacts with TMEM173, AIM2, PYCARD and CASP1. Interacts with BRCA1, TP53, E2F1, RB1 and SP1. INTERACTION: P38398:BRCA1; NbExp=9; IntAct=EBI-2867186, EBI-349905; Q86WV6:TMEM173; NbExp=2; IntAct=EBI-2867186, EBI-2800345; P04637:TP53; NbExp=3; IntAct=EBI-6273540, EBI-366083; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Cellular distribution is dependent on the acetylation status of the multipartite nuclear localization signal (NLS); NLS acetylation promotes cytoplasmic localization. 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). INDUCTION: Strongly induced by IFNG/IFN-gamma and, to a lesser extent, by alpha interferon. In HL-60 cells, maximum induction by IFNG/IFN-gamma occurs within 12 hours whereas, for IFN-alpha, only 10-fold induction was observed after 36 hours. Induced in vitro by dimethylsulfoxide, retinoic acid and 1,25 dihydroxyvitamin D3. Induced in monocytes by IFN-alpha and viral dsDNA. Induced by glucose restriction. DOMAIN: The HIN-20 domains mediates dsDNA binding via electrostatic interactions (PubMed:22483801). PTM: 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. PTM: Phosphorylated on Ser and Thr. PTM: Isoform 3 seems to show a minor degree of complex carbohydrate addition. SIMILARITY: Belongs to the HIN-200 family. SIMILARITY: Contains 1 DAPIN domain. SIMILARITY: Contains 2 HIN-200 domains. SEQUENCE CAUTION: Sequence=AAF20997.1; Type=Frameshift; Positions=776; Sequence=AAF20997.1; Type=Miscellaneous discrepancy; Note=Intron retention; Sequence=BAC04462.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAC04462.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact; Sequence=BAD92226.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q16666
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0001047 core promoter binding GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003690 double-stranded DNA binding GO:0003723 RNA binding GO:0005515 protein binding GO:0008134 transcription factor binding GO:0042802 identical protein 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:0002376 immune system process GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006914 autophagy GO:0006915 apoptotic process 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:0040029 regulation of gene expression, epigenetic 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 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