MGP Database

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MGP001561

UniProt Annotations

Entry Information
Gene Nameinterferon, gamma-inducible protein 16
Protein EntryIF16_HUMAN
UniProt IDQ16666
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=IFI 16A; IsoId=Q16666-1; Sequence=Displayed; Name=2; Synonyms=IFI 16B; IsoId=Q16666-2; Sequence=VSP_002676; Note=Major isoform.; Name=3; Synonyms=IFI 16C; IsoId=Q16666-3; Sequence=VSP_002675; Name=4; IsoId=Q16666-6; Sequence=VSP_044691; Note=No experimental confirmation available.;
DomainThe HIN-20 domains mediates dsDNA binding via electrostatic interactions. {ECO:0000269|PubMed:22483801}.
FunctionBinds 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:0000269|PubMed:11146555, ECO:0000269|PubMed:12894224, ECO:0000269|PubMed:14654789, ECO:0000269|PubMed:20890285, ECO:0000269|PubMed:21573174, ECO:0000269|PubMed:21575908, ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22291595, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:24198334, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:9642285}.
InductionStrongly 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. {ECO:0000269|PubMed:12894224, ECO:0000269|PubMed:20890285, ECO:0000269|PubMed:21573174, ECO:0000269|PubMed:7536752}.
InteractionP10275:AR; NbExp=3; IntAct=EBI-2867186, EBI-608057; 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;
PtmIsoform 3 seems to show a minor degree of complex carbohydrate addition.
PtmLysine acetylation in the multipartite nuclear localization signal (NLS) regulates the subcellular location. In vitro can be acetylated by p300/EP300 coupled to cytoplasmic localization. {ECO:0000269|PubMed:19608861, ECO:0000269|PubMed:22691496}.
PtmPhosphorylated on Ser and Thr. {ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:22691496, ECO:0000269|PubMed:9718316}.
PtmUbiquitinated by human herpes simplex virus 1 (HHV-1) ICP0 protein; leading to degradation by the proteasome.
Sequence CautionSequence=AAF20997.1; Type=Frameshift; Positions=776; Evidence={ECO:0000305}; Sequence=AAF20997.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAC04462.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; Sequence=BAD92226.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=BAG58950.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the HIN-200 family. {ECO:0000305}.
SimilarityContains 1 DAPIN domain. {ECO:0000255|PROSITE- ProRule:PRU00061}.
SimilarityContains 2 HIN-200 domains. {ECO:0000255|PROSITE- ProRule:PRU00106}.
Subcellular LocationNucleus. 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.
SubunitForms 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. Interacts with MTA1. {ECO:0000269|PubMed:11146555, ECO:0000269|PubMed:14654789, ECO:0000269|PubMed:20890285, ECO:0000269|PubMed:21575908, ECO:0000269|PubMed:22046441, ECO:0000269|PubMed:22291595, ECO:0000269|PubMed:22483801, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:9718316}.
Tissue SpecificityExpressed 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:0000269|PubMed:12894224}.
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