InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IFI16

Summary

InnateDB Protein

IDBP-103860.5

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

ENSP00000295809

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}.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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