IRF8

Interferon consensus sequence-binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-alpha and IFN-beta. IRF family proteins also control expression of IFN-alpha and IFN-beta-regulated genes that are induced by viral infection. [provided by RefSeq, Jul 2008]

Full Name

IRF8

Function

Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:25122610).
Can both act as a transcriptional activator or repressor (By similarity).
Plays a negative regulatory role in cells of the immune system (By similarity).
Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (By similarity).
Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (By similarity).
Positively regulates macroautophagy in dendritic cells (PubMed:29434592).

Biological Process

AutophagyIEA:UniProtKB-KW
Cellular response to interferon-gammaManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to lipopolysaccharideIEA:Ensembl
Defense response to bacteriumIEA:Ensembl
Defense response to protozoanIEA:Ensembl
Dendritic cell differentiationISS:UniProtKB
Follicular B cell differentiationIEA:Ensembl
Germinal center B cell differentiationIEA:Ensembl
Immune responseManual Assertion Based On ExperimentTAS:ProtInc
Immune system processManual Assertion Based On ExperimentIBA:GO_Central
Myeloid cell differentiationIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
PhagocytosisIEA:Ensembl
Plasmacytoid dendritic cell differentiationISS:UniProtKB
Positive regulation of interferon-gamma productionIEA:Ensembl
Positive regulation of interleukin-12 productionIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Regulation of type I interferon productionISS:UniProtKB

Cellular Location

Cytoplasm; Nucleus. In resting macrophages, localizes in the cytoplasm. Translocated in the nucleus upon IFN-gamma induction.

Involvement in disease

Immunodeficiency 32A (IMD32A):
An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections.
Immunodeficiency 32B (IMD32B):
An autosomal recessive primary immunodeficiency characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis.

PTM

Ubiquitinated (PubMed:25122610).
Ubiquitination by TRIM21 in macrophages, a process that is strongly increased upon interferon gamma stimulation, leds to the enhanced transcriptional activity of target cytokine genes (By similarity).
Ubiquitination leads to its degradation by the proteasome (PubMed:25122610).
Sumoylated with SUMO3. Desumoylated by SENP1.