Irf3
entrez
54131
canonical
uniprot
P70671
canonical
ensembl
ENSMUSG00000003184
resolver
ensp
ENSMUSP00000003284
resolver
ensp
ENSMUSP00000103465
resolver
ensp
ENSMUSP00000146773
resolver
ensp
ENSMUSP00000287835
resolver
enst
ENSMUST00000003284
resolver
enst
ENSMUST00000107834
resolver
enst
ENSMUST00000209066
resolver
genesymbol
Irf3
resolver
uniprot
C0IXK2
resolver
uniprot
Q3U9K6
resolver
uniprot_entry
IRF3_MOUSE
resolver
uniprot_entry
Q3U9K6_MOUSE
resolver
uniprot_sec
C0IXK2
resolver
activity_regulation
ACTIVITY REGULATION: In the absence of viral infection, maintained as a monomer in an autoinhibited state. Phosphorylation by TBK1 and IKBKE disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes. Phosphorylation and activation follow the following steps: innate adapter proteins, such as MAVS, STING1 or TICAM1, are first activated by viral RNA, cytosolic DNA and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE. These kinases then phosphorylate the adapter proteins on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs. {ECO:0000250|UniProtKB:Q14653}.
uniprot
proteins
amino_acid_sequence
METPKPRILPWLVSQLDLGQLEGVAWLDESRTRFRIPWKHGLRQDAQMADFGIFQAWAEASGAYTPGKDKPDVSTWKRNFRSALNRKEVLRLAADNSKDPYDPHKVYEFVTPGARDFVHLGASPDTNGKSSLPHSQENLPKLFDGLILGPLKDEGSSDLAIVSDPSQQLPSPNVNNFLNPAPQENPLKQLLAEEQWEFEVTAFYRGRQVFQQTLFCPGGLRLVGSTADMTLPWQPVTLPDPEGFLTDKLVKEYVGQVLKGLGNGLALWQAGQCLWAQRLGHSHAFWALGEELLPDSGRGPDGEVHKDKDGAVFDLRPFVADLIAFMEGSGHSPRYTLWFCMGEMWPQDQPWVKRLVMVKVVPTCLKELLEMAREGGASSLKTVDLHISNSQPISLTSDQYKAYLQDLVEDMDFQATGNI
uniprot
proteins
function
FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:15800576, PubMed:39719712). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:15800576, PubMed:39719712). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:16846591, PubMed:16979567, PubMed:20049431). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16846591, PubMed:16979567, PubMed:20049431). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591, PubMed:16979567, PubMed:20049431). {ECO:0000269|PubMed:15800576, ECO:0000269|PubMed:39719712, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}.; FUNCTION: [Isoform 2]: May participate in the regulation of type I interferon transcription. May act as a modulator of isoform 1 function, decreasing its transcriptional activity during viral infection. Specifically binds to IFN-stimulated response elements (ISREs) in promoters of target genes, such as that of IFNB1. {ECO:0000269|PubMed:18851954}.
uniprot
proteins
mass_dalton
46852
uniprot
proteins
mutagenesis
MUTAGEN 68; /note="K->A: Does not affect acetylation by KAT8."; /evidence="ECO:0000269|PubMed:30842237"; MUTAGEN 70; /note="K->A: Does not affect acetylation by KAT8."; /evidence="ECO:0000269|PubMed:30842237"; MUTAGEN 85; /note="N->D: Impaired ability to bind DNA and act as a transcription factor."; /evidence="ECO:0000269|PubMed:39719712"; MUTAGEN 152; /note="K->A: Does not affect acetylation by KAT8."; /evidence="ECO:0000269|PubMed:30842237"; MUTAGEN 359; /note="K->A,R: Abolished acetylation by KAT8, leading to increased transcription factor activity."; /evidence="ECO:0000269|PubMed:30842237"; MUTAGEN 388; /note="S->A: Decreased acetylation by KAT8."; /evidence="ECO:0000269|PubMed:30842237"; MUTAGEN 389; /note="N->D: Does not affect ability to bind DNA."; /evidence="ECO:0000269|PubMed:39719712
uniprot
proteins
post_translational_modification
PTM: Constitutively phosphorylated on many Ser/Thr residues (PubMed:22065572). Activated following phosphorylation by TBK1 and IKBKE (By similarity). Innate adapter proteins, such as MAVS, STING1 or TICAM1, are first activated by viral RNA, cytosolic DNA, and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE (By similarity). These kinases then phosphorylate the adapter proteins on the pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (By similarity). Phosphorylation at Ser-379 is followed by pyrophosphorylation at the same residue, promoting phosphorylation at Ser-388 (By similarity). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (By similarity). Phosphorylation of IRF3 at Ser-378 and Ser-379 plays an important role in the PBLD-triggered IFN-I cascade (By similarity). {ECO:0000250|UniProtKB:Q14653, ECO:0000269|PubMed:22065572}.; PTM: Pyrophosphorylated by UAP1 following phosphorylation at Ser-379 by TBK1 (By similarity). Pyrophosphorylation promotes subsequent phosphorylation at Ser-388, leading to homodimerization of IRF3 (By similarity). {ECO:0000250|UniProtKB:Q14653}.; PTM: Acetylation at Lys-359 by KAT8 inhibits recruitment to promoters and transcription factor activity (PubMed:30842237). Acetylation by KAT8 is promoted by phosphorylation at Ser-388 (PubMed:30842237). {ECO:0000269|PubMed:30842237}.; PTM: Deamidation of Asn-85 by CTPS1 prevents IRF3 from binding DNA, thereby inhibiting the transcription factor activity. {ECO:0000269|PubMed:39719712}.; PTM: Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation. Ubiquitinated by UBE3C, leading to its degradation. Deubiquitinated by USP5 on both 'Lys-48'-linked unanchored and 'Lys-63'-linked anchored polyubiquitin, leading to inhibition of anti-RNA viral innate immunity. {ECO:0000250|UniProtKB:Q14653}.; PTM: ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation. {ECO:0000250|UniProtKB:Q14653}.; PTM: Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation. Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction. {ECO:0000250|UniProtKB:Q14653}.
uniprot
proteins
protein_family
IRF family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15800576
uniprot
proteins
pubmed
16846591
uniprot
proteins
pubmed
16979567
uniprot
proteins
pubmed
18724932
uniprot
proteins
pubmed
18851954
uniprot
proteins
pubmed
20049431
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22065572
uniprot
proteins
pubmed
30842237
uniprot
proteins
pubmed
39719712
uniprot
proteins
sequence_length
419
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18851954}. Nucleus {ECO:0000250|UniProtKB:Q14653}. Mitochondrion {ECO:0000250|UniProtKB:Q14653}. Note=Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect. When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm. Recruited to mitochondria via TOMM70:HSP90AA1 upon Sendai virus infection. {ECO:0000250|UniProtKB:Q14653}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:18851954}. Nucleus {ECO:0000269|PubMed:18851954}. Note=Contrary to isoform 1, which is almost exclusively located in the cytoplasm under resting conditions, isoform 2 is located both in the cytoplasm and the nucleus in the absence of viral infection or dsRNA exposure. {ECO:0000269|PubMed:18851954}.
uniprot
proteins