IRF3 (interferon regulatory factor 3)

Gene

• Entrez ID: 3661
• Gene name: Interferon regulatory factor 3
• Gene symbol: IRF3
• Synonyms: IIAE7
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. The protein plays an important role in the innate immune response against DNA and RNA viruses. Mutations in this gene are associated with Encephalopathy, acute, infection-induced, herpes-specific, 7. [provided by RefSeq, Sep 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143769046	C>T	Likely-benign, risk-factor	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs750526659	C>G,T	Risk-factor	Coding sequence variant, non coding transcript variant, intron variant, missense variant

Transcription factors

Transcription factor	Regulation	Reference
E2F1	Repression	21225257;22464952
IRF4	Repression	19955181

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	8524823
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IMP	17560375
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	8524823
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001227	Function	DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	17560375
GO:0002376	Process	Immune system process	IBA	21873635
GO:0003677	Function	DNA binding	NAS	12062447
GO:0005515	Function	Protein binding	IPI	15841462, 16154084, 16362036, 17599067, 17761676, 18309294, 18583960, 18711448, 19153231, 20308324, 20581830, 20628368, 21903422, 21988832, 22908223, 23746807, 24622840, 24807708, 25609812, 25803835, 26347139, 27980081, 29429998, 29802199, 31413131, 32878885
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	17079289, 18818105
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	17079289, 18818105
GO:0005737	Component	Cytoplasm	IGI	23729669
GO:0005739	Component	Mitochondrion	IDA	25609812
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006915	Process	Apoptotic process	TAS	20049431
GO:0006974	Process	Cellular response to DNA damage stimulus	TAS	16979567
GO:0016032	Process	Viral process	IEA
GO:0019904	Function	Protein domain specific binding	IPI	11583620
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0032479	Process	Regulation of type I interferon production	TAS
GO:0032480	Process	Negative regulation of type I interferon production	TAS
GO:0032481	Process	Positive regulation of type I interferon production	IDA	25636800
GO:0032481	Process	Positive regulation of type I interferon production	TAS
GO:0032727	Process	Positive regulation of interferon-alpha production	ISS
GO:0032728	Process	Positive regulation of interferon-beta production	ISS
GO:0032728	Process	Positive regulation of interferon-beta production	TAS	16979567
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	IDA	25636800
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0039530	Process	MDA-5 signaling pathway	TAS	16979567
GO:0042802	Function	Identical protein binding	IPI	15841462, 16301520, 18725644, 19416887, 19454348, 20403326, 20581830, 21102435, 21782231, 22000020, 22728658, 23746807, 25609649
GO:0042803	Function	Protein homodimerization activity	IDA	22394562
GO:0042803	Function	Protein homodimerization activity	IPI	12062447
GO:0042981	Process	Regulation of apoptotic process	IDA	25609812
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	23332764
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	8524823, 9660935
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	17560375
GO:0050727	Process	Regulation of inflammatory response	IEA
GO:0051607	Process	Defense response to virus	ISS
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	TAS
GO:0060337	Process	Type I interferon signaling pathway	TAS
GO:0060340	Process	Positive regulation of type I interferon-mediated signaling pathway	IEA
GO:0071360	Process	Cellular response to exogenous dsRNA	IEA
GO:0071888	Process	Macrophage apoptotic process	TAS	16846591
GO:0097300	Process	Programmed necrotic cell death	IEA
GO:0098586	Process	Cellular response to virus	IDA	25609812
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 603734
• HGNC: 6118
• e!Ensembl: ENSG00000126456

Protein

• UniProt ID: Q14653
• Protein name: Interferon regulatory factor 3 (IRF-3)
• Protein 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:22394562, PubMed:25636800, PubMed:27302953). 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:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995). 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:22394562, PubMed:25636800, PubMed:27302953). 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:16154084, PubMed:27302953, PubMed:33440148). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148).
• PDB: 1J2F, 1QWT, 1T2K, 1ZOQ, 2O61, 2O6G, 2PI0, 3A77, 3QU6, 5JEJ, 5JEK, 5JEL, 5JEM, 5JEO, 5JER, 6SIV, 6SJA, 7JFL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00605	IRF	7 → 110	Interferon regulatory factor transcription factor	Domain
  PF10401	IRF-3	201 → 380	Interferon-regulatory factor 3	Family

• Sequence:

  MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEA
  TGAYVPGRDKPDLPTWKRNFRSALNRKEGLRLAEDRSKDPHDPHKIYEFVNSGVGDFSQP
  DTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPT
  PFPNLGPSENPLKRLLVPGEEWEFEVTAFYRGRQVFQQTISCPEGLRLVGSEVGDRTLPG
  WPVTLPDPGMSLTDRGVMSYVRHVLSCLGGGLALWRAGQWLWAQRLGHCHTYWAVSEELL
  PNSGHGPDGEVPKDKEGGVFDLGPFIVDLITFTEGSGRSPRYALWFCVGESWPQDQPWTK
  RLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISNSHPLSLTSDQYKAYLQDLVEGMD
  FQGPGES

• Sequence length: 427