InnateDB: Systems Biology of the Innate Immune Response

Bos taurus Protein: IRF3

Summary

InnateDB Protein

IDBP-692919.2

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

IRF3

Protein Name

Interferon regulatory factor 3

Synonyms

Species

Bos taurus

Ensembl Protein

ENSBTAP00000031815

InnateDB Gene

IDBG-640634 (IRF3)

Protein Structure

UniProt Annotation

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. 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. 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. 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. 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. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 83 interaction(s) predicted by orthology.

Predicted by orthology
Total	83 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000975	regulatory region DNA binding
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0044212	transcription regulatory region DNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0002376	immune system process
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0009617	response to bacterium
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032496	response to lipopolysaccharide
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0043330	response to exogenous dsRNA
GO:0045087	innate immune response
GO:0045351	type I interferon biosynthetic process
GO:0045358	negative regulation of interferon-beta biosynthetic process
GO:0050689	negative regulation of defense response to virus by host
GO:0051607	defense response to virus
GO:0060340	positive regulation of type I interferon-mediated signaling pathway
GO:0097300	programmed necrotic cell death

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR001346 Interferon regulatory factor DNA-binding domain
IPR008984 SMAD/FHA domain
IPR019471 Interferon regulatory factor-3

PFAM

PF00605
PF10401

PRINTS

PR00267

PIRSF

SMART

SM00348

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q4JF28

PhosphoSite

PhosphoSite-

TrEMBL

UniProt Splice Variant

Entrez Gene

516979

UniGene

Bt.45332

RefSeq

NP_001025016

HUGO

OMIM

CCDS

HPRD

IMGT

EMBL

AJ879589 BC102119 DQ103889 EU194377

GenPept

AAI02120 AAZ38325 ABW74073 CAI53672