P56477 · IRF5_MOUSE

  • Protein
    Interferon regulatory factor 5
  • Gene
    Irf5
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:15665823).
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:15665823).
Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (PubMed:15665823).

Activity regulation

Maintained as a monomer in an autoinhibited state (PubMed:25326420).
Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (By similarity).
Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326420).

Features

Showing features for dna binding.

149750100150200250300350400450
TypeIDPosition(s)Description
DNA binding14-122IRF tryptophan pentad repeat

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytoplasm
Cellular Componentnucleus
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionidentical protein binding
Molecular Functionprotein kinase binding
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Biological Processcellular response to virus
Biological Processcytokine-mediated signaling pathway
Biological Processdefense response to virus
Biological Processimmune system process
Biological Processinflammatory response
Biological Processinnate immune response
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of cytokine production involved in immune response
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processpositive regulation of type I interferon production
Biological Processregulation of transcription by RNA polymerase II
Biological Processresponse to muramyl dipeptide
Biological Processresponse to peptidoglycan

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Interferon regulatory factor 5
  • Short names
    IRF-5

Gene names

    • Name
      Irf5

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P56477

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Note: Shuttles between the nucleus and the cytoplasm: upon activation by the TLR adapter MYD88 and subsequent phosphorylation, translocates to the nucleus.

Keywords

Phenotypes & Variants

Disruption phenotype

Mice develop normally and no overt phenotype is observed in hematopoietic cell population (PubMed:15665823).
However, the induction of pro-inflammatory cytokines, such as interleukin-6 (IL6) and IL12 by various TLR ligands is impaired, whereas interferon-alpha induction is normal (PubMed:15665823).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis434Reduced homodimerization and subsequent activation.
Mutagenesis445Abolished homodimerization and subsequent activation.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 23 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00001545591-497Interferon regulatory factor 5
Modified residue157Phosphoserine; by TBK1
Modified residue300Phosphoserine
Cross-link410Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link411Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue430Phosphoserine
Modified residue434Phosphoserine; by IKKB
Modified residue436Phosphoserine
Modified residue439Phosphoserine
Modified residue445Phosphoserine; by IKKB

Post-translational modification

Phosphorylation of serine and threonine residues by IKBKB in a C-terminal autoinhibitory region, stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/EP300 and initiation of transcription.
'Lys-63'-linked polyubiquitination by TRAF6 is required for activation.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Homodimer, when phosphorylated (PubMed:25326420).
Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (By similarity).
Interacts with MYD88 and TRAF6 (PubMed:15665823).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for motif, region, compositional bias.

TypeIDPosition(s)Description
Motif12-18Nuclear localization signal
Region124-178Disordered
Compositional bias135-149Acidic residues
Motif149-159Nuclear export signal

Sequence similarities

Belongs to the IRF family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    497
  • Mass (Da)
    56,005
  • Last updated
    1998-07-15 v1
  • Checksum
    D8BD54DB946E354F
MNHSAPGIPPPPRRVRLKPWLVAQVNSCQYPGLQWVNGEKKLFYIPWRHATRHGPSQDGDNTIFKAWAKETGKYTEGVDEADPAKWKANLRCALNKSRDFQLFYDGPRDMPPQPYKIYEVCSNGPAPTESQPTDDYVLGEEEEEEEEELQRMLPGLSITEPALPGPPNAPYSLPKEDTKWPPALQPPVGLGPPVPDPNLLAPPSGNPAGFRQLLPEVLEPGPLASSQPPTEPLLPDLLISPHMLPLTDLEIKFQYRGRAPRTLTISNPQGCRLFYSQLEATQEQVELFGPVTLEQVRFPSPEDIPSDKQRFYTNQLLDVLDRGLILQLQGQDLYAIRLCQCKVFWSGPCALAHGSCPNPIQREVKTKLFSLEQFLNELILFQKGQTNTPPPFEIFFCFGEEWPDVKPREKKLITVQVVPVAARLLLEMFSGELSWSADSIRLQISNPDLKDHMVEQFKELHHLWQSQQQLQPMVQAPPVAGLDASQGPWPMHPVGMQ

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
E9Q5T2E9Q5T2_MOUSEIrf580
A0A0N4SVY5A0A0N4SVY5_MOUSEIrf5134
F6Z6C6F6Z6C6_MOUSEIrf5494

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias135-149Acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF028725
EMBL· GenBank· DDBJ
AAB81997.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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