The Human Transcription Factors

Conclusion

Assessment	Binding Mode	Motif Status	Notes	Comments
Known motif	1 Monomer or homomultimer	High-throughput in vitro

Description

Description:

interferon regulatory factor 3 [Source:HGNC Symbol;Acc:HGNC:6118]

Entrez 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]

Ensembl ID:

ENSG00000126456

External Link:

CisBP

Interpro

IPR001346; IPR008984; IPR019471; IPR019817;

Protein Domain:

ENSP00000310127

Protein Domain:

ENSP00000366339

Protein Domain:

ENSP00000366344

Protein Domain:

ENSP00000400378

Protein Domain:

ENSP00000472601

Protein Domain:

ENSP00000470512

Protein Domain:

ENSP00000470069

Protein Domain:

ENSP00000471358

Protein Domain:

ENSP00000472700

Protein Domain:

ENSP00000471896

Protein Domain:

ENSP00000471517

Protein Domain:

ENSP00000469113

Protein Domain:

ENSP00000471402

Protein Domain:

ENSP00000470140

Protein Domain:

ENSP00000473176

Protein Domain:

ENSP00000469067

Protein Domain:

ENSP00000468911

Protein Domain:

ENSP00000472223

Protein Domain:

ENSP00000470905

Domain:

Protein: ENSP00000310127	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000366339	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000366344	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000400378	DBD: Interferon regulatory factor (IRF)	Other:
Protein: ENSP00000472601	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000470512	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000470069	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000471358	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000472700	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000471896	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000471517	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000469113	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000471402	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000470140	DBD: Interferon regulatory factor (IRF)	Other:
Protein: ENSP00000473176	DBD: Interferon regulatory factor (IRF)	Other:
Protein: ENSP00000469067	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000468911	DBD: Interferon regulatory factor (IRF)	Other:
Protein: ENSP00000472223	DBD: Interferon regulatory factor (IRF)	Other: IRF-3
Protein: ENSP00000470905	DBD: Interferon regulatory factor (IRF)	Other:

Previous Annotations

Source	Annotation
TF-CAT classification	TF Gene_DNA-Binding sequence-specific_DNA Binding Transactivation_ PMIDS:9660935
Vaquerizas 2009 TF classification "a" Has direct evidence of TF function; "b" Has evidence for an orthologous TF; "c" contains likely DBDs, but has no functional evidence; "x" is an unlikely TF such as predicted gene, genes with likely non-specific DBDs or that have function outside transcription; "other" category contains proteins without clear DBDs they curated from external sources.	a
CisBP considers it as a TF?	Yes
TFclass considers it as a TF?	Yes
Has GO:0003700 "transcription factor activity, sequence-specific DNA binding"	No
GO-Info	GO:0003700 sequence-specific DNA binding transcription factor activity IEA - GO_REF:0000002
Initial Assessment 1a1 Protein has a high confidence PWM (HT-SELEX, PBM or B1H model) or there is a crystal structure that supports sequence specific DNA binding; 1a2 There is high confidence data for a close ortholog (as defined in CisBP); 2a1 There is lower confidence direct evidence, such as a Jaspar, Hocomoco or Transfac model; 2a2 There is lower confidence evidence for an close ortholog; 3a There is decent circumstantial evidence for its role as a TF or not; 4a Two or more datasets predict it as a TF; 5a One of the source datasets predicts is as a TF	1a1, Direct HQ evidence
TF has conditional DNA-binding requirements

DNA-Binding

Published Motif Data

Source	Annotation	Motif	Evidence
HT-SELEX	Jolma2013		Direct
HT-SELEX	Yin2017		Direct
HT-SELEX	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
Methyl-HT-SELEX	Yin2017		Direct
Transfac	Transfac	License required	Direct
Misc	HocoMoco		Direct
PBM	Badis09		Inferred - Irf3 (85% AA Identity, Mus musculus)

Structure

Structure	PDB	2O6G

Experimental History

Method	Constructs
Tried in PBM? (Whether the protein was tried in PBM or not)
Tried in HT-SELEX (Whether the protein was tried in HT-SELEX or not, and if so, then what kind of clones were tested)
Other Information? (Tried with another method and failed?)

External Contribution

Name
Email
Comment
Reference

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{"regions": [{"startStyle": "straight", "end": 234, "endStyle": "straight", "aliStart": 56, "text": "IRF-3", "colour": "#9999ff", "aliEnd": 233, "start": 55, "href": "http://pfam.xfam.org/family/PF10401.7", "type": "pfama", "display": "true", "metadata": {"end": 234, "description": "This is the interferon-regulatory factor 3 chain of the hetero-dimeric structure which also contains the shorter chain CREB-binding protein.  These two subunits make up the DRAF1 (double-stranded RNA-activated factor 1).          Viral dsRNA produced during viral transcription or replication leads to the activation of DRAF1. The DNA-binding specificity of DRAF1 correlates with transcriptional induction of ISG (interferon-alpha,beta-stimulated gene). IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation, and association with the CREB coactivator occurs only after infection.", "database": "PfamA", "aliStart": 56, "scoreName": "E-value", "accession": "PF10401.7", "start": 55, "score": 8.599999999999999e-52, "identifier": "Interferon-regulatory factor 3", "type": "DBD", "aliEnd": 233}}], "length": 282}

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{"regions": [{"startStyle": "straight", "end": 106, "endStyle": "jagged", "aliStart": 56, "text": "IRF-3", "colour": "#9999ff", "aliEnd": 103, "start": 55, "href": "http://pfam.xfam.org/family/PF10401.7", "type": "pfama", "display": "true", "metadata": {"end": 106, "description": "This is the interferon-regulatory factor 3 chain of the hetero-dimeric structure which also contains the shorter chain CREB-binding protein.  These two subunits make up the DRAF1 (double-stranded RNA-activated factor 1).          Viral dsRNA produced during viral transcription or replication leads to the activation of DRAF1. The DNA-binding specificity of DRAF1 correlates with transcriptional induction of ISG (interferon-alpha,beta-stimulated gene). IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation, and association with the CREB coactivator occurs only after infection.", "database": "PfamA", "aliStart": 56, "scoreName": "E-value", "accession": "PF10401.7", "start": 55, "score": 1.5e-07, "identifier": "Interferon-regulatory factor 3", "type": "DBD", "aliEnd": 103}}], "length": 106}

{"regions": [{"startStyle": "straight", "end": 84, "endStyle": "jagged", "aliStart": 56, "text": "IRF-3", "colour": "#9999ff", "aliEnd": 83, "start": 55, "href": "http://pfam.xfam.org/family/PF10401.7", "type": "pfama", "display": "true", "metadata": {"end": 84, "description": "This is the interferon-regulatory factor 3 chain of the hetero-dimeric structure which also contains the shorter chain CREB-binding protein.  These two subunits make up the DRAF1 (double-stranded RNA-activated factor 1).          Viral dsRNA produced during viral transcription or replication leads to the activation of DRAF1. The DNA-binding specificity of DRAF1 correlates with transcriptional induction of ISG (interferon-alpha,beta-stimulated gene). IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation, and association with the CREB coactivator occurs only after infection.", "database": "PfamA", "aliStart": 56, "scoreName": "E-value", "accession": "PF10401.7", "start": 55, "score": 4.5e-06, "identifier": "Interferon-regulatory factor 3", "type": "DBD", "aliEnd": 83}}], "length": 84}

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{"regions": [{"startStyle": "curved", "end": 110, "endStyle": "curved", "aliStart": 7, "text": "IRF", "colour": "#009900", "aliEnd": 109, "start": 7, "href": "http://pfam.xfam.org/family/PF00605.15", "type": "pfama", "display": "true", "metadata": {"end": 110, "description": "This family of transcription factors are important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. Three of the five conserved tryptophan residues bind to DNA.", "database": "PfamA", "aliStart": 7, "scoreName": "E-value", "accession": "PF00605.15", "start": 7, "score": 4.6e-35, "identifier": "Interferon regulatory factor transcription factor", "type": "DBD", "aliEnd": 109}}, {"startStyle": "straight", "end": 287, "endStyle": "jagged", "aliStart": 202, "text": "IRF-3", "colour": "#9999ff", "aliEnd": 286, "start": 201, "href": "http://pfam.xfam.org/family/PF10401.7", "type": "pfama", "display": "true", "metadata": {"end": 287, "description": "This is the interferon-regulatory factor 3 chain of the hetero-dimeric structure which also contains the shorter chain CREB-binding protein.  These two subunits make up the DRAF1 (double-stranded RNA-activated factor 1).          Viral dsRNA produced during viral transcription or replication leads to the activation of DRAF1. The DNA-binding specificity of DRAF1 correlates with transcriptional induction of ISG (interferon-alpha,beta-stimulated gene). IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation, and association with the CREB coactivator occurs only after infection.", "database": "PfamA", "aliStart": 202, "scoreName": "E-value", "accession": "PF10401.7", "start": 201, "score": 1.8e-19, "identifier": "Interferon-regulatory factor 3", "type": "DBD", "aliEnd": 286}}], "length": 287}

TF Info Page for IRF3 (IRF)

Conclusion

Description

Previous Annotations

DNA-Binding

Published Motif Data

Structure

Experimental History

External Contribution