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Protein

Interferon regulatory factor 9

Gene

IRF9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi9 – 116108IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. regulatory region DNA binding Source: InterPro
  2. sequence-specific DNA binding transcription factor activity Source: ProtInc

GO - Biological processi

  1. cell surface receptor signaling pathway Source: ProtInc
  2. cytokine-mediated signaling pathway Source: Reactome
  3. defense response to virus Source: UniProtKB-KW
  4. interferon-gamma-mediated signaling pathway Source: Reactome
  5. transcription from RNA polymerase II promoter Source: ProtInc
  6. type I interferon biosynthetic process Source: Ensembl
  7. type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Antiviral defense, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
SignaLinkiQ00978.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 9
Short name:
IRF-9
Alternative name(s):
IFN-alpha-responsive transcription factor subunit
ISGF3 p48 subunit
Interferon-stimulated gene factor 3 gamma
Short name:
ISGF-3 gamma
Transcriptional regulator ISGF3 subunit gamma
Gene namesi
Name:IRF9
Synonyms:ISGF3G
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:6131. IRF9.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: Translocated into the nucleus upon activation by IFN-alpha/beta.

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. nucleoplasm Source: Reactome
  4. nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162392259.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 393393Interferon regulatory factor 9PRO_0000154567Add
BLAST

Proteomic databases

MaxQBiQ00978.
PaxDbiQ00978.
PRIDEiQ00978.

PTM databases

PhosphoSiteiQ00978.

Expressioni

Inductioni

By IFN-alpha and IFNB1/IFN-beta.

Gene expression databases

BgeeiQ00978.
CleanExiHS_IRF9.
ExpressionAtlasiQ00978. baseline.
GenevestigatoriQ00978.

Organism-specific databases

HPAiHPA001862.

Interactioni

Subunit structurei

Interacts with STAT2 in the cytoplasm. Forms the interferon-stimulated gene factor 3 complex (ISGF3) with the heterodimer STAT1:STAT2; upon stimulation.

Binary interactionsi

WithEntry#Exp.IntActNotes
IFNAR2P485516EBI-626526,EBI-958408
STAT2P526306EBI-626526,EBI-1546963

Protein-protein interaction databases

BioGridi115652. 22 interactions.
IntActiQ00978. 6 interactions.
MINTiMINT-1526689.
STRINGi9606.ENSP00000380073.

Structurei

3D structure databases

ProteinModelPortaliQ00978.
SMRiQ00978. Positions 4-116, 253-380.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi181 – 1877Poly-Ser

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation
Contains 1 IRF tryptophan pentad repeat DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG43166.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000010107.
HOVERGENiHBG003072.
InParanoidiQ00978.
KOiK04693.
OMAiRCTRKLR.
OrthoDBiEOG7CCBR1.
PhylomeDBiQ00978.
TreeFamiTF328512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q00978-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASGRARCTR KLRNWVVEQV ESGQFPGVCW DDTAKTMFRI PWKHAGKQDF
60 70 80 90 100
REDQDAAFFK AWAIFKGKYK EGDTGGPAVW KTRLRCALNK SSEFKEVPER
110 120 130 140 150
GRMDVAEPYK VYQLLPPGIV SGQPGTQKVP SKRQHSSVSS ERKEEEDAMQ
160 170 180 190 200
NCTLSPSVLQ DSLNNEEEGA SGGAVHSDIG SSSSSSSPEP QEVTDTTEAP
210 220 230 240 250
FQGDQRSLEF LLPPEPDYSL LLTFIYNGRV VGEAQVQSLD CRLVAEPSGS
260 270 280 290 300
ESSMEQVLFP KPGPLEPTQR LLSQLERGIL VASNPRGLFV QRLCPIPISW
310 320 330 340 350
NAPQAPPGPG PHLLPSNECV ELFRTAYFCR DLVRYFQGLG PPPKFQVTLN
360 370 380 390
FWEESHGSSH TPQNLITVKM EQAFARYLLE QTPEQQAAIL SLV
Length:393
Mass (Da):43,696
Last modified:April 1, 1993 - v1
Checksum:iF8E3784354BFD4A9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87503 mRNA. Translation: AAA58687.1.
CH471078 Genomic DNA. Translation: EAW66093.1.
CH471078 Genomic DNA. Translation: EAW66094.1.
BC035716 mRNA. Translation: AAH35716.1.
CCDSiCCDS9615.1.
PIRiA45017.
RefSeqiNP_006075.3. NM_006084.4.
UniGeneiHs.1706.

Genome annotation databases

EnsembliENST00000396864; ENSP00000380073; ENSG00000213928.
GeneIDi10379.
KEGGihsa:10379.
UCSCiuc001wmq.3. human.

Polymorphism databases

DMDMi266392.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87503 mRNA. Translation: AAA58687.1.
CH471078 Genomic DNA. Translation: EAW66093.1.
CH471078 Genomic DNA. Translation: EAW66094.1.
BC035716 mRNA. Translation: AAH35716.1.
CCDSiCCDS9615.1.
PIRiA45017.
RefSeqiNP_006075.3. NM_006084.4.
UniGeneiHs.1706.

3D structure databases

ProteinModelPortaliQ00978.
SMRiQ00978. Positions 4-116, 253-380.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115652. 22 interactions.
IntActiQ00978. 6 interactions.
MINTiMINT-1526689.
STRINGi9606.ENSP00000380073.

PTM databases

PhosphoSiteiQ00978.

Polymorphism databases

DMDMi266392.

Proteomic databases

MaxQBiQ00978.
PaxDbiQ00978.
PRIDEiQ00978.

Protocols and materials databases

DNASUi10379.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000396864; ENSP00000380073; ENSG00000213928.
GeneIDi10379.
KEGGihsa:10379.
UCSCiuc001wmq.3. human.

Organism-specific databases

CTDi10379.
GeneCardsiGC14P024630.
HGNCiHGNC:6131. IRF9.
HPAiHPA001862.
MIMi147574. gene.
neXtProtiNX_Q00978.
PharmGKBiPA162392259.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43166.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000010107.
HOVERGENiHBG003072.
InParanoidiQ00978.
KOiK04693.
OMAiRCTRKLR.
OrthoDBiEOG7CCBR1.
PhylomeDBiQ00978.
TreeFamiTF328512.

Enzyme and pathway databases

ReactomeiREACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
SignaLinkiQ00978.

Miscellaneous databases

GeneWikiiIRF9.
ISGF3G.
GenomeRNAii10379.
NextBioi39319.
PROiQ00978.
SOURCEiSearch...

Gene expression databases

BgeeiQ00978.
CleanExiHS_IRF9.
ExpressionAtlasiQ00978. baseline.
GenevestigatoriQ00978.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins."
    Veals S.A., Schindler C., Leonard D.G.B., Fu X.-Y., Aebersold R.H., Darnell J.E. Jr., Levy D.E.
    Mol. Cell. Biol. 12:3315-3324(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Ovary.
  4. "Nuclear/cytoplasmic localization of IRFs in response to viral infection or interferon stimulation."
    Reich N.C.
    J. Interferon Cytokine Res. 22:103-109(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  5. "Viral inhibition of interferon signal transduction."
    Cebulla C.M., Miller D.M., Sedmak D.D.
    Intervirology 42:325-330(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiIRF9_HUMAN
AccessioniPrimary (citable) accession number: Q00978
Secondary accession number(s): D3DS61
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: January 7, 2015
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.