IRF9_HUMAN
ID IRF9_HUMAN Reviewed; 393 AA.
AC Q00978; D3DS61;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Interferon regulatory factor 9;
DE Short=IRF-9;
DE AltName: Full=IFN-alpha-responsive transcription factor subunit;
DE AltName: Full=ISGF3 p48 subunit;
DE AltName: Full=Interferon-stimulated gene factor 3 gamma;
DE Short=ISGF-3 gamma;
DE AltName: Full=Transcriptional regulator ISGF3 subunit gamma;
GN Name=IRF9; Synonyms=ISGF3G;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1630447; DOI=10.1128/mcb.12.8.3315-3324.1992;
RA Veals S.A., Schindler C., Leonard D.G.B., Fu X.-Y., Aebersold R.H.,
RA Darnell J.E. Jr., Levy D.E.;
RT "Subunit of an alpha-interferon-responsive transcription factor is related
RT to interferon regulatory factor and Myb families of DNA-binding proteins.";
RL Mol. Cell. Biol. 12:3315-3324(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=11846981; DOI=10.1089/107999002753452719;
RA Reich N.C.;
RT "Nuclear/cytoplasmic localization of IRFs in response to viral infection or
RT interferon stimulation.";
RL J. Interferon Cytokine Res. 22:103-109(2002).
RN [5]
RP REVIEW.
RX PubMed=10702714; DOI=10.1159/000053968;
RA Cebulla C.M., Miller D.M., Sedmak D.D.;
RT "Viral inhibition of interferon signal transduction.";
RL Intervirology 42:325-330(1999).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN IMD65, VARIANTS HIS-127 AND
RP CYS-292, CHARACTERIZATION OF VARIANTS HIS-127 AND CYS-292, AND MUTAGENESIS
RP OF LYS-81 AND ARG-292.
RX PubMed=30143481; DOI=10.1084/jem.20180628;
RA Hernandez N., Melki I., Jing H., Habib T., Huang S.S.Y., Danielson J.,
RA Kula T., Drutman S., Belkaya S., Rattina V., Lorenzo-Diaz L., Boulai A.,
RA Rose Y., Kitabayashi N., Rodero M.P., Dumaine C., Blanche S., Lebras M.N.,
RA Leung M.C., Mathew L.S., Boisson B., Zhang S.Y., Boisson-Dupuis S.,
RA Giliani S., Chaussabel D., Notarangelo L.D., Elledge S.J.,
RA Ciancanelli M.J., Abel L., Zhang Q., Marr N., Crow Y.J., Su H.C.,
RA Casanova J.L.;
RT "Life-threatening influenza pneumonitis in a child with inherited IRF9
RT deficiency.";
RL J. Exp. Med. 215:2567-2585(2018).
RN [7]
RP FUNCTION, AND INVOLVEMENT IN IMD65.
RX PubMed=30826365; DOI=10.1016/j.jaci.2019.02.019;
RA Bravo Garcia-Morato M., Calvo Apalategi A., Bravo-Gallego L.Y.,
RA Blazquez Moreno A., Simon-Fuentes M., Garmendia J.V., Mendez Echevarria A.,
RA Del Rosal Rabes T., Dominguez-Soto A., Lopez-Granados E., Reyburn H.T.,
RA Rodriguez Pena R.;
RT "Impaired control of multiple viral infections in a family with complete
RT IRF9 deficiency.";
RL J. Allergy Clin. Immunol. 144:309-312(2019).
RN [8]
RP UBIQUITINATION BY HERPES SIMPLEX VIRUS 2 PROTEIN ICP22 (MICROBIAL
RP INFECTION).
RX PubMed=32699158; DOI=10.4049/jimmunol.2000418;
RA Zhang M., Fu M., Li M., Hu H., Gong S., Hu Q.;
RT "Herpes Simplex Virus Type 2 Inhibits Type I IFN Signaling Mediated by the
RT Novel E3 Ubiquitin Protein Ligase Activity of Viral Protein ICP22.";
RL J. Immunol. 205:1281-1292(2020).
CC -!- FUNCTION: Transcription factor that plays an essential role in anti-
CC viral immunity. It mediates signaling by type I IFNs (IFN-alpha and
CC IFN-beta). Following type I IFN binding to cell surface receptors, Jak
CC kinases (TYK2 and JAK1) are activated, leading to tyrosine
CC phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the
CC phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3
CC transcription factor, that enters the nucleus. ISGF3 binds to the IFN
CC stimulated response element (ISRE) to activate the transcription of
CC interferon stimulated genes, which drive the cell in an antiviral
CC state. {ECO:0000269|PubMed:30143481}.
CC -!- SUBUNIT: Interacts with STAT2 in the cytoplasm. Forms the interferon-
CC stimulated gene factor 3 complex (ISGF3) with the heterodimer
CC STAT1:STAT2; upon stimulation.
CC -!- INTERACTION:
CC Q00978; P48551: IFNAR2; NbExp=6; IntAct=EBI-626526, EBI-958408;
CC Q00978; P52630: STAT2; NbExp=7; IntAct=EBI-626526, EBI-1546963;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11846981}. Nucleus
CC {ECO:0000269|PubMed:11846981, ECO:0000269|PubMed:30143481}.
CC Note=Translocated into the nucleus upon activation by IFN-alpha/beta.
CC -!- INDUCTION: By IFN-alpha and IFNB1/IFN-beta.
CC -!- PTM: (Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3
CC ubiquitin ligase ICP22. {ECO:0000269|PubMed:32699158}.
CC -!- DISEASE: Immunodeficiency 65 (IMD65) [MIM:618648]: An autosomal
CC recessive immunologic disorder characterized by recurrent viral
CC infections from early infancy. Clinical consequences are pneumonia,
CC bronchiectasis, and septic shock. Affected individuals have lymphopenia
CC or hypogammaglobulinemia, particularly during infection, and impaired
CC cellular type I interferon response. Patients may have adverse response
CC to vaccination with live attenuated vaccines.
CC {ECO:0000269|PubMed:30143481, ECO:0000269|PubMed:30826365}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC ProRule:PRU00840}.
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DR EMBL; M87503; AAA58687.1; -; mRNA.
DR EMBL; CH471078; EAW66093.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66094.1; -; Genomic_DNA.
DR EMBL; BC035716; AAH35716.1; -; mRNA.
DR CCDS; CCDS9615.1; -.
DR PIR; A45017; A45017.
DR RefSeq; NP_006075.3; NM_006084.4.
DR AlphaFoldDB; Q00978; -.
DR SMR; Q00978; -.
DR BioGRID; 115652; 39.
DR ComplexPortal; CPX-6016; ISGF3 complex.
DR CORUM; Q00978; -.
DR IntAct; Q00978; 25.
DR MINT; Q00978; -.
DR STRING; 9606.ENSP00000380073; -.
DR iPTMnet; Q00978; -.
DR PhosphoSitePlus; Q00978; -.
DR BioMuta; IRF9; -.
DR DMDM; 266392; -.
DR EPD; Q00978; -.
DR jPOST; Q00978; -.
DR MassIVE; Q00978; -.
DR MaxQB; Q00978; -.
DR PaxDb; Q00978; -.
DR PeptideAtlas; Q00978; -.
DR PRIDE; Q00978; -.
DR ProteomicsDB; 57888; -.
DR Antibodypedia; 663; 294 antibodies from 34 providers.
DR DNASU; 10379; -.
DR Ensembl; ENST00000396864.8; ENSP00000380073.3; ENSG00000213928.9.
DR Ensembl; ENST00000646071.2; ENSP00000494792.1; ENSG00000285048.2.
DR GeneID; 10379; -.
DR KEGG; hsa:10379; -.
DR MANE-Select; ENST00000396864.8; ENSP00000380073.3; NM_006084.5; NP_006075.3.
DR UCSC; uc058zzb.1; human.
DR CTD; 10379; -.
DR DisGeNET; 10379; -.
DR GeneCards; IRF9; -.
DR HGNC; HGNC:6131; IRF9.
DR HPA; ENSG00000213928; Low tissue specificity.
DR MalaCards; IRF9; -.
DR MIM; 147574; gene.
DR MIM; 618648; phenotype.
DR neXtProt; NX_Q00978; -.
DR OpenTargets; ENSG00000213928; -.
DR PharmGKB; PA162392259; -.
DR VEuPathDB; HostDB:ENSG00000213928; -.
DR eggNOG; ENOG502RR4E; Eukaryota.
DR GeneTree; ENSGT00940000162115; -.
DR HOGENOM; CLU_031544_1_2_1; -.
DR InParanoid; Q00978; -.
DR OMA; EVTTKNC; -.
DR OrthoDB; 648909at2759; -.
DR PhylomeDB; Q00978; -.
DR TreeFam; TF328512; -.
DR PathwayCommons; Q00978; -.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; Q00978; -.
DR SIGNOR; Q00978; -.
DR BioGRID-ORCS; 10379; 19 hits in 1107 CRISPR screens.
DR ChiTaRS; IRF9; human.
DR GeneWiki; IRF9; -.
DR GeneWiki; ISGF3G; -.
DR GenomeRNAi; 10379; -.
DR Pharos; Q00978; Tbio.
DR PRO; PR:Q00978; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q00978; protein.
DR Bgee; ENSG00000213928; Expressed in spleen and 97 other tissues.
DR ExpressionAtlas; Q00978; baseline and differential.
DR Genevisible; Q00978; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070721; C:ISGF3 complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IMP:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR CDD; cd00103; IRF; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.200.10; -; 1.
DR InterPro; IPR019817; Interferon_reg_fac_CS.
DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR InterPro; IPR019471; Interferon_reg_factor-3.
DR InterPro; IPR017855; SMAD-like_dom_sf.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00605; IRF; 1.
DR Pfam; PF10401; IRF-3; 1.
DR PRINTS; PR00267; INTFRNREGFCT.
DR SMART; SM00348; IRF; 1.
DR SMART; SM01243; IRF-3; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS00601; IRF_1; 1.
DR PROSITE; PS51507; IRF_2; 1.
PE 1: Evidence at protein level;
KW Activator; Antiviral defense; Cytoplasm; Direct protein sequencing;
KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..393
FT /note="Interferon regulatory factor 9"
FT /id="PRO_0000154567"
FT DNA_BIND 9..116
FT /note="IRF tryptophan pentad repeat"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT REGION 120..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..149
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 176..202
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61179"
FT VARIANT 127
FT /note="Q -> H (does not affect transcriptional activation
FT in response to type I interferon stimulation; does not
FT affect anti-viral immunity; dbSNP:rs145480303)"
FT /evidence="ECO:0000269|PubMed:30143481"
FT /id="VAR_083496"
FT VARIANT 292
FT /note="R -> C (decreased transcriptional activation in
FT response to type I interferon stimulation;
FT dbSNP:rs1452927917)"
FT /evidence="ECO:0000269|PubMed:30143481"
FT /id="VAR_083497"
FT MUTAGEN 81
FT /note="K->R: Loss of transcriptional activation in response
FT to type I interferon stimulation. Impaired anti-viral
FT immunity."
FT /evidence="ECO:0000269|PubMed:30143481"
FT MUTAGEN 292
FT /note="R->Q: Decreased transcriptional activation in
FT response to type I interferon stimulation. Decreased anti-
FT viral immunity."
FT /evidence="ECO:0000269|PubMed:30143481"
SQ SEQUENCE 393 AA; 43696 MW; F8E3784354BFD4A9 CRC64;
MASGRARCTR KLRNWVVEQV ESGQFPGVCW DDTAKTMFRI PWKHAGKQDF REDQDAAFFK
AWAIFKGKYK EGDTGGPAVW KTRLRCALNK SSEFKEVPER GRMDVAEPYK VYQLLPPGIV
SGQPGTQKVP SKRQHSSVSS ERKEEEDAMQ NCTLSPSVLQ DSLNNEEEGA SGGAVHSDIG
SSSSSSSPEP QEVTDTTEAP FQGDQRSLEF LLPPEPDYSL LLTFIYNGRV VGEAQVQSLD
CRLVAEPSGS ESSMEQVLFP KPGPLEPTQR LLSQLERGIL VASNPRGLFV QRLCPIPISW
NAPQAPPGPG PHLLPSNECV ELFRTAYFCR DLVRYFQGLG PPPKFQVTLN FWEESHGSSH
TPQNLITVKM EQAFARYLLE QTPEQQAAIL SLV
