ID IRF4_HUMAN Reviewed; 451 AA. AC Q15306; Q5VUI7; Q99660; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 28-JAN-2026, entry version 226. DE RecName: Full=Interferon regulatory factor 4 {ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8921401}; DE Short=IRF-4; DE AltName: Full=Lymphocyte-specific interferon regulatory factor {ECO:0000303|PubMed:9326949}; DE Short=LSIRF; DE AltName: Full=Multiple myeloma oncogene 1 {ECO:0000303|PubMed:9326949}; DE AltName: Full=NF-EM5; GN Name=IRF4 {ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8921401}; GN Synonyms=MUM1 {ECO:0000303|PubMed:9326949}; 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] (ISOFORMS 1 AND 2). RC TISSUE=Spleen; RX PubMed=8921401; DOI=10.1006/geno.1996.0547; RA Grossman A., Mittrucker H.W., Nicholl J., Suzuki A., Chung S., Antonio L., RA Sugga S., Sutherland G.R., Siderovski D.P., Mak T.W.; RT "Cloning of human lymphocyte-specific interferon regulatory factor RT (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25."; RL Genomics 37:229-233(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INVOLVEMENT IN MULTIPLE RP MYELOMA. RC TISSUE=Spleen; RX PubMed=9326949; DOI=10.1038/ng1097-226; RA Iida S., Rao P.H., Butler M., Corradini P., Boccadoro M., Klein B., RA Chaganti R.S.K., Dalla-Favera R.; RT "Deregulation of MUM1/IRF4 by chromosomal translocation in multiple RT myeloma."; RL Nat. Genet. 17:226-230(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; 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 [5] RP INTERACTION WITH SPIB. RX PubMed=10196196; DOI=10.1074/jbc.274.16.11115; RA Rao S., Matsumura A., Yoon J., Simon M.C.; RT "SPI-B activates transcription via a unique proline, serine, and threonine RT domain and exhibits DNA binding affinity differences from PU.1."; RL J. Biol. Chem. 274:11115-11124(1999). RN [6] RP INTERACTION WITH DEF6. RC TISSUE=Lymph node; RX PubMed=12651066; DOI=10.1016/s0198-8859(03)00024-7; RA Gupta S., Lee A.E., Hu C., Fanzo J.C., Goldberg I., Cattoretti G., RA Pernis A.B.; RT "Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly RT expressed in the immune system."; RL Hum. Immunol. 64:389-401(2003). RN [7] RP POLYMORPHISM. RX PubMed=18483556; DOI=10.1371/journal.pgen.1000074; RA Han J., Kraft P., Nan H., Guo Q., Chen C., Qureshi A., Hankinson S.E., RA Hu F.B., Duffy D.L., Zhao Z.Z., Martin N.G., Montgomery G.W., Hayward N.K., RA Thomas G., Hoover R.N., Chanock S., Hunter D.J.; RT "A genome-wide association study identifies novel alleles associated with RT hair color and skin pigmentation."; RL PLoS Genet. 4:E1000074-E1000074(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP POLYMORPHISM. RX PubMed=24267888; DOI=10.1016/j.cell.2013.10.022; RA Praetorius C., Grill C., Stacey S.N., Metcalf A.M., Gorkin D.U., RA Robinson K.C., Van Otterloo E., Kim R.S., Bergsteinsdottir K., RA Ogmundsdottir M.H., Magnusdottir E., Mishra P.J., Davis S.R., Guo T., RA Zaidi M.R., Helgason A.S., Sigurdsson M.I., Meltzer P.S., Merlino G., RA Petit V., Larue L., Loftus S.K., Adams D.R., Sobhiafshar U., Emre N.C., RA Pavan W.J., Cornell R., Smith A.G., McCallion A.S., Fisher D.E., RA Stefansson K., Sturm R.A., Steingrimsson E.; RT "A polymorphism in IRF4 affects human pigmentation through a tyrosinase- RT dependent MITF/TFAP2A pathway."; RL Cell 155:1022-1033(2013). RN [10] RP INVOLVEMENT IN IMD131. RX PubMed=29408330; DOI=10.1016/j.jaci.2017.12.995; RA Bravo Garcia-Morato M., Aracil Santos F.J., Briones A.C., RA Blazquez Moreno A., Del Pozo Mate A., Dominguez-Soto A., Beato Merino M.J., RA Del Pino Molina L., Torres Canizales J., Marin A.V., Vallespin Garcia E., RA Feito Rodriguez M., Plaza Lopez Sabando D., Jimenez-Reinoso A., RA Mozo Del Castillo Y., Sanz Santaeufemia F.J., de Lucas-Laguna R., RA Cardenas P.P., Casamayor Polo L., Coronel Diaz M., Vales-Gomez M., RA Roldan Santiago E., Ferreira Cerdan A., Nevado Blanco J., Corbi A.L., RA Reyburn H.T., Regueiro J.R., Lopez-Granados E., Rodriguez Pena R.; RT "New human combined immunodeficiency caused by interferon regulatory factor RT 4 (IRF4) deficiency inherited by uniparental isodisomy."; RL J. Allergy Clin. Immunol. 141:1924-1927.e18(2018). RN [11] RP INTERACTION WITH SPI1. RX PubMed=33951726; DOI=10.1084/jem.20201750; RA Le Coz C., Nguyen D.N., Su C., Nolan B.E., Albrecht A.V., Xhani S., Sun D., RA Demaree B., Pillarisetti P., Khanna C., Wright F., Chen P.A., Yoon S., RA Stiegler A.L., Maurer K., Garifallou J.P., Rymaszewski A., Kroft S.H., RA Olson T.S., Seif A.E., Wertheim G., Grant S.F.A., Vo L.T., Puck J.M., RA Sullivan K.E., Routes J.M., Zakharova V., Shcherbina A., Mukhina A., RA Rudy N.L., Hurst A.C.E., Atkinson T.P., Boggon T.J., Hakonarson H., RA Abate A.R., Hajjar J., Nicholas S.K., Lupski J.R., Verbsky J., Chinn I.K., RA Gonzalez M.V., Wells A.D., Marson A., Poon G.M.K., Romberg N.; RT "Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia RT patients."; RL J. Exp. Med. 218:0-0(2021). RN [12] RP STRUCTURE BY NMR OF 22-130. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the IRF domain of human interferon regulator factor RT 4."; RL Submitted (OCT-2006) to the PDB data bank. RN [13] RP VARIANT IMD131 TRP-98, CHARACTERIZATION OF VARIANT IMD131 TRP-98, RP INVOLVEMENT IN IMD131, MUTAGENESIS OF ARG-98 AND CYS-99, AND FUNCTION. RX PubMed=29537367; DOI=10.7554/elife.32340; RA Guerin A., Kerner G., Marr N., Markle J.G., Fenollar F., Wong N., RA Boughorbel S., Avery D.T., Ma C.S., Bougarn S., Bouaziz M., Beziat V., RA Della Mina E., Oleaga-Quintas C., Lazarov T., Worley L., Nguyen T., RA Patin E., Deswarte C., Martinez-Barricarte R., Boucherit S., Ayral X., RA Edouard S., Boisson-Dupuis S., Rattina V., Bigio B., Vogt G., Geissmann F., RA Quintana-Murci L., Chaussabel D., Tangye S.G., Raoult D., Abel L., RA Bustamante J., Casanova J.L.; RT "IRF4 haploinsufficiency in a family with Whipple's disease."; RL Elife 7:0-0(2018). RN [14] RP VARIANT IMD131 LEU-359, CHARACTERIZATION OF VARIANT IMD131 LEU-359, RP INVOLVEMENT IN IMD131, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LEU-368. RX PubMed=36917008; DOI=10.1084/jem.20221292; RA Thouenon R., Chentout L., Moreno-Corona N., Poggi L., Lombardi E.P., RA Hoareau B., Schmitt Y., Lagresle-Peyrou C., Bustamante J., Andre I., RA Cavazzana M., Durandy A., Casanova J.L., Galicier L., Fadlallah J., RA Fischer A., Kracker S.; RT "A neomorphic mutation in the interferon activation domain of IRF4 causes a RT dominant primary immunodeficiency."; RL J. Exp. Med. 220:0-0(2023). RN [15] RP VARIANT IMD131 ARG-95, CHARACTERIZATION OF VARIANT IMD131 ARG-95, RP INVOLVEMENT IN IMD131, AND FUNCTION. RX PubMed=36662884; DOI=10.1126/sciimmunol.ade7953; RG IRF4 International Consortium; RA Fornes O., Jia A., Kuehn H.S., Min Q., Pannicke U., Schleussner N., RA Thouenon R., Yu Z., de Los Angeles Astbury M., Biggs C.M., Galicchio M., RA Garcia-Campos J.A., Gismondi S., Gonzalez Villarreal G., Hildebrand K.J., RA Hoenig M., Hou J., Moshous D., Pittaluga S., Qian X., Rozmus J., RA Schulz A.S., Staines-Boone A.T., Sun B., Sun J., Uwe S., RA Venegas-Montoya E., Wang W., Wang X., Ying W., Zhai X., Zhou Q., Akalin A., RA Andre I., Barth T.F.E., Baumann B., Bruestle A., Burgio G., RA Bustamante J.C., Casanova J.L., Casarotto M.G., Cavazzana M., Chentout L., RA Cockburn I.A., Costanza M., Cui C., Daumke O., Del Bel K.L., Eibel H., RA Feng X., Franke V., Gebhardt J.C.M., Goetz A., Grunwald S., Hoareau B., RA Hughes T.R., Jacobsen E.M., Janz M., Jolma A., Lagresle-Peyrou C., Lai N., RA Li Y., Lin S., Lu H.Y., Lugo-Reyes S.O., Meng X., Moeller P., RA Moreno-Corona N., Niemela J.E., Novakovsky G., Perez-Caraballo J.J., RA Picard C., Poggi L., Puig-Lombardi M.E., Randall K.L., Reisser A., RA Schmitt Y., Seneviratne S., Sharma M., Stoddard J., Sundararaj S., RA Sutton H., Tran L.Q., Wang Y., Wasserman W.W., Wen Z., Winkler W., RA Xiong E., Yang A.W.H., Yu M., Zhang L., Zhang H., Zhao Q., Zhen X., RA Enders A., Kracker S., Martinez-Barricarte R., Mathas S., Rosenzweig S.D., RA Schwarz K., Turvey S.E., Wang J.Y.; RT "A multimorphic mutation in IRF4 causes human autosomal dominant combined RT immunodeficiency."; RL Sci. Immunol. 8:eade7953-eade7953(2023). CC -!- FUNCTION: Transcriptional activator. Binds to the interferon-stimulated CC response element (ISRE) of the MHC class I promoter. Binds the CC immunoglobulin lambda light chain enhancer, together with PU.1. CC Probably plays a role in ISRE-targeted signal transduction mechanisms CC specific to lymphoid cells. Involved in CD8(+) dendritic cell CC differentiation by forming a complex with the BATF-JUNB heterodimer in CC immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA- CC 3'), an immune-specific regulatory element, followed by cooperative CC binding of BATF and IRF4 and activation of genes. CC {ECO:0000269|PubMed:29537367, ECO:0000269|PubMed:36662884, CC ECO:0000269|PubMed:36917008}. CC -!- SUBUNIT: Interacts with the BATF-JUNB heterodimer. Interacts with BATF CC (via bZIP domain); the interaction is direct (By similarity). Interacts CC with SPIB (PubMed:10196196). Interacts with DEF6 (PubMed:12651066). CC Directly interacts with NLRP3 in the nucleus of Th2 cells; this CC interaction enhances IRF4 ability to bind to the IL4 promoter and is CC required for optimal IRF4-dependent IL4 transcription (By similarity). CC Interacts with SPI1 (PubMed:33951726). {ECO:0000250, CC ECO:0000250|UniProtKB:Q64287, ECO:0000269|PubMed:10196196, CC ECO:0000269|PubMed:12651066, ECO:0000269|PubMed:33951726}. CC -!- INTERACTION: CC Q15306; O95163: ELP1; NbExp=2; IntAct=EBI-751345, EBI-347559; CC Q15306; Q8TF65: GIPC2; NbExp=5; IntAct=EBI-751345, EBI-712067; CC Q15306; P51617: IRAK1; NbExp=2; IntAct=EBI-751345, EBI-358664; CC Q15306; Q86UE8: TLK2; NbExp=2; IntAct=EBI-751345, EBI-1047967; CC Q15306; Q7Z6J9: TSEN54; NbExp=3; IntAct=EBI-751345, EBI-2559824; CC Q15306; Q9H6S0: YTHDC2; NbExp=2; IntAct=EBI-751345, EBI-1057466; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:36917008}. Cytoplasm CC {ECO:0000269|PubMed:36917008}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15306-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15306-2; Sequence=VSP_002755; CC -!- TISSUE SPECIFICITY: Lymphoid cells. CC -!- INDUCTION: Not induced by interferons. CC -!- PTM: Phosphorylation by ROCK2 regulates IL-17 and IL-21 production. CC {ECO:0000250}. CC -!- POLYMORPHISM: Genetic variants in IRF4 define the skin/hair/eye CC pigmentation variation locus 8 (SHEP8) [MIM:611724]. Hair, eye and skin CC pigmentation are among the most visible examples of human phenotypic CC variation, with a broad normal range that is subject to substantial CC geographic stratification. In the case of skin, individuals tend to CC have lighter pigmentation with increasing distance from the equator. By CC contrast, the majority of variation in human eye and hair color is CC found among individuals of European ancestry, with most other human CC populations fixed for brown eyes and black hair. CC {ECO:0000269|PubMed:18483556, ECO:0000269|PubMed:24267888}. CC -!- DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of CC plasma cells usually arising in the bone marrow and characterized by CC diffuse involvement of the skeletal system, hyperglobulinemia, Bence- CC Jones proteinuria and anemia. Complications of multiple myeloma are CC bone pain, hypercalcemia, renal failure and spinal cord compression. CC The aberrant antibodies that are produced lead to impaired humoral CC immunity and patients have a high prevalence of infection. Amyloidosis CC may develop in some patients. Multiple myeloma is part of a spectrum of CC diseases ranging from monoclonal gammopathy of unknown significance CC (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:9326949}. Note=The CC gene represented in this entry may be involved in disease pathogenesis. CC A chromosomal aberration involving IRF4 has been found in multiple CC myeloma. Translocation t(6;14)(p25;q32) with the IgH locus. CC -!- DISEASE: Immunodeficiency 131 (IMD131) [MIM:621097]: An immunologic CC disorder characterized by recurrent infections, including infections CC with opportunistic pathogens, and low IgM, IgG, and IgA serum levels, CC low plasma cell counts and abnormal T-cell subsets. IMD131 inheritance CC can be autosomal dominant or autosomal recessive. CC {ECO:0000269|PubMed:29408330, ECO:0000269|PubMed:29537367, CC ECO:0000269|PubMed:36662884, ECO:0000269|PubMed:36917008}. 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}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/231/IRF4"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U52682; AAC50779.1; -; mRNA. DR EMBL; U63738; AAB37258.1; -; mRNA. DR EMBL; AL365272; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL589962; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015752; AAH15752.1; -; mRNA. DR CCDS; CCDS4469.1; -. [Q15306-1] DR CCDS; CCDS93847.1; -. [Q15306-2] DR RefSeq; NP_001182215.1; NM_001195286.2. [Q15306-2] DR RefSeq; NP_002451.2; NM_002460.4. [Q15306-1] DR PDB; 2DLL; NMR; -; A=23-130. DR PDB; 6TD4; X-ray; 1.71 A; A=20-132. DR PDB; 7JM4; X-ray; 2.95 A; A/B/G/H=21-129. DR PDB; 7O56; X-ray; 2.60 A; A/B/C=20-139. DR PDB; 7OGS; X-ray; 2.37 A; A/B/E/F=20-139. DR PDB; 7OOT; X-ray; 2.25 A; A/B=20-139. DR PDB; 7RH2; X-ray; 2.47 A; A/B/G/H=21-129. DR PDBsum; 2DLL; -. DR PDBsum; 6TD4; -. DR PDBsum; 7JM4; -. DR PDBsum; 7O56; -. DR PDBsum; 7OGS; -. DR PDBsum; 7OOT; -. DR PDBsum; 7RH2; -. DR AlphaFoldDB; Q15306; -. DR SMR; Q15306; -. DR BioGRID; 109870; 82. DR FunCoup; Q15306; 2292. DR IntAct; Q15306; 74. DR MINT; Q15306; -. DR STRING; 9606.ENSP00000370343; -. DR GlyGen; Q15306; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15306; -. DR PhosphoSitePlus; Q15306; -. DR BioMuta; IRF4; -. DR DMDM; 2497445; -. DR MassIVE; Q15306; -. DR PaxDb; 9606-ENSP00000370343; -. DR PeptideAtlas; Q15306; -. DR ProteomicsDB; 60524; -. [Q15306-1] DR ProteomicsDB; 60525; -. [Q15306-2] DR Antibodypedia; 1057; 710 antibodies from 48 providers. DR DNASU; 3662; -. DR Ensembl; ENST00000380956.9; ENSP00000370343.4; ENSG00000137265.17. [Q15306-1] DR Ensembl; ENST00000696871.1; ENSP00000512940.1; ENSG00000137265.17. [Q15306-2] DR GeneID; 3662; -. DR KEGG; hsa:3662; -. DR MANE-Select; ENST00000380956.9; ENSP00000370343.4; NM_002460.4; NP_002451.2. DR UCSC; uc003msz.5; human. [Q15306-1] DR AGR; HGNC:6119; -. DR CIViC; 3662; 1 evidence item across 1 molecular profile. DR ClinPGx; PA29918; -. DR CTD; 3662; -. DR DisGeNET; 3662; -. DR GeneCards; IRF4; -. DR HGNC; HGNC:6119; IRF4. DR HPA; ENSG00000137265; Tissue enhanced (bone marrow, cervix, lymphoid tissue). DR MalaCards; IRF4; -. DR MIM; 254500; phenotype. DR MIM; 601900; gene. DR MIM; 611724; phenotype. DR MIM; 621097; phenotype. DR OpenTargets; ENSG00000137265; -. DR Orphanet; 3452; Whipple disease. DR VEuPathDB; HostDB:ENSG00000137265; -. DR eggNOG; ENOG502QUE4; Eukaryota. DR GeneTree; ENSGT00940000159059; -. DR InParanoid; Q15306; -. DR OMA; AKQLYYF; -. DR OrthoDB; 8537190at2759; -. DR PAN-GO; Q15306; 5 GO annotations based on evolutionary models. DR PhylomeDB; Q15306; -. DR PathwayCommons; Q15306; -. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer. DR Reactome; R-HSA-9824585; Regulation of MITF-M-dependent genes involved in pigmentation. DR SignaLink; Q15306; -. DR SIGNOR; Q15306; -. DR Agora; ENSG00000137265; -. DR BioGRID-ORCS; 3662; 39 hits in 1182 CRISPR screens. DR ChiTaRS; IRF4; human. DR EvolutionaryTrace; Q15306; -. DR GeneWiki; IRF4; -. DR GenomeRNAi; 3662; -. DR Pharos; Q15306; Tbio. DR PRO; PR:Q15306; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q15306; protein. DR Bgee; ENSG00000137265; Expressed in lymph node and 131 other cell types or tissues. DR ExpressionAtlas; Q15306; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0000786; C:nucleosome; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IMP:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB. 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; IDA:NTNU_SB. DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IEA:Ensembl. DR GO; GO:0042832; P:defense response to protozoan; ISS:UniProtKB. DR GO; GO:0002376; P:immune system process; IBA:GO_Central. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IEA:Ensembl. DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Ensembl. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:UniProtKB. DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IDA:UniProtKB. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IDA:UniProtKB. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0045622; P:regulation of T-helper cell differentiation; NAS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0042110; P:T cell activation; NAS:UniProtKB. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB. DR CDD; cd00103; IRF; 1. DR FunFam; 1.10.10.10:FF:000041; Interferon regulatory factor 4; 1. DR FunFam; 2.60.200.10:FF:000005; Interferon regulatory factor 4 deltaE6; 1. DR Gene3D; 2.60.200.10; -; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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 PANTHER; PTHR11949; INTERFERON REGULATORY FACTOR; 1. DR PANTHER; PTHR11949:SF6; INTERFERON REGULATORY FACTOR 4; 1. 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; SSF49879; SMAD/FHA domain; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS00601; IRF_1; 1. DR PROSITE; PS51507; IRF_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Chromosomal rearrangement; KW Cytoplasm; Disease variant; DNA-binding; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..451 FT /note="Interferon regulatory factor 4" FT /id="PRO_0000154556" FT DNA_BIND 21..129 FT /note="IRF tryptophan pentad repeat" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840" FT MOD_RES 447 FT /note="Phosphoserine; by ROCK2" FT /evidence="ECO:0000250|UniProtKB:Q64287" FT MOD_RES 448 FT /note="Phosphoserine; by ROCK2" FT /evidence="ECO:0000250|UniProtKB:Q64287" FT VAR_SEQ 165 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8921401" FT /id="VSP_002755" FT VARIANT 95 FT /note="T -> R (in IMD131; pathogenic; the orthologous FT mutation in knockin mice recapitulates the patient FT phenotype; affects DNA-binding transcription activator FT activity; the mutant is able to bind GATA-containing FT sequences that are not recognized by the wild type and is FT able to activate transcription from such non-canonical FT sequences; results in decreased transcription activation FT from a reporter construct containing canonical ISRE; FT increased nuclear localization; increased DNA binding)" FT /evidence="ECO:0000269|PubMed:36662884" FT /id="VAR_090448" FT VARIANT 98 FT /note="R -> W (in IMD131; likely pathogenic; loss of DNA- FT binding transcription activator activity)" FT /evidence="ECO:0000269|PubMed:29537367, FT ECO:0000269|PubMed:36917008" FT /id="VAR_090449" FT VARIANT 359 FT /note="F -> L (in IMD131; likely pathogenic; loss of DNA- FT binding transcription activator activity; no effect on FT subcellular location)" FT /evidence="ECO:0000269|PubMed:36917008" FT /id="VAR_090450" FT MUTAGEN 98..99 FT /note="RC->AA: Loss of DNA-binding transcription activator FT activity." FT /evidence="ECO:0000269|PubMed:29537367, FT ECO:0000269|PubMed:36917008" FT MUTAGEN 368 FT /note="L->P: Loss of DNA-binding transcription activator FT activity." FT /evidence="ECO:0000269|PubMed:36917008" FT CONFLICT 300 FT /note="Q -> H (in Ref. 2; AAB37258)" FT /evidence="ECO:0000305" FT CONFLICT 306 FT /note="K -> N (in Ref. 2; AAB37258)" FT /evidence="ECO:0000305" FT CONFLICT 333 FT /note="R -> T (in Ref. 2; AAB37258)" FT /evidence="ECO:0000305" FT HELIX 24..34 FT /evidence="ECO:0007829|PDB:6TD4" FT STRAND 37..39 FT /evidence="ECO:0007829|PDB:2DLL" FT STRAND 41..44 FT /evidence="ECO:0007829|PDB:6TD4" FT TURN 45..48 FT /evidence="ECO:0007829|PDB:6TD4" FT STRAND 49..53 FT /evidence="ECO:0007829|PDB:6TD4" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:7O56" FT HELIX 64..67 FT /evidence="ECO:0007829|PDB:7OOT" FT HELIX 69..77 FT /evidence="ECO:0007829|PDB:6TD4" FT TURN 83..85 FT /evidence="ECO:0007829|PDB:6TD4" FT HELIX 90..103 FT /evidence="ECO:0007829|PDB:6TD4" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:6TD4" FT HELIX 111..113 FT /evidence="ECO:0007829|PDB:6TD4" FT STRAND 117..120 FT /evidence="ECO:0007829|PDB:6TD4" FT STRAND 122..127 FT /evidence="ECO:0007829|PDB:6TD4" SQ SEQUENCE 451 AA; 51772 MW; 17CD1327C6F5BFFA CRC64; MNLEGGGRGG EFGMSAVSCG NGKLRQWLID QIDSGKYPGL VWENEEKSIF RIPWKHAGKQ DYNREEDAAL FKAWALFKGK FREGIDKPDP PTWKTRLRCA LNKSNDFEEL VERSQLDISD PYKVYRIVPE GAKKGAKQLT LEDPQMSMSH PYTMTTPYPS LPAQQVHNYM MPPLDRSWRD YVPDQPHPEI PYQCPMTFGP RGHHWQGPAC ENGCQVTGTF YACAPPESQA PGVPTEPSIR SAEALAFSDC RLHICLYYRE ILVKELTTSS PEGCRISHGH TYDASNLDQV LFPYPEDNGQ RKNIEKLLSH LERGVVLWMA PDGLYAKRLC QSRIYWDGPL ALCNDRPNKL ERDQTCKLFD TQQFLSELQA FAHHGRSLPR FQVTLCFGEE FPDPQRQRKL ITAHVEPLLA RQLYYFAQQN SGHFLRGYDL PEHISNPEDY HRSIRHSSIQ E //