ID IRF5_HUMAN Reviewed; 498 AA. AC Q13568; A4D1J8; A8DUA8; A8DUA9; E7EQ16; E7EW54; Q1A7B4; Q64GA9; Q64GB1; AC Q64GB2; Q6RCM8; Q9BQF0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 24-JAN-2024, entry version 195. DE RecName: Full=Interferon regulatory factor 5 {ECO:0000303|PubMed:11303025}; DE Short=IRF-5 {ECO:0000303|PubMed:11303025}; GN Name=IRF5 {ECO:0000303|PubMed:11303025, ECO:0000312|HGNC:HGNC:6120}; 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] (ISOFORM 4), AND FUNCTION. RX PubMed=11303025; DOI=10.1074/jbc.m101216200; RA Barnes B.J., Moore P.A., Pitha P.M.; RT "Virus-specific activation of a novel interferon regulatory factor, IRF-5, RT results in the induction of distinct interferon alpha genes."; RL J. Biol. Chem. 276:23382-23390(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, SUBCELLULAR LOCATION, AND RP PHOSPHORYLATION. RX PubMed=15695821; DOI=10.1074/jbc.m412584200; RA Schoenemeyer A., Barnes B.J., Mancl M.E., Latz E., Goutagny N., Pitha P.M., RA Fitzgerald K.A., Golenbock D.T.; RT "The interferon regulatory factor, IRF5, is a central mediator of toll-like RT receptor 7 signaling."; RL J. Biol. Chem. 280:17005-17012(2005). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 5), AND ALTERNATIVE SPLICING. RX PubMed=15805103; DOI=10.1074/jbc.m500543200; RA Mancl M.E., Hu G., Sangster-Guity N., Olshalsky S.L., Hoops K., RA Fitzgerald-Bocarsly P., Pitha P.M., Pinder K., Barnes B.J.; RT "Two discrete promoters regulate the alternatively spliced human interferon RT regulatory factor-5 isoforms. Multiple isoforms with distinct cell type- RT specific expression, localization, regulation, and function."; RL J. Biol. Chem. 280:21078-21090(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6). RX PubMed=16642019; DOI=10.1038/ng1782; RA Graham R.R., Kozyrev S.V., Baechler E.C., Reddy M.V., Plenge R.M., RA Bauer J.W., Ortmann W.A., Koeuth T., Escribano M.F., RA Collaborative Groups T.A., Pons-Estel B., Petri M., Daly M., RA Gregersen P.K., Martin J., Altshuler D., Behrens T.W., RA Alarcon-Riquelme M.E.; RT "A common haplotype of interferon regulatory factor 5 (IRF5) regulates RT splicing and expression and is associated with increased risk of systemic RT lupus erythematosus."; RL Nat. Genet. 38:550-555(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Grossman A., Mittrucker H.W., Lantonio L., Mak T.W.; RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., RA Nickerson D.A.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [9] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; 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 [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 130-253 (ISOFORMS 2 AND 3). RA Kozyrev S.V., Lewen S., Linga-Reddy P.M.V., Alarcon-Riquelme M.E.; RT "Structural indel variation in IRF5 is associated with a risk haplotype and RT defines the precise IRF5 isoforms expressed in SLE."; RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases. RN [12] RP SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL. RX PubMed=12138184; DOI=10.1128/mcb.22.16.5721-5740.2002; RA Barnes B.J., Kellum M.J., Field A.E., Pitha P.M.; RT "Multiple regulatory domains of IRF-5 control activation, cellular RT localization, and induction of chemokines that mediate recruitment of T RT lymphocytes."; RL Mol. Cell. Biol. 22:5721-5740(2002). RN [13] RP INVOLVEMENT IN SUSCEPTIBILITY TO SLEB10. RX PubMed=15657875; DOI=10.1086/428480; RA Sigurdsson S., Nordmark G., Goering H.H.H., Lindroos K., Wiman A.-C., RA Sturfelt G., Joensen A., Rantapaeae-Dahlqvist S., Moeller B., Kere J., RA Koskenmies S., Widen E., Eloranta M.-L., Julkunen H., Kristjansdottir H., RA Steinsson K., Alm G., Roennblom L., Syvaenen A.-C.; RT "Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 RT genes are associated with systemic lupus erythematosus."; RL Am. J. Hum. Genet. 76:528-537(2005). RN [14] RP SUBCELLULAR LOCATION, AND NUCLEAR EXPORT SIGNAL. RX PubMed=15556946; DOI=10.1074/jbc.m408452200; RA Lin R., Yang L., Arguello M., Penafuerte C., Hiscott J.; RT "A CRM1-dependent nuclear export pathway is involved in the regulation of RT IRF-5 subcellular localization."; RL J. Biol. Chem. 280:3088-3095(2005). RN [15] RP INVOLVEMENT IN SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS. RX PubMed=17599733; DOI=10.1002/art.22704; RA Sigurdsson S., Padyukov L., Kurreeman F.A., Liljedahl U., Wiman A.C., RA Alfredsson L., Toes R., Ronnelid J., Klareskog L., Huizinga T.W., Alm G., RA Syvanen A.C., Ronnblom L.; RT "Association of a haplotype in the promoter region of the interferon RT regulatory factor 5 gene with rheumatoid arthritis."; RL Arthritis Rheum. 56:2202-2210(2007). RN [16] RP INVOLVEMENT IN SUSCEPTIBILITY TO IBD14. RX PubMed=17881657; DOI=10.1093/hmg/ddm259; RA Dideberg V., Kristjansdottir G., Milani L., Libioulle C., Sigurdsson S., RA Louis E., Wiman A.-C., Vermeire S., Rutgeerts P., Belaiche J., RA Franchimont D., Van Gossum A., Bours V., Syvaenen A.-C.; RT "An insertion-deletion polymorphism in the interferon regulatory Factor 5 RT (IRF5) gene confers risk of inflammatory bowel diseases."; RL Hum. Mol. Genet. 16:3008-3016(2007). RN [17] RP UBIQUITINATION AT LYS-411 AND LYS-412 BY TRAF6. RX PubMed=18824541; DOI=10.1128/mcb.00662-08; RA Balkhi M.Y., Fitzgerald K.A., Pitha P.M.; RT "Functional regulation of MyD88-activated interferon regulatory factor 5 by RT K63-linked polyubiquitination."; RL Mol. Cell. Biol. 28:7296-7308(2008). RN [18] RP FUNCTION, PHOSPHORYLATION AT THR-10; SER-158; SER-293; SER-301; SER-435 AND RP SER-446, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION. RX PubMed=22412986; DOI=10.1371/journal.pone.0033098; RA Chang Foreman H.C., Van Scoy S., Cheng T.F., Reich N.C.; RT "Activation of interferon regulatory factor 5 by site specific RT phosphorylation."; RL PLoS ONE 7:E33098-E33098(2012). RN [19] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, ACTIVITY REGULATION, RP PHOSPHORYLATION AT SER-446, AND MUTAGENESIS OF SER-446. RX PubMed=25326418; DOI=10.1073/pnas.1418399111; RA Lopez-Pelaez M., Lamont D.J., Peggie M., Shpiro N., Gray N.S., Cohen P.; RT "Protein kinase IKKbeta-catalyzed phosphorylation of IRF5 at Ser462 induces RT its dimerization and nuclear translocation in myeloid cells."; RL Proc. Natl. Acad. Sci. U.S.A. 111:17432-17437(2014). RN [20] RP FUNCTION, INTERACTION WITH TASL, PHOSPHORYLATION, AND ACTIVITY REGULATION. RX PubMed=32433612; DOI=10.1038/s41586-020-2282-0; RA Heinz L.X., Lee J., Kapoor U., Kartnig F., Sedlyarov V., Papakostas K., RA Cesar-Razquin A., Essletzbichler P., Goldmann U., Stefanovic A., RA Bigenzahn J.W., Scorzoni S., Pizzagalli M.D., Bensimon A., Mueller A.C., RA King F.J., Li J., Girardi E., Mbow M.L., Whitehurst C.E., Rebsamen M., RA Superti-Furga G.; RT "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9."; RL Nature 581:316-322(2020). RN [21] RP FUNCTION, AND ACTIVITY REGULATION (MICROBIAL INFECTION). RX PubMed=33440148; DOI=10.1016/j.celrep.2020.108628; RA Yin X., Riva L., Pu Y., Martin-Sancho L., Kanamune J., Yamamoto Y., RA Sakai K., Gotoh S., Miorin L., De Jesus P.D., Yang C.C., Herbert K.M., RA Yoh S., Hultquist J.F., Garcia-Sastre A., Chanda S.K.; RT "MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial RT Cells."; RL Cell Rep. 34:108628-108628(2021). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 232-477 OF MUTANT ASP-440, RP SUBUNIT, ACTIVITY REGULATION, AND PHOSPHORYLATION AT SER-435; SER-437; RP SER-440 AND SER-446. RX PubMed=18836453; DOI=10.1038/nsmb.1496; RA Chen W., Lam S.S., Srinath H., Jiang Z., Correia J.J., Schiffer C.A., RA Fitzgerald K.A., Lin K., Royer W.E. Jr.; RT "Insights into interferon regulatory factor activation from the crystal RT structure of dimeric IRF5."; RL Nat. Struct. Mol. Biol. 15:1213-1220(2008). CC -!- FUNCTION: Transcription factor that plays a critical role in innate CC immunity by activating expression of type I interferon (IFN) IFNA and CC INFB and inflammatory cytokines downstream of endolysosomal toll-like CC receptors TLR7, TLR8 and TLR9 (PubMed:11303025, PubMed:15695821, CC PubMed:22412986, PubMed:25326418, PubMed:32433612). Regulates the CC transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN- CC stimulated genes (ISG) by binding to an interferon-stimulated response CC element (ISRE) in their promoters (By similarity). Can efficiently CC activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and CC mediate their induction downstream of the TLR-activated, MyD88- CC dependent pathway (By similarity). Key transcription factor regulating CC the IFN response during SARS-CoV-2 infection (PubMed:33440148). CC {ECO:0000250|UniProtKB:P56477, ECO:0000269|PubMed:11303025, CC ECO:0000269|PubMed:15695821, ECO:0000269|PubMed:22412986, CC ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:32433612, CC ECO:0000269|PubMed:33440148}. CC -!- ACTIVITY REGULATION: Maintained as a monomer in an autoinhibited state CC (PubMed:25326418, PubMed:18836453, PubMed:22412986). Phosphorylation CC and activation follow the following steps: innate adapter protein TASL CC recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB CC (PubMed:32433612). Phosphorylated IRF5 dissociates from the adapter CC proteins, dimerizes, and then enters the nucleus to induce IFNs CC (PubMed:25326418, PubMed:32433612). {ECO:0000269|PubMed:18836453, CC ECO:0000269|PubMed:22412986, ECO:0000269|PubMed:25326418, CC ECO:0000269|PubMed:32433612}. CC -!- ACTIVITY REGULATION: (Microbial infection) Activated upon coronavirus CC SARS-CoV-2 infection. {ECO:0000269|PubMed:33440148}. CC -!- SUBUNIT: Homodimer, when phosphorylated (PubMed:25326418, CC PubMed:18836453). Interacts with TASL (via pLxIS motif); interaction CC takes place downstream of TLR7, TLR8 or TLR9, leading to its activation CC (PubMed:32433612). Interacts with MYD88 and TRAF6 (By similarity). CC {ECO:0000250|UniProtKB:P56477, ECO:0000269|PubMed:18836453, CC ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:32433612}. CC -!- INTERACTION: CC Q13568; Q92793: CREBBP; NbExp=3; IntAct=EBI-3931258, EBI-81215; CC Q13568; Q13568: IRF5; NbExp=3; IntAct=EBI-3931258, EBI-3931258; CC Q13568; Q7Z434: MAVS; NbExp=2; IntAct=EBI-3931258, EBI-995373; CC Q13568; Q04206: RELA; NbExp=4; IntAct=EBI-3931258, EBI-73886; CC Q13568; O43765: SGTA; NbExp=3; IntAct=EBI-3931258, EBI-347996; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12138184, CC ECO:0000269|PubMed:15556946, ECO:0000269|PubMed:15695821, CC ECO:0000269|PubMed:22412986, ECO:0000269|PubMed:25326418}. Nucleus CC {ECO:0000269|PubMed:12138184, ECO:0000269|PubMed:15556946, CC ECO:0000269|PubMed:15695821, ECO:0000269|PubMed:22412986, CC ECO:0000269|PubMed:25326418}. Note=Shuttles between the nucleus and the CC cytoplasm: upon activation by the TLR adapter MYD88 and subsequent CC phosphorylation, translocates to the nucleus. CC {ECO:0000269|PubMed:12138184, ECO:0000269|PubMed:15556946, CC ECO:0000269|PubMed:15695821, ECO:0000269|PubMed:22412986, CC ECO:0000269|PubMed:25326418}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q13568-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13568-2; Sequence=VSP_041375; CC Name=3; CC IsoId=Q13568-3; Sequence=VSP_043924; CC Name=4; CC IsoId=Q13568-4; Sequence=VSP_043925; CC Name=5; CC IsoId=Q13568-5; Sequence=VSP_044822; CC Name=6; CC IsoId=Q13568-6; Sequence=VSP_053330, VSP_053331; CC -!- PTM: Phosphorylation of serine and threonine residues by IKBKB in a C- CC terminal autoinhibitory region, stimulates dimerization, transport into CC the nucleus, assembly with the coactivator CBP/EP300 and initiation of CC transcription. {ECO:0000269|PubMed:15695821, CC ECO:0000269|PubMed:18836453, ECO:0000269|PubMed:22412986, CC ECO:0000269|PubMed:25326418}. CC -!- PTM: 'Lys-63'-linked polyubiquitination by TRAF6 is required for CC activation. {ECO:0000269|PubMed:18824541}. CC -!- DISEASE: Inflammatory bowel disease 14 (IBD14) [MIM:612245]: A chronic, CC relapsing inflammation of the gastrointestinal tract with a complex CC etiology. It is subdivided into Crohn disease and ulcerative colitis CC phenotypes. Crohn disease may affect any part of the gastrointestinal CC tract from the mouth to the anus, but most frequently it involves the CC terminal ileum and colon. Bowel inflammation is transmural and CC discontinuous; it may contain granulomas or be associated with CC intestinal or perianal fistulas. In contrast, in ulcerative colitis, CC the inflammation is continuous and limited to rectal and colonic CC mucosal layers; fistulas and granulomas are not observed. Both diseases CC include extraintestinal inflammation of the skin, eyes, or joints. CC {ECO:0000269|PubMed:17881657}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Systemic lupus erythematosus 10 (SLEB10) [MIM:612251]: A CC chronic, relapsing, inflammatory, and often febrile multisystemic CC disorder of connective tissue, characterized principally by involvement CC of the skin, joints, kidneys and serosal membranes. It is of unknown CC etiology, but is thought to represent a failure of the regulatory CC mechanisms of the autoimmune system. The disease is marked by a wide CC range of system dysfunctions, an elevated erythrocyte sedimentation CC rate, and the formation of LE cells in the blood or bone marrow. CC {ECO:0000269|PubMed:15657875}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory CC disease with autoimmune features and a complex genetic component. It CC primarily affects the joints and is characterized by inflammatory CC changes in the synovial membranes and articular structures, widespread CC fibrinoid degeneration of the collagen fibers in mesenchymal tissues, CC and by atrophy and rarefaction of bony structures. CC {ECO:0000269|PubMed:17599733}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE- CC ProRule:PRU00840}. 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; AY504947; AAR90326.1; -; mRNA. DR EMBL; AY504946; AAR90325.1; -; mRNA. DR EMBL; AY693665; AAU12877.1; -; mRNA. DR EMBL; AY693666; AAU12878.1; -; mRNA. DR EMBL; AY693668; AAU12880.1; -; mRNA. DR EMBL; DQ277633; ABB88960.1; -; mRNA. DR EMBL; DQ277634; ABB88961.1; -; mRNA. DR EMBL; U51127; AAA96056.1; -; mRNA. DR EMBL; EF064718; ABK41901.1; -; Genomic_DNA. DR EMBL; AC025594; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236950; EAL24107.1; -; Genomic_DNA. DR EMBL; CH236950; EAL24108.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83703.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83705.1; -; Genomic_DNA. DR EMBL; BC004201; AAH04201.1; -; mRNA. DR EMBL; BC004139; AAH04139.1; -; mRNA. DR EMBL; DQ995495; ABL96293.1; -; Genomic_DNA. DR EMBL; DQ995496; ABL96294.1; -; Genomic_DNA. DR CCDS; CCDS43645.1; -. [Q13568-2] DR CCDS; CCDS56512.1; -. [Q13568-5] DR CCDS; CCDS5808.1; -. [Q13568-1] DR PIR; G02474; G02474. DR RefSeq; NP_001092097.2; NM_001098627.3. [Q13568-1] DR RefSeq; NP_001092099.1; NM_001098629.2. [Q13568-2] DR RefSeq; NP_001092100.1; NM_001098630.2. [Q13568-1] DR RefSeq; NP_001229381.1; NM_001242452.2. [Q13568-5] DR RefSeq; NP_001334857.1; NM_001347928.1. [Q13568-2] DR RefSeq; NP_116032.1; NM_032643.4. [Q13568-1] DR RefSeq; XP_005250374.1; XM_005250317.3. DR RefSeq; XP_006716037.1; XM_006715974.2. [Q13568-2] DR RefSeq; XP_011514460.1; XM_011516158.2. [Q13568-2] DR RefSeq; XP_011514461.1; XM_011516159.2. [Q13568-2] DR RefSeq; XP_011514462.1; XM_011516160.1. [Q13568-2] DR RefSeq; XP_011514463.1; XM_011516161.1. DR RefSeq; XP_011514464.1; XM_011516162.1. DR RefSeq; XP_011514465.1; XM_011516163.2. DR RefSeq; XP_011514466.1; XM_011516164.1. DR PDB; 3DSH; X-ray; 2.00 A; A=232-477. DR PDBsum; 3DSH; -. DR AlphaFoldDB; Q13568; -. DR SMR; Q13568; -. DR BioGRID; 109871; 48. DR DIP; DIP-46348N; -. DR IntAct; Q13568; 24. DR STRING; 9606.ENSP00000418037; -. DR GlyGen; Q13568; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13568; -. DR PhosphoSitePlus; Q13568; -. DR BioMuta; IRF5; -. DR DMDM; 20178305; -. DR EPD; Q13568; -. DR jPOST; Q13568; -. DR MassIVE; Q13568; -. DR MaxQB; Q13568; -. DR PaxDb; 9606-ENSP00000349770; -. DR PeptideAtlas; Q13568; -. DR ProteomicsDB; 18776; -. DR ProteomicsDB; 59569; -. [Q13568-1] DR ProteomicsDB; 59570; -. [Q13568-2] DR ProteomicsDB; 59571; -. [Q13568-3] DR ProteomicsDB; 59572; -. [Q13568-4] DR ProteomicsDB; 61205; -. DR ABCD; Q13568; 1 sequenced antibody. DR Antibodypedia; 17820; 701 antibodies from 45 providers. DR DNASU; 3663; -. DR Ensembl; ENST00000357234.10; ENSP00000349770.5; ENSG00000128604.21. [Q13568-2] DR Ensembl; ENST00000402030.6; ENSP00000385352.2; ENSG00000128604.21. [Q13568-1] DR Ensembl; ENST00000465603.5; ENSP00000418534.1; ENSG00000128604.21. [Q13568-6] DR Ensembl; ENST00000473745.5; ENSP00000419149.1; ENSG00000128604.21. [Q13568-1] DR Ensembl; ENST00000477535.5; ENSP00000419950.1; ENSG00000128604.21. [Q13568-5] DR Ensembl; ENST00000489702.6; ENSP00000418037.2; ENSG00000128604.21. [Q13568-2] DR GeneID; 3663; -. DR KEGG; hsa:3663; -. DR MANE-Select; ENST00000357234.10; ENSP00000349770.5; NM_001098629.3; NP_001092099.1. [Q13568-2] DR UCSC; uc003vog.4; human. [Q13568-1] DR AGR; HGNC:6120; -. DR CTD; 3663; -. DR DisGeNET; 3663; -. DR GeneCards; IRF5; -. DR HGNC; HGNC:6120; IRF5. DR HPA; ENSG00000128604; Low tissue specificity. DR MalaCards; IRF5; -. DR MIM; 180300; phenotype. DR MIM; 607218; gene. DR MIM; 612245; phenotype. DR MIM; 612251; phenotype. DR neXtProt; NX_Q13568; -. DR OpenTargets; ENSG00000128604; -. DR Orphanet; 220393; Diffuse cutaneous systemic sclerosis. DR Orphanet; 220402; Limited cutaneous systemic sclerosis. DR Orphanet; 206; NON RARE IN EUROPE: Crohn disease. DR Orphanet; 771; NON RARE IN EUROPE: Ulcerative colitis. DR Orphanet; 186; Primary biliary cholangitis. DR Orphanet; 536; Systemic lupus erythematosus. DR PharmGKB; PA29919; -. DR VEuPathDB; HostDB:ENSG00000128604; -. DR eggNOG; ENOG502QSKM; Eukaryota. DR GeneTree; ENSGT00940000159926; -. DR HOGENOM; CLU_031544_0_1_1; -. DR InParanoid; Q13568; -. DR OMA; WTGPCAG; -. DR OrthoDB; 3740806at2759; -. DR PhylomeDB; Q13568; -. DR TreeFam; TF328512; -. DR PathwayCommons; Q13568; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR SignaLink; Q13568; -. DR SIGNOR; Q13568; -. DR BioGRID-ORCS; 3663; 15 hits in 1175 CRISPR screens. DR EvolutionaryTrace; Q13568; -. DR GeneWiki; IRF5; -. DR GenomeRNAi; 3663; -. DR Pharos; Q13568; Tbio. DR PRO; PR:Q13568; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q13568; Protein. DR Bgee; ENSG00000128604; Expressed in monocyte and 135 other cell types or tissues. DR ExpressionAtlas; Q13568; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IMP:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0098586; P:cellular response to virus; IDA:ARUK-UCL. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB. 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:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:BHF-UCL. DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IDA:ARUK-UCL. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IC:BHF-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IC:BHF-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IC:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0032495; P:response to muramyl dipeptide; IDA:BHF-UCL. DR GO; GO:0032494; P:response to peptidoglycan; IDA:BHF-UCL. DR CDD; cd00103; IRF; 1. DR DisProt; DP01907; -. 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 IDEAL; IID00471; -. 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:SF10; INTERFERON REGULATORY FACTOR 5; 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. DR Genevisible; Q13568; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Antiviral defense; Cytoplasm; KW DNA-binding; Immunity; Inflammatory response; Innate immunity; KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; KW Systemic lupus erythematosus; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..498 FT /note="Interferon regulatory factor 5" FT /id="PRO_0000154558" FT DNA_BIND 14..122 FT /note="IRF tryptophan pentad repeat" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840" FT REGION 121..207 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 478..498 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 12..18 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:12138184" FT MOTIF 150..160 FT /note="Nuclear export signal" FT /evidence="ECO:0000269|PubMed:15556946" FT COMPBIAS 169..206 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 10 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:22412986" FT MOD_RES 158 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000269|PubMed:22412986" FT MOD_RES 293 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000269|PubMed:22412986" FT MOD_RES 301 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:22412986" FT MOD_RES 431 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P56477" FT MOD_RES 435 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18836453, FT ECO:0000269|PubMed:22412986" FT MOD_RES 437 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18836453" FT MOD_RES 440 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18836453" FT MOD_RES 446 FT /note="Phosphoserine; by IKKB" FT /evidence="ECO:0000269|PubMed:18836453, FT ECO:0000269|PubMed:22412986, ECO:0000269|PubMed:25326418" FT CROSSLNK 411 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18824541" FT CROSSLNK 412 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18824541" FT VAR_SEQ 120..147 FT /note="VCSNGPAPTDSQPPEDYSFGAGEEEEEE -> TPSPLRITLLVQERRRKKRK FT SCRGCCQA (in isoform 6)" FT /evidence="ECO:0000303|PubMed:16642019" FT /id="VSP_053330" FT VAR_SEQ 148..498 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:16642019" FT /id="VSP_053331" FT VAR_SEQ 160 FT /note="T -> TDAVQSGPHMTPYSLLK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15805103, ECO:0000303|Ref.11" FT /id="VSP_041375" FT VAR_SEQ 161..247 FT /note="EDVKWPPTLQPPTLRPPTLQPPTLQPPVVLGPPAPDPSPLAPPPGNPAGFRE FT LLSEVLEPGPLPASLPPAGEQLLPDLLISPHMLPL -> V (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15805103" FT /id="VSP_044822" FT VAR_SEQ 161..175 FT /note="EDVKWPPTLQPPTLR -> DAVQSGPHMTPYSLLKEDVKW (in isoform FT 3)" FT /evidence="ECO:0000303|Ref.11, ECO:0000303|Ref.5" FT /id="VSP_043924" FT VAR_SEQ 166..175 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11303025, FT ECO:0000303|PubMed:15695821, ECO:0000303|PubMed:16642019" FT /id="VSP_043925" FT MUTAGEN 446 FT /note="S->A: Abolished nuclear translocation." FT /evidence="ECO:0000269|PubMed:25326418" FT CONFLICT 253 FT /note="K -> KK (in Ref. 3; AAU12880)" FT /evidence="ECO:0000305" FT HELIX 235..239 FT /evidence="ECO:0007829|PDB:3DSH" FT TURN 242..244 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 250..256 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 262..266 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 272..275 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 283..285 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 286..289 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 294..298 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 308..318 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 325..330 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 333..338 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 344..348 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 367..371 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 372..383 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 395..401 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 409..411 FT /evidence="ECO:0007829|PDB:3DSH" FT STRAND 413..420 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 421..431 FT /evidence="ECO:0007829|PDB:3DSH" FT HELIX 450..465 FT /evidence="ECO:0007829|PDB:3DSH" SQ SEQUENCE 498 AA; 56044 MW; 01B2ED95C28384E8 CRC64; MNQSIPVAPT PPRRVRLKPW LVAQVNSCQY PGLQWVNGEK KLFCIPWRHA TRHGPSQDGD NTIFKAWAKE TGKYTEGVDE ADPAKWKANL RCALNKSRDF RLIYDGPRDM PPQPYKIYEV CSNGPAPTDS QPPEDYSFGA GEEEEEEEEL QRMLPSLSLT EDVKWPPTLQ PPTLRPPTLQ PPTLQPPVVL GPPAPDPSPL APPPGNPAGF RELLSEVLEP GPLPASLPPA GEQLLPDLLI SPHMLPLTDL EIKFQYRGRP PRALTISNPH GCRLFYSQLE ATQEQVELFG PISLEQVRFP SPEDIPSDKQ RFYTNQLLDV LDRGLILQLQ GQDLYAIRLC QCKVFWSGPC ASAHDSCPNP IQREVKTKLF SLEHFLNELI LFQKGQTNTP PPFEIFFCFG EEWPDRKPRE KKLITVQVVP VAARLLLEMF SGELSWSADS IRLQISNPDL KDRMVEQFKE LHHIWQSQQR LQPVAQAPPG AGLGVGQGPW PMHPAGMQ //