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 02-OCT-2024, entry version 198.
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:18836453, PubMed:22412986, PubMed:25326418). 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:18836453,
CC PubMed:25326418). 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=6; IntAct=EBI-3931258, EBI-73886;
CC Q13568; O43765: SGTA; NbExp=3; IntAct=EBI-3931258, EBI-347996;
CC Q13568; Q13263: TRIM28; NbExp=5; IntAct=EBI-3931258, EBI-78139;
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}.
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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; 26.
DR MINT; Q13568; -.
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 jPOST; Q13568; -.
DR MassIVE; 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; 702 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; 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 Reactome; R-HSA-9860276; SLC15A4:TASL-dependent IRF5 activation.
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.
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; Proteomics identification;
KW Reference proteome; Systemic lupus erythematosus; Transcription;
KW Transcription regulation; 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
//