IRF1_HUMAN
ID IRF1_HUMAN Reviewed; 325 AA.
AC P10914; Q96GG7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Interferon regulatory factor 1;
DE Short=IRF-1;
GN Name=IRF1;
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].
RX PubMed=2726461; DOI=10.1093/nar/17.8.3292;
RA Maruyama M., Fujita T., Taniguchi T.;
RT "Sequence of a cDNA coding for human IRF-1.";
RL Nucleic Acids Res. 17:3292-3292(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3409321; DOI=10.1016/s0092-8674(88)91307-4;
RA Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y.,
RA Miyata T., Taniguchi T.;
RT "Regulated expression of a gene encoding a nuclear factor, IRF-1, that
RT specifically binds to IFN-beta gene regulatory elements.";
RL Cell 54:903-913(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=1382447; DOI=10.1089/dna.1992.11.605;
RA Cha Y., Sims S.H., Romine M.F., Kaufmann M., Deisseroth A.B.;
RT "Human interferon regulatory factor 1: intron-exon organization.";
RL DNA Cell Biol. 11:605-611(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [6]
RP INVOLVEMENT IN LEUKEMIAS.
RX PubMed=8438156; DOI=10.1126/science.8438156;
RA Willman C.L., Sever C.E., Pallavicini M.G., Harada H., Tanaka N.,
RA Slovak M.L., Yamamoto H., Harada K., Meeker T.C., List A.F., Taniguchi T.;
RT "Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and
RT preleukemic myelodysplasia.";
RL Science 259:968-971(1993).
RN [7]
RP PHOSPHORYLATION.
RX PubMed=10094406; DOI=10.1023/a:1006850009017;
RA Lin R., Hiscott J.;
RT "A role for casein kinase II phosphorylation in the regulation of IRF-1
RT transcriptional activity.";
RL Mol. Cell. Biochem. 191:169-180(1999).
RN [8]
RP REVIEW ON FUNCTION.
RX PubMed=11244049; DOI=10.1146/annurev.immunol.19.1.623;
RA Taniguchi T., Ogasawara K., Takaoka A., Tanaka N.;
RT "IRF family of transcription factors as regulators of host defense.";
RL Annu. Rev. Immunol. 19:623-655(2001).
RN [9]
RP REVIEW ON FUNCTION.
RX PubMed=11846971; DOI=10.1089/107999002753452610;
RA Kroeger A., Koester M., Schroeder K., Hauser H., Mueller P.P.;
RT "Activities of IRF-1.";
RL J. Interferon Cytokine Res. 22:5-14(2002).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=11846974; DOI=10.1089/107999002753452647;
RA Romeo G., Fiorucci G., Chiantore M.V., Percario Z.A., Vannucchi S.,
RA Affabris E.;
RT "IRF-1 as a negative regulator of cell proliferation.";
RL J. Interferon Cytokine Res. 22:39-47(2002).
RN [11]
RP FUNCTION, AND INDUCTION BY IFN.
RX PubMed=15226432; DOI=10.1128/mcb.24.14.6298-6310.2004;
RA Oshima S., Nakamura T., Namiki S., Okada E., Tsuchiya K., Okamoto R.,
RA Yamazaki M., Yokota T., Aida M., Yamaguchi Y., Kanai T., Handa H.,
RA Watanabe M.;
RT "Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate
RT gene expression and production of interleukin-7 in human intestinal
RT epithelial cells.";
RL Mol. Cell. Biol. 24:6298-6310(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH EP300.
RX PubMed=15509808; DOI=10.1128/mcb.24.22.10083-10098.2004;
RA Dornan D., Eckert M., Wallace M., Shimizu H., Ramsay E., Hupp T.R.,
RA Ball K.L.;
RT "Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent
RT acetylation of p53.";
RL Mol. Cell. Biol. 24:10083-10098(2004).
RN [13]
RP REVIEW ON FUNCTION.
RX PubMed=16932750; DOI=10.1038/nri1900;
RA Honda K., Taniguchi T.;
RT "IRFs: master regulators of signalling by Toll-like receptors and cytosolic
RT pattern-recognition receptors.";
RL Nat. Rev. Immunol. 6:644-658(2006).
RN [14]
RP FUNCTION, AND INDUCTION BY IFN.
RX PubMed=17516545; DOI=10.1002/jcp.21128;
RA Su Z.Z., Sarkar D., Emdad L., Barral P.M., Fisher P.B.;
RT "Central role of interferon regulatory factor-1 (IRF-1) in controlling
RT retinoic acid inducible gene-I (RIG-I) expression.";
RL J. Cell. Physiol. 213:502-510(2007).
RN [15]
RP FUNCTION.
RX PubMed=18084608; DOI=10.1593/neo.07640;
RA Maratheftis C.I., Giannouli S., Spachidou M.P., Panayotou G.,
RA Voulgarelis M.;
RT "RNA interference of interferon regulatory factor-1 gene expression in THP-
RT 1 cell line leads to Toll-like receptor-4 overexpression/activation as well
RT as up-modulation of annexin-II.";
RL Neoplasia 9:1012-1020(2007).
RN [16]
RP SUMOYLATION AT LYS-275 AND LYS-299, UBIQUITINATION AT LYS-275 AND LYS-299,
RP FUNCTION, INDUCTION BY IFN, AND MUTAGENESIS OF LYS-275 AND LYS-299.
RX PubMed=17942705; DOI=10.1073/pnas.0609852104;
RA Park J., Kim K., Lee E.-J., Seo Y.-J., Lim S.-N., Park K., Rho S.B.,
RA Lee S.-H., Lee J.-H.;
RT "Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-
RT mediated apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:17028-17033(2007).
RN [17]
RP FUNCTION.
RX PubMed=18497060; DOI=10.1007/978-0-387-69080-3_35;
RA Bowie M.L., Ibarra C., Seewalt V.L.;
RT "IRF-1 promotes apoptosis in p53-damaged basal-type human mammary
RT epithelial cells: a model for early basal-type mammary carcinogenesis.";
RL Adv. Exp. Med. Biol. 617:367-374(2008).
RN [18]
RP FUNCTION.
RX PubMed=18641303; DOI=10.4049/jimmunol.181.3.1673;
RA Fragale A., Gabriele L., Stellacci E., Borghi P., Perrotti E., Ilari R.,
RA Lanciotti A., Remoli A.L., Venditti M., Belardelli F., Battistini A.;
RT "IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell
RT differentiation by repressing Foxp3 expression.";
RL J. Immunol. 181:1673-1682(2008).
RN [19]
RP FUNCTION, AND INDUCTION BY HIV AND IFN.
RX PubMed=19404407; DOI=10.1371/journal.pone.0005397;
RA Huang Y., Walstrom A., Zhang L., Zhao Y., Cui M., Ye L., Zheng J.C.;
RT "Type I interferons and interferon regulatory factors regulate TNF-related
RT apoptosis-inducing ligand (TRAIL) in HIV-1-infected macrophages.";
RL PLoS ONE 4:E5397-E5397(2009).
RN [20]
RP REVIEW ON FUNCTION.
RX PubMed=20049431; DOI=10.1007/s00262-009-0804-6;
RA Savitsky D., Tamura T., Yanai H., Taniguchi T.;
RT "Regulation of immunity and oncogenesis by the IRF transcription factor
RT family.";
RL Cancer Immunol. Immunother. 59:489-510(2010).
RN [21]
RP FUNCTION, AND INDUCTION BY IFN.
RX PubMed=19851330; DOI=10.1038/cdd.2009.156;
RA Gao J., Senthil M., Ren B., Yan J., Xing Q., Yu J., Zhang L., Yim J.H.;
RT "IRF-1 transcriptionally upregulates PUMA, which mediates the mitochondrial
RT apoptotic pathway in IRF-1-induced apoptosis in cancer cells.";
RL Cell Death Differ. 17:699-709(2010).
RN [22]
RP FUNCTION, AND INDUCTION BY HPV16 E5.
RX PubMed=21389130; DOI=10.1128/jvi.02114-10;
RA Muto V., Stellacci E., Lamberti A.G., Perrotti E., Carrabba A., Matera G.,
RA Sgarbanti M., Battistini A., Liberto M.C., Foca A.;
RT "Human papillomavirus type 16 E5 protein induces expression of beta
RT interferon through interferon regulatory factor 1 in human keratinocytes.";
RL J. Virol. 85:5070-5080(2011).
RN [23]
RP FUNCTION.
RX PubMed=22200613; DOI=10.1016/j.canlet.2011.12.027;
RA Armstrong M.J., Stang M.T., Liu Y., Gao J., Ren B., Zuckerbraun B.S.,
RA Mahidhara R.S., Xing Q., Pizzoferrato E., Yim J.H.;
RT "Interferon regulatory factor 1 (IRF-1) induces p21(WAF1/CIP1) dependent
RT cell cycle arrest and p21(WAF1/CIP1) independent modulation of survivin in
RT cancer cells.";
RL Cancer Lett. 319:56-65(2012).
RN [24]
RP FUNCTION, INDUCTION BY N-METHYL-N'-NITRO-N-NITROSOGUANIDINE, ACETYLATION AT
RP LYS-78, AND MUTAGENESIS OF LYS-78.
RX PubMed=22367195; DOI=10.1074/jbc.m111.313429;
RA Qi H., Zhu H., Lou M., Fan Y., Liu H., Shen J., Li Z., Lv X., Shan J.,
RA Zhu L., Chin Y.E., Shao J.;
RT "Interferon regulatory factor 1 transactivates the expression of human DNA
RT polymerase eta in response to the carcinogen N-methyl-N'-nitro-N-
RT nitrosoguanidine.";
RL J. Biol. Chem. 287:12622-12633(2012).
RN [25]
RP FUNCTION.
RX PubMed=32385160; DOI=10.1073/pnas.1921484117;
RA Somerville T.D.D., Xu Y., Wu X.S., Maia-Silva D., Hur S.K.,
RA de Almeida L.M.N., Preall J.B., Koo P.K., Vakoc C.R.;
RT "ZBED2 is an antagonist of interferon regulatory factor 1 and modifies cell
RT identity in pancreatic cancer.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:11471-11482(2020).
RN [26]
RP VARIANT GASC LEU-8, AND CHARACTERIZATION OF VARIANT GASC LEU-8.
RX PubMed=9679752;
RX DOI=10.1002/(sici)1097-0215(19980812)77:4<522::aid-ijc8>3.0.co;2-w;
RA Nozawa H., Oda E., Ueda S., Tamura G., Maesawa C., Muto T., Taniguchi T.,
RA Tanaka N.;
RT "Functionally inactivating point mutation in the tumor-suppressor IRF-1
RT gene identified in human gastric cancer.";
RL Int. J. Cancer 77:522-527(1998).
RN [27]
RP VARIANT GASC ARG-11.
RX PubMed=10395927; DOI=10.1016/s0167-4781(99)00078-0;
RA Eason D.D., Shepherd A.T., Blanck G.;
RT "Interferon regulatory factor 1 tryptophan 11 to arginine point mutation
RT abolishes DNA binding.";
RL Biochim. Biophys. Acta 1446:140-144(1999).
CC -!- FUNCTION: Transcriptional regulator which displays a remarkable
CC functional diversity in the regulation of cellular responses
CC (PubMed:15226432, PubMed:15509808, PubMed:17516545, PubMed:17942705,
CC PubMed:18497060, PubMed:19404407, PubMed:19851330, PubMed:22367195,
CC PubMed:32385160). Regulates transcription of IFN and IFN-inducible
CC genes, host response to viral and bacterial infections, regulation of
CC many genes expressed during hematopoiesis, inflammation, immune
CC responses and cell proliferation and differentiation, regulation of the
CC cell cycle and induction of growth arrest and programmed cell death
CC following DNA damage (PubMed:15226432, PubMed:15509808,
CC PubMed:17516545, PubMed:17942705, PubMed:18497060, PubMed:19404407,
CC PubMed:19851330, PubMed:22367195). Stimulates both innate and acquired
CC immune responses through the activation of specific target genes and
CC can act as a transcriptional activator and repressor regulating target
CC genes by binding to an interferon-stimulated response element (ISRE) in
CC their promoters (PubMed:15226432, PubMed:15509808, PubMed:17516545,
CC PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330,
CC PubMed:21389130, PubMed:22367195). Competes with the transcriptional
CC repressor ZBED2 for binding to a common consensus sequence in gene
CC promoters (PubMed:32385160). Its target genes for transcriptional
CC activation activity include: genes involved in anti-viral response,
CC such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, ZBP1, OAS1/2,
CC PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such
CC as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and
CC CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune
CC response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA
CC damage responses and DNA repair, such as POLQ/POLH; MHC class I
CC expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M
CC and MHC class II expression, such as CIITA; metabolic enzymes, such as
CC ACOD1/IRG1 (PubMed:15226432, PubMed:15509808, PubMed:17516545,
CC PubMed:17942705, PubMed:18497060, PubMed:19404407, PubMed:19851330,
CC PubMed:22367195). Represses genes involved in anti-proliferative
CC response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and
CC in immune response, such as FOXP3, IL4, ANXA2 and TLR4
CC (PubMed:18641303, PubMed:22200613). Stimulates p53/TP53-dependent
CC transcription through enhanced recruitment of EP300 leading to
CC increased acetylation of p53/TP53 (PubMed:15509808, PubMed:18084608).
CC Plays an important role in immune response directly affecting NK
CC maturation and activity, macrophage production of IL12, Th1 development
CC and maturation of CD8+ T-cells (PubMed:11244049, PubMed:11846971,
CC PubMed:11846974, PubMed:16932750). Also implicated in the
CC differentiation and maturation of dendritic cells and in the
CC suppression of regulatory T (Treg) cells development (PubMed:11244049,
CC PubMed:11846971, PubMed:11846974, PubMed:16932750). Acts as a tumor
CC suppressor and plays a role not only in antagonism of tumor cell growth
CC but also in stimulating an immune response against tumor cells
CC (PubMed:20049431). {ECO:0000269|PubMed:15226432,
CC ECO:0000269|PubMed:15509808, ECO:0000269|PubMed:17516545,
CC ECO:0000269|PubMed:17942705, ECO:0000269|PubMed:18084608,
CC ECO:0000269|PubMed:18497060, ECO:0000269|PubMed:18641303,
CC ECO:0000269|PubMed:19404407, ECO:0000269|PubMed:19851330,
CC ECO:0000269|PubMed:21389130, ECO:0000269|PubMed:22200613,
CC ECO:0000269|PubMed:22367195, ECO:0000269|PubMed:32385160,
CC ECO:0000303|PubMed:11244049, ECO:0000303|PubMed:11846971,
CC ECO:0000303|PubMed:11846974, ECO:0000303|PubMed:16932750,
CC ECO:0000303|PubMed:20049431}.
CC -!- ACTIVITY REGULATION: Activated by MYD88.
CC {ECO:0000250|UniProtKB:P15314}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (By similarity). Interacts
CC with EP300 (PubMed:15509808). Interacts with MYD88 (By similarity).
CC Interacts with PIAS3 (By similarity). {ECO:0000250|UniProtKB:P15314,
CC ECO:0000269|PubMed:15509808}.
CC -!- INTERACTION:
CC P10914; Q14653: IRF3; NbExp=5; IntAct=EBI-1055781, EBI-2650369;
CC P10914; Q16236: NFE2L2; NbExp=3; IntAct=EBI-1055781, EBI-2007911;
CC P10914; P63165: SUMO1; NbExp=2; IntAct=EBI-1055781, EBI-80140;
CC P10914; P03129: E7; Xeno; NbExp=3; IntAct=EBI-1055781, EBI-866453;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P15314}. Cytoplasm
CC {ECO:0000250|UniProtKB:P15314}. Note=MYD88-associated IRF1 migrates
CC into the nucleus more efficiently than non-MYD88-associated IRF1.
CC {ECO:0000250|UniProtKB:P15314}.
CC -!- INDUCTION: Induced by HPV16 E5 (PubMed:21389130). Induced by HIV
CC (PubMed:19404407). By interferon (IFN) (PubMed:15226432,
CC PubMed:17516545, PubMed:17942705, PubMed:19404407, PubMed:19851330,
CC PubMed:32385160). Induced by N-methyl-N'-nitro-N-nitrosoguanidine
CC (PubMed:22367195). {ECO:0000269|PubMed:15226432,
CC ECO:0000269|PubMed:17516545, ECO:0000269|PubMed:17942705,
CC ECO:0000269|PubMed:19404407, ECO:0000269|PubMed:19851330,
CC ECO:0000269|PubMed:21389130, ECO:0000269|PubMed:22367195,
CC ECO:0000269|PubMed:32385160}.
CC -!- PTM: Phosphorylated by CK2 and this positively regulates its activity.
CC {ECO:0000269|PubMed:10094406}.
CC -!- PTM: Sumoylation represses the transcriptional activity and displays
CC enhanced resistance to protein degradation (PubMed:17942705).
CC Sumolyated by UBE2I/UBC9 and SUMO1 (By similarity). Inactivates the
CC tumor suppressor activity (PubMed:17942705). Elevated levels in tumor
CC cells (PubMed:17942705). Major site is Lys-275 (PubMed:17942705).
CC Sumoylation is enhanced by PIAS3 (By similarity). Desumoylated by SENP1
CC in tumor cells and appears to compete with ubiquitination on C-terminal
CC sites (PubMed:17942705). {ECO:0000250|UniProtKB:P15314,
CC ECO:0000269|PubMed:17942705}.
CC -!- PTM: Ubiquitinated. Appears to compete with sumoylation on C-terminal
CC sites. {ECO:0000269|PubMed:17942705}.
CC -!- DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which
CC starts in the stomach, can spread to the esophagus or the small
CC intestine, and can extend through the stomach wall to nearby lymph
CC nodes and organs. It also can metastasize to other parts of the body.
CC The term gastric cancer or gastric carcinoma refers to adenocarcinoma
CC of the stomach that accounts for most of all gastric malignant tumors.
CC Two main histologic types are recognized, diffuse type and intestinal
CC type carcinomas. Diffuse tumors are poorly differentiated infiltrating
CC lesions, resulting in thickening of the stomach. In contrast,
CC intestinal tumors are usually exophytic, often ulcerating, and
CC associated with intestinal metaplasia of the stomach, most often
CC observed in sporadic disease. {ECO:0000269|PubMed:10395927,
CC ECO:0000269|PubMed:9679752}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Deletion or rearrangement of IRF1 are found in
CC preleukemic myelodysplastic syndrome (MDS) and acute myelogenous
CC leukemia (AML).
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="http://atlasgeneticsoncology.org/Genes/IRF1ID40990ch5q23.html";
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DR EMBL; X14454; CAA32624.1; -; mRNA.
DR EMBL; L05072; AAA36043.1; -; Genomic_DNA.
DR EMBL; BT019756; AAV38561.1; -; mRNA.
DR EMBL; BC009483; AAH09483.1; -; mRNA.
DR CCDS; CCDS4155.1; -.
DR PIR; B31595; B31595.
DR PIR; I52998; I52998.
DR RefSeq; NP_002189.1; NM_002198.2.
DR AlphaFoldDB; P10914; -.
DR SMR; P10914; -.
DR BioGRID; 109867; 67.
DR DIP; DIP-40988N; -.
DR IntAct; P10914; 32.
DR MINT; P10914; -.
DR STRING; 9606.ENSP00000245414; -.
DR iPTMnet; P10914; -.
DR PhosphoSitePlus; P10914; -.
DR BioMuta; IRF1; -.
DR DMDM; 20178295; -.
DR EPD; P10914; -.
DR jPOST; P10914; -.
DR MassIVE; P10914; -.
DR PaxDb; P10914; -.
DR PeptideAtlas; P10914; -.
DR PRIDE; P10914; -.
DR ProteomicsDB; 52676; -.
DR Antibodypedia; 3180; 494 antibodies from 37 providers.
DR DNASU; 3659; -.
DR Ensembl; ENST00000245414.9; ENSP00000245414.4; ENSG00000125347.15.
DR Ensembl; ENST00000405885.6; ENSP00000384406.1; ENSG00000125347.15.
DR GeneID; 3659; -.
DR KEGG; hsa:3659; -.
DR MANE-Select; ENST00000245414.9; ENSP00000245414.4; NM_002198.3; NP_002189.1.
DR CTD; 3659; -.
DR DisGeNET; 3659; -.
DR GeneCards; IRF1; -.
DR HGNC; HGNC:6116; IRF1.
DR HPA; ENSG00000125347; Tissue enhanced (bone).
DR MalaCards; IRF1; -.
DR MIM; 147575; gene.
DR MIM; 613659; phenotype.
DR neXtProt; NX_P10914; -.
DR OpenTargets; ENSG00000125347; -.
DR PharmGKB; PA29915; -.
DR VEuPathDB; HostDB:ENSG00000125347; -.
DR eggNOG; ENOG502QVVN; Eukaryota.
DR GeneTree; ENSGT00940000156288; -.
DR HOGENOM; CLU_056386_1_0_1; -.
DR InParanoid; P10914; -.
DR OMA; PGLVWIN; -.
DR OrthoDB; 734108at2759; -.
DR PhylomeDB; P10914; -.
DR TreeFam; TF328512; -.
DR PathwayCommons; P10914; -.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P10914; -.
DR SIGNOR; P10914; -.
DR BioGRID-ORCS; 3659; 18 hits in 1098 CRISPR screens.
DR ChiTaRS; IRF1; human.
DR GeneWiki; IRF1; -.
DR GenomeRNAi; 3659; -.
DR Pharos; P10914; Tbio.
DR PRO; PR:P10914; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P10914; protein.
DR Bgee; ENSG00000125347; Expressed in granulocyte and 180 other tissues.
DR ExpressionAtlas; P10914; baseline and differential.
DR Genevisible; P10914; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; TAS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:ARUK-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0043374; P:CD8-positive, alpha-beta T cell differentiation; IEA:Ensembl.
DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:BHF-UCL.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:UniProtKB.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0002819; P:regulation of adaptive immune response; TAS:UniProtKB.
DR GO; GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; TAS:UniProtKB.
DR GO; GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; ISS:UniProtKB.
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; IEA:Ensembl.
DR CDD; cd00103; IRF; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR019817; Interferon_reg_fac_CS.
DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR InterPro; IPR031215; IRF1.
DR InterPro; IPR017431; IRF1/IRF2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11949:SF3; PTHR11949:SF3; 1.
DR Pfam; PF00605; IRF; 1.
DR PIRSF; PIRSF038196; IFN_RF1/2; 1.
DR PRINTS; PR00267; INTFRNREGFCT.
DR SMART; SM00348; IRF; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00601; IRF_1; 1.
DR PROSITE; PS51507; IRF_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Antiviral defense; Cytoplasm; Disease variant;
KW DNA-binding; Immunity; Innate immunity; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..325
FT /note="Interferon regulatory factor 1"
FT /id="PRO_0000154545"
FT DNA_BIND 5..113
FT /note="IRF tryptophan pentad repeat"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT REGION 92..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..162
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 78
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:22367195"
FT CROSSLNK 275
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT VARIANT 8
FT /note="M -> L (in GASC; somatic mutation; produces a
FT protein with markedly reduced transcriptional activity but
FT unaltered DNA-binding activity; dbSNP:rs121912469)"
FT /evidence="ECO:0000269|PubMed:9679752"
FT /id="VAR_065134"
FT VARIANT 11
FT /note="W -> R (in GASC; the mutation abolishes DNA binding
FT and transactivating activities; dbSNP:rs121912470)"
FT /evidence="ECO:0000269|PubMed:10395927"
FT /id="VAR_065135"
FT MUTAGEN 78
FT /note="K->R: Loss of acetylation. Partial loss of DNA-
FT binding and transcriptional activity."
FT /evidence="ECO:0000269|PubMed:22367195"
FT MUTAGEN 275
FT /note="K->R: Some loss of sumoylation. Partial inhibition
FT of acetylation and activity. Abolishes sumoylation,
FT diminished ubiquitination, higher resistance to
FT degradation, and increased apoptotic activity; when
FT associated with R-299."
FT /evidence="ECO:0000269|PubMed:17942705"
FT MUTAGEN 299
FT /note="K->R: Large loss of sumoylation. Abolishes
FT sumoylation, diminished ubiquitination, higher resistance
FT to degradation, and increased apoptotic activity; when
FT associated with R-275."
FT /evidence="ECO:0000269|PubMed:17942705"
FT CONFLICT 5
FT /note="R -> W (in Ref. 1; no nucleotide entry and 2; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 34..35
FT /note="FQ -> LE (in Ref. 1; no nucleotide entry and 2; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="T -> I (in Ref. 1; no nucleotide entry and 2; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 325 AA; 36502 MW; 2E06245A212D1541 CRC64;
MPITRMRMRP WLEMQINSNQ IPGLIWINKE EMIFQIPWKH AAKHGWDINK DACLFRSWAI
HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN KGSSAVRVYR MLPPLTKNQR
KERKSKSSRD AKSKAKRKSC GDSSPDTFSD GLSSSTLPDD HSSYTVPGYM QDLEVEQALT
PALSPCAVSS TLPDWHIPVE VVPDSTSDLY NFQVSPMPST SEATTDEDEE GKLPEDIMKL
LEQSEWQPTN VDGKGYLLNE PGVQPTSVYG DFSCKEEPEI DSPGGDIGLS LQRVFTDLKN
MDATWLDSLL TPVRLPSIQA IPCAP
