CPLM-003860

Genbank Nucleotide ID

Interferon regulatory factor 1

Protein Synonyms/Alias

Homo sapiens (Human)

Position	Peptide	Type	References
50	KHGWDINKDACLFRS	ubiquitination	[1]
78	EPDPKTWKANFRCAM	ubiquitination	[1]
95	LPDIEEVKDQSRNKG	ubiquitination	[1]
117	RMLPPLTKNQRKERK	ubiquitination	[1]
275	VYGDFSCKEEPEIDS	sumoylation	[2, 3]
299	QRVFTDLKNMDATWL	sumoylation	[2, 3]
299	QRVFTDLKNMDATWL	ubiquitination	[1]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] Elevated level of SUMOylated IRF-1 in tumor cells interferes with IRF-1-mediated apoptosis.
Park J, Kim K, Lee EJ, Seo YJ, Lim SN, Park K, Rho SB, Lee SH, Lee JH.
Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17028-33. [PMID: 17942705]
[3] SUMOylated IRF-1 shows oncogenic potential by mimicking IRF-2.
Park SM, Chae M, Kim BK, Seo T, Jang IS, Choi JS, Kim IC, Lee JH, Park J.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):926-30. [PMID: 19962964]

Functional Description

Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon- stimulated response element (ISRE) in their promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti- proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.

DNA_BIND 5 113 IRF tryptophan pentad repeat.
MOD_RES 78 78 N6-acetyllysine.
CROSSLNK 275 275 Glycyl lysine isopeptide (Lys-Gly)
CROSSLNK 299 299 Glycyl lysine isopeptide (Lys-Gly)

Acetylation; Activator; Antiviral defense; Complete proteome; Cytoplasm; Disease mutation; DNA-binding; Immunity; Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription; Transcription regulation; Tumor suppressor; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL.
GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Compara.
GO:0007596; P:blood coagulation; TAS:Reactome.
GO:0043374; P:CD8-positive, alpha-beta T cell differentiation; IEA:Compara.
GO:0007050; P:cell cycle arrest; IDA:UniProtKB.
GO:0035458; P:cellular response to interferon-beta; IDA:BHF-UCL.
GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
GO:0051607; P:defense response to virus; IDA:UniProtKB.
GO:0006917; P:induction of apoptosis; IDA:UniProtKB.
GO:0060333; P:interferon-gamma-mediated signaling pathway; ISS:UniProtKB.
GO:0008285; P:negative regulation of cell proliferation; TAS:UniProtKB.
GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
GO:0045892; P:negative regulation of transcription, DNA-dependent; IMP:UniProtKB.
GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
GO:0045084; P:positive regulation of interleukin-12 biosynthetic process; IEA:Compara.
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
GO:0002819; P:regulation of adaptive immune response; TAS:UniProtKB.
GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
GO:0045088; P:regulation of innate immune response; TAS:UniProtKB.
GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; ISS:UniProtKB.
GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.

IPR017431; Interferon_reg_fac-1/2.
IPR019817; Interferon_reg_fac_CS.
IPR001346; Interferon_reg_fact_DNA-bd_dom.
IPR011991; WHTH_DNA-bd_dom.

PS00601; IRF_1
PS51507; IRF_2

PR00267; INTFRNREGFCT.