Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

IRF1

contributors: mct/npt/pgu - updated : 28-03-2020

HGNC name	interferon regulatory factor 1
HGNC id	6116

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	9.18 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	role for discrete motifs in the enhancer domain of IRF1 in directing polyubiquitination and degradation

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D5S86 - D5S404 - D5S150 - D5S642 - D5S2110 - D5S2057 - CSF2 - TCF7 - D5S666 - IL4 - D5S1427 - IL5 - D5S1548 - IL13 - IRF1 - D5S1984 - (D5S1995 - IL3 IL3 - D5S396 - IGES - SMAD5 - D5S2002 - D5S2117 - D5S2056 - D5S1995 - D5S2115 - D5S458 - D5S1657 ) - IL9 - D5S393 - D5S399 - [D5S479 - SPOCK1 - D5S52 - D5S166 - D5S500 - CDC25C - D5S414 - D5S1701 - EGR1 ] - qter
Text	(CDKL3 ), see CSF1R and NETH

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001354924 9 - 3431 NP_001341853 - 284 - 2009 19129219 NM_002198 10 - 3567 NP_002189 36.4 325 - 2009 19129219 NM_001354925 8 - 3368 NP_001341854 - 263 - 2009 19129219

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive stomach       moderately Endocrine pancreas       moderately Lymphoid/Immune lymph node       moderately   spleen       moderately   tonsils       predominantly Reproductive female system ovary     moderately   female system uterus     highly Respiratory lung       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Lymphoid

cell lineage
cell lines
fluid/secretion	moderately in blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a tryptophan pentad repeat DNA-binding domain
	C-terminal 70 AAs inhibits both its degradation and polyubiquitination, whereas removal of the C-terminal 25 AAs inhibits degradation of the protein but does not prevent its ubiquitination

HOMOLOGY

interspecies	homolog to rattus Irf1 (85.2 pc)
	homolog to murine Irf1 (85.5 pc)

Homologene

FAMILY

interferon regulatory transcription factor (IRF) family

CATEGORY

immunity/defense , regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	acting as a transcriptional activator for IFNA, IFNB and IFN-stimulated genes
	being tumor suppressor transcription factor inducing apoptosis of tumorigenic cell lines
	playing a role of modulator of virus-induced signaling
	exhibiting a growth inhibitory function in coronary artery smooth muscle cells (limitation of neointimal hyperplasia)
	mediates upregulation PSMB8 by IFN-gamma and concerted expression of immunosubunits of the proteasome
	acts as a master regulator for the concerted expression of immunoproteasome components
	transcription factor that regulates the functions of type I and II interferons and plays a role in host protection
	transcription factor that regulates key processes in the immune system and in tumour suppression (F
	role for IRF1 in regulating the DNA interstrand crosslink DNA damage response
	tumour suppressor protein that is activated in response to viral infection and cell signalling activated by double stranded DNA lesions
	may play a potentially important role as a breast cancer tumor suppressor gene
	plays a critical role in eliminating TP53-damaged cells, and may play a more global role in mammary gland homeostasis
	IFNG-induced transcription factor pivotal in the regulation of infection and inflammation
	IRF1 and IRF2 may regulate the progression of pancreatic cancer by functioning as an antioncoprotein and oncoprotein, respectively
	plays a key role in the terminal effector pathways of human preterm labor
	IRF1 is one of the key transcriptional factors for the prevention of neointimal formation involving AGTR1, AGTR2
	critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation
	expression of IRF1 in adipocytes contributes to upregulation of inflammatory processes, leading to phenotypes associated with metabolic disease
	downstream target of TNF-mediated signal transduction in endothelial cells
	although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues
	IRF1 promotes DNA binding of STAT1, which can in turn participate in a positive feedback loop of JAK-STAT signaling
	XAF1 forms a positive feedback loop with IRF1 to drive apoptotic stress response and suppress tumorigenesis
	IRF1-dependent genes in neurons play a role in ischemic neuronal death
	has a protective effect on cognitive decline in a normal conditionbut not after chronic cerebral hypoperfusion treatment
	IRF1-mediated suppression of specific Endogenous retroviruses (ERVs) may contribute to the overall tumor suppressor activity of this host factor
	IRF1 is involved in the activation of TRIM14 by IFNA1

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text	negative regulation of cell cycle
	positive regulation of interleukin-12 biosynthetic process
	positive regulation of transcription from RNA polymerase II promoter

PATHWAY

metabolism

signaling

IRF1-mediated proinflammatory signaling pathway that specifically regulates LPS-mediated VCAM1 expression, independent of NFKB1

a component

INTERACTION

DNA	binding to upstream regulatory region of type I/FN and IFN inducible MHC class I genes (the interferon consensus sequence (ICS))

RNA

small molecule

protein	IRF1 and IRF9 are sequentially activated and recruited to the IL27 IFN-stimulated regulatory element site
	SMARCA4 may help IRF1 to overcome the chromatin barrier to activate TRIM22 transcription
	IRF1 cooperates with NFKB to activate optineurin promoter
	IRF1 and IRF2 could bind to IFP35 promoter and upregulate endogenous IFP35 protein level, and IRF1 activates IFP35 expression in an IFNG1-inducible manner
	SMAD7 recruits IRF1 protein on the CASP8 promoter and functions as a transcriptional coactivator
	IRF1-NOS2 axis is a crucial regulator of cardiac remodeling
	IRF1 is critical dual regulator of DIABLO mimetic-induced apoptosis and inflammatory cytokine response
	(IRF1) regulates downstream signals of tumor necrosis factor alpha (TNF)
	PPARGC1A is able to suppress the induction of IRF1 mediated by Jak/Stat signaling pathway
	interactions of IRF1, IFNB1 and IRF5 are involved in the M1 polarization of macrophages and have antitumor functions
	IRF1 is involved in the IFN-inducible expression of NMI
	IRF1 could induce STAT1 phosphorylation and in turn STAT1 activation
	XAF1 functions as a transcriptional coactivator of IRF1 to suppress tumorigenesis
	IRF1 is a transcriptional target of FOXM1c and a FOXM1c-binding site is in the IRF1 promoter region
	IRF1 and IRF2 bind to the TRIM14 promoter and activate transcription of TRIM14
	PARP1 is a crucial regulator of IRF1-mediated immune response
	IRF2 was found to be a transcriptional activator of CASP4, and in its absence, induction of IRF1 could substitute to maintain CASP4 expression
	ATG10S as a transcription factor competes with IRF1 for the same binding site to promote IFNL2 gene transcription
	IRF1 mediates the suppressive effects of MTOR inhibition on arterial endothelium

cell & other

REGULATION

induced by

viruses and IFN

repressed by

UBE2I (UBE2I functions as a transcriptional repressor of IRF1 by inducing sumoylation, and this effect may be required for the physiological activity of IRF1)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in MDS, AML, differentiated gastric adenocarcinomas (see TSG5D)

Susceptibility

putative susceptibility gene for rheumatoid arthritis and for asthma to Beh et disease with thrombotic event

Variant & Polymorphism other	frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS