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FLASH GENE

Symbol

IRF5

contributors: SGE/npt - updated : 13-07-2018

HGNC name	interferon regulatory factor 5
HGNC id	6120

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	7q32.1      Physical location : 128.577.993 - 128.590.086
Synonym symbol(s)	IBD14, SLEB10

DNA

TYPE	functioning gene
STRUCTURE	13.01 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

regionally located

mapped in a region containing a cluster of imprinted genes

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant 1 - splicing 2870 isoform 1 56.7 504 - 2014 25084355 exon 1A containing an additional 48 nt region in the CDS lacking a 30 nt region in the CDS NM_032643 9 splicing 2771 NP_116032 56 498 - 2014 25084355 also called variant 2 using an alternative exon for the 5' UTR, exon 1B lacking a 48 nt region in the CDS containing an additional 30 nt region in the CDS variant 4 - - 2126 isoform 4 - - plasmacytoid dendritic cells 2014 25084355 exon 1A NM_001098629 9 - 2910 NP_001092099 - 514 peripheral blood mononuclear cells 2014 25084355 also called variant 5 exon 1A NM_001098630 9 - 2852 NP_001092100 - 498 - 2014 25084355 also called variant 6 exon 1A variant 7 - - 1217 isoform 7 - 389 peripheral blood mononuclear cells 2014 25084355 exon 1A variant 8 - - 1377 isoform 8 - 413 only in cancers 2014 25084355 exon 1A varaint 9 - - - - 157 only in cancer 2014 25084355 exon 1B NM_001098628 9 - 3031 NP_001334857 - 514 - 2014 25084355 NM_001242452 8 - 2604 NP_001229381 - 412 - 2014 25084355 NM_001098627 9 - 2955 NP_001092097 - 498 - 2014 25084355 NM_001364314 9 - 2937 NP_001351243 - 514 - 2014 25084355

EXPRESSION

Type

widely

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 Lymphoid/Immune lymph node       highly   spleen       highly   thymus       highly Nervous brain         Respiratory lung         Urinary kidney       highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Homo sapiens Blood/Hematopoietic neutrophil Homo sapiens Lymphoid/Immune B cell Homo sapiens Lymphoid/Immune dendritic cell Homo sapiens Lymphoid/Immune macrophage Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a conserved N-terminal DNA-binding domain
	a PESTv domain
	a protein interaction/transactivation domain
	tryptophan (W) repeats

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	ortholog to murine Irf5
	homolog to C.elegans Y87G2A.7

Homologene

FAMILY

interferon regulatory factor (IRF) family

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	nuclear translocation resulting of TLR activation

basic FUNCTION	stimulating transcription of numerous inflammatory proteins in a virus-specific manner
	involved downstream of the TLR-MYD88 signaling pathway for gene induction of proinflammatory cytokines
	having a role in the response to kinases involved in viral infections or in Toll-like-receptor (TLR) signaling
	acting as repressor or activator of type I interferon genes, but also as inducer of pro-inflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumor-necrosis factor-alpha
	playing a general role in autoimmune diseases
	involved in the innate immune response to pathogens (hu 2009)
	critical regulator of DNA damage-induced apoptosis (Hu 2009)
	promoting apoptosis upon signaling through TRAIL death receptors (Hu 2009)
	required for B-cell maturation and expression of PRDM1 a hallmark of plasma cells (Lien 2010)
	having a key role in the induction of the antiviral and inflammatory response (Lien 2010)
	critical specificity-determining residue that inhibits IRF5 binding to the interferon-stimulated response element (ISRE)-variants present in the IFN gene promoters
	IRF5 is an important tumor suppressor that regulates multiple cellular processes involved in the conversion of normal mammary epithelial cells to tumor epithelial cells with metastatic potential
	IRF5-IKZF1 axis is a critical modulator of IgG2a/c class switching
	roles of IRF5 in autoimmune lupus
	is a specific marker of inflammatory macrophages
	likely a central role for IRF5 in the regulation of the immune response
	is essential for the induction of inflammatory cytokines
	new function for IRF5 in controlling the relative mass of different adipose tissue depots and thus insulin sensitivity in obesity
	IRF5 and IRF8, two transcription factors with opposing functions, control TLR9 signaling in human plasmacytoid dendritic cells (pDCs)
	is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection
	IRF5-expressing macrophages are a key component of the immune defense of the airways

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

heterodimerizing with IRF3

INTERACTION

DNA

binding

RNA

small molecule

protein	MYD88
	TRAF6
	interacting with CHUK (CHUK and alkaline phosphatase are negative regulators of IRF5 activity in MYD88 pathway and have role in the control of the inflammatory response by attenuation of IRF5 activity)
	is a transcription factor activated by toll like receptor TLR7 and TLR9 during innate immune responses
	TRIM28 is a novel protein-protein interaction partner of IRF5, and is an inhibitor of IRF5 function in inflammatory macrophages
	IRF5 is degraded following TLR7 activation and TRIM21 is involved in this process
	IKBKB activates two "master" transcription factors of the innate immune system, IRF5 and NFKB1
	IKBKB is an IRF5 kinase that instigates inflammation
	IRF8 inhibits TLR9-dependent gene expression by directly blocking the activity of IRF5
	interactions of IRF1, IFNB1 and IRF5 are involved in the M1 polarization of macrophages and have antitumor functions
	SP1 transcription factor is the primary determinant for activating the basal transcription of the IRF5
	IRF5 targeted the expression of vascular cell adhesion molecule 1 (VCAM1) at the transcriptional level by binding to its promoter
	IRAK4 kinase activity controls the activation of IRF5, a transcription factor implicated in the pathogenesis of multiple autoimmune diseases
	IKBKB, an upstream IRF5 activator, is phosphorylated in response to the agonist-induced TLR signaling
	IRAK4 activity regulates MAP3K7 and IKBKB activation, leading to the nuclear translocation of IRF5 and induction of inflammatory cytokines in human monocytes

cell & other

REGULATION

activated by	the MyD88 signaling pathway (Lien 2010)
	TRAF6
	phosphorylation (due to a signaling cascade induced by TRAIL), resulting in transcativation of key death receptor signaling components (Hu 2009)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in peripheral blood mononuclear cells from SLE patients carrying the risk allele of the CGGGG indel

Susceptibility

to lupus erythematosus to inflammatory bowel diseases to primary biliary cirrhosis to Systemic sclerosis (SSc)

Variant & Polymorphism SNP , repeat , other	IRF5 exon 1B isoforms strongly linked to elevated expression of IRF5 and to risk of lupus erythematosus
	exceptionally strong association signal for a 5 bp insertion
	deletion polymorphism (CGGGG indel) in the promoter region in inflammatory bowel diseases patients
	polymorphisms in the IRF5 gene are associated with a predisposition to autoimmune diseases (Lien 2010)
	rs10488631 at the locus IRF5-TNPO3, strongly assocated to primary biliary cirrhosis
	polymorphisms of IRF5 may play an important role in susceptibility to SSc

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury

ANIMAL & CELL MODELS

	Irf5&
	8722;/&
	8722; mice show higher susceptibility to viral infection and decreased serum levels of type I IFN and the inflammatory cytokines IL-6 and TNF-alpha (Lien 2010)
	mice lacking Irf5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1