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FLASH GENE

Symbol

IRF4

contributors: mct - updated : 17-12-2014

HGNC name	interferon regulatory factor 4
HGNC id	6119

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	6p25.3      Physical location : 391.738 - 411.442
Synonym name	multiple myeloma oncogene 1
	lymphocyte-specific interferon regulatory factor
Synonym symbol(s)	LSIRF, MUM1

DNA

TYPE	functioning gene
STRUCTURE	19.69 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	mutations in the distal and proximal sites of the GC-rich sequence resulted in 62 and 81% reductions in the IRF4 promoter activity, respectively

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002460 9 - 5314 NP_002451 - 451 - 1999 10453013 NM_001195286 9 - 5329 NP_001182215 - 450 - -

EXPRESSION

Type	restricted

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   tonsils       highly Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal DNA-binding domain that recognizes GAAAnnGAAA motifs, but IRF4 only weakly binds DNA due to its C-terminal auto-inhibitory domain
	a IRF association domain, essential for its tumor suppressor function (IAD), with a nuclear localization signal

HOMOLOGY

Homologene

FAMILY

growing family of IRF proteins

CATEGORY

regulatory , transcription factor , protooncogene , signaling cytokine

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,chromatin/chromosome,nucleosome
text	localizes in both the nucleus and the cytoplasm (PMID;

basic FUNCTION	controlling the B-cell proliferation and differentiation and proliferation of mitogen-activated T cells
	with IRF8 are dichotomous regulators of transcription in macrophages
	lymphoid-specific transcription factor that plays crucial roles in the development and the functions of immune cells
	IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation
	suppresses BCL6 transcription and regulates receptor editing, Ig class switching, and plasma cell differentiation
	essential for the development of T helper 2 (Th2) and Th17 cells
	central function in the development of Th9 cells (contribution of this T helper cell subset to the pathogenesis of asthma)
	central regulator of T helper 2 (Th2) immune responses, and also has a major impact on innate immune cells
	having a non-redundant role in shaping the phenotype of alternatively primed macrophages
	PRDM1 and IRF4 jointly control the differentiation and function of effector regulatory T cells
	functions as a tumor suppressor in the myeloid lineage and in early stages of B cell development
	acts as an oncogene primarily through its transcription-regulation function
	is a pleiotropic IRF family transcription factor with broad immunological actions
	IRF4 was essential for the SMAD2/3-mediated IL9 promoter activation

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

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding to interferon stimulated response element (ISRE)

RNA

small molecule

protein	regulates IL10 gene expression in CD4(+) T cells through differential nuclear translocation
	IRF4 activates IL2 and IL4 promoters in cooperation with REL
	suppresses BCR/ABL transformation by a novel cytoplasmic function involving its IAD domain
	can signal via complexes containing ETS or AP1 motifs depending on the cellular context, thus indicating new approaches for modulating IRF4-dependent transcription
	is transiently up-regulated during thymic development as cells undergo positive selection and ITK is required for optimal IRF4 expression
	required to suppress EOMES expression following CD8+ T-Cell activation

cell & other

REGULATION

induced by

ESR1 (Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4)

Other

post translationally regulated by FKBP4

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   translocation     deregulated in multiple myeloma with translocation t(6;14)(p25;q32), in B cell non Hodkin lymphoma and diffuse large B cell lymphoma tumoral     --low   in HTLV.1 induced adult T cell leukemia phenotype tumoral     --over   in B-cell chronic lymphocytic leukemia with unfavorable prognostic tumoral     --low   promoter methylation is a putative mechanism of down-regulated IRF4 expression in leukemia tumoral somatic mutation       recurrent heterozygous somatic mutation in the DNA-binding domain of IRF4 in chronic lymphocytic leukemia with a good prognosis constitutional     --over   of IRF4 expression in T cells requires the Tec family tyrosine kinase, ITK, and in turn, IRF4 suppresses the up-regulation of EOMES, following TCR stimulation ( :

Susceptibility

to facial pigmented spots during aging

Variant & Polymorphism other	variants in IRF4, notably rs12203592, are associated with eye color, hair color, skin color, and freckling, and association of the rs12203592*C allele with melanoma on the trunk in case-control sets from Australia, the UK, and Sweden
	genetic variations in IRF4, contribute to the acquired amount of facial pigmented spots during aging, through pathways independent of the basal melanin production

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   attractive target for the therapy of chronic intestinal inflammation (blocking IRF4 might be an interesting option to modulate inflammation in the advanced state of inflammation)

ANIMAL & CELL MODELS