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FLASH GENE

Symbol

IRAK1

contributors: mct/ - updated : 13-07-2018

HGNC name	interleukin-1 receptor-associated kinase 1
HGNC id	6112

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	Xq28      Physical location : 153.275.956 - 153.285.342
Synonym name	Pelle (Drosophila) homolog
Synonym symbol(s)	IRAK, PELLE, IRA1
EC.number	2.7.11.1

DNA

TYPE	functioning gene
STRUCTURE	9.39 kb     14 Exon(s)

10 Kb 5' upstream gene genomic sequence study

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_001569 14 splicing 3589 NP_001560 76.4 712 - 2007 16690127 NM_001025242 14 splicing 3499 NP_001020413 73.3 682 widely 2007 16690127 lacking an in-frame segment in the CDS compared to variant 1 NM_001025243 13 splicing 3352 NP_001020414 67 633 - 2007 16690127 lacking an in-frame exon compared to variant 1

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 Digestive intestine large intestine colon   highly   salivary gland       moderately   stomach       moderately Endocrine pancreas       highly Reproductive female system uterus cervix   predominantly   female system placenta     moderately   female system breast mammary gland   moderately   female system ovary     moderately   male system prostate     moderately Respiratory lung       moderately Skin/Tegument skin       highly Urinary kidney       moderately Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Connective bone     moderately Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular       moderately

cell lineage
cell lines
fluid/secretion	moderately in lymph

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

an N terminal death domain including a threonine residue (Thr66) critical for dimerization and function

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to rattus Irak1 (81 pc)
	homolog to murine Irak1 (80.8 pc)

Homologene

FAMILY	protein kinase superfamily
	Ser/Thr family of protein kinase
	PELLE subfamily

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic

basic FUNCTION	acting as a serine/threonine kinase involved in the IL1 pathway, partially involved in IL1-induced upregulation of the transcription factor NF-kappa B
	playing an essential role in the activation of NFKB and JNK in response to IL18
	its activation is a key event in the transmission of signals from Toll-like receptors (TLRs)
	initiate a cascade of signaling events eventually leading to induction of inflammatory target gene expression
	serine/threonine protein kinase involved in the signaling cascade of the Toll/IL-1 receptor (TIR) family
	being an essential regulator for lipopolysaccharide-induced interleukin-10 gene expression
	pivotal regulator of the NFKB pathway
	having a kinase activity redundant with that of IRAK4
	MYD88 and the associated kinases IRAK1 and IRAK4 are essential for activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) survival
	MYD88 and IRAK1 are required to maintain the viability of ABC DLBCL cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

signal transduction

bacterial LPS proapoptotic complex pathways diverging downstream IRAK1 towards to NF-kappa BL activation or apoptosis

a component	forming a complex with IL1R1 after induction by IL1 through its association with IL1RAP
	subsequently interacting with TRAF6 required for IL-1 mediated NFKB activation (see symbols)

INTERACTION

DNA

RNA

small molecule	cofactor, nucleotide,
	Mg2+
	ATP

protein	MYD88, TRAF6, IKK complex (to mediating IL1 beta signal transduction)
	binding to the IL-1 type I receptor following IL-1 engagement
	activating PELI1, PELI2, PELI3
	TIRAP is a substrate for IRAK1 and IRAK4 and is likely an important control mechanism in TLR2 and TLR4 signal transduction
	IRAK1 catalytic activity is not triggered by a covalent modification but by an allosteric mechanism induced by its interaction with IRAK4

cell & other

REGULATION

inhibited by

IRAK4 (induce the degradation of IRAK1 in a proteosome-independent manner)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   aberrantly expressed in the nucleus of the peripheral blood mononuclear cells from atherosclerosis patients

Susceptibility

to systemic lupus erythematosus

Variant & Polymorphism other	4 SNP haplotype (GGGG) being strongly associated with systemic lupus erythematosus, raising the possibility that the gender difference in SLE may in part be attributed to sex chromosome genes

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS