IRAK1 (interleukin 1 receptor associated kinase 1)

Gene

• Entrez ID: 3654
• Gene name: Interleukin 1 receptor associated kinase 1
• Gene symbol: IRAK1
• Synonyms: IRAK, pelle
• Chromosome: X
• Chromosome location: Xq28
• Summary: This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000712	hsa-miR-146a-5p	Western blot, Northern blot	18504431
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay, Western blot	20061417
MIRT000712	hsa-miR-146a-5p	qRT-PCR	18759964
MIRT000712	hsa-miR-146a-5p	qRT-PCR, Western blot, Immunofluorescence	19918258
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay, Microarray, Northern blot, qRT-PCR	16885212
MIRT000712	hsa-miR-146a-5p	ELISA, Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	20542134
MIRT000712	hsa-miR-146a-5p	qRT-PCR, Western blot	21178010
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay, Western blot	21632853
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay	22593544
MIRT000712	hsa-miR-146a-5p	Western blot	20110513
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay, qRT-PCR, Western blot	23680172
MIRT000712	hsa-miR-146a-5p	In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	22992343
MIRT000712	hsa-miR-146a-5p	qRT-PCR, Western blot	23018031
MIRT000712	hsa-miR-146a-5p	QRTPCR, Western blot	24867582
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay	24107356
MIRT000712	hsa-miR-146a-5p	Microarray, Western blot	23952003
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay	25623956
MIRT000712	hsa-miR-146a-5p	Luciferase reporter assay, qRT-PCR, Western blot	26151128
MIRT000712	hsa-miR-146a-5p	ELISA, Immunohistochemistry, qRT-PCR, Western blot	27636999
MIRT000712	hsa-miR-146a-5p	qRT-PCR, Western blot	25889446
MIRT000712	hsa-miR-146a-5p	ELISA, EMSA, Microarray, qRT-PCR, Western blot	27922090
MIRT000712	hsa-miR-146a-5p	qRT-PCR, Western blot	25805648
MIRT005395	hsa-miR-146b-5p	Luciferase reporter assay, Microarray, Northern blot, qRT-PCR	16885212
MIRT005395	hsa-miR-146b-5p	Luciferase reporter assay, qRT-PCR, Western blot	23680172
MIRT005395	hsa-miR-146b-5p	Luciferase reporter assay, qRT-PCR, Western blot	27533309
MIRT024479	hsa-miR-215-5p	Microarray	19074876
MIRT026216	hsa-miR-192-5p	Microarray	19074876
MIRT036505	hsa-miR-1226-3p	CLASH	23622248
MIRT037612	hsa-miR-744-5p	CLASH	23622248
MIRT038255	hsa-miR-330-5p	CLASH	23622248
MIRT038891	hsa-miR-93-3p	CLASH	23622248
MIRT041223	hsa-miR-193b-3p	CLASH	23622248
MIRT042485	hsa-miR-423-3p	CLASH	23622248
MIRT043810	hsa-miR-328-3p	CLASH	23622248
MIRT045847	hsa-miR-132-3p	CLASH	23622248
MIRT046662	hsa-miR-222-3p	CLASH	23622248
MIRT049357	hsa-miR-92a-3p	CLASH	23622248
MIRT051021	hsa-miR-17-5p	CLASH	23622248
MIRT054357	hsa-miR-21-5p	Chip, ELISA, Flow cytometry, Luciferase reporter assay, QRTPCR, Western blot	23633945
MIRT440429	hsa-miR-142-3p	HITS-CLIP	22473208
MIRT734968	hsa-miR-146b-3p	Luciferase reporter assay	25771167

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000187	Process	Activation of MAPK activity	TAS
GO:0001959	Process	Regulation of cytokine-mediated signaling pathway	IMP	10383454
GO:0002224	Process	Toll-like receptor signaling pathway	TAS
GO:0002755	Process	MyD88-dependent toll-like receptor signaling pathway	TAS	10383454
GO:0004672	Function	Protein kinase activity	IBA	21873635
GO:0004672	Function	Protein kinase activity	IDA	12054681
GO:0004672	Function	Protein kinase activity	TAS
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	11960013
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004704	Function	NF-kappaB-inducing kinase activity	TAS	8599092
GO:0005515	Function	Protein binding	IPI	10854325, 11397809, 11518704, 12242293, 12496252, 12860405, 12874243, 12925853, 16203735, 16884718, 17567694, 19081057, 19264966, 21743479, 21903422, 22037600, 28436939, 29883609
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005811	Component	Lipid droplet	ISS
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0006468	Process	Protein phosphorylation	TAS	8599092
GO:0007250	Process	Activation of NF-kappaB-inducing kinase activity	IDA	11397809
GO:0007254	Process	JNK cascade	TAS
GO:0007568	Process	Aging	IEA
GO:0010008	Component	Endosome membrane	TAS
GO:0016032	Process	Viral process	IEA
GO:0016301	Function	Kinase activity	IDA	12054681
GO:0019221	Process	Cytokine-mediated signaling pathway	IBA	21873635
GO:0031072	Function	Heat shock protein binding	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IMP	10383454
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IMP	10383454
GO:0032481	Process	Positive regulation of type I interferon production	IMP	23633945
GO:0032496	Process	Response to lipopolysaccharide	IMP	10383454
GO:0032991	Component	Protein-containing complex	IDA	10854325
GO:0034134	Process	Toll-like receptor 2 signaling pathway	IBA	21873635
GO:0034134	Process	Toll-like receptor 2 signaling pathway	IMP	10383454
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IBA	21873635
GO:0034162	Process	Toll-like receptor 9 signaling pathway	TAS
GO:0034605	Process	Cellular response to heat	IEA
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0042802	Function	Identical protein binding	IPI	11397809
GO:0042803	Function	Protein homodimerization activity	IPI	10383454
GO:0043066	Process	Negative regulation of apoptotic process	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	22158417
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	TAS
GO:0043406	Process	Positive regulation of MAP kinase activity	IBA	21873635
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0046777	Process	Protein autophosphorylation	IDA	10383454, 12054681
GO:0046982	Function	Protein heterodimerization activity	IPI	10383454
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	10383454
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	TAS
GO:0060337	Process	Type I interferon signaling pathway	IMP	23633945
GO:0070423	Process	Nucleotide-binding oligomerization domain containing signaling pathway	TAS
GO:0070498	Process	Interleukin-1-mediated signaling pathway	IBA	21873635
GO:0070498	Process	Interleukin-1-mediated signaling pathway	IMP	10383454
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0070555	Process	Response to interleukin-1	IMP	10383454
GO:0071222	Process	Cellular response to lipopolysaccharide	IBA	21873635
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IMP	25515214
GO:1904996	Process	Positive regulation of leukocyte adhesion to vascular endothelial cell	IMP	25515214

Other IDs

• MIM: 300283
• HGNC: 6112
• e!Ensembl: ENSG00000184216

Protein

• UniProt ID: P51617
• Protein name: Interleukin-1 receptor-associated kinase 1 (IRAK-1) (EC 2.7.11.1)
• Protein function: Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.
• PDB: 6BFN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00531	Death	27 → 103	Death domain	Domain
  PF00069	Pkinase	212 → 517	Protein kinase domain	Domain

• Sequence:

  MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCE
  RSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSS
  IPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTK
  PGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKR
  LKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRL
  HCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFG
  LARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAG
  QRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDP
  RPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQVYERLEKLQAVVAGVPGHSEAASCIPP
  SPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALR
  SWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQI
  IINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS

• Sequence length: 712

Pathways

KEGG:

MAPK signaling pathway
NF-kappa B signaling pathway
Toll-like receptor signaling pathway
Neurotrophin signaling pathway
Alcoholic liver disease
Pathogenic Escherichia coli infection
Salmonella infection
Pertussis
Yersinia infection
Leishmaniasis
Chagas disease
Toxoplasmosis
Tuberculosis
Hepatitis B
Measles
Herpes simplex virus 1 infection
Epstein-Barr virus infection
Human immunodeficiency virus 1 infection
Coronavirus disease - COVID-19
Lipid and atherosclerosis

Reactome:

PIP3 activates AKT signaling
MyD88:MAL(TIRAP) cascade initiated on plasma membrane
NOD1/2 Signaling Pathway
p75NTR recruits signalling complexes
NF-kB is activated and signals survival
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
activated TAK1 mediates p38 MAPK activation
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
Interleukin-1 signaling
IRAK1 recruits IKK complex
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
MyD88 dependent cascade initiated on endosome
MyD88 cascade initiated on plasma membrane

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Nephrotic syndrome	Nephrotic Syndrome	rs876657369, rs121912601, rs121912602, rs876657370, rs121912603, rs121912604, rs121912605, rs121907900, rs121907901, rs28941778, rs587776576, rs28942089, rs587776577, rs28941777, rs121907910, rs1568296260, rs119473033, rs74315342, rs74315343, rs74315345, rs74315346, rs74315347, rs74315348, rs121434394, rs267606919, rs121912488, rs267606953, rs267606954, rs267606955, rs104886210, rs1591732280, rs1591750243, rs140511594, rs140781106, rs147972030, rs587776969, rs386833863, rs386833880, rs386833882, rs386833892, rs386833895, rs386833909, rs386833911, rs386833920, rs386833935, rs386833947, rs1555763603, rs398122978, rs398122979, rs398122980, rs369573693, rs398122981, rs398122982, rs398122983, rs200482683, rs730882194, rs180177201, rs587777552, rs587777553, rs775170915, rs749740335, rs12568913, rs530318579, rs786204583, rs786204708, rs786204632, rs138656762, rs797044992, rs797044994, rs797044995, rs864321632, rs864321687, rs864321688, rs864321633, rs869025495, rs869025541, rs869312747, rs145473779, rs757674160, rs869320695, rs138909849, rs869312984, rs1057516900, rs763818901, rs199506378, rs1057517164, rs1057516523, rs1057516414, rs778055996, rs1057516395, rs1057516747, rs1057516880, rs1057516680, rs778217926, rs1057519347, rs764587648, rs1060499703, rs121907903, rs769259446, rs1131692252, rs1131692253, rs1131692254, rs1131692255, rs1131692256, rs746887949, rs1131692235, rs1135402911, rs1135402912, rs1135402913, rs1554946480, rs1555331969, rs773173317, rs1555816634, rs775006954, rs1320543506, rs534522842, rs1272948499, rs1191455921, rs1291398331, rs1554939785, rs776016942, rs1031744496, rs748812981, rs755972674, rs1553312833, rs967339926, rs1462028977, rs1212702104, rs1167223941, rs762631237, rs1553316575, rs1553315173, rs1553316648, rs1553316611, rs780761368, rs368572297, rs1568070817, rs1321552081, rs1558108130, rs1558091788, rs1565707103, rs1558355124, rs1564622701, rs1351580598, rs1589475328, rs1589413498, rs1572255744, rs1572262824, rs761410195, rs1602413491, rs1590326226, rs375998390, rs570583897, rs369363545, rs201488687, rs1334894971, rs763782471, rs138047529, rs895782232, rs1572255047, rs1589433172, rs1589509476, rs1572277600, rs1572282458, rs1584675898, rs759043857, rs1853443391
Systemic lupus erythematosus	Systemic lupus erythematosus, Pediatric systemic lupus erythematosus	rs77571059, rs10954213, rs2070197, rs72556554, rs3219018, rs121912990, rs1575496354, rs7574865, rs1307379746, rs758750492, rs1575497576
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963	23143596
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	20524934
Lung adenocarcinoma	Adenocarcinoma of lung (disorder)	rs-1, rs28934576, rs121913530, rs397516975, rs587776805, rs121913469, rs121913364, rs121913351, rs121913366, rs397516896, rs397516977, rs397516981, rs397517127, rs121913344, rs727504233, rs121913370, rs760043106, rs1057519788, rs1131692238, rs1131692237, rs1554350382
Glioblastoma	Glioblastoma Multiforme	rs121913500, rs886042842, rs1555138291, rs1558518449, rs1567176006, rs1558650888
Arthritis	Arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470
Renal insufficiency	Renal Insufficiency	rs1596536873

Unknown
Disease name	Disease term	dbSNP ID	References
Hypoxic-ischemic encephalopathy	Hypoxic-Ischemic Encephalopathy	rs-1	21925238
Alopecia	Alopecia
Anorexia	Anoxia-Ischemia, Brain, Anoxia-Ischemia, Cerebral		21925238
Anoxic-ischemic encephalopathy	Anoxic-Ischemic Encephalopathy		21925238
Cerebral hypoxia-ischemia	Cerebral Hypoxia-Ischemia		21925238
Coronary arteriosclerosis	Coronary Arteriosclerosis		20524934
Impaired cognition	Impaired cognition
Ischemic encephalopathy	Hypoxia-Ischemia, Brain		21925238
Language disorders	Language Disorders
Lupus anticoagulant	Lupus anticoagulant disorder
Lupus erythematosus	Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic		22904263, 26606652, 18050247, 19440199, 23435933, 23943494, 22654485
Lymphopenia	Lymphopenia
Microangiopathic hemolytic anemia	Microangiopathic hemolytic anemia
Myositis	Myositis
Nephritis	Nephritis
Oral ulcer	Oral Ulcer
Pericardial effusion	Pericardial effusion
Pleural effusion	Pleural effusion disorder
Psychosis	Psychotic Disorders
Raynaud phenomenon	Raynaud Phenomenon
Syndromic mental retardation, x-linked	Lubs X-linked mental retardation syndrome		28302064