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Protein

Interleukin-1 receptor-associated kinase 1

Gene

IRAK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 STAT3.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei239 – 2391ATP
Active sitei340 – 3401Proton acceptorPROSITE-ProRule annotation
Binding sitei358 – 3581ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi218 – 2269ATPPROSITE-ProRule annotation
Nucleotide bindingi342 – 3454ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: MGI
  • NF-kappaB-inducing kinase activity Source: ProtInc
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • protein kinase activity Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Reactome

GO - Biological processi

  • activation of MAPK activity Source: Reactome
  • activation of NF-kappaB-inducing kinase activity Source: UniProtKB
  • aging Source: Ensembl
  • cellular response to heat Source: Ensembl
  • cellular response to hypoxia Source: Ensembl
  • innate immune response Source: Reactome
  • interleukin-1-mediated signaling pathway Source: BHF-UCL
  • JNK cascade Source: Reactome
  • lipopolysaccharide-mediated signaling pathway Source: BHF-UCL
  • MyD88-dependent toll-like receptor signaling pathway Source: BHF-UCL
  • MyD88-independent toll-like receptor signaling pathway Source: Reactome
  • negative regulation of apoptotic process Source: Reactome
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • neurotrophin TRK receptor signaling pathway Source: Reactome
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of MAP kinase activity Source: GO_Central
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein oligomerization Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • protein ubiquitination Source: GOC
  • regulation of cytokine-mediated signaling pathway Source: BHF-UCL
  • response to interleukin-1 Source: BHF-UCL
  • response to lipopolysaccharide Source: BHF-UCL
  • response to peptidoglycan Source: Ensembl
  • signal transduction Source: UniProtKB
  • stress-activated MAPK cascade Source: Reactome
  • toll-like receptor 10 signaling pathway Source: Reactome
  • toll-like receptor 2 signaling pathway Source: BHF-UCL
  • toll-like receptor 3 signaling pathway Source: Reactome
  • toll-like receptor 4 signaling pathway Source: GO_Central
  • toll-like receptor 5 signaling pathway Source: Reactome
  • toll-like receptor 9 signaling pathway Source: Reactome
  • toll-like receptor signaling pathway Source: Reactome
  • toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  • toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  • transmembrane receptor protein serine/threonine kinase signaling pathway Source: UniProtKB
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiREACT_13415. p75NTR recruits signalling complexes.
REACT_13696. NF-kB is activated and signals survival.
REACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_21399. activated TAK1 mediates p38 MAPK activation.
REACT_22442. Interleukin-1 signaling.
REACT_24918. IRAK1 recruits IKK complex.
REACT_25024. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_25120. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_25222. MyD88 dependent cascade initiated on endosome.
REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
REACT_27215. MyD88 cascade initiated on plasma membrane.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinkiP51617.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 receptor-associated kinase 1 (EC:2.7.11.1)
Short name:
IRAK-1
Gene namesi
Name:IRAK1
Synonyms:IRAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:6112. IRAK1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication
  • Lipid droplet By similarity

  • Note: Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • endosome membrane Source: Reactome
  • interleukin-1 receptor complex Source: UniProtKB
  • lipid particle Source: UniProtKB
  • nucleus Source: HPA
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lipid droplet, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi209 – 2091T → A: Completely abolishes auto-phosphorylation in the kinase domain. 1 Publication
Mutagenesisi239 – 2391K → S: Loss of kinase activity. 1 Publication
Mutagenesisi387 – 3871T → A: Loss of kinase activity. 1 Publication

Organism-specific databases

Orphaneti93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBiPA29912.

Polymorphism and mutation databases

BioMutaiIRAK1.
DMDMi8928535.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 712712Interleukin-1 receptor-associated kinase 1PRO_0000086030Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei66 – 661Phosphothreonine; by PKC/PRKCI1 Publication
Modified residuei131 – 1311Phosphoserine1 Publication
Cross-linki134 – 134Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki180 – 180Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei209 – 2091Phosphothreonine; by IRAK41 Publication
Modified residuei387 – 3871Phosphothreonine1 Publication

Post-translational modificationi

Following recruitment on the activated receptor complex, phosphorylated on Thr-209, probably by IRAK4, resulting in a conformational change of the kinase domain, allowing further phosphorylations to take place. Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity.4 Publications
Polyubiquitinated by TRAF6 after cell stimulation with IL-1-beta by PELI1, PELI2 and PELI3. Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'. Ubiquitination promotes interaction with NEMO/IKBKG. Also sumoylated; leading to nuclear translocation.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP51617.
PaxDbiP51617.
PRIDEiP51617.

PTM databases

PhosphoSiteiP51617.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.1 Publication

Gene expression databases

BgeeiP51617.
CleanExiHS_IRAK1.
ExpressionAtlasiP51617. baseline and differential.
GenevestigatoriP51617.

Organism-specific databases

HPAiCAB004461.
HPA054476.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with TOLLIP; this interaction occurs in the cytosol prior to receptor activation. Interacts with IL1RL1. Forms a complex with TRAF6, PELI1, IRAK4 and MYD88. Interaction with MYD88 recruits IRAK1 to the stimulated receptor complex. The TRAF6-PELI1-IRAK1-IRAK4-MYD88 complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Interacts with IRAK1BP1 (By similarity). Interacts (when polyubiquitinated) with IKBKG/NEMO. Interacts with RSAD2/viperin (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
IRF4Q153062EBI-358664,EBI-751345
IRF7Q929852EBI-358664,EBI-968267
MYD88Q998362EBI-358664,EBI-447677
PELI1Q96FA33EBI-358664,EBI-448369
PELI2Q9HAT83EBI-358664,EBI-448407
PIN1Q1352610EBI-358664,EBI-714158
TIRAPP587532EBI-358664,EBI-528644
TMEM173Q86WV62EBI-358664,EBI-2800345
TRAF6Q9Y4K32EBI-358664,EBI-359276
Unc93b1Q8VCW42EBI-358664,EBI-6116986From a different organism.
Zc3h12aQ5D1E73EBI-358664,EBI-5326026From a different organism.

Protein-protein interaction databases

BioGridi109863. 89 interactions.
DIPiDIP-397N.
IntActiP51617. 56 interactions.
MINTiMINT-97088.
STRINGi9606.ENSP00000358997.

Structurei

3D structure databases

ProteinModelPortaliP51617.
SMRiP51617. Positions 18-102, 184-523.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 10680DeathAdd
BLAST
Domaini212 – 521310Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni110 – 211102ProST regionAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi649 – 6557Poly-Ser
Compositional biasi688 – 6914Poly-Ser

Domaini

The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation.1 Publication

Sequence similaritiesi

Contains 1 death domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000015226.
HOVERGENiHBG052144.
InParanoidiP51617.
KOiK04730.
OMAiVYGFLPN.
PhylomeDBiP51617.
TreeFamiTF328924.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51617-1) [UniParc]FASTAAdd to basket

Also known as: a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGGPGPGEP AAPGAQHFLY EVPPWVMCRF YKVMDALEPA DWCQFAALIV
60 70 80 90 100
RDQTELRLCE RSGQRTASVL WPWINRNARV ADLVHILTHL QLLRARDIIT
110 120 130 140 150
AWHPPAPLPS PGTTAPRPSS IPAPAEAEAW SPRKLPSSAS TFLSPAFPGS
160 170 180 190 200
QTHSGPELGL VPSPASLWPP PPSPAPSSTK PGPESSVSLL QGARPFPFCW
210 220 230 240 250
PLCEISRGTH NFSEELKIGE GGFGCVYRAV MRNTVYAVKR LKENADLEWT
260 270 280 290 300
AVKQSFLTEV EQLSRFRHPN IVDFAGYCAQ NGFYCLVYGF LPNGSLEDRL
310 320 330 340 350
HCQTQACPPL SWPQRLDILL GTARAIQFLH QDSPSLIHGD IKSSNVLLDE
360 370 380 390 400
RLTPKLGDFG LARFSRFAGS SPSQSSMVAR TQTVRGTLAY LPEEYIKTGR
410 420 430 440 450
LAVDTDTFSF GVVVLETLAG QRAVKTHGAR TKYLKDLVEE EAEEAGVALR
460 470 480 490 500
STQSTLQAGL AADAWAAPIA MQIYKKHLDP RPGPCPPELG LGLGQLACCC
510 520 530 540 550
LHRRAKRRPP MTQVYERLEK LQAVVAGVPG HSEAASCIPP SPQENSYVSS
560 570 580 590 600
TGRAHSGAAP WQPLAAPSGA SAQAAEQLQR GPNQPVESDE SLGGLSAALR
610 620 630 640 650
SWHLTPSCPL DPAPLREAGC PQGDTAGESS WGSGPGSRPT AVEGLALGSS
660 670 680 690 700
ASSSSEPPQI IINPARQKMV QKLALYEDGA LDSLQLLSSS SLPGLGLEQD
710
RQGPEESDEF QS
Length:712
Mass (Da):76,537
Last modified:December 1, 2000 - v2
Checksum:iA7ADED75D3A3981D
GO
Isoform 2 (identifier: P51617-2) [UniParc]FASTAAdd to basket

Also known as: b

The sequence of this isoform differs from the canonical sequence as follows:
     513-542: Missing.

Note: Inactive.

Show »
Length:682
Mass (Da):73,421
Checksum:i687C7EB6064FA918
GO
Isoform 3 (identifier: P51617-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     45-45: F → FGGWRRAAGGREARGLLAPTPDAPRPA
     478-492: Missing.
     513-542: Missing.

Note: No experimental confirmation available.

Show »
Length:693
Mass (Da):74,560
Checksum:iD744A32E997E1246
GO
Isoform 4 (identifier: P51617-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     435-513: Missing.

Show »
Length:633
Mass (Da):68,022
Checksum:i419926E55C935F38
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti194 – 1941R → H.
Corresponds to variant rs11465830 [ dbSNP | Ensembl ].
VAR_051629
Natural varianti196 – 1961F → S.1 Publication
Corresponds to variant rs1059702 [ dbSNP | Ensembl ].
VAR_051630
Natural varianti203 – 2031C → S.
Corresponds to variant rs10127175 [ dbSNP | Ensembl ].
VAR_051631
Natural varianti398 – 3981T → M.1 Publication
Corresponds to variant rs56340948 [ dbSNP | Ensembl ].
VAR_040573
Natural varianti412 – 4121V → M in a glioblastoma multiforme sample; somatic mutation. 1 Publication
VAR_040574
Natural varianti421 – 4211Q → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication
VAR_040575
Natural varianti532 – 5321S → L.2 Publications
Corresponds to variant rs1059703 [ dbSNP | Ensembl ].
VAR_040576
Natural varianti619 – 6191G → S.1 Publication
Corresponds to variant rs34112487 [ dbSNP | Ensembl ].
VAR_040577
Natural varianti625 – 6251T → M.1 Publication
Corresponds to variant rs35638718 [ dbSNP | Ensembl ].
VAR_040578
Natural varianti638 – 6381R → W.1 Publication
Corresponds to variant rs56082801 [ dbSNP | Ensembl ].
VAR_040579
Natural varianti690 – 6901S → G in a lung adenocarcinoma sample; somatic mutation. 1 Publication
VAR_040580

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei45 – 451F → FGGWRRAAGGREARGLLAPT PDAPRPA in isoform 3. 1 PublicationVSP_011849
Alternative sequencei435 – 51379Missing in isoform 4. 2 PublicationsVSP_041950Add
BLAST
Alternative sequencei478 – 49215Missing in isoform 3. 1 PublicationVSP_011850Add
BLAST
Alternative sequencei513 – 54230Missing in isoform 2 and isoform 3. 2 PublicationsVSP_011851Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76191 mRNA. Translation: AAC41949.1.
AF030876 Genomic DNA. Translation: AAC08756.1.
AF346607 mRNA. Translation: AAK62888.1.
DQ054788 mRNA. Translation: AAY88246.1.
U52112 Genomic DNA. No translation available.
CH471172 Genomic DNA. Translation: EAW72762.1.
CH471172 Genomic DNA. Translation: EAW72763.1.
CH471172 Genomic DNA. Translation: EAW72764.1.
CH471172 Genomic DNA. Translation: EAW72765.1.
BC054000 mRNA. Translation: AAH54000.1.
BC014963 mRNA. Translation: AAH14963.1.
CCDSiCCDS14740.1. [P51617-1]
CCDS35443.1. [P51617-4]
CCDS35444.1. [P51617-2]
PIRiG02512.
RefSeqiNP_001020413.1. NM_001025242.1. [P51617-2]
NP_001020414.1. NM_001025243.1. [P51617-4]
NP_001560.2. NM_001569.3. [P51617-1]
UniGeneiHs.522819.

Genome annotation databases

EnsembliENST00000369974; ENSP00000358991; ENSG00000184216. [P51617-4]
ENST00000369980; ENSP00000358997; ENSG00000184216. [P51617-1]
ENST00000393687; ENSP00000377291; ENSG00000184216. [P51617-2]
GeneIDi3654.
KEGGihsa:3654.
UCSCiuc004fjr.1. human. [P51617-2]
uc004fjs.1. human. [P51617-1]
uc004fjt.1. human. [P51617-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76191 mRNA. Translation: AAC41949.1.
AF030876 Genomic DNA. Translation: AAC08756.1.
AF346607 mRNA. Translation: AAK62888.1.
DQ054788 mRNA. Translation: AAY88246.1.
U52112 Genomic DNA. No translation available.
CH471172 Genomic DNA. Translation: EAW72762.1.
CH471172 Genomic DNA. Translation: EAW72763.1.
CH471172 Genomic DNA. Translation: EAW72764.1.
CH471172 Genomic DNA. Translation: EAW72765.1.
BC054000 mRNA. Translation: AAH54000.1.
BC014963 mRNA. Translation: AAH14963.1.
CCDSiCCDS14740.1. [P51617-1]
CCDS35443.1. [P51617-4]
CCDS35444.1. [P51617-2]
PIRiG02512.
RefSeqiNP_001020413.1. NM_001025242.1. [P51617-2]
NP_001020414.1. NM_001025243.1. [P51617-4]
NP_001560.2. NM_001569.3. [P51617-1]
UniGeneiHs.522819.

3D structure databases

ProteinModelPortaliP51617.
SMRiP51617. Positions 18-102, 184-523.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109863. 89 interactions.
DIPiDIP-397N.
IntActiP51617. 56 interactions.
MINTiMINT-97088.
STRINGi9606.ENSP00000358997.

Chemistry

BindingDBiP51617.
ChEMBLiCHEMBL3357.
GuidetoPHARMACOLOGYi2042.

PTM databases

PhosphoSiteiP51617.

Polymorphism and mutation databases

BioMutaiIRAK1.
DMDMi8928535.

Proteomic databases

MaxQBiP51617.
PaxDbiP51617.
PRIDEiP51617.

Protocols and materials databases

DNASUi3654.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000369974; ENSP00000358991; ENSG00000184216. [P51617-4]
ENST00000369980; ENSP00000358997; ENSG00000184216. [P51617-1]
ENST00000393687; ENSP00000377291; ENSG00000184216. [P51617-2]
GeneIDi3654.
KEGGihsa:3654.
UCSCiuc004fjr.1. human. [P51617-2]
uc004fjs.1. human. [P51617-1]
uc004fjt.1. human. [P51617-4]

Organism-specific databases

CTDi3654.
GeneCardsiGC0XM153277.
H-InvDBHIX0017146.
HGNCiHGNC:6112. IRAK1.
HPAiCAB004461.
HPA054476.
MIMi300283. gene.
neXtProtiNX_P51617.
Orphaneti93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBiPA29912.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000015226.
HOVERGENiHBG052144.
InParanoidiP51617.
KOiK04730.
OMAiVYGFLPN.
PhylomeDBiP51617.
TreeFamiTF328924.

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiREACT_13415. p75NTR recruits signalling complexes.
REACT_13696. NF-kB is activated and signals survival.
REACT_21281. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_21399. activated TAK1 mediates p38 MAPK activation.
REACT_22442. Interleukin-1 signaling.
REACT_24918. IRAK1 recruits IKK complex.
REACT_25024. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_25120. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_25222. MyD88 dependent cascade initiated on endosome.
REACT_25354. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
REACT_27215. MyD88 cascade initiated on plasma membrane.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_75776. NOD1/2 Signaling Pathway.
SignaLinkiP51617.

Miscellaneous databases

GeneWikiiIRAK1.
GenomeRNAii3654.
NextBioi14289.
PROiP51617.
SOURCEiSearch...

Gene expression databases

BgeeiP51617.
CleanExiHS_IRAK1.
ExpressionAtlasiP51617. baseline and differential.
GenevestigatoriP51617.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "IRAK: a kinase associated with the interleukin-1 receptor."
    Cao Z., Henzel W.J., Gao X.
    Science 271:1128-1131(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANTS SER-196 AND LEU-532.
  2. "Comparative sequence analysis of the MECP2-locus in human and mouse reveals new transcribed regions."
    Reichwald K., Thiesen J., Wiehe T., Weitzel J., Poustka W.A., Rosenthal A., Platzer M., Stratling W.H., Kioschis P.
    Mamm. Genome 11:182-190(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
  3. "IRAK1b, a novel alternative splice variant of interleukin-1 receptor-associated kinase (IRAK), mediates interleukin-1 signaling and has prolonged stability."
    Jensen L.E., Whitehead A.S.
    J. Biol. Chem. 276:29037-29044(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION.
  4. "A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in Toll/IL-1R-induced inflammatory signaling."
    Rao N., Nguyen S., Ngo K., Fung-Leung W.P.
    Mol. Cell. Biol. 25:6521-6532(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
  5. "The DNA sequence of the human X chromosome."
    Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.
    , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
    Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
    Tissue: Placenta.
  8. "MyD88: an adapter that recruits IRAK to the IL-1 receptor complex."
    Wesche H., Henzel W.J., Shillinglaw W., Li S., Cao Z.
    Immunity 7:837-847(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MYD88.
  9. "Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1 receptor."
    Burns K., Clatworthy J., Martin L., Martinon F., Plumpton C., Maschera B., Lewis A., Ray K., Tschopp J., Volpe F.
    Nat. Cell Biol. 2:346-351(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TOLLIP.
  10. "IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase."
    Li S., Strelow A., Fontana E.J., Wesche H.
    Proc. Natl. Acad. Sci. U.S.A. 99:5567-5572(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IRAK4.
  11. "Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex."
    Jiang Z., Johnson H.J., Nie H., Qin J., Bird T.A., Li X.
    J. Biol. Chem. 278:10952-10956(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PELI1 AND TRAF6.
  12. "Characterization of Pellino2, a substrate of IRAK1 and IRAK4."
    Strelow A., Kollewe C., Wesche H.
    FEBS Lett. 547:157-161(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PELI2.
  13. "Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4."
    Burns K., Janssens S., Brissoni B., Olivos N., Beyaert R., Tschopp J.
    J. Exp. Med. 197:263-268(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY IRAK4.
  14. "Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein."
    Jensen L.E., Whitehead A.S.
    J. Immunol. 171:1500-1506(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PELI3.
  15. "Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C."
    Mamidipudi V., Lin C., Seibenhener M.L., Wooten M.W.
    J. Biol. Chem. 279:4161-4165(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT THR-66.
  16. "Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling."
    Kollewe C., Mackensen A.C., Neumann D., Knop J., Cao P., Li S., Wesche H., Martin M.U.
    J. Biol. Chem. 279:5227-5236(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-209 AND THR-387, DOMAIN, MUTAGENESIS OF THR-209 AND THR-387.
  17. "IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness."
    Qin J., Jiang Z., Qian Y., Casanova J.-L., Li X.
    J. Biol. Chem. 279:26748-26753(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF LYS-239.
  18. "IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression."
    Huang Y., Li T., Sane D.C., Li L.
    J. Biol. Chem. 279:51697-51703(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3.
  19. "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST 2 and induces T helper type 2-associated cytokines."
    Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K., Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F., Kastelein R.A.
    Immunity 23:479-490(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IL1RL1.
  20. "Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction."
    Uematsu S., Sato S., Yamamoto M., Hirotani T., Kato H., Takeshita F., Matsuda M., Coban C., Ishii K.J., Kawai T., Takeuchi O., Akira S.
    J. Exp. Med. 201:915-923(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF IRF7.
  21. "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
    Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
    Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN COMPLEX WITH IRAK4; MYD88; PELI1 AND TRAF6.
  22. "Differential regulation of interleukin-1 receptor associated kinase 1 (IRAK1) splice variants."
    Su J., Richter K., Zhang C., Gu Q., Li L.
    Mol. Immunol. 44:900-905(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION, SUBCELLULAR LOCATION.
  23. "The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1."
    Ordureau A., Smith H., Windheim M., Peggie M., Carrick E., Morrice N., Cohen P.
    Biochem. J. 409:43-52(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF PELI1.
  24. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. "Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation."
    Conze D.B., Wu C.J., Thomas J.A., Landstrom A., Ashwell J.D.
    Mol. Cell. Biol. 28:3538-3547(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION AT LYS-134 AND LYS-180 BY TRAF6, INTERACTION WITH IKBKG/NEMO.
  26. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  27. "Direct activation of protein kinases by unanchored polyubiquitin chains."
    Xia Z.-P., Sun L., Chen X., Pineda G., Jiang X., Adhikari A., Zeng W., Chen Z.J.
    Nature 461:114-119(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION.
  28. "IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal)."
    Dunne A., Carpenter S., Brikos C., Gray P., Strelow A., Wesche H., Morrice N., O'Neill L.A.
    J. Biol. Chem. 285:18276-18282(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF TIRAP.
  29. "IRAK1: a critical signaling mediator of innate immunity."
    Gottipati S., Rao N.L., Fung-Leung W.P.
    Cell. Signal. 20:269-276(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  30. "The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling."
    Moynagh P.N.
    Trends Immunol. 30:33-42(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  31. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  32. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-398; MET-412; HIS-421; LEU-532; SER-619; MET-625; TRP-638 AND GLY-690.

Entry informationi

Entry nameiIRAK1_HUMAN
AccessioniPrimary (citable) accession number: P51617
Secondary accession number(s): D3DWW3
, D3DWW4, Q7Z5V4, Q96C06, Q96RL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 1, 2000
Last modified: May 27, 2015
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.