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P51617 (IRAK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-1 receptor-associated kinase 1

Short name=IRAK-1
EC=2.7.11.1
Gene names
Name:IRAK1
Synonyms:IRAK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length712 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3 Ref.12 Ref.15 Ref.17 Ref.18 Ref.20 Ref.23 Ref.28

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Subunit structure

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. Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.19 Ref.21 Ref.25

Subcellular location

Cytoplasm. Nucleus. Lipid droplet By similarity. Note: Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet By similarity. Ref.22

Tissue specificity

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2. Ref.3

Domain

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. Ref.16

Post-translational modification

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. Ref.3 Ref.13 Ref.15 Ref.16

Polyubiquitinated 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. Ref.22

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.

Contains 1 death domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
   Cellular componentCytoplasm
Lipid droplet
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Magnesium
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement PubMed 10383454. Source: BHF-UCL

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

activation of NF-kappaB-inducing kinase activity

Inferred from direct assay Ref.3. Source: UniProtKB

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

interleukin-1-mediated signaling pathway

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

lipopolysaccharide-mediated signaling pathway

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

negative regulation of apoptotic process

Traceable author statement. Source: Reactome

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay PubMed 10383454. Source: BHF-UCL

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Non-traceable author statement Ref.3. Source: UniProtKB

protein autophosphorylation

Non-traceable author statement Ref.3. Source: UniProtKB

protein oligomerization

Inferred from mutant phenotype PubMed 16831874. Source: UniProtKB

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

protein ubiquitination

Traceable author statement. Source: GOC

regulation of cytokine-mediated signaling pathway

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

response to interleukin-1

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

response to lipopolysaccharide

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

response to peptidoglycan

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.9. Source: UniProtKB

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Inferred from mutant phenotype PubMed 10383454. Source: BHF-UCL

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transmembrane receptor protein serine/threonine kinase signaling pathway

Non-traceable author statement Ref.3. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

interleukin-1 receptor complex

Non-traceable author statement Ref.9. Source: UniProtKB

lipid particle

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

NF-kappaB-inducing kinase activity

Traceable author statement Ref.1. Source: ProtInc

kinase activity

Inferred from direct assay PubMed 12054681. Source: MGI

protein binding

Inferred from physical interaction Ref.3PubMed 16831874. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction PubMed 10383454. Source: BHF-UCL

protein homodimerization activity

Non-traceable author statement Ref.3. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 12054681. Source: MGI

protein serine/threonine kinase activity

Non-traceable author statement Ref.3. Source: UniProtKB

ubiquitin-protein transferase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51617-1)

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.
Isoform 2 (identifier: P51617-2)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     513-542: Missing.
Note: Inactive.
Isoform 3 (identifier: P51617-3)

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.
Isoform 4 (identifier: P51617-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 712712Interleukin-1 receptor-associated kinase 1
PRO_0000086030

Regions

Domain27 – 10680Death
Domain212 – 521310Protein kinase
Nucleotide binding218 – 2269ATP By similarity
Nucleotide binding342 – 3454ATP By similarity
Region110 – 211102ProST region
Compositional bias649 – 6557Poly-Ser
Compositional bias688 – 6914Poly-Ser

Sites

Active site3401Proton acceptor By similarity
Binding site2391ATP
Binding site3581ATP By similarity

Amino acid modifications

Modified residue661Phosphothreonine; by PKC/PRKCI Ref.15
Modified residue1311Phosphoserine Ref.24
Modified residue2091Phosphothreonine; by IRAK4 Probable
Modified residue3871Phosphothreonine Ref.16

Natural variations

Alternative sequence451F → FGGWRRAAGGREARGLLAPT PDAPRPA in isoform 3.
VSP_011849
Alternative sequence435 – 51379Missing in isoform 4.
VSP_041950
Alternative sequence478 – 49215Missing in isoform 3.
VSP_011850
Alternative sequence513 – 54230Missing in isoform 2 and isoform 3.
VSP_011851
Natural variant1941R → H.
Corresponds to variant rs11465830 [ dbSNP | Ensembl ].
VAR_051629
Natural variant1961F → S. Ref.1
Corresponds to variant rs1059702 [ dbSNP | Ensembl ].
VAR_051630
Natural variant2031C → S.
Corresponds to variant rs10127175 [ dbSNP | Ensembl ].
VAR_051631
Natural variant3981T → M. Ref.32
Corresponds to variant rs56340948 [ dbSNP | Ensembl ].
VAR_040573
Natural variant4121V → M in a glioblastoma multiforme sample; somatic mutation. Ref.32
VAR_040574
Natural variant4211Q → H in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.32
VAR_040575
Natural variant5321S → L. Ref.1 Ref.32
Corresponds to variant rs1059703 [ dbSNP | Ensembl ].
VAR_040576
Natural variant6191G → S. Ref.32
Corresponds to variant rs34112487 [ dbSNP | Ensembl ].
VAR_040577
Natural variant6251T → M. Ref.32
Corresponds to variant rs35638718 [ dbSNP | Ensembl ].
VAR_040578
Natural variant6381R → W. Ref.32
Corresponds to variant rs56082801 [ dbSNP | Ensembl ].
VAR_040579
Natural variant6901S → G in a lung adenocarcinoma sample; somatic mutation. Ref.32
VAR_040580

Experimental info

Mutagenesis2091T → A: Completely abolishes auto-phosphorylation in the kinase domain. Ref.16
Mutagenesis2391K → S: Loss of kinase activity. Ref.17
Mutagenesis3871T → A: Loss of kinase activity. Ref.16

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (a) [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: A7ADED75D3A3981D

FASTA71276,537
        10         20         30         40         50         60 
MAGGPGPGEP AAPGAQHFLY EVPPWVMCRF YKVMDALEPA DWCQFAALIV RDQTELRLCE 

        70         80         90        100        110        120 
RSGQRTASVL WPWINRNARV ADLVHILTHL QLLRARDIIT AWHPPAPLPS PGTTAPRPSS 

       130        140        150        160        170        180 
IPAPAEAEAW SPRKLPSSAS TFLSPAFPGS QTHSGPELGL VPSPASLWPP PPSPAPSSTK 

       190        200        210        220        230        240 
PGPESSVSLL QGARPFPFCW PLCEISRGTH NFSEELKIGE GGFGCVYRAV MRNTVYAVKR 

       250        260        270        280        290        300 
LKENADLEWT AVKQSFLTEV EQLSRFRHPN IVDFAGYCAQ NGFYCLVYGF LPNGSLEDRL 

       310        320        330        340        350        360 
HCQTQACPPL SWPQRLDILL GTARAIQFLH QDSPSLIHGD IKSSNVLLDE RLTPKLGDFG 

       370        380        390        400        410        420 
LARFSRFAGS SPSQSSMVAR TQTVRGTLAY LPEEYIKTGR LAVDTDTFSF GVVVLETLAG 

       430        440        450        460        470        480 
QRAVKTHGAR TKYLKDLVEE EAEEAGVALR STQSTLQAGL AADAWAAPIA MQIYKKHLDP 

       490        500        510        520        530        540 
RPGPCPPELG LGLGQLACCC LHRRAKRRPP MTQVYERLEK LQAVVAGVPG HSEAASCIPP 

       550        560        570        580        590        600 
SPQENSYVSS TGRAHSGAAP WQPLAAPSGA SAQAAEQLQR GPNQPVESDE SLGGLSAALR 

       610        620        630        640        650        660 
SWHLTPSCPL DPAPLREAGC PQGDTAGESS WGSGPGSRPT AVEGLALGSS ASSSSEPPQI 

       670        680        690        700        710 
IINPARQKMV QKLALYEDGA LDSLQLLSSS SLPGLGLEQD RQGPEESDEF QS 

« Hide

Isoform 2 (b) [UniParc].

Checksum: 687C7EB6064FA918
Show »

FASTA68273,421
Isoform 3 [UniParc].

Checksum: D744A32E997E1246
Show »

FASTA69374,560
Isoform 4 [UniParc].

Checksum: 419926E55C935F38
Show »

FASTA63368,022

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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, INTERACTION WITH IKBKG/NEMO.
[26]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS14740.1. [P51617-1]
CCDS35443.1. [P51617-4]
CCDS35444.1. [P51617-2]
PIRG02512.
RefSeqNP_001020413.1. NM_001025242.1. [P51617-2]
NP_001020414.1. NM_001025243.1. [P51617-4]
NP_001560.2. NM_001569.3. [P51617-1]
UniGeneHs.522819.

3D structure databases

ProteinModelPortalP51617.
SMRP51617. Positions 18-102, 184-523.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109863. 85 interactions.
DIPDIP-397N.
IntActP51617. 26 interactions.
MINTMINT-97088.
STRING9606.ENSP00000358997.

Chemistry

BindingDBP51617.
ChEMBLCHEMBL3357.
GuidetoPHARMACOLOGY2042.

PTM databases

PhosphoSiteP51617.

Polymorphism databases

DMDM8928535.

Proteomic databases

MaxQBP51617.
PaxDbP51617.
PRIDEP51617.

Protocols and materials databases

DNASU3654.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369974; ENSP00000358991; ENSG00000184216. [P51617-4]
ENST00000369980; ENSP00000358997; ENSG00000184216. [P51617-1]
ENST00000393682; ENSP00000377287; ENSG00000184216. [P51617-3]
ENST00000393687; ENSP00000377291; ENSG00000184216. [P51617-2]
ENST00000596145; ENSP00000470203; ENSG00000268944. [P51617-1]
ENST00000606231; ENSP00000475277; ENSG00000268944. [P51617-2]
ENST00000606709; ENSP00000476227; ENSG00000268944. [P51617-3]
ENST00000606905; ENSP00000475726; ENSG00000268944. [P51617-4]
GeneID3654.
KEGGhsa:3654.
UCSCuc004fjr.1. human. [P51617-2]
uc004fjs.1. human. [P51617-1]
uc004fjt.1. human. [P51617-4]

Organism-specific databases

CTD3654.
GeneCardsGC0XM153277.
H-InvDBHIX0017146.
HGNCHGNC:6112. IRAK1.
HPACAB004461.
HPA054476.
MIM300283. gene.
neXtProtNX_P51617.
Orphanet93552. Pediatric systemic lupus erythematosus.
536. Systemic lupus erythematosus.
PharmGKBPA29912.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000015226.
HOVERGENHBG052144.
InParanoidP51617.
KOK04730.
OMASPFCWPL.
PhylomeDBP51617.
TreeFamTF328924.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP51617.

Gene expression databases

ArrayExpressP51617.
BgeeP51617.
CleanExHS_IRAK1.
GenevestigatorP51617.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. 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]
PfamPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiIRAK1.
GenomeRNAi3654.
NextBio14289.
PROP51617.
SOURCESearch...

Entry information

Entry nameIRAK1_HUMAN
AccessionPrimary (citable) accession number: P51617
Secondary accession number(s): D3DWW3 expand/collapse secondary AC list , D3DWW4, Q7Z5V4, Q96C06, Q96RL2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 1, 2000
Last modified: July 9, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM