true1996-10-012024-01-24228IRAK1_HUMANIRAK: a kinase associated with the interleukin-1 receptor.Cao Z.Henzel W.J.Gao X.doi:10.1126/science.271.5252.11281996Science2711128-1131NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)PARTIAL PROTEIN SEQUENCEVARIANTS SER-196 AND LEU-532Comparative 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.doi:10.1007/s0033500100352000Mamm. Genome11182-190NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)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.doi:10.1074/jbc.m1038152002001J. Biol. Chem.27629037-29044NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)FUNCTIONTISSUE SPECIFICITYPHOSPHORYLATIONA 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.doi:10.1128/mcb.25.15.6521-6532.20052005Mol. Cell. Biol.256521-6532NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)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.doi:10.1038/nature034402005Nature434325-337NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]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.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.2005-09EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4)PlacentaMyD88: an adapter that recruits IRAK to the IL-1 receptor complex.Wesche H.Henzel W.J.Shillinglaw W.Li S.Cao Z.doi:10.1016/s1074-7613(00)80402-11997Immunity7837-847INTERACTION WITH MYD88Tollip, 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.doi:10.1038/350140382000Nat. Cell Biol.2346-351INTERACTION WITH TOLLIPIRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase.Li S.Strelow A.Fontana E.J.Wesche H.doi:10.1073/pnas.0821003992002Proc. Natl. Acad. Sci. U.S.A.995567-5572INTERACTION WITH IRAK4Pellino 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.doi:10.1074/jbc.m2121122002003J. Biol. Chem.27810952-10956INTERACTION WITH PELI1 AND TRAF6Characterization of Pellino2, a substrate of IRAK1 and IRAK4.Strelow A.Kollewe C.Wesche H.doi:10.1016/s0014-5793(03)00697-52003FEBS Lett.547157-161FUNCTION IN PHOSPHORYLATION OF PELI2Inhibition 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.doi:10.1084/jem.200217902003J. Exp. Med.197263-268PHOSPHORYLATION BY IRAK4Pellino3, 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.doi:10.4049/jimmunol.171.3.15002003J. Immunol.1711500-1506INTERACTION WITH PELI3Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C.Mamidipudi V.Lin C.Seibenhener M.L.Wooten M.W.doi:10.1074/jbc.c3004312002004J. Biol. Chem.2794161-4165FUNCTIONPHOSPHORYLATION AT THR-66Sequential 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.doi:10.1074/jbc.m3092512002004J. Biol. Chem.2795227-5236PHOSPHORYLATION AT THR-209 AND THR-387DOMAINMUTAGENESIS OF THR-209 AND THR-387IRAK4 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.doi:10.1074/jbc.m4007852002004J. Biol. Chem.27926748-26753FUNCTIONMUTAGENESIS OF LYS-239IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression.Huang Y.Li T.Sane D.C.Li L.doi:10.1074/jbc.m4103692002004J. Biol. Chem.27951697-51703FUNCTION IN PHOSPHORYLATION OF STAT3IL-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.doi:10.1016/j.immuni.2005.09.0152005Immunity23479-490INTERACTION WITH IL1RL1Interleukin-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.doi:10.1084/jem.200423722005J. Exp. Med.201915-923FUNCTION IN PHOSPHORYLATION OF IRF7Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adapter 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.doi:10.1038/ni13832006Nat. Immunol.71057-1065IDENTIFICATION IN COMPLEX WITH IRAK4; MYD88; PELI1 AND TRAF6Differential regulation of interleukin-1 receptor associated kinase 1 (IRAK1) splice variants.Su J.Richter K.Zhang C.Gu Q.Li L.doi:10.1016/j.molimm.2006.03.0212007Mol. Immunol.44900-905SUMOYLATIONSUBCELLULAR LOCATIONThe 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.doi:10.1042/bj200713652008Biochem. J.40943-52FUNCTION IN PHOSPHORYLATION OF PELI1Kinase-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.doi:10.1016/j.molcel.2008.07.0072008Mol. Cell31438-448PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Cervix carcinomaLys63-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.doi:10.1128/mcb.02098-072008Mol. Cell. Biol.283538-3547UBIQUITINATION AT LYS-134 AND LYS-180 BY TRAF6INTERACTION WITH IKBKG/NEMOA quantitative atlas of mitotic phosphorylation.Dephoure N.Zhou C.Villen J.Beausoleil S.A.Bakalarski C.E.Elledge S.J.Gygi S.P.doi:10.1073/pnas.08051391052008Proc. Natl. Acad. Sci. U.S.A.10510762-10767IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]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.doi:10.1038/nature082472009Nature461114-119UBIQUITINATIONIRAK1 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.doi:10.1074/jbc.m109.0981372010J. Biol. Chem.28518276-18282FUNCTION IN PHOSPHORYLATION OF TIRAPIRAK1: a critical signaling mediator of innate immunity.Gottipati S.Rao N.L.Fung-Leung W.P.doi:10.1016/j.cellsig.2007.08.0092008Cell. Signal.20269-276REVIEW ON FUNCTIONThe interleukin-1 receptor associated kinase 1 contributes to the regulation of NFAT.Wang D.Fasciano S.Li L.doi:10.1016/j.molimm.2008.06.0232008Mol. Immunol.453902-3908INTERACTION WITH NFATC4MUTAGENESIS OF ASP-340The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling.Moynagh P.N.doi:10.1016/j.it.2008.10.0012009Trends Immunol.3033-42REVIEW ON FUNCTIONInitial 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.doi:10.1186/1752-0509-5-172011BMC Syst. Biol.517IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Toward a comprehensive characterization of a human cancer cell phosphoproteome.Zhou H.Di Palma S.Preisinger C.Peng M.Polat A.N.Heck A.J.Mohammed S.doi:10.1021/pr300630k2013J. Proteome Res.12260-271PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371; SER-375 AND SER-556IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]ErythroleukemiaAn inflammatory bowel disease-risk variant in INAVA decreases pattern recognition receptor-induced outcomes.Yan J.Hedl M.Abraham C.doi:10.1172/jci862822017J. Clin. Invest.1272192-2205INTERACTION WITH INAVAMumps virus SH protein inhibits NF-kappaB activation by interacting with tumor necrosis factor receptor 1, interleukin-1 receptor 1, and Toll-like receptor 3 complexes.Franz S.Rennert P.Woznik M.Gruetzke J.Luedde A.Arriero Pais E.M.Finsterbusch T.Geyer H.Mankertz A.Friedrich N.doi:10.1128/jvi.01037-172017J. Virol.91INTERACTION WITH MUMPS VIRUS PROTEIN SHPELI1 selectively targets kinase-active RIP3 for ubiquitylation-dependent proteasomal degradation.Choi S.W.Park H.H.Kim S.Chung J.M.Noh H.J.Kim S.K.Song H.K.Lee C.W.Morgan M.J.Kang H.C.Kim Y.S.doi:10.1016/j.molcel.2018.05.0162018Mol. Cell70920-935INTERACTION WITH PELI1The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling.Landers V.D.Wilkey D.W.Merchant M.L.Mitchell T.C.Sokoloski K.J.doi:10.3390/v130303772021Viruses13INTERACTION WITH ALPHAVIRUS CAPSID PROTEINS (MICROBIAL INFECTION)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.doi:10.1038/nature056102007Nature446153-158VARIANTS [LARGE SCALE ANALYSIS] MET-398; MET-412; HIS-421; LEU-532; SER-619; MET-625; TRP-638 AND GLY-6902.26A/B=194-530347190Fostamatinib1 site, 1 O-linked glycan (1 site)1274 antibodies from 47 providershumanIRAK1Low tissue specificitygenePediatric systemic lupus erythematosusSystemic lupus erythematosusEukaryota2681PIP3 activates AKT signalingMyD88:MAL(TIRAP) cascade initiated on plasma membraneNOD1/2 Signaling Pathwayp75NTR recruits signalling complexesNF-kB is activated and signals survivalTAK1-dependent IKK and NF-kappa-B activationactivated TAK1 mediates p38 MAPK activationJNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingTranscriptional Regulation by MECP2Interleukin-1 signalingIRAK1 recruits IKK complexSARS-CoV-2 activates/modulates innate and adaptive immune responsesTRAF6 mediated IRF7 activation in TLR7/8 or 9 signalingTRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationIRAK1 recruits IKK complex upon TLR7/8 or 9 stimulationMyD88 dependent cascade initiated on endosomeMyD88 cascade initiated on plasma membrane20 hits in 816 CRISPR screenshumanTchemProteinExpressed in parotid gland and 203 other cell types or tissuesbaseline and differentialHSDeath_IRAK1Death Domain, FasTransferase(Phosphotransferase) domain 1DEATH-like_dom_sfDeath_domainDeath_IRAK1Kinase-like_dom_sfProt_kinase_domProtein_kinase_ATP_BSSer/Thr_kinase_ASINTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASEINTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 1DeathPkinaseS_TKcDEATH domainProtein kinase-like (PK-like)PROTEIN_KINASE_ATPPROTEIN_KINASE_DOMPROTEIN_KINASE_STInterleukin-1 receptor-associated kinase 1IRAK-12.7.11.1IRAK1IRAKSerine/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.Homodimer (By similarity). Forms a complex with TRAF6, PELI1, IRAK4 and MYD88 (PubMed:16951688). Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression (PubMed:16951688). The TRAF6-PELI1-IRAK4-MYD88 complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation (PubMed:16951688). Interaction with MYD88 recruits IRAK1 to the stimulated receptor complex (PubMed:9430229). Interacts with TOLLIP; this interaction occurs in the cytosol prior to receptor activation (PubMed:10854325). Interacts with IL1RL1 (PubMed:16286016). Interacts with PELI1 and TRAF6 (PubMed:12496252). Interacts (when polyubiquitinated) with IKBKG/NEMO (PubMed:18347055). Interacts with RSAD2/viperin (By similarity). Interacts with IRAK1BP1 (By similarity). Interacts with PELI2 (By similarity). Interacts with ZC3H12A; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (By similarity). Interacts with IRAK4 (PubMed:11960013). Interacts with PELI3 (PubMed:12874243). Interacts with INAVA; the interaction takes place upon PRR stimulation (PubMed:28436939). Interacts (via C-terminus) with NFATC4 (via N-terminus) (PubMed:18691762).(Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation.(Microbial infection) Interacts with alphaviruses SINV, CHIKV, RRV, VEEV and EEEV capsid proteins; the interactions lead to inhibition of IRAK1-dependent signaling.Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity).Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.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.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.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.Inactive.Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.Interleukin-1 receptor-associated kinase 1765371712Death27106Protein kinase212521Disordered105187ProST region110211Disordered532591Disordered613660Disordered690Polar residues134151Pro residues163179Polar residues538556Polar residues572590Polar residues646Proton acceptor340218226239342345358Phosphothreonine; by PKC/PRKCI66Phosphoserine131Phosphothreonine; by IRAK4209Phosphoserine371Phosphoserine375Phosphothreonine387PhosphoserineGlycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)180In isoform 3.FGGWRRAAGGREARGLLAPTPDAPRPA45In isoform 4.435513In isoform 3.478492In isoform 2 and isoform 3.542H194S196S203M398In a glioblastoma multiforme sample; somatic mutation.M412In a breast pleomorphic lobular carcinoma sample; somatic mutation.H421LS619M625W638In a lung adenocarcinoma sample; somatic mutation.GCompletely abolishes auto-phosphorylation in the kinase domain.ALoss of kinase activity.SLoss of kinase activity.NLoss of kinase activity.A195197202210217220222231234241249265274280283289296301304307312331332334348354356359361388390393397403419423427430433434436437445464466467476487500505507511522524false2false2false3false4false4false2false10false2false2false3true2true3IRF4IRF7MYD88PELI1PELI2PELI3PIN1STING1TIRAPTRAF6Unc93b1Zc3h12a2000-12-012765377c465f9a42dc946204c257c884beda6a1aMAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQVYERLEKLQAVVAGVPGHSEAASCIPPSPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS2bMAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS3MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFGGWRRAAGGREARGLLAPTPDAPRPAAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLGQLACCCLHRRAKRRPPMTQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS4MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLVYERLEKLQAVVAGVPGHSEAASCIPPSPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQStruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue