Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Details on Person UniProt:P51617 IRAK1

Class:Id	ReferenceGeneProduct:404288
_chainChangeLog	chain:1-712 added on Fri February 6 2015
_displayName	UniProt:P51617 IRAK1
_timestamp	2025-02-21 20:00:03
chain	chain:1-712
checksum	A7ADED75D3A3981D
comment	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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)COFACTOR 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).SUBUNIT (Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation.SUBUNIT (Microbial infection) Interacts with alphaviruses SINV, CHIKV, RRV, VEEV and EEEV capsid proteins; the interactions lead to inhibition of IRAK1-dependent signaling.INTERACTION Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity).ALTERNATIVE PRODUCTS Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.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.PTM 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.PTM 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.MISCELLANEOUS Inactive.SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.
created	[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
description	recommendedName: fullName evidence="35"Interleukin-1 receptor-associated kinase 1 shortName evidence="35"IRAK-1 ecNumber: 2.7.11.1
geneName	IRAK1 IRAK
identifier	P51617
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing ATP-binding Cytoplasm Direct protein sequencing Host-virus interaction Immunity Innate immunity Isopeptide bond Kinase Lipid droplet Magnesium Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	IRAK1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8990188] ENSEMBL:ENSG00000184216 IRAK1 [Homo sapiens]
secondaryIdentifier	IRAK1_HUMAN D3DWW3 D3DWW4 Q7Z5V4 Q96C06 Q96RL2
sequenceLength	712
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:57465] UniProt:P51617-1 IRAK1 [Homo sapiens] [ReferenceIsoform:148931] UniProt:P51617-2 IRAK1 [Homo sapiens] [ReferenceIsoform:148932] UniProt:P51617-3 IRAK1 [Homo sapiens] [ReferenceIsoform:8965653] UniProt:P51617-4 IRAK1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:166113] p-T209-IRAK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:166279] p-T209,T387-IRAK1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:446639] IRAK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:446682] p-2S,S376,T,T209,T387-IRAK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:446687] p-S376,T387-IRAK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:451565] K63polyUb-hp-IRAK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:937011] p-2S,S376,T,T209,T387-IRAK1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:937031] p-T209-IRAK1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:937045] IRAK1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:975112] K63polyUb-hp-IRAK1 [endosome membrane] [Homo sapiens] List all 16 refering instances
(referenceSequence)	[ModifiedResidue:446697] O-phospho-L-serine at 376 [ModifiedResidue:446700] O-phospho-L-threonine at 387 [ModifiedResidue:446703] O-phospho-L-threonine at unknown position [ModifiedResidue:446705] O-phospho-L-serine at unknown position [ModifiedResidue:446707] O-phospho-L-threonine at 209 [GroupModifiedResidue:3080582] ubiquitinylated lysine (K63polyUb [endosome membrane]) at 134 [GroupModifiedResidue:3080585] ubiquitinylated lysine (K63polyUb [endosome membrane]) at 180 [GroupModifiedResidue:3080595] ubiquitinylated lysine (K63-polyubiquitin [cytosol]) at 134 [GroupModifiedResidue:3080597] ubiquitinylated lysine (K63-polyubiquitin [cytosol]) at 160 [ModifiedResidue:9012107] phosphorylated residue at unknown position
[Change default viewing format]

No pathways have been reviewed or authored by UniProt:P51617 IRAK1 (404288)