IRAK1
entrez
3654
canonical
uniprot
P51617
canonical
ensembl
ENSG00000184216
resolver
ensp
ENSP00000358991
resolver
ensp
ENSP00000358997
resolver
ensp
ENSP00000377291
resolver
ensp
ENSP00000392662
resolver
enst
ENST00000429936
resolver
genesymbol
IRAK1
resolver
genesymbol_syn
IRAK
resolver
hgnc
HGNC:6112
resolver
uniprot
D3DWW3
resolver
uniprot
D3DWW4
resolver
uniprot
D3YTB5
resolver
uniprot
Q7Z5V4
resolver
uniprot
Q96C06
resolver
uniprot
Q96RL2
resolver
uniprot_entry
D3YTB5_HUMAN
resolver
uniprot_entry
IRAK1_HUMAN
resolver
uniprot_sec
D3DWW3
resolver
uniprot_sec
D3DWW4
resolver
uniprot_sec
Q7Z5V4
resolver
uniprot_sec
Q96C06
resolver
uniprot_sec
Q96RL2
resolver
amino_acid_sequence
MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQVYERLEKLQAVVAGVPGHSEAASCIPPSPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}.
uniprot
proteins
mass_dalton
76537
uniprot
proteins
mutagenesis
MUTAGEN 209; /note="T->A: Completely abolishes auto-phosphorylation in the kinase domain."; /evidence="ECO:0000269|PubMed:14625308"; MUTAGEN 239; /note="K->S: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:15084582"; MUTAGEN 340; /note="D->N: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:18691762"; MUTAGEN 387; /note="T->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:14625308
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:14625308, ECO:0000269|PubMed:14684752}.; 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. {ECO:0000269|PubMed:16690127, ECO:0000269|PubMed:18347055, ECO:0000269|PubMed:19675569}.
uniprot
proteins
protein_family
Pelle subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TKL Ser/Thr protein kinase family
uniprot
proteins
pubmed
10723722
uniprot
proteins
pubmed
10854325
uniprot
proteins
pubmed
11397809
uniprot
proteins
pubmed
11960013
uniprot
proteins
pubmed
12496252
uniprot
proteins
pubmed
12538665
uniprot
proteins
pubmed
12860405
uniprot
proteins
pubmed
12874243
uniprot
proteins
pubmed
14625308
uniprot
proteins
pubmed
14684752
uniprot
proteins
pubmed
15084582
uniprot
proteins
pubmed
15465816
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15767370
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
16024789
uniprot
proteins
pubmed
16286016
uniprot
proteins
pubmed
16690127
uniprot
proteins
pubmed
16951688
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17890055
uniprot
proteins
pubmed
17997719
uniprot
proteins
pubmed
18347055
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691762
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19022706
uniprot
proteins
pubmed
19675569
uniprot
proteins
pubmed
20400509
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
28436939
uniprot
proteins
pubmed
28659487
uniprot
proteins
pubmed
29883609
uniprot
proteins
pubmed
33673546
uniprot
proteins
pubmed
8599092
uniprot
proteins
pubmed
9430229
uniprot
proteins
sequence_length
712
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16690127}. Nucleus {ECO:0000269|PubMed:16690127}. Lipid droplet {ECO:0000250}. Note=Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity). {ECO:0000250}.
uniprot
proteins