UniProtKB - Q62406 (IRAK1_MOUSE)
Interleukin-1 receptor-associated kinase 1
Irak1
Functioni
Catalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 239 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 340 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Binding sitei | 358 | ATPPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 218 – 226 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 342 – 345 | ATPPROSITE-ProRule annotation | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- heat shock protein binding Source: MGI
- identical protein binding Source: MGI
- interleukin-1 receptor binding Source: MGI
- kinase activity Source: MGI
- protein heterodimerization activity Source: MGI
- protein homodimerization activity Source: MGI
- protein kinase activity Source: MGI
- protein serine/threonine kinase activity Source: MGI
- protein serine kinase activity Source: UniProtKB-EC
- protein threonine kinase activity Source: UniProtKB-EC
GO - Biological processi
- activation of NF-kappaB-inducing kinase activity Source: MGI
- cellular response to heat Source: MGI
- cellular response to lipopolysaccharide Source: GO_Central
- cytokine-mediated signaling pathway Source: MGI
- innate immune response Source: UniProtKB
- interleukin-1-mediated signaling pathway Source: UniProtKB
- intracellular signal transduction Source: GO_Central
- JNK cascade Source: MGI
- lipopolysaccharide-mediated signaling pathway Source: MGI
- negative regulation of cholesterol efflux Source: UniProtKB
- negative regulation of NF-kappaB transcription factor activity Source: MGI
- negative regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
- positive regulation of JUN kinase activity Source: BHF-UCL
- positive regulation of leukocyte adhesion to vascular endothelial cell Source: MGI
- positive regulation of MAP kinase activity Source: BHF-UCL
- positive regulation of NF-kappaB transcription factor activity Source: MGI
- positive regulation of NIK/NF-kappaB signaling Source: MGI
- positive regulation of smooth muscle cell proliferation Source: MGI
- positive regulation of type I interferon production Source: MGI
- protein autophosphorylation Source: MGI
- protein phosphorylation Source: MGI
- regulation of cytokine-mediated signaling pathway Source: MGI
- response to interleukin-1 Source: MGI
- response to lipopolysaccharide Source: MGI
- response to peptidoglycan Source: MGI
- toll-like receptor 2 signaling pathway Source: MGI
- toll-like receptor 4 signaling pathway Source: MGI
- type I interferon signaling pathway Source: MGI
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Immunity, Innate immunity |
Ligand | ATP-binding, Magnesium, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 3474 |
Reactomei | R-MMU-1257604, PIP3 activates AKT signaling R-MMU-168638, NOD1/2 Signaling Pathway R-MMU-209543, p75NTR recruits signalling complexes R-MMU-209560, NF-kB is activated and signals survival R-MMU-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-MMU-450302, activated TAK1 mediates p38 MAPK activation R-MMU-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-MMU-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-MMU-9020702, Interleukin-1 signaling R-MMU-937039, IRAK1 recruits IKK complex R-MMU-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-1 receptor-associated kinase 1 (EC:2.7.11.1)Short name: IRAK Short name: IRAK-1 Alternative name(s): Pelle-like protein kinase Short name: mPLK |
Gene namesi | Name:Irak1 Synonyms:Il1rak |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:107420, Irak1 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Cytoplasm By similarity
- Lipid droplet 1 Publication
Note: Translocates to the nucleus when sumoylated (By similarity). RSAD2/viperin recruits it to the lipid droplet.By similarity
Cytosol
- cytosol Source: MGI
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: GO_Central
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
- lipid droplet Source: UniProtKB
- membrane Source: UniProtKB
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Lipid droplet, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 66 | T → A: Abolishes dimerization. 1 Publication | 1 | |
Mutagenesisi | 66 | T → E: Abolishes dimerization. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086031 | 1 – 710 | Interleukin-1 receptor-associated kinase 1Add BLAST | 710 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 66 | Phosphothreonine; by PKC/PRKCIBy similarity | 1 | |
Modified residuei | 131 | PhosphoserineBy similarity | 1 | |
Cross-linki | 134 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 180 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 209 | Phosphothreonine; by IRAK4By similarity | 1 | |
Modified residuei | 375 | PhosphoserineBy similarity | 1 | |
Modified residuei | 387 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 553 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PRIDEi | Q62406 |
PTM databases
iPTMneti | Q62406 |
PhosphoSitePlusi | Q62406 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSMUSG00000031392, Expressed in pancreas and 303 other tissues |
ExpressionAtlasi | Q62406, baseline and differential |
Genevisiblei | Q62406, MM |
Interactioni
Subunit structurei
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 (By similarity). The TRAF6-PELI1-IRAK4-MYD88 complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation (By similarity). Interaction with MYD88 recruits IRAK1 to the stimulated receptor complex (By similarity).
Interacts with TOLLIP; this interaction occurs in the cytosol prior to receptor activation (By similarity).
Interacts with IL1RL1 (By similarity).
Interacts (when polyubiquitinated) with IKBKG/NEMO (By similarity).
Interacts with RSAD2/viperin (PubMed:21435586).
Interacts with IRAK1BP1 (PubMed:11096118).
Interacts with PELI2 (PubMed:12370331).
Interacts with ZC3H12A; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (PubMed:22037600).
Interacts with IRAK4 (By similarity).
Interacts with PELI3 (By similarity).
Interacts with PELI1 and TRAF6 (By similarity).
Interacts with INAVA; the interaction takes place upon PRR stimulation (By similarity).
Interacts (via C-terminus) with NFATC4 (via N-terminus) (By similarity).
By similarity5 PublicationsBinary interactionsi
Hide detailsQ62406
With | #Exp. | IntAct |
---|---|---|
Myd88 [P22366] | 3 | EBI-448533,EBI-525108 |
Peli2 [Q8BST6] | 2 | EBI-448533,EBI-448554 |
Tifa [Q793I8] | 2 | EBI-448533,EBI-524817 |
Tollip [Q9QZ06] | 2 | EBI-448533,EBI-74272 |
Traf2 [P39429] | 2 | EBI-448533,EBI-520016 |
Isoform 1 [Q62406-1]
With | #Exp. | IntAct |
---|---|---|
Aarsd1 [Q3THG9] | 4 | EBI-488313,EBI-646572 |
Fbln2 - isoform 1 [P37889-1] | 10 | EBI-488313,EBI-645953 |
Traf6 [P70196] | 4 | EBI-488313,EBI-448028 |
GO - Molecular functioni
- heat shock protein binding Source: MGI
- identical protein binding Source: MGI
- interleukin-1 receptor binding Source: MGI
- protein heterodimerization activity Source: MGI
- protein homodimerization activity Source: MGI
Protein-protein interaction databases
BioGRIDi | 200627, 24 interactors |
DIPi | DIP-31491N |
ELMi | Q62406 |
IntActi | Q62406, 28 interactors |
STRINGi | 10090.ENSMUSP00000033769 |
Miscellaneous databases
RNActi | Q62406, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 27 – 106 | DeathAdd BLAST | 80 | |
Domaini | 212 – 521 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 310 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 110 – 211 | ProST regionBy similarityAdd BLAST | 102 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1187, Eukaryota |
GeneTreei | ENSGT00940000160502 |
InParanoidi | Q62406 |
Family and domain databases
CDDi | cd08794, Death_IRAK1, 1 hit |
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR035533, Death_IRAK1 IPR035536, IRAK1 IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
PANTHERi | PTHR24419:SF1, PTHR24419:SF1, 1 hit |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGGPGPGEP VVPGAQHFLY EVPPWVMCRF YKVMDALEPA DWCQFAALIV
60 70 80 90 100
RDQTELRLCE RSEQRTASVL WPWINRNARV ADLVHILTHL QLLRARDIIT
110 120 130 140 150
AWHPPAPVVP PSTAAPRPSS ISAGSEAGDW SPRKLQSSAS TFLSPAFPGS
160 170 180 190 200
QTHSESELLQ VPLPVSLGPP LPSSAPSSTK SSPESPVSGL QRAHPSPFCW
210 220 230 240 250
PFCEISQGTC NFSEELRIGE GGFGCVYRAV MRNTTYAVKR LKEEADLEWT
260 270 280 290 300
MVKQSFLTEV EQLSRFRHPN IVDFAGYCAE SGLYCLVYGF LPNGSLEDQL
310 320 330 340 350
HLQTQACSPL SWPQRLDILL GTARAIQFLH QDSPSLIHGD IKSSNVLLDE
360 370 380 390 400
RLMPKLGDFG LARFSRFAGA KASQSSTVAR TSTVRGTLAY LPEEYIKTGR
410 420 430 440 450
LAVDTDTFSF GVVILETLAG QRAVRTQGAK TKYLKDLIED EAEEAGVTLK
460 470 480 490 500
STQPTLWVGV ATDAWAAPIA AQIYKKHLDS RPGPCPPQLG LALAQLACCC
510 520 530 540 550
MHRRAKKRPP MTQVYKRLEG LQAGPPWELE VAGHGSPSPQ ENSYMSTTGS
560 570 580 590 600
AQSGDEPWQP LVVTTRAPAQ AAQQLQRSPN QPVESDESVP GLSATLHSWH
610 620 630 640 650
LTPGSHPSPA SFREASCTQG GTTRESSVRS SPGFQPTTME GSPTGSSSLL
660 670 680 690 700
SSEPPQIIIN PARQKMVQKL ALYEEGVLDS LQLLSSGFFP GLDLEPEKSQ
710
GPEESDEFQS
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB1AUW6 | B1AUW6_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 750 | Annotation score: | ||
Q8BR10 | Q8BR10_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 711 | Annotation score: | ||
B1AUW8 | B1AUW8_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 631 | Annotation score: | ||
F6THK7 | F6THK7_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 383 | Annotation score: | ||
B1AUW9 | B1AUW9_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 683 | Annotation score: | ||
B1AUW1 | B1AUW1_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 147 | Annotation score: | ||
F6TQF4 | F6TQF4_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 257 | Annotation score: | ||
F7ANU5 | F7ANU5_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 199 | Annotation score: | ||
F6ZGQ1 | F6ZGQ1_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 128 | Annotation score: | ||
F7CUT1 | F7CUT1_MOUSE | Interleukin-1 receptor-associated k... | Irak1 | 216 | Annotation score: | ||
There is more potential isoformShow all |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 702 | P → L in AAO63013 (PubMed:10723722).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_011852 | 691 – 710 | GLDLE…DEFQS → DFVDIDAIGIEAFMSELFIN HI in isoform 2. 1 PublicationAdd BLAST | 20 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF103876 mRNA Translation: AAD13224.1 Different initiation. AY184363 mRNA Translation: AAO63013.1 AY184364 mRNA Translation: AAO63014.1 AL672002 Genomic DNA No translation available. U56773 mRNA Translation: AAC52694.2 |
CCDSi | CCDS30219.2 [Q62406-1] CCDS53103.1 [Q62406-2] |
RefSeqi | NP_001171445.1, NM_001177974.1 [Q62406-1] NP_001171447.1, NM_001177976.1 [Q62406-2] NP_032389.2, NM_008363.2 [Q62406-1] |
Genome annotation databases
Ensembli | ENSMUST00000068286; ENSMUSP00000064448; ENSMUSG00000031392 [Q62406-1] ENSMUST00000114352; ENSMUSP00000109992; ENSMUSG00000031392 [Q62406-1] ENSMUST00000114360; ENSMUSP00000110000; ENSMUSG00000031392 [Q62406-2] |
GeneIDi | 16179 |
KEGGi | mmu:16179 |
UCSCi | uc009tnn.2, mouse [Q62406-1] uc012hkn.1, mouse [Q62406-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF103876 mRNA Translation: AAD13224.1 Different initiation. AY184363 mRNA Translation: AAO63013.1 AY184364 mRNA Translation: AAO63014.1 AL672002 Genomic DNA No translation available. U56773 mRNA Translation: AAC52694.2 |
CCDSi | CCDS30219.2 [Q62406-1] CCDS53103.1 [Q62406-2] |
RefSeqi | NP_001171445.1, NM_001177974.1 [Q62406-1] NP_001171447.1, NM_001177976.1 [Q62406-2] NP_032389.2, NM_008363.2 [Q62406-1] |
3D structure databases
SMRi | Q62406 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200627, 24 interactors |
DIPi | DIP-31491N |
ELMi | Q62406 |
IntActi | Q62406, 28 interactors |
STRINGi | 10090.ENSMUSP00000033769 |
PTM databases
iPTMneti | Q62406 |
PhosphoSitePlusi | Q62406 |
Proteomic databases
PRIDEi | Q62406 |
Protocols and materials databases
Antibodypediai | 3845, 993 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000068286; ENSMUSP00000064448; ENSMUSG00000031392 [Q62406-1] ENSMUST00000114352; ENSMUSP00000109992; ENSMUSG00000031392 [Q62406-1] ENSMUST00000114360; ENSMUSP00000110000; ENSMUSG00000031392 [Q62406-2] |
GeneIDi | 16179 |
KEGGi | mmu:16179 |
UCSCi | uc009tnn.2, mouse [Q62406-1] uc012hkn.1, mouse [Q62406-2] |
Organism-specific databases
CTDi | 3654 |
MGIi | MGI:107420, Irak1 |
Phylogenomic databases
eggNOGi | KOG1187, Eukaryota |
GeneTreei | ENSGT00940000160502 |
InParanoidi | Q62406 |
Enzyme and pathway databases
BRENDAi | 2.7.10.2, 3474 |
Reactomei | R-MMU-1257604, PIP3 activates AKT signaling R-MMU-168638, NOD1/2 Signaling Pathway R-MMU-209543, p75NTR recruits signalling complexes R-MMU-209560, NF-kB is activated and signals survival R-MMU-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-MMU-450302, activated TAK1 mediates p38 MAPK activation R-MMU-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-MMU-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-MMU-9020702, Interleukin-1 signaling R-MMU-937039, IRAK1 recruits IKK complex R-MMU-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
Miscellaneous databases
BioGRID-ORCSi | 16179, 0 hits in 17 CRISPR screens |
ChiTaRSi | Irak1, mouse |
PROi | PR:Q62406 |
RNActi | Q62406, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000031392, Expressed in pancreas and 303 other tissues |
ExpressionAtlasi | Q62406, baseline and differential |
Genevisiblei | Q62406, MM |
Family and domain databases
CDDi | cd08794, Death_IRAK1, 1 hit |
InterProi | View protein in InterPro IPR011029, DEATH-like_dom_sf IPR000488, Death_domain IPR035533, Death_IRAK1 IPR035536, IRAK1 IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
PANTHERi | PTHR24419:SF1, PTHR24419:SF1, 1 hit |
Pfami | View protein in Pfam PF00531, Death, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IRAK1_MOUSE | |
Accessioni | Q62406Primary (citable) accession number: Q62406 Secondary accession number(s): B1AUW4, Q6Y3Z5, Q6Y3Z6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 11, 2001 |
Last sequence update: | August 14, 2001 | |
Last modified: | February 10, 2021 | |
This is version 193 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families