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Protein

Interleukin-1 receptor-associated kinase-like 2

Gene

IRAK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei237ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi216 – 224ATPPROSITE-ProRule annotation9
Nucleotide bindingi337 – 340ATPPROSITE-ProRule annotation4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  • activation of MAPK activity Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: ProtInc
  • inflammatory response Source: ProtInc
  • interleukin-1-mediated signaling pathway Source: BHF-UCL
  • JNK cascade Source: Reactome
  • lipopolysaccharide-mediated signaling pathway Source: Ensembl
  • MyD88-dependent toll-like receptor signaling pathway Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • protein phosphorylation Source: ProtInc
  • regulation of cytokine-mediated signaling pathway Source: BHF-UCL
  • response to interleukin-1 Source: BHF-UCL
  • toll-like receptor 9 signaling pathway Source: Reactome
  • toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134070-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-937042. IRAK2 mediated activation of TAK1 complex.
R-HSA-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
R-HSA-975155. MyD88 dependent cascade initiated on endosome.
R-HSA-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
R-HSA-975871. MyD88 cascade initiated on plasma membrane.
SignaLinkiO43187.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 receptor-associated kinase-like 2
Short name:
IRAK-2
Gene namesi
Name:IRAK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6113. IRAK2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi3656.
OpenTargetsiENSG00000134070.
PharmGKBiPA29913.

Polymorphism and mutation databases

BioMutaiIRAK2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860321 – 625Interleukin-1 receptor-associated kinase-like 2Add BLAST625

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei144PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO43187.
PaxDbiO43187.
PeptideAtlasiO43187.
PRIDEiO43187.

PTM databases

iPTMnetiO43187.
PhosphoSitePlusiO43187.

Expressioni

Tissue specificityi

Expressed in spleen, thymus, prostate, lung, liver, skeletal muscle, kidney, pancreas and peripheral blood leukocytes.1 Publication

Gene expression databases

BgeeiENSG00000134070.
CleanExiHS_IRAK2.
GenevisibleiO43187. HS.

Organism-specific databases

HPAiCAB013483.
HPA050520.

Interactioni

Subunit structurei

Interacts with MYD88. IL-1 stimulation leads to the formation of a signaling complex which dissociates from the IL-1 receptor following the binding of PELI1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ARAFP103982EBI-447733,EBI-365961
K7RP684672EBI-447733,EBI-8022707From a different organism.
Sarm1Q6PDS32EBI-447733,EBI-6117196From a different organism.
STT3AP469772EBI-447733,EBI-719212
TARDBPQ131482EBI-447733,EBI-372899
TIRAPP587532EBI-447733,EBI-528644
TOLLIPQ9H0E22EBI-447733,EBI-74615
ZC3H12AQ5D1E82EBI-447733,EBI-747793

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi109865. 34 interactors.
DIPiDIP-31800N.
IntActiO43187. 30 interactors.
MINTiMINT-97184.
STRINGi9606.ENSP00000256458.

Structurei

Secondary structure

1625
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 7Combined sources3
Helixi10 – 16Combined sources7
Turni17 – 22Combined sources6
Helixi25 – 32Combined sources8
Turni33 – 36Combined sources4
Helixi39 – 47Combined sources9
Helixi48 – 50Combined sources3
Helixi56 – 65Combined sources10
Turni66 – 68Combined sources3
Helixi72 – 76Combined sources5
Turni77 – 81Combined sources5
Helixi84 – 87Combined sources4
Turni88 – 91Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MOPX-ray3.40K/L/M/N2-112[»]
ProteinModelPortaliO43187.
SMRiO43187.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43187.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 94DeathAdd BLAST82
Domaini210 – 489Protein kinasePROSITE-ProRule annotationAdd BLAST280

Domaini

The protein kinase domain is predicted to be catalytically inactive.

Sequence similaritiesi

Contains 1 death domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000113102.
HOVERGENiHBG052145.
InParanoidiO43187.
KOiK04731.
OMAiLSEWDWM.
OrthoDBiEOG091G0YKT.
PhylomeDBiO43187.
TreeFamiTF328924.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR033611. IRAK2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PANTHERiPTHR24419:SF2. PTHR24419:SF2. 1 hit.
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O43187-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACYIYQLPS WVLDDLCRNM DALSEWDWME FASYVITDLT QLRKIKSMER
60 70 80 90 100
VQGVSITREL LWWWGMRQAT VQQLVDLLCR LELYRAAQII LNWKPAPEIR
110 120 130 140 150
CPIPAFPDSV KPEKPLAASV RKAEDEQEEG QPVRMATFPG PGSSPARAHQ
160 170 180 190 200
PAFLQPPEED APHSLRSDLP TSSDSKDFST SIPKQEKLLS LAGDSLFWSE
210 220 230 240 250
ADVVQATDDF NQNRKISQGT FADVYRGHRH GKPFVFKKLR ETACSSPGSI
260 270 280 290 300
ERFFQAELQI CLRCCHPNVL PVLGFCAARQ FHSFIYPYMA NGSLQDRLQG
310 320 330 340 350
QGGSDPLPWP QRVSICSGLL CAVEYLHGLE IIHSNVKSSN VLLDQNLTPK
360 370 380 390 400
LAHPMAHLCP VNKRSKYTMM KTHLLRTSAA YLPEDFIRVG QLTKRVDIFS
410 420 430 440 450
CGIVLAEVLT GIPAMDNNRS PVYLKDLLLS DIPSSTASLC SRKTGVENVM
460 470 480 490 500
AKEICQKYLE KGAGRLPEDC AEALATAACL CLRRRNTSLQ EVCGSVAAVE
510 520 530 540 550
ERLRGRETLL PWSGLSEGTG SSSNTPEETD DVDNSSLDAS SSMSVAPWAG
560 570 580 590 600
AATPLLPTEN GEGRLRVIVG READSSSEAC VGLEPPQDVT ETSWQIEINE
610 620
AKRKLMENIL LYKEEKVDSI ELFGP
Length:625
Mass (Da):69,433
Last modified:February 6, 2007 - v2
Checksum:i715C954BC9452710
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04134243R → Q.1 PublicationCorresponds to variant rs34945585dbSNPEnsembl.1
Natural variantiVAR_03052747S → Y.1 PublicationCorresponds to variant rs11465864dbSNPEnsembl.1
Natural variantiVAR_04134399I → V.1 PublicationCorresponds to variant rs55898544dbSNPEnsembl.1
Natural variantiVAR_041344147R → T.1 PublicationCorresponds to variant rs56053222dbSNPEnsembl.1
Natural variantiVAR_041345214R → G.1 PublicationCorresponds to variant rs35060588dbSNPEnsembl.1
Natural variantiVAR_041346249S → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030528392L → V.1 PublicationCorresponds to variant rs3844283dbSNPEnsembl.1
Natural variantiVAR_041347421P → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030529431D → E.3 PublicationsCorresponds to variant rs708035dbSNPEnsembl.1
Natural variantiVAR_030530439L → V.1 PublicationCorresponds to variant rs11465927dbSNPEnsembl.1
Natural variantiVAR_041348469D → N.1 PublicationCorresponds to variant rs56242986dbSNPEnsembl.1
Natural variantiVAR_030531503L → I.1 PublicationCorresponds to variant rs9854688dbSNPEnsembl.1
Natural variantiVAR_041349566R → W.1 PublicationCorresponds to variant rs55740652dbSNPEnsembl.1
Natural variantiVAR_030532574D → H.Corresponds to variant rs11465930dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ496794 mRNA. Translation: CAD43180.3.
AK299033 mRNA. Translation: BAG61108.1.
BC125184 mRNA. Translation: AAI25185.1.
AF026273 mRNA. Translation: AAB87669.1.
CCDSiCCDS33697.1.
RefSeqiNP_001561.3. NM_001570.3.
UniGeneiHs.449207.

Genome annotation databases

EnsembliENST00000256458; ENSP00000256458; ENSG00000134070.
GeneIDi3656.
KEGGihsa:3656.
UCSCiuc003bve.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ496794 mRNA. Translation: CAD43180.3.
AK299033 mRNA. Translation: BAG61108.1.
BC125184 mRNA. Translation: AAI25185.1.
AF026273 mRNA. Translation: AAB87669.1.
CCDSiCCDS33697.1.
RefSeqiNP_001561.3. NM_001570.3.
UniGeneiHs.449207.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MOPX-ray3.40K/L/M/N2-112[»]
ProteinModelPortaliO43187.
SMRiO43187.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109865. 34 interactors.
DIPiDIP-31800N.
IntActiO43187. 30 interactors.
MINTiMINT-97184.
STRINGi9606.ENSP00000256458.

PTM databases

iPTMnetiO43187.
PhosphoSitePlusiO43187.

Polymorphism and mutation databases

BioMutaiIRAK2.

Proteomic databases

MaxQBiO43187.
PaxDbiO43187.
PeptideAtlasiO43187.
PRIDEiO43187.

Protocols and materials databases

DNASUi3656.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256458; ENSP00000256458; ENSG00000134070.
GeneIDi3656.
KEGGihsa:3656.
UCSCiuc003bve.2. human.

Organism-specific databases

CTDi3656.
DisGeNETi3656.
GeneCardsiIRAK2.
HGNCiHGNC:6113. IRAK2.
HPAiCAB013483.
HPA050520.
MIMi603304. gene.
neXtProtiNX_O43187.
OpenTargetsiENSG00000134070.
PharmGKBiPA29913.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000113102.
HOVERGENiHBG052145.
InParanoidiO43187.
KOiK04731.
OMAiLSEWDWM.
OrthoDBiEOG091G0YKT.
PhylomeDBiO43187.
TreeFamiTF328924.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134070-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-937042. IRAK2 mediated activation of TAK1 complex.
R-HSA-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
R-HSA-975155. MyD88 dependent cascade initiated on endosome.
R-HSA-975163. IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
R-HSA-975871. MyD88 cascade initiated on plasma membrane.
SignaLinkiO43187.

Miscellaneous databases

EvolutionaryTraceiO43187.
GeneWikiiIRAK2.
GenomeRNAii3656.
PROiO43187.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134070.
CleanExiHS_IRAK2.
GenevisibleiO43187. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR033611. IRAK2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PANTHERiPTHR24419:SF2. PTHR24419:SF2. 1 hit.
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIRAK2_HUMAN
AccessioniPrimary (citable) accession number: O43187
Secondary accession number(s): B4DQZ6, Q08AG6, Q5K546
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 6, 2007
Last modified: November 2, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

Asn-335 is present instead of the conserved Asp which is expected to be an active site residue. This enzyme has been shown to be catalytically inactive.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.