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Protein

Interleukin-1 receptor-associated kinase-like 2

Gene

IRAK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

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: Reactome
  • inflammatory response Source: ProtInc
  • interleukin-1-mediated signaling pathway Source: BHF-UCL
  • intracellular signal transduction Source: GO_Central
  • 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

Keywordsi

LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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-450302 activated TAK1 mediates p38 MAPK activation
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-9020702 Interleukin-1 signaling
R-HSA-937042 IRAK2 mediated activation of TAK1 complex
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 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

EuPathDBiHostDB:ENSG00000134070.4
HGNCiHGNC:6113 IRAK2
MIMi603304 gene
neXtProtiNX_O43187

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

EPDiO43187
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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi10986536 interactors.
CORUMiO43187
DIPiDIP-31800N
ELMiO43187
IntActiO43187 31 interactors.
MINTiO43187
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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR033611 IRAK2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
PANTHERiPTHR24419:SF2 PTHR24419:SF2, 1 hit
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF00069 Pkinase, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit

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 → Q1 PublicationCorresponds to variant dbSNP:rs34945585Ensembl.1
Natural variantiVAR_03052747S → Y1 PublicationCorresponds to variant dbSNP:rs11465864Ensembl.1
Natural variantiVAR_04134399I → V1 PublicationCorresponds to variant dbSNP:rs55898544Ensembl.1
Natural variantiVAR_041344147R → T1 PublicationCorresponds to variant dbSNP:rs56053222Ensembl.1
Natural variantiVAR_041345214R → G1 PublicationCorresponds to variant dbSNP:rs35060588Ensembl.1
Natural variantiVAR_041346249S → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030528392L → V1 PublicationCorresponds to variant dbSNP:rs3844283Ensembl.1
Natural variantiVAR_041347421P → T in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030529431D → E3 PublicationsCorresponds to variant dbSNP:rs708035Ensembl.1
Natural variantiVAR_030530439L → V1 PublicationCorresponds to variant dbSNP:rs11465927Ensembl.1
Natural variantiVAR_041348469D → N1 PublicationCorresponds to variant dbSNP:rs56242986Ensembl.1
Natural variantiVAR_030531503L → I1 PublicationCorresponds to variant dbSNP:rs9854688Ensembl.1
Natural variantiVAR_041349566R → W1 PublicationCorresponds to variant dbSNP:rs55740652Ensembl.1
Natural variantiVAR_030532574D → H. Corresponds to variant dbSNP:rs11465930Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiIRAK2_HUMAN
AccessioniPrimary (citable) accession number: O43187
Secondary accession number(s): B4DQZ6, Q08AG6, Q5K546
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 6, 2007
Last modified: March 28, 2018
This is version 163 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome