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O43187 (IRAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-1 receptor-associated kinase-like 2

Short name=IRAK-2
Gene names
Name:IRAK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length625 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. Ref.4 Ref.5

Subunit structure

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. Ref.4

Tissue specificity

Expressed in spleen, thymus, prostate, lung, liver, skeletal muscle, kidney, pancreas and peripheral blood leukocytes. Ref.4

Domain

The protein kinase domain is predicted to be catalytically inactive.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.

Contains 1 death domain.

Contains 1 protein kinase domain.

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.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Traceable author statement Ref.4. Source: ProtInc

JNK cascade

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement Ref.5. Source: BHF-UCL

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

inflammatory response

Traceable author statement Ref.4. Source: ProtInc

innate immune response

Traceable author statement. Source: Reactome

interleukin-1-mediated signaling pathway

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

protein phosphorylation

Traceable author statement Ref.4. Source: ProtInc

regulation of cytokine-mediated signaling pathway

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

response to interleukin-1

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 11544529PubMed 18636090PubMed 21903422. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction Ref.5. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction Ref.5. Source: BHF-UCL

protein kinase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 625625Interleukin-1 receptor-associated kinase-like 2
PRO_0000086032

Regions

Domain13 – 9482Death
Domain210 – 489280Protein kinase
Nucleotide binding216 – 2249ATP By similarity
Nucleotide binding337 – 3404ATP By similarity

Sites

Binding site2371ATP By similarity

Natural variations

Natural variant431R → Q. Ref.7
Corresponds to variant rs34945585 [ dbSNP | Ensembl ].
VAR_041342
Natural variant471S → Y. Ref.7
Corresponds to variant rs11465864 [ dbSNP | Ensembl ].
VAR_030527
Natural variant991I → V. Ref.7
Corresponds to variant rs55898544 [ dbSNP | Ensembl ].
VAR_041343
Natural variant1471R → T. Ref.7
Corresponds to variant rs56053222 [ dbSNP | Ensembl ].
VAR_041344
Natural variant2141R → G. Ref.7
Corresponds to variant rs35060588 [ dbSNP | Ensembl ].
VAR_041345
Natural variant2491S → L in a lung adenocarcinoma sample; somatic mutation. Ref.7
VAR_041346
Natural variant3921L → V. Ref.7
Corresponds to variant rs3844283 [ dbSNP | Ensembl ].
VAR_030528
Natural variant4211P → T in a lung adenocarcinoma sample; somatic mutation. Ref.7
VAR_041347
Natural variant4311D → E. Ref.1 Ref.4 Ref.7
Corresponds to variant rs708035 [ dbSNP | Ensembl ].
VAR_030529
Natural variant4391L → V. Ref.7
Corresponds to variant rs11465927 [ dbSNP | Ensembl ].
VAR_030530
Natural variant4691D → N. Ref.7
Corresponds to variant rs56242986 [ dbSNP | Ensembl ].
VAR_041348
Natural variant5031L → I. Ref.7
Corresponds to variant rs9854688 [ dbSNP | Ensembl ].
VAR_030531
Natural variant5661R → W. Ref.7
Corresponds to variant rs55740652 [ dbSNP | Ensembl ].
VAR_041349
Natural variant5741D → H.
Corresponds to variant rs11465930 [ dbSNP | Ensembl ].
VAR_030532

Secondary structure

..................... 625
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43187 [UniParc].

Last modified February 6, 2007. Version 2.
Checksum: 715C954BC9452710

FASTA62569,433
        10         20         30         40         50         60 
MACYIYQLPS WVLDDLCRNM DALSEWDWME FASYVITDLT QLRKIKSMER VQGVSITREL 

        70         80         90        100        110        120 
LWWWGMRQAT VQQLVDLLCR LELYRAAQII LNWKPAPEIR CPIPAFPDSV KPEKPLAASV 

       130        140        150        160        170        180 
RKAEDEQEEG QPVRMATFPG PGSSPARAHQ PAFLQPPEED APHSLRSDLP TSSDSKDFST 

       190        200        210        220        230        240 
SIPKQEKLLS LAGDSLFWSE ADVVQATDDF NQNRKISQGT FADVYRGHRH GKPFVFKKLR 

       250        260        270        280        290        300 
ETACSSPGSI ERFFQAELQI CLRCCHPNVL PVLGFCAARQ FHSFIYPYMA NGSLQDRLQG 

       310        320        330        340        350        360 
QGGSDPLPWP QRVSICSGLL CAVEYLHGLE IIHSNVKSSN VLLDQNLTPK LAHPMAHLCP 

       370        380        390        400        410        420 
VNKRSKYTMM KTHLLRTSAA YLPEDFIRVG QLTKRVDIFS CGIVLAEVLT GIPAMDNNRS 

       430        440        450        460        470        480 
PVYLKDLLLS DIPSSTASLC SRKTGVENVM AKEICQKYLE KGAGRLPEDC AEALATAACL 

       490        500        510        520        530        540 
CLRRRNTSLQ EVCGSVAAVE ERLRGRETLL PWSGLSEGTG SSSNTPEETD DVDNSSLDAS 

       550        560        570        580        590        600 
SSMSVAPWAG AATPLLPTEN GEGRLRVIVG READSSSEAC VGLEPPQDVT ETSWQIEINE 

       610        620 
AKRKLMENIL LYKEEKVDSI ELFGP 

« Hide

References

« Hide 'large scale' references
[1]"Identification of Exon 13 and the 3'UTR region of human IRAK-2 and characterisation of the full length gene."
Rosati O., Martin M.U.
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-431.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling."
Muzio M., Ni J., Feng P., Dixit V.M.
Science 278:1612-1615(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-590, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH TRAF6; MYD88 AND IL1R1, VARIANT GLU-431.
Tissue: Endothelial cell.
[5]"IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family."
Wesche H., Gao X., Li X., Kirschning C.J., Stark G.R., Cao Z.
J. Biol. Chem. 274:19403-19410(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling."
Lin S.-C., Lo Y.-C., Wu H.
Nature 465:885-890(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 2-112.
[7]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-43; TYR-47; VAL-99; THR-147; GLY-214; LEU-249; VAL-392; THR-421; GLU-431; VAL-439; ASN-469; ILE-503 AND TRP-566.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ496794 mRNA. Translation: CAD43180.3.
AK299033 mRNA. Translation: BAG61108.1.
BC125184 mRNA. Translation: AAI25185.1.
AF026273 mRNA. Translation: AAB87669.1.
CCDSCCDS33697.1.
RefSeqNP_001561.3. NM_001570.3.
UniGeneHs.449207.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3MOPX-ray3.40K/L/M/N2-112[»]
ProteinModelPortalO43187.
SMRO43187. Positions 2-94, 197-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109865. 33 interactions.
DIPDIP-31800N.
IntActO43187. 30 interactions.
MINTMINT-97184.
STRING9606.ENSP00000256458.

PTM databases

PhosphoSiteO43187.

Proteomic databases

MaxQBO43187.
PaxDbO43187.
PeptideAtlasO43187.
PRIDEO43187.

Protocols and materials databases

DNASU3656.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256458; ENSP00000256458; ENSG00000134070.
GeneID3656.
KEGGhsa:3656.
UCSCuc003bve.1. human.

Organism-specific databases

CTD3656.
GeneCardsGC03P010206.
HGNCHGNC:6113. IRAK2.
HPACAB013483.
MIM603304. gene.
neXtProtNX_O43187.
PharmGKBPA29913.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000113102.
HOVERGENHBG052145.
InParanoidO43187.
KOK04731.
OMALSEWDWM.
OrthoDBEOG747PHP.
PhylomeDBO43187.
TreeFamTF328924.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkO43187.

Gene expression databases

BgeeO43187.
CleanExHS_IRAK2.
GenevestigatorO43187.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PfamPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO43187.
GeneWikiIRAK2.
GenomeRNAi3656.
NextBio14303.
PROO43187.
SOURCESearch...

Entry information

Entry nameIRAK2_HUMAN
AccessionPrimary (citable) accession number: O43187
Secondary accession number(s): B4DQZ6, Q08AG6, Q5K546
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: February 6, 2007
Last modified: July 9, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM