Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8K4B2 (IRAK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 3

Short name=IRAK-3
EC=2.7.11.1
Alternative name(s):
IL-1 receptor-associated kinase M
Short name=IRAK-M
Gene names
Name:Irak3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length609 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex. Ref.1 Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.2

Cofactor

Magnesium. Ref.2

Tissue specificity

Highly expressed in liver and thymus and at lower levels in heart, brain, spleen and kidney. Ref.2

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-306 is present instead of the conserved Asp which is expected to be an active site residue. Low level autophosphorylation activity has been reported in Ref.2, while other authors describe this as an inactive kinase.

Ontologies

Keywords
   LigandATP-binding
Magnesium
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcytokine-mediated signaling pathway

Inferred from direct assay Ref.2. Source: UniProtKB

interleukin-1-mediated signaling pathway

Inferred from direct assay Ref.2. Source: MGI

negative regulation of MAP kinase activity

Inferred from mutant phenotype PubMed 17379480. Source: BHF-UCL

negative regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of cytokine-mediated signaling pathway

Inferred by curator Ref.1. Source: BHF-UCL

negative regulation of innate immune response

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of interleukin-12 production

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of interleukin-6 production

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of macrophage cytokine production

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of protein catabolic process

Inferred from mutant phenotype PubMed 17379480. Source: BHF-UCL

negative regulation of protein complex disassembly

Inferred from electronic annotation. Source: Ensembl

negative regulation of toll-like receptor signaling pathway

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of tumor necrosis factor production

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.2. Source: MGI

positive regulation of macrophage tolerance induction

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

protein autophosphorylation

Inferred from direct assay Ref.2. Source: MGI

protein phosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

regulation of protein complex disassembly

Inferred from direct assay Ref.2. Source: UniProtKB

response to exogenous dsRNA

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

response to lipopolysaccharide

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

response to peptidoglycan

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

response to virus

Inferred by curator Ref.1. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17379480. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 17379480. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from direct assay Ref.2. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.2. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15102471PubMed 23376919. Source: IntAct

protein kinase activity

Inferred from direct assay Ref.2. Source: MGI

protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IRAK4Q9NWZ34EBI-646179,EBI-448378From a different organism.
Irak4Q8R4K27EBI-646179,EBI-3842721
Traf6P701963EBI-646179,EBI-448028

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 609609Interleukin-1 receptor-associated kinase 3
PRO_0000086034

Regions

Domain41 – 10666Death
Domain178 – 463286Protein kinase
Nucleotide binding184 – 1929ATP By similarity UniProtKB P51617
Nucleotide binding308 – 3114ATP By similarity

Sites

Binding site2051ATP By similarity UniProtKB P51617
Binding site3241ATP By similarity

Amino acid modifications

Modified residue4801Phosphoserine By similarity

Experimental info

Sequence conflict351C → W in AAM83393. Ref.1
Sequence conflict421R → W in AAM83393. Ref.1
Sequence conflict621V → L in AAM83393. Ref.1
Sequence conflict1261P → L in AAM83393. Ref.1
Sequence conflict1471V → M in AAM83393. Ref.1
Sequence conflict2821S → G in BAC33612. Ref.3
Sequence conflict2821S → N in AAM83393. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8K4B2 [UniParc].

Last modified October 25, 2004. Version 2.
Checksum: A63E010C9F29D856

FASTA60968,455
        10         20         30         40         50         60 
MAGRCGARGA LSPQLLLFDL PPALLGELCG ILDSCDGPLG WRGLAERLSN SWLDVRHIEK 

        70         80         90        100        110        120 
YVNQGKSGTR ELLWSWAQKN KTIGDLLEVL QDMGHQRAIH LIINYGVSWT PSVQTHHELP 

       130        140        150        160        170        180 
FPSFPPEVKH ACRENDPGPL EPANVTVDNV LVPEHNEKGT LQKTPISFQS ILEGTKHFHK 

       190        200        210        220        230        240 
DFLIGEGEIF EVYRVDIRNQ AYAVKLFKQE KKMQLKKHWK RFLSELEVLL LFRHPHILEL 

       250        260        270        280        290        300 
AAYFTETEKL CLVYPYMSNG TLFDRLQCTN GTTPLSWHVR ISVLIGIAKA IQYLHNTQPC 

       310        320        330        340        350        360 
AVICGNVSSA NILLDDQLQP KLTDFAAAHF RPNLEQQSST INMTGGGRKH LWYMPEEYIR 

       370        380        390        400        410        420 
QGRLSVKTDV YSFGIVIMEV LTGCKVVLDD PKHVQLRDLL MELMEKRGLD SCLSFLDRKI 

       430        440        450        460        470        480 
PPCPRNFSAK LFSLAGRCVA TKAKLRPTMD EVLSSLESTQ PSLYFAEDPP TSLKSFRCPS 

       490        500        510        520        530        540 
PLFLDNVPSI PVEDDENQNN HSVPPKEVLG TDRVTQKTPF ECSQSEVTFL GLDRNRGNRG 

       550        560        570        580        590        600 
SEADCNVPSS SHEECWSPEL VAPSQDLSPT VISLGSSWEV PGHSYGSKPM EKRCSSGLFC 


SEHEQSKKQ 

« Hide

References

« Hide 'large scale' references
[1]"IRAK-M is a negative regulator of Toll-like receptor signaling."
Kobayashi K., Hernandez L.D., Galan J.E., Janeway C.A. Jr., Medzhitov R., Flavell R.A.
Cell 110:191-202(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Strain: C57BL/6.
Tissue: Macrophage.
[2]"Identification and characterization of murine IRAK-M."
Rosati O., Martin M.U.
Biochem. Biophys. Res. Commun. 293:1472-1477(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, TISSUE SPECIFICITY.
Strain: BALB/c.
Tissue: Macrophage.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Skin.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF461763 mRNA. Translation: AAM83393.1.
AJ440757 mRNA. Translation: CAD29448.2.
AK029057 mRNA. Translation: BAC26270.1.
AK049210 mRNA. Translation: BAC33612.1.
CCDSCCDS24204.1.
RefSeqNP_082955.2. NM_028679.3.
UniGeneMm.146194.

3D structure databases

ProteinModelPortalQ8K4B2.
SMRQ8K4B2. Positions 184-457.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid216351. 2 interactions.
IntActQ8K4B2. 6 interactions.

PTM databases

PhosphoSiteQ8K4B2.

Proteomic databases

PRIDEQ8K4B2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020448; ENSMUSP00000020448; ENSMUSG00000020227.
GeneID73914.
KEGGmmu:73914.
UCSCuc007het.1. mouse.

Organism-specific databases

CTD11213.
MGIMGI:1921164. Irak3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000063073.
HOGENOMHOG000060319.
HOVERGENHBG052146.
InParanoidQ8K4B2.
KOK04732.
OMAFKQEKKM.
OrthoDBEOG7KQ21F.
PhylomeDBQ8K4B2.
TreeFamTF328924.

Gene expression databases

ArrayExpressQ8K4B2.
BgeeQ8K4B2.
CleanExMM_IRAK3.
GenevestigatorQ8K4B2.

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.
PROSITEPS50017. DEATH_DOMAIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio339332.
PROQ8K4B2.
SOURCESearch...

Entry information

Entry nameIRAK3_MOUSE
AccessionPrimary (citable) accession number: Q8K4B2
Secondary accession number(s): Q8C7U8, Q8CE40, Q8K1S8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: October 25, 2004
Last modified: July 9, 2014
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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