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Protein

Interleukin-1 receptor-associated kinase 3

Gene

Irak3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei205 – 2051ATPBy similarityPROSITE-ProRule annotation
Binding sitei324 – 3241ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi184 – 1929ATPBy similarityPROSITE-ProRule annotation
Nucleotide bindingi308 – 3114ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. magnesium ion binding Source: UniProtKB
  3. protein heterodimerization activity Source: MGI
  4. protein homodimerization activity Source: MGI
  5. protein kinase activity Source: MGI
  6. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. cytokine-mediated signaling pathway Source: UniProtKB
  2. interleukin-1-mediated signaling pathway Source: MGI
  3. negative regulation of cytokine-mediated signaling pathway Source: BHF-UCL
  4. negative regulation of innate immune response Source: BHF-UCL
  5. negative regulation of interleukin-12 production Source: BHF-UCL
  6. negative regulation of interleukin-6 production Source: BHF-UCL
  7. negative regulation of macrophage cytokine production Source: BHF-UCL
  8. negative regulation of MAP kinase activity Source: BHF-UCL
  9. negative regulation of NF-kappaB transcription factor activity Source: MGI
  10. negative regulation of protein catabolic process Source: BHF-UCL
  11. negative regulation of protein complex disassembly Source: MGI
  12. negative regulation of toll-like receptor signaling pathway Source: BHF-UCL
  13. negative regulation of tumor necrosis factor production Source: BHF-UCL
  14. positive regulation of macrophage tolerance induction Source: BHF-UCL
  15. positive regulation of NF-kappaB transcription factor activity Source: MGI
  16. protein autophosphorylation Source: MGI
  17. protein phosphorylation Source: UniProtKB
  18. regulation of protein complex disassembly Source: UniProtKB
  19. response to exogenous dsRNA Source: BHF-UCL
  20. response to interleukin-1 Source: MGI
  21. response to lipopolysaccharide Source: BHF-UCL
  22. response to peptidoglycan Source: BHF-UCL
  23. response to virus Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_224208. Interleukin-1 signaling.
REACT_230045. MyD88:Mal cascade initiated on plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 receptor-associated kinase 3 (EC:2.7.11.1)
Short name:
IRAK-3
Alternative name(s):
IL-1 receptor-associated kinase M
Short name:
IRAK-M
Gene namesi
Name:Irak3Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:1921164. Irak3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. interleukin-1 receptor complex Source: GO_Central
  3. nucleus Source: BHF-UCL
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 609609Interleukin-1 receptor-associated kinase 3PRO_0000086034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei480 – 4801PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8K4B2.
PRIDEiQ8K4B2.

PTM databases

PhosphoSiteiQ8K4B2.

Expressioni

Tissue specificityi

Highly expressed in liver and thymus and at lower levels in heart, brain, spleen and kidney.1 Publication

Gene expression databases

BgeeiQ8K4B2.
CleanExiMM_IRAK3.
ExpressionAtlasiQ8K4B2. baseline and differential.
GenevestigatoriQ8K4B2.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
IRAK4Q9NWZ34EBI-646179,EBI-448378From a different organism.
Irak4Q8R4K27EBI-646179,EBI-3842721
Traf6P701963EBI-646179,EBI-448028

Protein-protein interaction databases

BioGridi216351. 2 interactions.
IntActiQ8K4B2. 6 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ8K4B2.
SMRiQ8K4B2. Positions 181-485.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 10666DeathPROSITE-ProRule annotationAdd
BLAST
Domaini178 – 463286Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000060319.
HOVERGENiHBG052146.
InParanoidiQ8K4B2.
KOiK04732.
OMAiFKQEKKM.
OrthoDBiEOG7KQ21F.
PhylomeDBiQ8K4B2.
TreeFamiTF328924.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8K4B2-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAGRCGARGA LSPQLLLFDL PPALLGELCG ILDSCDGPLG WRGLAERLSN
60 70 80 90 100
SWLDVRHIEK YVNQGKSGTR ELLWSWAQKN KTIGDLLEVL QDMGHQRAIH
110 120 130 140 150
LIINYGVSWT PSVQTHHELP FPSFPPEVKH ACRENDPGPL EPANVTVDNV
160 170 180 190 200
LVPEHNEKGT LQKTPISFQS ILEGTKHFHK DFLIGEGEIF EVYRVDIRNQ
210 220 230 240 250
AYAVKLFKQE KKMQLKKHWK RFLSELEVLL LFRHPHILEL AAYFTETEKL
260 270 280 290 300
CLVYPYMSNG TLFDRLQCTN GTTPLSWHVR ISVLIGIAKA IQYLHNTQPC
310 320 330 340 350
AVICGNVSSA NILLDDQLQP KLTDFAAAHF RPNLEQQSST INMTGGGRKH
360 370 380 390 400
LWYMPEEYIR QGRLSVKTDV YSFGIVIMEV LTGCKVVLDD PKHVQLRDLL
410 420 430 440 450
MELMEKRGLD SCLSFLDRKI PPCPRNFSAK LFSLAGRCVA TKAKLRPTMD
460 470 480 490 500
EVLSSLESTQ PSLYFAEDPP TSLKSFRCPS PLFLDNVPSI PVEDDENQNN
510 520 530 540 550
HSVPPKEVLG TDRVTQKTPF ECSQSEVTFL GLDRNRGNRG SEADCNVPSS
560 570 580 590 600
SHEECWSPEL VAPSQDLSPT VISLGSSWEV PGHSYGSKPM EKRCSSGLFC

SEHEQSKKQ
Length:609
Mass (Da):68,455
Last modified:October 25, 2004 - v2
Checksum:iA63E010C9F29D856
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti35 – 351C → W in AAM83393. (PubMed:12150927)Curated
Sequence conflicti42 – 421R → W in AAM83393. (PubMed:12150927)Curated
Sequence conflicti62 – 621V → L in AAM83393. (PubMed:12150927)Curated
Sequence conflicti126 – 1261P → L in AAM83393. (PubMed:12150927)Curated
Sequence conflicti147 – 1471V → M in AAM83393. (PubMed:12150927)Curated
Sequence conflicti282 – 2821S → G in BAC33612. (PubMed:16141072)Curated
Sequence conflicti282 – 2821S → N in AAM83393. (PubMed:12150927)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF461763 mRNA. Translation: AAM83393.1.
AJ440757 mRNA. Translation: CAD29448.2.
AK029057 mRNA. Translation: BAC26270.1.
AK049210 mRNA. Translation: BAC33612.1.
CCDSiCCDS24204.1.
RefSeqiNP_082955.2. NM_028679.3.
UniGeneiMm.146194.

Genome annotation databases

EnsembliENSMUST00000020448; ENSMUSP00000020448; ENSMUSG00000020227.
GeneIDi73914.
KEGGimmu:73914.
UCSCiuc007het.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF461763 mRNA. Translation: AAM83393.1.
AJ440757 mRNA. Translation: CAD29448.2.
AK029057 mRNA. Translation: BAC26270.1.
AK049210 mRNA. Translation: BAC33612.1.
CCDSiCCDS24204.1.
RefSeqiNP_082955.2. NM_028679.3.
UniGeneiMm.146194.

3D structure databases

ProteinModelPortaliQ8K4B2.
SMRiQ8K4B2. Positions 181-485.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi216351. 2 interactions.
IntActiQ8K4B2. 6 interactions.

PTM databases

PhosphoSiteiQ8K4B2.

Proteomic databases

MaxQBiQ8K4B2.
PRIDEiQ8K4B2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020448; ENSMUSP00000020448; ENSMUSG00000020227.
GeneIDi73914.
KEGGimmu:73914.
UCSCiuc007het.1. mouse.

Organism-specific databases

CTDi11213.
MGIiMGI:1921164. Irak3.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000060319.
HOVERGENiHBG052146.
InParanoidiQ8K4B2.
KOiK04732.
OMAiFKQEKKM.
OrthoDBiEOG7KQ21F.
PhylomeDBiQ8K4B2.
TreeFamiTF328924.

Enzyme and pathway databases

ReactomeiREACT_224208. Interleukin-1 signaling.
REACT_230045. MyD88:Mal cascade initiated on plasma membrane.

Miscellaneous databases

NextBioi339332.
PROiQ8K4B2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8K4B2.
CleanExiMM_IRAK3.
ExpressionAtlasiQ8K4B2. baseline and differential.
GenevestigatoriQ8K4B2.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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/6Imported.
    Tissue: Macrophage1 Publication.
  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/cImported.
    Tissue: Macrophage1 Publication.
  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.
    , 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.

Entry informationi

Entry nameiIRAK3_MOUSE
AccessioniPrimary (citable) accession number: Q8K4B2
Secondary accession number(s): Q8C7U8, Q8CE40, Q8K1S8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: October 25, 2004
Last modified: February 4, 2015
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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 PubMed:12054681, while other authors describe this as an inactive kinase.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.