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Protein

Interleukin-1 receptor-associated kinase 3

Gene

IRAK3

Organism
Homo sapiens (Human)
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.By similarity1 Publication

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei192ATPPROSITE-ProRule annotationBy similarity1
Binding sitei311ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi171 – 179ATPPROSITE-ProRule annotationBy similarity9
Nucleotide bindingi295 – 298ATPPROSITE-ProRule annotation4

GO - Molecular functioni

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

GO - Biological processi

  • cytokine-mediated signaling pathway Source: UniProtKB
  • interleukin-1-mediated signaling pathway Source: BHF-UCL
  • MyD88-dependent toll-like receptor signaling pathway Source: BHF-UCL
  • negative regulation of cytokine-mediated signaling pathway Source: BHF-UCL
  • negative regulation of innate immune response Source: BHF-UCL
  • negative regulation of interleukin-12 production Source: BHF-UCL
  • negative regulation of interleukin-6 production Source: BHF-UCL
  • negative regulation of macrophage cytokine production Source: BHF-UCL
  • negative regulation of MAP kinase activity Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • negative regulation of protein catabolic process Source: BHF-UCL
  • negative regulation of protein complex disassembly Source: BHF-UCL
  • negative regulation of toll-like receptor signaling pathway Source: BHF-UCL
  • negative regulation of tumor necrosis factor production Source: BHF-UCL
  • positive regulation of macrophage tolerance induction Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • protein autophosphorylation Source: Ensembl
  • protein phosphorylation Source: UniProtKB
  • regulation of protein complex disassembly Source: UniProtKB
  • response to exogenous dsRNA Source: BHF-UCL
  • response to interleukin-1 Source: BHF-UCL
  • response to lipopolysaccharide Source: BHF-UCL
  • response to peptidoglycan Source: BHF-UCL
  • 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

BioCyciZFISH:HS01686-MONOMER.
ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-446652. Interleukin-1 signaling.
SignaLinkiQ9Y616.
SIGNORiQ9Y616.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:17020. IRAK3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • nucleus Source: BHF-UCL
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Asthma-related traits 5 (ASRT5)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionAsthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy and atopic dermatitis.
See also OMIM:611064
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03521222P → L May be associated with ASRT5. 1 PublicationCorresponds to variant rs536546109dbSNPEnsembl.1
Natural variantiVAR_035213111P → A May be associated with ASRT5. 1 PublicationCorresponds to variant rs373806603dbSNPEnsembl.1
Natural variantiVAR_035214134V → M May be associated with ASRT5. 1 PublicationCorresponds to variant rs138559915dbSNPEnsembl.1
Natural variantiVAR_035215400L → V May be associated with ASRT5. 1 PublicationCorresponds to variant rs146120640dbSNPEnsembl.1
Natural variantiVAR_035216429R → Q May be associated with ASRT5. 1 PublicationCorresponds to variant rs140671957dbSNPEnsembl.1

Keywords - Diseasei

Asthma

Organism-specific databases

DisGeNETi11213.
MalaCardsiIRAK3.
MIMi611064. phenotype.
OpenTargetsiENSG00000090376.
PharmGKBiPA38431.

Chemistry databases

ChEMBLiCHEMBL5081.
GuidetoPHARMACOLOGYi2044.

Polymorphism and mutation databases

BioMutaiIRAK3.
DMDMi322510038.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860331 – 596Interleukin-1 receptor-associated kinase 3Add BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei467PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y616.
PaxDbiQ9Y616.
PeptideAtlasiQ9Y616.
PRIDEiQ9Y616.

PTM databases

iPTMnetiQ9Y616.
PhosphoSitePlusiQ9Y616.

Expressioni

Tissue specificityi

Expressed predominantly in peripheral blood lymphocytes.1 Publication

Gene expression databases

BgeeiENSG00000090376.
CleanExiHS_IRAK3.
ExpressionAtlasiQ9Y616. baseline and differential.
GenevisibleiQ9Y616. HS.

Organism-specific databases

HPAiHPA043097.

Interactioni

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi116382. 18 interactors.
IntActiQ9Y616. 17 interactors.
MINTiMINT-97148.
STRINGi9606.ENSP00000261233.

Chemistry databases

BindingDBiQ9Y616.

Structurei

3D structure databases

ProteinModelPortaliQ9Y616.
SMRiQ9Y616.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 106DeathPROSITE-ProRule annotationAdd BLAST66
Domaini165 – 452Protein kinasePROSITE-ProRule annotationAdd BLAST288

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000060319.
HOVERGENiHBG052146.
InParanoidiQ9Y616.
KOiK04732.
OMAiKLTDFAM.
OrthoDBiEOG091G0YKT.
PhylomeDBiQ9Y616.
TreeFamiTF328924.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR033610. IRAK3.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PANTHERiPTHR24419:SF7. PTHR24419:SF7. 1 hit.
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y616-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGNCGARGA LSAHTLLFDL PPALLGELCA VLDSCDGALG WRGLAERLSS
60 70 80 90 100
SWLDVRHIEK YVDQGKSGTR ELLWSWAQKN KTIGDLLQVL QEMGHRRAIH
110 120 130 140 150
LITNYGAVLS PSEKSYQEGG FPNILFKETA NVTVDNVLIP EHNEKGILLK
160 170 180 190 200
SSISFQNIIE GTRNFHKDFL IGEGEIFEVY RVEIQNLTYA VKLFKQEKKM
210 220 230 240 250
QCKKHWKRFL SELEVLLLFH HPNILELAAY FTETEKFCLI YPYMRNGTLF
260 270 280 290 300
DRLQCVGDTA PLPWHIRIGI LIGISKAIHY LHNVQPCSVI CGSISSANIL
310 320 330 340 350
LDDQFQPKLT DFAMAHFRSH LEHQSCTINM TSSSSKHLWY MPEEYIRQGK
360 370 380 390 400
LSIKTDVYSF GIVIMEVLTG CRVVLDDPKH IQLRDLLREL MEKRGLDSCL
410 420 430 440 450
SFLDKKVPPC PRNFSAKLFC LAGRCAATRA KLRPSMDEVL NTLESTQASL
460 470 480 490 500
YFAEDPPTSL KSFRCPSPLF LENVPSIPVE DDESQNNNLL PSDEGLRIDR
510 520 530 540 550
MTQKTPFECS QSEVMFLSLD KKPESKRNEE ACNMPSSSCE ESWFPKYIVP
560 570 580 590
SQDLRPYKVN IDPSSEAPGH SCRSRPVESS CSSKFSWDEY EQYKKE
Length:596
Mass (Da):67,767
Last modified:February 8, 2011 - v2
Checksum:iD050150B7BDA5B9A
GO
Isoform 2 (identifier: Q9Y616-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     45-105: Missing.

Note: No experimental confirmation available.
Show »
Length:535
Mass (Da):60,608
Checksum:i54DEDA8A162DD662
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti560N → D in BAG60819 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03521222P → L May be associated with ASRT5. 1 PublicationCorresponds to variant rs536546109dbSNPEnsembl.1
Natural variantiVAR_04058157H → R.1 PublicationCorresponds to variant rs35239505dbSNPEnsembl.1
Natural variantiVAR_04058284G → S.1 PublicationCorresponds to variant rs34443407dbSNPEnsembl.1
Natural variantiVAR_035213111P → A May be associated with ASRT5. 1 PublicationCorresponds to variant rs373806603dbSNPEnsembl.1
Natural variantiVAR_035214134V → M May be associated with ASRT5. 1 PublicationCorresponds to variant rs138559915dbSNPEnsembl.1
Natural variantiVAR_019812147I → V.4 PublicationsCorresponds to variant rs1152888dbSNPEnsembl.1
Natural variantiVAR_040583171I → V.1 PublicationCorresponds to variant rs34682166dbSNPEnsembl.1
Natural variantiVAR_033901269G → S.Corresponds to variant rs35823766dbSNPEnsembl.1
Natural variantiVAR_031077270I → V.Corresponds to variant rs11465972dbSNPEnsembl.1
Natural variantiVAR_040584288S → L.1 PublicationCorresponds to variant rs35574245dbSNPEnsembl.1
Natural variantiVAR_040585384R → Q.1 PublicationCorresponds to variant rs34272472dbSNPEnsembl.1
Natural variantiVAR_040586391M → T.1 PublicationCorresponds to variant rs35737689dbSNPEnsembl.1
Natural variantiVAR_035215400L → V May be associated with ASRT5. 1 PublicationCorresponds to variant rs146120640dbSNPEnsembl.1
Natural variantiVAR_035216429R → Q May be associated with ASRT5. 1 PublicationCorresponds to variant rs140671957dbSNPEnsembl.1
Natural variantiVAR_040587482D → N.1 PublicationCorresponds to variant rs35756811dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04102045 – 105Missing in isoform 2. 1 PublicationAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF113136 mRNA. Translation: AAD40879.1.
AK298645 mRNA. Translation: BAG60819.1.
AC078889 Genomic DNA. No translation available.
AC078927 Genomic DNA. No translation available.
BC057800 mRNA. Translation: AAH57800.1.
BC069388 mRNA. Translation: AAH69388.1.
CCDSiCCDS44937.1. [Q9Y616-2]
CCDS8975.1. [Q9Y616-1]
RefSeqiNP_001135995.1. NM_001142523.1. [Q9Y616-2]
NP_009130.2. NM_007199.2. [Q9Y616-1]
UniGeneiHs.369265.

Genome annotation databases

EnsembliENST00000261233; ENSP00000261233; ENSG00000090376. [Q9Y616-1]
ENST00000457197; ENSP00000409852; ENSG00000090376. [Q9Y616-2]
GeneIDi11213.
KEGGihsa:11213.
UCSCiuc001sth.4. human. [Q9Y616-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF113136 mRNA. Translation: AAD40879.1.
AK298645 mRNA. Translation: BAG60819.1.
AC078889 Genomic DNA. No translation available.
AC078927 Genomic DNA. No translation available.
BC057800 mRNA. Translation: AAH57800.1.
BC069388 mRNA. Translation: AAH69388.1.
CCDSiCCDS44937.1. [Q9Y616-2]
CCDS8975.1. [Q9Y616-1]
RefSeqiNP_001135995.1. NM_001142523.1. [Q9Y616-2]
NP_009130.2. NM_007199.2. [Q9Y616-1]
UniGeneiHs.369265.

3D structure databases

ProteinModelPortaliQ9Y616.
SMRiQ9Y616.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116382. 18 interactors.
IntActiQ9Y616. 17 interactors.
MINTiMINT-97148.
STRINGi9606.ENSP00000261233.

Chemistry databases

BindingDBiQ9Y616.
ChEMBLiCHEMBL5081.
GuidetoPHARMACOLOGYi2044.

PTM databases

iPTMnetiQ9Y616.
PhosphoSitePlusiQ9Y616.

Polymorphism and mutation databases

BioMutaiIRAK3.
DMDMi322510038.

Proteomic databases

EPDiQ9Y616.
PaxDbiQ9Y616.
PeptideAtlasiQ9Y616.
PRIDEiQ9Y616.

Protocols and materials databases

DNASUi11213.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261233; ENSP00000261233; ENSG00000090376. [Q9Y616-1]
ENST00000457197; ENSP00000409852; ENSG00000090376. [Q9Y616-2]
GeneIDi11213.
KEGGihsa:11213.
UCSCiuc001sth.4. human. [Q9Y616-1]

Organism-specific databases

CTDi11213.
DisGeNETi11213.
GeneCardsiIRAK3.
HGNCiHGNC:17020. IRAK3.
HPAiHPA043097.
MalaCardsiIRAK3.
MIMi604459. gene.
611064. phenotype.
neXtProtiNX_Q9Y616.
OpenTargetsiENSG00000090376.
PharmGKBiPA38431.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000060319.
HOVERGENiHBG052146.
InParanoidiQ9Y616.
KOiK04732.
OMAiKLTDFAM.
OrthoDBiEOG091G0YKT.
PhylomeDBiQ9Y616.
TreeFamiTF328924.

Enzyme and pathway databases

BioCyciZFISH:HS01686-MONOMER.
ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-446652. Interleukin-1 signaling.
SignaLinkiQ9Y616.
SIGNORiQ9Y616.

Miscellaneous databases

GeneWikiiIRAK3.
GenomeRNAii11213.
PROiQ9Y616.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090376.
CleanExiHS_IRAK3.
ExpressionAtlasiQ9Y616. baseline and differential.
GenevisibleiQ9Y616. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR033610. IRAK3.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PANTHERiPTHR24419:SF7. PTHR24419:SF7. 1 hit.
PfamiPF00531. Death. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00005. DEATH. 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...

Entry informationi

Entry nameiIRAK3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y616
Secondary accession number(s): B4DQ57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: February 8, 2011
Last modified: November 30, 2016
This is version 146 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

Ser-293 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:10383454, while other authors describe this as an inactive kinase.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.