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Protein

Interleukin-1 receptor-associated kinase 3

Gene

IRAK3

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

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

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

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-9020702 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

EuPathDBiHostDB:ENSG00000090376.8
HGNCiHGNC:17020 IRAK3
MIMi604459 gene
neXtProtiNX_Q9Y616

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

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

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, 24 interactors
CORUMiQ9Y616
IntActiQ9Y616, 17 interactors
MINTiQ9Y616
STRINGi9606.ENSP00000261233

Chemistry databases

BindingDBiQ9Y616

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 19Combined sources3
Turni22 – 24Combined sources3
Helixi25 – 31Combined sources7
Helixi32 – 34Combined sources3
Beta strandi36 – 39Combined sources4
Helixi43 – 48Combined sources6
Helixi54 – 61Combined sources8
Helixi62 – 64Combined sources3
Helixi68 – 74Combined sources7
Beta strandi76 – 78Combined sources3
Helixi83 – 93Combined sources11
Helixi96 – 102Combined sources7
Beta strandi107 – 109Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5UKENMR-A1-119[»]
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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR033610 IRAK3
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
PANTHERiPTHR24419:SF7 PTHR24419:SF7, 1 hit
PfamiView protein in Pfam
PF00531 Death, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00005 DEATH, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50017 DEATH_DOMAIN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

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 dbSNP:rs536546109Ensembl.1
Natural variantiVAR_04058157H → R1 PublicationCorresponds to variant dbSNP:rs35239505Ensembl.1
Natural variantiVAR_04058284G → S1 PublicationCorresponds to variant dbSNP:rs34443407Ensembl.1
Natural variantiVAR_035213111P → A May be associated with ASRT5. 1 PublicationCorresponds to variant dbSNP:rs373806603Ensembl.1
Natural variantiVAR_035214134V → M May be associated with ASRT5. 1 PublicationCorresponds to variant dbSNP:rs138559915Ensembl.1
Natural variantiVAR_019812147I → V4 PublicationsCorresponds to variant dbSNP:rs1152888Ensembl.1
Natural variantiVAR_040583171I → V1 PublicationCorresponds to variant dbSNP:rs34682166Ensembl.1
Natural variantiVAR_033901269G → S. Corresponds to variant dbSNP:rs35823766Ensembl.1
Natural variantiVAR_031077270I → V. Corresponds to variant dbSNP:rs11465972Ensembl.1
Natural variantiVAR_040584288S → L1 PublicationCorresponds to variant dbSNP:rs35574245Ensembl.1
Natural variantiVAR_040585384R → Q1 PublicationCorresponds to variant dbSNP:rs34272472Ensembl.1
Natural variantiVAR_040586391M → T1 PublicationCorresponds to variant dbSNP:rs35737689Ensembl.1
Natural variantiVAR_035215400L → V May be associated with ASRT5. 1 PublicationCorresponds to variant dbSNP:rs146120640Ensembl.1
Natural variantiVAR_035216429R → Q May be associated with ASRT5. 1 PublicationCorresponds to variant dbSNP:rs140671957Ensembl.1
Natural variantiVAR_040587482D → N1 PublicationCorresponds to variant dbSNP:rs35756811Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiIRAK3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y616
Secondary accession number(s): B4DQ57
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: February 8, 2011
Last modified: May 23, 2018
This is version 158 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

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