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Aliases for IRAK1 Gene

Aliases for IRAK1 Gene

  • Interleukin-1 Receptor-Associated Kinase 1 2 3
  • EC 2.7.11.1 4 64
  • IRAK-1 3 4
  • IRAK 3 4
  • Pelle Homolog 3
  • EC 2.7.11 64
  • Pelle 3

External Ids for IRAK1 Gene

Summaries for IRAK1 Gene

Entrez Gene Summary for IRAK1 Gene

  • This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for IRAK1 Gene

IRAK1 (Interleukin-1 Receptor-Associated Kinase 1) is a Protein Coding gene. Diseases associated with IRAK1 include pediatric systemic lupus erythematosus and systemic lupus erythematosus. Among its related pathways are Signaling by FGFR and Signaling by GPCR. GO annotations related to this gene include protein homodimerization activity and protein serine/threonine kinase activity. An important paralog of this gene is IRAK4.

UniProtKB/Swiss-Prot for IRAK1 Gene

  • Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.

Gene Wiki entry for IRAK1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IRAK1 Gene

Genomics for IRAK1 Gene

Genomic Location for IRAK1 Gene

Start:
154,010,500 bp from pter
End:
154,019,980 bp from pter
Size:
9,481 bases
Orientation:
Minus strand

Genomic View for IRAK1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for IRAK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRAK1 Gene

Regulatory Elements for IRAK1 Gene

Proteins for IRAK1 Gene

  • Protein details for IRAK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51617-IRAK1_HUMAN
    Recommended name:
    Interleukin-1 receptor-associated kinase 1
    Protein Accession:
    P51617
    Secondary Accessions:
    • D3DWW3
    • D3DWW4
    • Q7Z5V4
    • Q96C06
    • Q96RL2

    Protein attributes for IRAK1 Gene

    Size:
    712 amino acids
    Molecular mass:
    76537 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Homodimer (By similarity). Interacts with TOLLIP; this interaction occurs in the cytosol prior to receptor activation. Interacts with IL1RL1. Forms a complex with TRAF6, PELI1, IRAK4 and MYD88. Interaction with MYD88 recruits IRAK1 to the stimulated receptor complex. The TRAF6-PELI1-IRAK1-IRAK4-MYD88 complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Interacts with IRAK1BP1 (By similarity). Interacts (when polyubiquitinated) with IKBKG/NEMO. Interacts with RSAD2/viperin (By similarity).

    Alternative splice isoforms for IRAK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IRAK1 Gene

Proteomics data for IRAK1 Gene at MOPED

Selected DME Specific Peptides for IRAK1 Gene

Post-translational modifications for IRAK1 Gene

  • Following recruitment on the activated receptor complex, phosphorylated on Thr-209, probably by IRAK4, resulting in a conformational change of the kinase domain, allowing further phosphorylations to take place. Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity.
  • Polyubiquitinated by TRAF6 after cell stimulation with IL-1-beta by PELI1, PELI2 and PELI3. Polyubiquitination occurs with polyubiquitin chains linked through Lys-63. Ubiquitination promotes interaction with NEMO/IKBKG. Also sumoylated; leading to nuclear translocation.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys342, Lys355, and Lys397

Domains for IRAK1 Gene

UniProtKB/Swiss-Prot:

IRAK1_HUMAN
Domain:
  • The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation.:
    • P51617
  • Contains 1 death domain.:
    • P51617
  • Contains 1 protein kinase domain.:
    • P51617
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.:
    • P51617
genes like me logo Genes that share domains with IRAK1: view

Function for IRAK1 Gene

Molecular function for IRAK1 Gene

GENATLAS Biochemistry: interleukin-1 receptor-associated kinase,100kDa,Drosophila Pelle homolog,forming a complex with IL1R1 after induction by IL1 through its association with IL1RAP and subsequently interacting with TRAF6 required for IL-1 mediated NFKB activation,see symbols
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot Function: Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.

Enzyme Numbers (IUBMB) for IRAK1 Gene

Gene Ontology (GO) - Molecular Function for IRAK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity TAS --
GO:0004674 protein serine/threonine kinase activity NAS 11397809
GO:0004704 NF-kappaB-inducing kinase activity TAS 8599092
GO:0004713 protein tyrosine kinase activity --
GO:0004842 ubiquitin-protein transferase activity TAS --
genes like me logo Genes that share ontologies with IRAK1: view
genes like me logo Genes that share phenotypes with IRAK1: view

Animal Models for IRAK1 Gene

MGI Knock Outs for IRAK1:

No data available for Transcription Factor Targeting and HOMER Transcription for IRAK1 Gene

Localization for IRAK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IRAK1 Gene

Cytoplasm. Nucleus. Lipid droplet. Note=Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for IRAK1 Gene COMPARTMENTS Subcellular localization image for IRAK1 gene
Compartment Confidence
nucleus 5
plasma membrane 5
cytosol 4
endosome 4
peroxisome 2

Gene Ontology (GO) - Cellular Components for IRAK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm IDA --
GO:0005811 lipid particle ISS --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with IRAK1: view

Pathways for IRAK1 Gene

genes like me logo Genes that share pathways with IRAK1: view

Gene Ontology (GO) - Biological Process for IRAK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity TAS --
GO:0001959 regulation of cytokine-mediated signaling pathway IMP 10383454
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS 10383454
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with IRAK1: view

Compounds for IRAK1 Gene

(3) HMDB Compounds for IRAK1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(25) Novoseek inferred chemical compound relationships for IRAK1 Gene

Compound -log(P) Hits PubMed IDs
tab-2 79.6 8
tab-1 65.1 4
lipoteichoic acid 56.1 5
threonine 43.1 9
endotoxin 40.3 3
genes like me logo Genes that share compounds with IRAK1: view

Transcripts for IRAK1 Gene

Unigene Clusters for IRAK1 Gene

Interleukin-1 receptor-associated kinase 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for IRAK1 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b ^ 8a · 8b · 8c ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b · 12c ^ 13 ^ 14a · 14b · 14c
SP1: -
SP2: - -
SP3: - -
SP4: - -
SP5: - -
SP6: - -
SP7: - - -
SP8:
SP9: - -

Relevant External Links for IRAK1 Gene

GeneLoc Exon Structure for
IRAK1
ECgene alternative splicing isoforms for
IRAK1

Expression for IRAK1 Gene

mRNA expression in normal human tissues for IRAK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for IRAK1 Gene

SOURCE GeneReport for Unigene cluster for IRAK1 Gene Hs.522819

mRNA Expression by UniProt/SwissProt for IRAK1 Gene

P51617-IRAK1_HUMAN
Tissue specificity: Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.
genes like me logo Genes that share expressions with IRAK1: view

Orthologs for IRAK1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for IRAK1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia IRAK1 36
  • 99.49 (n)
  • 99.02 (a)
IRAK1 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia IRAK1 36
  • 83.47 (n)
  • 81.69 (a)
IRAK1 37
  • 80 (a)
OneToOne
dog
(Canis familiaris)
Mammalia IRAK1 36
  • 85.11 (n)
  • 83.83 (a)
IRAK1 37
  • 83 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Irak1 36
  • 82.04 (n)
  • 81.38 (a)
Irak1 16
Irak1 37
  • 77 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia IRAK1 37
  • 60 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia IRAK1 37
  • 58 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Irak1 36
  • 81.57 (n)
  • 80.96 (a)
lizard
(Anolis carolinensis)
Reptilia IRAK1 37
  • 47 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.15551 36
tropical clawed frog
(Silurana tropicalis)
Amphibia irak1 36
  • 53.65 (n)
  • 48.64 (a)
zebrafish
(Danio rerio)
Actinopterygii irak1 36
  • 51.27 (n)
  • 46.18 (a)
irak1 37
  • 40 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta pll 37
  • 28 (a)
OneToMany
pll 38
  • 34 (a)
worm
(Caenorhabditis elegans)
Secernentea pik-1 37
  • 27 (a)
OneToMany
pik-1 38
  • 40 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G32710 36
  • 48.47 (n)
  • 42.51 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 43 (a)
OneToMany
Species with no ortholog for IRAK1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for IRAK1 Gene

ENSEMBL:
Gene Tree for IRAK1 (if available)
TreeFam:
Gene Tree for IRAK1 (if available)

Paralogs for IRAK1 Gene

Paralogs for IRAK1 Gene

Pseudogenes.org Pseudogenes for IRAK1 Gene

genes like me logo Genes that share paralogs with IRAK1: view

Variants for IRAK1 Gene

Sequence variations from dbSNP and Humsavar for IRAK1 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type MAF
rs731642 -- 154,012,056(+) TGTTC(A/G)TTTGT intron-variant
rs763737 -- 154,012,856(+) GGGGG(A/G)AGGGC intron-variant
rs1059701 -- 154,019,032(-) CTGGT(A/C/T)CCAAG synonymous-codon, reference
rs1059702 - 154,018,741(-) CCCCT(C/T)TCCGT missense, reference
rs1059703 - 154,013,378(-) GCATT(C/T)GGAGG intron-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for IRAK1 Gene

Variant ID Type Subtype PubMed ID
esv33199 CNV Gain+Loss 17666407
nsv469867 CNV Complex 16826518
esv33784 CNV Gain+Loss 17666407

Relevant External Links for IRAK1 Gene

HapMap Linkage Disequilibrium report
IRAK1
Human Gene Mutation Database (HGMD)
IRAK1
Locus Specific Mutation Databases (LSDB)
IRAK1

Disorders for IRAK1 Gene

(13) Novoseek inferred disease relationships for IRAK1 Gene

Disease -log(P) Hits PubMed IDs
necrosis 54.1 21
inflammation 41.7 4
bacterial infections 36.3 2
tumors 32.8 26
atherosclerosis 2.04 5

Relevant External Links for IRAK1

Genetic Association Database (GAD)
IRAK1
Human Genome Epidemiology (HuGE) Navigator
IRAK1
genes like me logo Genes that share disorders with IRAK1: view

No data available for UniProtKB/Swiss-Prot for IRAK1 Gene

Publications for IRAK1 Gene

  1. IRAK: a kinase associated with the interleukin-1 receptor. (PMID: 8599092) Cao Z. … Gao X. (Science 1996) 2 3 4 23
  2. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. (PMID: 9374458) Muzio M. … Dixit V.M. (Science 1997) 2 3 23
  3. Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1 receptor. (PMID: 10854325) Burns K. … Volpe F. (Nat. Cell Biol. 2000) 3 4 23
  4. IRAK1b, a novel alternative splice variant of interleukin-1 receptor- associated kinase (IRAK), mediates interleukin-1 signaling and has prolonged stability. (PMID: 11397809) Jensen L.E. … Whitehead A.S. (J. Biol. Chem. 2001) 3 4 23
  5. IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase. (PMID: 11960013) Li S. … Wesche H. (Proc. Natl. Acad. Sci. U.S.A. 2002) 3 4 23

Products for IRAK1 Gene

  • Addgene plasmids for IRAK1

Sources for IRAK1 Gene

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