IRAK2

Last updated
IRAK2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IRAK2 , IRAK-2, interleukin 1 receptor associated kinase 2
External IDs OMIM: 603304 MGI: 2429603 HomoloGene: 1207 GeneCards: IRAK2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001570

NM_001113553
NM_172161

RefSeq (protein)

NP_001561

NP_001107025
NP_751893

Location (UCSC) Chr 3: 10.16 – 10.24 Mb Chr 6: 113.62 – 113.67 Mb
PubMed search [3] [4]
Wikidata
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Interleukin-1 receptor-associated kinase-like 2 is an enzyme that in humans is encoded by the IRAK2 gene. [5] [6]

Contents

Function

IRAK2 encodes the interleukin-1 receptor-associated kinase 2, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. IRAK2 is reported to participate in the IL1-induced upregulation of NF-kappaB. [6]

Interactions

IRAK2 has been shown to interact with TRAF6 [5] [7] and Myd88. [5] [7] [8]

Related Research Articles

<span class="mw-page-title-main">IRAK4</span> Protein-coding gene in humans

IRAK-4, in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. IRAK4 contains domain structures which are similar to those of IRAK1, IRAK2, IRAKM and Pelle. IRAK4 is unique compared to IRAK1, IRAK2 and IRAKM in that it functions upstream of the other IRAKs, but is more similar to Pelle in this trait. IRAK4 has important clinical applications.

<span class="mw-page-title-main">MYD88</span> Protein found in humans

Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene. originally discovered in the laboratory of Dan A. Liebermann as a Myeloid differentiation primary response gene.

<span class="mw-page-title-main">TICAM1</span> Protein found in humans

TIR domain containing adaptor molecule 1 is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter.

<span class="mw-page-title-main">TRAF6</span> Protein-coding gene in the species Homo sapiens

TRAF6 is a TRAF human protein.

<span class="mw-page-title-main">Janus kinase 2</span> Non-receptor tyrosine kinase and coding gene in humans

Janus kinase 2 is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family, the gp130 receptor family, and the single chain receptors.

<span class="mw-page-title-main">TRAF5</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 5 is a protein that in humans is encoded by the TRAF5 gene.

<span class="mw-page-title-main">IRAK1</span> Protein-coding gene in humans

Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the IRAK1 gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, which in turn help the immune system in eliminating bacteria, viruses, and other pathogens. IRAK-1 is part of the IRAK family consisting of IRAK-1, IRAK-2, IRAK-3, and IRAK-4, and is activated by inflammatory molecules released by signaling pathways during pathogenic attack. IRAK-1 is classified as a kinase enzyme, which regulates pathways in both innate and adaptive immune systems.

<span class="mw-page-title-main">TRAF3</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.

<span class="mw-page-title-main">Interleukin 1 receptor, type I</span> Type of interleukin receptor

Interleukin 1 receptor, type I (IL1R1) also known as CD121a, is an interleukin receptor. IL1R1 also denotes its human gene.

<span class="mw-page-title-main">MAP3K7IP2</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the MAP3K7IP2 gene.

<span class="mw-page-title-main">TAB1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the TAB1 gene.

<span class="mw-page-title-main">IL1RAP</span> Protein-coding gene in the species Homo sapiens

Interleukin-1 receptor accessory protein is a protein that in humans is encoded by the IL1RAP gene.

<span class="mw-page-title-main">Signal transducing adaptor molecule</span> Protein-coding gene in the species Homo sapiens

Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.

<span class="mw-page-title-main">TOLLIP</span> Protein-coding gene in the species Homo sapiens

Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene.

<span class="mw-page-title-main">SH2D3C</span> Protein-coding gene in the species Homo sapiens

SH2 domain containing 3C, also known as SH2D3C, is a protein that in humans is encoded by the SH2D3C gene.

<span class="mw-page-title-main">IRAK3</span>

Interleukin-1 receptor-associated kinase 3 is an enzyme that in humans is encoded by the IRAK3 gene. Using in vivo liposome-mediated delivery of CRISPR/Cas9 plasmid expressing IRAK3 gRNA, IRAK3 was shown to be responsible for endotoxin-induced expression of A20 and VE-cadherin in endothelial cells. Thus, IRAK3 is crucial for maintenance and repair of endothelial barrier after endotoxin-induced lung injury.

<span class="mw-page-title-main">PELI1</span> Protein-coding gene in the species Homo sapiens

Protein pellino homolog 1 is a protein that in humans is encoded by the PELI1 gene.

<span class="mw-page-title-main">Toll-interleukin receptor</span> Intracellular signaling domain

The toll-interleukin-1 receptor (TIR) homology domain is an intracellular signaling domain found in MyD88, SARM1, interleukin-1 receptors, toll receptors and many plant R proteins. It contains three highly conserved regions, and mediates protein-protein interactions between the toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins where they are involved in resistance to disease and in bacteria where they are associated with virulence. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 (UniProt Q99836) and TOLLIP (toll-interacting protein, UniProt Q9H0E2). In turn, these associate with various kinases to set off signaling cascades. Some TIR domains have also been found to have intrinsic NAD+ cleavage activity, such as in SARM1. In the case of SARM1, the TIR NADase activity leads to the production of Nam, ADPR and cADPR and the activation of downstream pathways involved in Wallerian degeneration and neuron death.

The interleukin-1 receptor (IL-1R) associated kinase (IRAK) family plays a crucial role in the protective response to pathogens introduced into the human body by inducing acute inflammation followed by additional adaptive immune responses. IRAKs are essential components of the Interleukin-1 receptor signaling pathway and some Toll-like receptor signaling pathways. Toll-like receptors (TLRs) detect microorganisms by recognizing specific pathogen-associated molecular patterns (PAMPs) and IL-1R family members respond the interleukin-1 (IL-1) family cytokines. These receptors initiate an intracellular signaling cascade through adaptor proteins, primarily, MyD88. This is followed by the activation of IRAKs. TLRs and IL-1R members have a highly conserved amino acid sequence in their cytoplasmic domain called the Toll/Interleukin-1 (TIR) domain. The elicitation of different TLRs/IL-1Rs results in similar signaling cascades due to their homologous TIR motif leading to the activation of mitogen-activated protein kinases (MAPKs) and the IκB kinase (IKK) complex, which initiates a nuclear factor-κB (NF-κB) and AP-1-dependent transcriptional response of pro-inflammatory genes. Understanding the key players and their roles in the TLR/IL-1R pathway is important because the presence of mutations causing the abnormal regulation of Toll/IL-1R signaling leading to a variety of acute inflammatory and autoimmune diseases.

<span class="mw-page-title-main">IL17RD</span>

Interleukin 17 receptor D is a protein that in humans is encoded by the IL17RD gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134070 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000060477 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 Muzio M, Ni J, Feng P, Dixit VM (Nov 1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling". Science. 278 (5343): 1612–5. Bibcode:1997Sci...278.1612M. doi:10.1126/science.278.5343.1612. PMID   9374458.
  6. 1 2 "Entrez Gene: IRAK2 interleukin-1 receptor-associated kinase 2".
  7. 1 2 Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (Jul 1999). "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family". The Journal of Biological Chemistry. 274 (27): 19403–10. doi: 10.1074/jbc.274.27.19403 . PMID   10383454.
  8. Fitzgerald KA, Palsson-McDermott EM, Bowie AG, Jefferies CA, Mansell AS, Brady G, Brint E, Dunne A, Gray P, Harte MT, McMurray D, Smith DE, Sims JE, Bird TA, O'Neill LA (Sep 2001). "Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction". Nature. 413 (6851): 78–83. Bibcode:2001Natur.413...78F. doi:10.1038/35092578. PMID   11544529. S2CID   4333764.

Further reading