TOLLIP

Last updated
TOLLIP
Protein TOLLIP PDB 1wgl.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TOLLIP , IL-1RAcPIP, toll interacting protein
External IDs OMIM: 606277; MGI: 1891808; HomoloGene: 10375; GeneCards: TOLLIP; OMA:TOLLIP - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_019009
NM_001318512
NM_001318514
NM_001318515
NM_001318516

Contents

NM_023764
NM_001347562

RefSeq (protein)

NP_001334491
NP_076253

Location (UCSC) Chr 11: 1.27 – 1.31 Mb Chr 7: 141.43 – 141.47 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene. [5] [6] [7]

Function and regulation

It is an inhibitory adaptor protein within Toll-like receptors (TLR). [8] The TLR pathway is a part of the innate immune system that recognizes structurally conserved molecular patterns of microbial pathogens, leading to an inflammatory immune response.

Tollip interacts with cellular and subcellular membrane compartments such as endosome and lysosome through its C2 domain binding with phosphoinositides. [9] By coordinating organelle communications, Tollip can contribute to the fusion of endo-lysosome and autophagosome. Mice with Tollip deletion exhibit elevated risks for inflammatory diseases such as atherosclerosis and neurodegeneration. [10]

Clinical significance

Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis. [11] Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis. [12] [13]

Interactions

TOLLIP has been shown to interact with TOM1, [14] TLR 2, [15] TLR 4 [15] and IL1RAP. [7]

Related Research Articles

<span class="mw-page-title-main">Toll-like receptor</span> Class of immune system proteins

Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13. Humans lack genes for TLR11, TLR12 and TLR13 and mice lack a functional gene for TLR10. The receptors TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are located on the cell membrane, whereas TLR3, TLR7, TLR8, and TLR9 are located in intracellular vesicles.

<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">Toll-like receptor 2</span> Cell surface receptor found in humans

Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the TLR2 gene. TLR2 has also been designated as CD282. TLR2 is one of the toll-like receptors and plays a role in the immune system. TLR2 is a membrane protein, a receptor, which is expressed on the surface of certain cells and recognizes foreign substances and passes on appropriate signals to the cells of the immune system.

<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">Toll-like receptor 4</span> Cell surface receptor found in humans

Toll-like receptor 4 (TLR4), also designated as CD284, is a key activator of the innate immune response and plays a central role in the fight against bacterial infections. TLR4 is a transmembrane protein of approximately 95 kDa that is encoded by the TLR4 gene.

<span class="mw-page-title-main">Lymphocyte antigen 96</span> Protein-coding gene in the species Homo sapiens

Lymphocyte antigen 96, also known as "Myeloid Differentiation factor 2 (MD-2)," is a protein that in humans is encoded by the LY96 gene.

<span class="mw-page-title-main">TRAF1</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

<span class="mw-page-title-main">AP2M1</span> Protein-coding gene in the species Homo sapiens

AP-2 complex subunit mu is a protein that in humans is encoded by the AP2M1 gene.

<span class="mw-page-title-main">NOD1</span> Protein receptor that recognizes bacterial molecules and stimulates an immune reaction

Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor that in humans is encoded by the NOD1 gene. It recognizes bacterial molecules and stimulates an immune reaction.

<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">Arrestin beta 1</span> Human protein and coding gene

Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 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">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">SNX9</span> Protein-coding gene in the species Homo sapiens

Sorting nexin-9 is a protein that in humans is encoded by the SNX9 gene.

<span class="mw-page-title-main">RNF216</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase RNF216 is an enzyme that in humans is encoded by the RNF216 gene.

<span class="mw-page-title-main">TOM1</span>

Target of Myb protein 1 is a protein that in humans is encoded by the TOM1 gene.

<span class="mw-page-title-main">RIPK3</span> Protein-coding gene in humans

Receptor-interacting serine/threonine-protein kinase 3 is an enzyme that is encoded by the RIPK3 gene in humans.

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

Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene SIGIRR, which modulate inflammation, immune response, and tumorigenesis of colonic epithelial cells.

<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.

<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: ENSG00000078902 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025139 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. "Entrez Gene: TOLLIP toll interacting protein".
  6. Volpe F, Clatworthy J, Kaptein A, Maschera B, Griffin AM, Ray K (December 1997). "The IL1 receptor accessory protein is responsible for the recruitment of the interleukin-1 receptor associated kinase to the IL1/IL1 receptor I complex". FEBS Letters. 419 (1): 41–44. Bibcode:1997FEBSL.419...41V. doi:10.1016/S0014-5793(97)01426-9. PMID   9426216. S2CID   39772937.
  7. 1 2 Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, et al. (June 2000). "Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor". Nature Cell Biology. 2 (6): 346–351. doi:10.1038/35014038. PMID   10854325. S2CID   32036101.
  8. Bulut Y, Faure E, Thomas L, Equils O, Arditi M (July 2001). "Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling". Journal of Immunology. 167 (2): 987–994. doi: 10.4049/jimmunol.167.2.987 . PMID   11441107.
  9. Li T, Hu J, Li L (May 2004). "Characterization of Tollip protein upon Lipopolysaccharide challenge". Molecular Immunology. 41 (1): 85–92. doi:10.1016/j.molimm.2004.03.009. PMID   15140579.
  10. Kowalski EJ, Li L (May 2017). "Toll-Interacting Protein in Resolving and Non-Resolving Inflammation". Frontiers in Immunology. 8 (511): 511. doi: 10.3389/fimmu.2017.00511 . PMC   5418219 . PMID   28529512.
  11. Schimming TT, Parwez Q, Petrasch-Parwez E, Nothnagel M, Epplen JT, Hoffjan S (March 2007). "Association of toll-interacting protein gene polymorphisms with atopic dermatitis". BMC Dermatology. 7: 3. doi: 10.1186/1471-5945-7-3 . PMC   1832210 . PMID   17362526.
  12. Shah JA, Vary JC, Chau TT, Bang ND, Yen NT, Farrar JJ, et al. (August 2012). "Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis". Journal of Immunology. 189 (4): 1737–1746. doi:10.4049/jimmunol.1103541. PMC   3428135 . PMID   22778396.
  13. Noth I, Zhang Y, Ma SF, Flores C, Barber M, Huang Y, et al. (June 2013). "Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study". The Lancet. Respiratory Medicine. 1 (4): 309–317. doi:10.1016/S2213-2600(13)70045-6. PMC   3894577 . PMID   24429156.
  14. Yamakami M, Yoshimori T, Yokosawa H (December 2003). "Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin". The Journal of Biological Chemistry. 278 (52): 52865–52872. doi: 10.1074/jbc.M306740200 . PMID   14563850.
  15. 1 2 Zhang G, Ghosh S (March 2002). "Negative regulation of toll-like receptor-mediated signaling by Tollip". The Journal of Biological Chemistry. 277 (9): 7059–7065. doi: 10.1074/jbc.M109537200 . PMID   11751856.

Further reading