TOLLIP

TOLLIP

TOLLIP

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.[5][6][7]

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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]


References

  1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 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. doi:10.1016/S0014-5793(97)01426-9. PMID 9426216. S2CID 39772937.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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


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