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Protein TOLLIP PDB 1wgl.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases TOLLIP, IL-1RAcPIP, toll interacting protein
External IDs MGI: 1891808 HomoloGene: 10375 GeneCards: 54472
RNA expression pattern
PBB GE TOLLIP 217930 s at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)


Location (UCSC) Chr 11: 1.27 – 1.31 Mb Chr 7: 141.87 – 141.92 Mb
PubMed search [1] [2]
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Toll interacting protein, also known as TOLLIP, is an inhibitory adaptor protein that in humans is encoded by the TOLLIP gene.[3][4][5]


It is an inhibitory adaptor protein within Toll-like receptors (TLR).[6] 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.

Clinical significance[edit]

Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis.[7] Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis.[8][9]


TOLLIP has been shown to interact with TOM1,[10] TLR 2,[11] TLR 4[11] and IL1RAP.[5]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ "Entrez Gene: TOLLIP toll interacting protein". 
  4. ^ 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 Lett. 419 (1): 41–4. doi:10.1016/S0014-5793(97)01426-9. PMID 9426216. 
  5. ^ a b Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, Lewis A, Ray K, Tschopp J, Volpe F (June 2000). "Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor". Nat. Cell Biol. 2 (6): 346–51. doi:10.1038/35014038. PMID 10854325. 
  6. ^ 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". J. Immunol. 167 (2): 987–94. doi:10.4049/jimmunol.167.2.987. PMID 11441107. 
  7. ^ Schimming TT, Parwez Q, Petrasch-Parwez E, Nothnagel M, Epplen JT, Hoffjan S (2007). "Association of toll-interacting protein gene polymorphisms with atopic dermatitis". BMC Dermatol. 7: 3. doi:10.1186/1471-5945-7-3. PMC 1832210free to read. PMID 17362526. 
  8. ^ "Human TOLLIP Regulates TLR2 and TLR4 Signaling and Its Polymorphisms Are Associated with Susceptibility to Tuberculosis". J Immunol. 189 (4): 1737–46. 2012. doi:10.4049/jimmunol.1103541. 
  9. ^ "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. 
  10. ^ Yamakami, Megumi; Yoshimori Tamotsu; Yokosawa Hideyoshi (Dec 2003). "Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin". J. Biol. Chem. United States. 278 (52): 52865–72. doi:10.1074/jbc.M306740200. ISSN 0021-9258. PMID 14563850. 
  11. ^ a b Zhang, Guolong; Ghosh Sankar (Mar 2002). "Negative regulation of toll-like receptor-mediated signaling by Tollip". J. Biol. Chem. United States. 277 (9): 7059–65. doi:10.1074/jbc.M109537200. ISSN 0021-9258. PMID 11751856. 

Further reading[edit]