TOLLIP

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

TOLLIP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WGL, 2N31
Identifiers
Aliases	TOLLIP, IL-1RAcPIP, toll interacting protein
External IDs	OMIM: 606277 MGI: 1891808 HomoloGene: 10375 GeneCards: TOLLIP
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p15.5 Start 1,274,371 bp[1] End 1,309,654 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F5 Start 141,874,813 bp[2] End 141,918,507 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • signal transducer activity • Toll-like receptor binding • SUMO binding • kinase binding • GO:0001948 protein binding • interleukin-1, Type I receptor binding • ubiquitin protein ligase binding • ubiquitin conjugating enzyme binding • ubiquitin binding Cellular component • interleukin-18 receptor complex • cytosol • nuclear body • perinuclear region of cytoplasm • interleukin-1 receptor complex • extracellular exosome • extracellular region • cytoplasm • azurophil granule lumen • specific granule lumen Biological process • GO:0007243 intracellular signal transduction • epithelial cell differentiation • phosphorylation • immune system process • leukocyte activation • cell-cell signaling • positive regulation of protein sumoylation • autophagy • protein localization to endosome • innate immune system • inflammatory response • signal transduction • ubiquitin-dependent protein catabolic process • neutrophil degranulation • interleukin-1-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	54472	54473
Ensembl	ENSG00000078902	ENSMUSG00000025139
UniProt	Q9H0E2 Q6FIE9	Q9QZ06
RefSeq (mRNA)	NM_019009 NM_001318512 NM_001318514 NM_001318515 NM_001318516	NM_023764 NM_001347562
RefSeq (protein)	NP_001305441 NP_001305443 NP_001305444 NP_001305445 NP_061882 NP_061882.2	NP_001334491 NP_076253
Location (UCSC)	Chr 11: 1.27 – 1.31 Mb	Chr 7: 141.87 – 141.92 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

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.

Clinical significance

Polymorphisms in TLR genes have been implicated in various diseases like atopic dermatitis.[9] Recently, variations in the TOLLIP gene have been associated with tuberculosis and idiopathic pulmonary fibrosis.[10][11]

Interactions

TOLLIP has been shown to interact with TOM1,[12] TLR 2,[13] TLR 4[13] and IL1RAP.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000078902 - Ensembl, May 2017
2. 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): 41–4. doi:10.1016/S0014-5793(97)01426-9. PMID 9426216. S2CID 39772937.
7. 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): 346–51. 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): 987–94. doi:10.4049/jimmunol.167.2.987. PMID 11441107.
9. 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.
10. 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): 1737–46. doi:10.4049/jimmunol.1103541. PMC 3428135. PMID 22778396.
11. Gilgenkrantz S, Droulle P, Schweitzer M, Foliguet B, Gérard H, Plénat F (June 1985). "[Prenatal diagnosis of triploidy. I. Echographic, clinical and anatomic studies]". Journal de Génétique Humaine. 33 (2): 143–52. doi:10.1016/S2213-2600(13)70045-6. PMC 3894577. PMID 24429156.
12. 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): 52865–72. doi:10.1074/jbc.M306740200. PMID 14563850.
13. Zhang G, Ghosh S (March 2002). "Negative regulation of toll-like receptor-mediated signaling by Tollip". The Journal of Biological Chemistry. 277 (9): 7059–65. doi:10.1074/jbc.M109537200. PMID 11751856.

Further reading

• Nilsen KH (May 1976). "Malignant lymphoma and rheumatic symptoms". The New Zealand Medical Journal. 83 (563): 320–2. PMID 1085432.
• 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): 41–4. doi:10.1016/S0014-5793(97)01426-9. PMID 9426216. S2CID 39772937.
• 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): 346–51. doi:10.1038/35014038. PMID 10854325. S2CID 32036101.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• 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): 987–94. doi:10.4049/jimmunol.167.2.987. PMID 11441107.
• Zhang G, Ghosh S (March 2002). "Negative regulation of toll-like receptor-mediated signaling by Tollip". The Journal of Biological Chemistry. 277 (9): 7059–65. doi:10.1074/jbc.M109537200. PMID 11751856.
• 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): 52865–72. doi:10.1074/jbc.M306740200. PMID 14563850.
• Katoh Y, Shiba Y, Mitsuhashi H, Yanagida Y, Takatsu H, Nakayama K (June 2004). "Tollip and Tom1 form a complex and recruit ubiquitin-conjugated proteins onto early endosomes". The Journal of Biological Chemistry. 279 (23): 24435–43. doi:10.1074/jbc.M400059200. PMID 15047686.
• Lehner B, Sanderson CM (July 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Ohnuma K, Yamochi T, Uchiyama M, Nishibashi K, Iwata S, Hosono O, et al. (September 2005). "CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells". Molecular and Cellular Biology. 25 (17): 7743–57. doi:10.1128/MCB.25.17.7743-7757.2005. PMC 1190283. PMID 16107720.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Katoh Y, Imakagura H, Futatsumori M, Nakayama K (March 2006). "Recruitment of clathrin onto endosomes by the Tom1-Tollip complex". Biochemical and Biophysical Research Communications. 341 (1): 143–9. doi:10.1016/j.bbrc.2005.12.156. PMID 16412388.
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
• Brissoni B, Agostini L, Kropf M, Martinon F, Swoboda V, Lippens S, et al. (November 2006). "Intracellular trafficking of interleukin-1 receptor I requires Tollip". Current Biology. 16 (22): 2265–70. doi:10.1016/j.cub.2006.09.062. PMID 17113392. S2CID 13938932.