TOLLIP

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

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; OMA:TOLLIP - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11p15.5 Start 1,274,371 bp End 1,309,654 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 F5 Start 141,428,550 bp End 141,472,244 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right frontal lobe anterior cingulate cortex prefrontal cortex left testis right testis dorsolateral prefrontal cortex right lobe of liver Brodmann area 9 right hemisphere of cerebellum amygdala Top expressed in spermatocyte ankle joint dentate gyrus of hippocampal formation granule cell cumulus cell spermatid olfactory epithelium cerebellar cortex seminiferous tubule medial dorsal nucleus gastrula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signal transducer activity Toll-like receptor binding SUMO binding kinase binding 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 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 response 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: 141.43 – 141.47 Mb PubMed search
Wikidata
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Function and regulation

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

Clinical significance

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

Interactions

TOLLIP has been shown to interact with TOM1, TLR 2, TLR 4 and IL1RAP.

Further reading

• Nilsen KH (May 1976). "Malignant lymphoma and rheumatic symptoms". The New Zealand Medical Journal. 83 (563): 320–322. 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): 41–44. Bibcode:1997FEBSL.419...41V. 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): 346–351. 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): 1788–1795. 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): 987–994. 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): 7059–7065. 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): 52865–52872. 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): 24435–24443. 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): 1315–1323. 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): 2136–2144. 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): 7743–7757. 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–D418. 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): 143–149. 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): 801–814. 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): 2265–2270. Bibcode:2006CBio...16.2265B. doi:10.1016/j.cub.2006.09.062. PMID 17113392. S2CID 13938932.