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]

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