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; OMA:TOLLIP - orthologs
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 141,428,550 bp[2] End 141,472,244 bp[2]
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 [3] [4]
Wikidata
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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]