Property Summary

NCBI Gene PubMed Count 67
PubMed Score 72.69
PubTator Score 48.85

Knowledge Summary


No data available


  Differential Expression (16)

Disease log2 FC p
astrocytic glioma -1.700 1.7e-02
posterior fossa group A ependymoma -1.700 1.7e-11
esophageal adenocarcinoma -1.100 3.0e-02
psoriasis 1.200 7.9e-03
glioblastoma -1.900 2.9e-06
oligodendroglioma -1.300 7.5e-15
osteosarcoma -2.082 9.3e-07
medulloblastoma -2.100 1.1e-11
atypical teratoid / rhabdoid tumor -2.200 3.6e-09
medulloblastoma, large-cell -3.200 9.7e-07
primitive neuroectodermal tumor -2.100 2.2e-05
pancreatic ductal adenocarcinoma liver m... -1.074 1.6e-02
interstitial cystitis -1.300 1.5e-03
adult high grade glioma -1.900 9.4e-06
pilocytic astrocytoma -1.400 2.5e-07
Pick disease -1.200 3.7e-04

Protein-protein Interaction (7)

Gene RIF (41)

26610735 These data suggest that M. leprae upregulates IL-1Ra by a TOLLIP-dependent mechanism; inhibition of TOLLIP may decrease an individual's susceptibility to leprosy and offer a novel therapeutic target for IL-1-dependent diseases.
26462859 Observed expression patterns of several TLR inhibitory proteins with a noticeable suppression in expression of two of these; PPARgamma and TOLLIP in both ulcerative colitis and Crohn's disease and in both active and inactive disease states.
26331942 TOLLIP encodes toll-interacting protein (TOLLIP), which is an inhibitory adaptor protein acting downstream from the toll-like receptors (TLRs). Read More:
26320582 Tom1 modulates binding of Tollip to phosphatidylinositol 3-phosphate via a coupled folding and binding mechanism.
26110841 we identify a novel function of Tollip in regulating the canonical Wnt pathway which is evolutionarily conserved between fish and humans. Tollip-mediated inhibition of Wnt signaling may contribute to embryonic development and to carcinogenesis.
26107286 The two polymorphisms, rs5743899 and rs3750920, in the TOLLIP gene are independently associated with an increased risk of developing cutaneous leishmaniasis (CL).
26011492 Tollip acts as a novel modulator of I/R injury by promoting neuronal apoptosis and ischaemic inflammation, which are largely mediated by suppression of Akt signalling.
25915421 Study shows that host factor Tollip inhibits HIV LTR-driven gene expression by suppressing NF-kappaB activation revealing its novel role in modulating HIV-1 infection.
25765712 TOLLIP contributes to mortality following myocardial infarction through promoting inflammation and apoptosis
25275363 The MUC5B promoter polynmorphism, TOLLIP, is a strong risk factor for idiopathic pulmonary fibrosis in a Mexican population but is very rare in a Korean population.
25152369 Which is achieved by elevated level of toll-interacting protein (TOLLIP) in presence of porin.
25042851 Tollip depletion causes cytotoxicity toward polyQ proteins, whereas Tollip overexpression clears human cells from Huntington's disease-linked polyQ proteins by autophagy; Tollip is a Functional Homolog of Yeast Cue5.
24294608 Just the individuals with genotype C/C of rs3750920 of the TOLLIP have a trend of protective effect to developing lepromatous leprosy .
24285748 negative regulator of pathological cardiac hypertrophy by blocking the AKT signalling pathway
23880770 in the absence of polyubiquitinated cargo, the dual binding of ubiquitin partitions Tollip into membrane-bound and membrane-free states, a function that contributes to the engagement of Tollip in both membrane trafficking and cytosolic pathways.
23027871 Tollip cooperates with Smad7 to modulate intracellular trafficking and degradation of ubiquitinated TbetaRI, whereby negatively regulates TGF-beta signaling pathway.
22778396 These data demonstrate that TOLLIP has an anti-inflammatory effect on TLR2 and TLR4 signaling in humans
22582869 located in the cytoplasm of cytotrophoblasts in the first-trimester placental tissues
21867680 the results indicate that insufficient O-GlcNAc modification prevents Elf-1-mediated transcriptional repression and thereby upregulates Tollip gene expression in intestinal epithelial cells.
21294713 These findings suggest that basic residues of the C2 domain mediate membrane targeting of Tollip by interaction with phosphoinositides, which contribute to the observed partition of the protein in different subcellular compartments.
21291504 Data show that knockdown of Tollip reduces CNF1-induced Rac1-dependent UPEC entry.
21219635 Our findings indicated that the variants in TOLLIP were significantly associated with sepsis susceptibility in the Chinese Han population.
21048031 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20406964 Observational study of gene-disease association. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
20198315 Observational study of gene-disease association. (HuGE Navigator)
19851296 Observational study of gene-disease association. (HuGE Navigator)
19716405 DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation.
19423540 Observational study of gene-disease association. (HuGE Navigator)
18987746 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
18987746 Significant & strong 2- & 3-locus interactions between SNPs in TOLLIP (rs4963060), TLR4 (rs6478317) & IRAK1 (rs1059703)were associated with the response to whole-cell vaccine pertussis vaccination in 490 1-yr-old children.
18985539 Expression of TLR-8, but not Tollip, is highly up-regulated in the colonic epithelium from patients with active IBD
17362526 Observational study of gene-disease association. (HuGE Navigator)
17362526 Variation in the TOLLIP gene may play a role in the pathogenesis of AD.
17113392 Tollip is required for sorting of IL-1RI at late endosomes.
16107720 following stimulation by exogenous CD26, Tollip and IRAK-1 dissociate from caveolin-1, and IRAK-1 is then phosphorylated in the cytosol, leading to the upregulation of CD86 via activation of NF-kappaB
15047686 Tollip and Tom1 form a complex and regulate endosomal trafficking of ubiquitinated proteins
14563850 a Tom1-Tollip complex functions as a factor that links polyubiquitinated proteins to clathrin
11751856 Here we report that Tollip also associates directly with TLR2 and TLR4 and plays an inhibitory role in TLR-mediated cell activation
11441107 Overexpression of Tollip inhibits NF-kappa B activation in response to Toll-like receptor-2 and Toll-like receptor-4 signaling in vitro.

AA Sequence


Text Mined References (71)

PMID Year Title
26610735 2016 Genetic Variation in Toll-Interacting Protein Is Associated With Leprosy Susceptibility and Cutaneous Expression of Interleukin 1 Receptor Antagonist.
26462859 2016 Differential expression of key regulators of Toll-like receptors in ulcerative colitis and Crohn's disease: a role for Tollip and peroxisome proliferator-activated receptor gamma?
26331942 2015 TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis.
26320582 2015 Tom1 Modulates Binding of Tollip to Phosphatidylinositol 3-Phosphate via a Coupled Folding and Binding Mechanism.
26110841 2015 Endocytic Adaptor Protein Tollip Inhibits Canonical Wnt Signaling.
26107286 2015 Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil.
26011492 2015 Tollip is a critical mediator of cerebral ischaemia-reperfusion injury.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25915421 2015 Toll-Interacting Protein Suppresses HIV-1 Long-Terminal-Repeat-Driven Gene Expression and Silences the Post-Integrational Transcription of Viral Proviral DNA.
25765712 2015 Toll-interacting protein contributes to mortality following myocardial infarction through promoting inflammation and apoptosis.
25416956 2014 A proteome-scale map of the human interactome network.
25275363 2015 The MUC5B promoter polymorphism is associated with idiopathic pulmonary fibrosis in a Mexican cohort but is rare among Asian ancestries.
25152369 2014 Activation of TOLLIP by porin prevents TLR2-associated IFN-? and TNF-?-induced apoptosis of intestinal epithelial cells.
25042851 2014 Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family.
24429156 2013 Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study.
24294608 2013 Role of toll-interacting protein gene polymorphisms in leprosy Mexican patients.
24285748 2014 Toll-interacting protein (Tollip) negatively regulates pressure overload-induced ventricular hypertrophy in mice.
23880770 2013 Ubiquitin interacts with the Tollip C2 and CUE domains and inhibits binding of Tollip to phosphoinositides.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23027871 2012 Tollip, an intracellular trafficking protein, is a novel modulator of the transforming growth factor-? signaling pathway.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22778396 2012 Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis.
22582869 2012 Expression and localization of TLR4 and its negative regulator Tollip in the placenta of early-onset and late-onset preeclampsia.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21903422 2011 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production.
21867680 2011 Transcription of the Tollip gene is elevated in intestinal epithelial cells through impaired O-GlcNAcylation-dependent nuclear translocation of the negative regulator Elf-1.
21492153 2011 Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2.
21294713 2011 The C2 domain of Tollip, a Toll-like receptor signalling regulator, exhibits broad preference for phosphoinositides.
21291504 2011 Escherichia coli producing CNF1 toxin hijacks Tollip to trigger Rac1-dependent cell invasion.
21269460 2011 Initial characterization of the human central proteome.
21219635 2011 Variants in the Toll-interacting protein gene are associated with susceptibility to sepsis in the Chinese Han population.
21048031 2011 Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
20936779 2010 A human MAP kinase interactome.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20198315 2010 Association of genetic variants with hemorrhagic stroke in Japanese individuals.
19851296 2010 Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.
19716405 2009 Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling.
19447967 2009 Shifted Transversal Design smart-pooling for high coverage interactome mapping.
19444506 2009 Diversification of TOLLIP isoforms in mouse and man.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19060904 2009 An empirical framework for binary interactome mapping.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18987746 2008 Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.
18985539 2009 Expression and function of toll-like receptor 8 and Tollip in colonic epithelial cells from patients with inflammatory bowel disease.
17362526 2007 Association of toll-interacting protein gene polymorphisms with atopic dermatitis.
17113392 2006 Intracellular trafficking of interleukin-1 receptor I requires Tollip.
16713569 2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
16554811 2006 Human chromosome 11 DNA sequence and analysis including novel gene identification.
16412388 2006 Recruitment of clathrin onto endosomes by the Tom1-Tollip complex.
16381901 2006 The LIFEdb database in 2006.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
16107720 2005 CD26 mediates dissociation of Tollip and IRAK-1 from caveolin-1 and induces upregulation of CD86 on antigen-presenting cells.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15231747 2004 A protein interaction framework for human mRNA degradation.
15047686 2004 Tollip and Tom1 form a complex and recruit ubiquitin-conjugated proteins onto early endosomes.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14563850 2003 Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11751856 2002 Negative regulation of toll-like receptor-mediated signaling by Tollip.
11441107 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.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10854325 2000 Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.
9426216 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.
8837778 1996 TRAF6 is a signal transducer for interleukin-1.
1085432 1976 Malignant lymphoma and rheumatic symptoms.