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Aliases for TOLLIP Gene

Aliases for TOLLIP Gene

  • Toll Interacting Protein 2 3 5
  • Adapter Protein 3
  • IL-1RAcPIP 3

External Ids for TOLLIP Gene

Previous GeneCards Identifiers for TOLLIP Gene

  • GC11M001759
  • GC11M001558
  • GC11M001261
  • GC11M001262
  • GC11M001252
  • GC11M001087
  • GC11M001295

Summaries for TOLLIP Gene

Entrez Gene Summary for TOLLIP Gene

  • This gene encodes a ubiquitin-binding protein that interacts with several Toll-like receptor (TLR) signaling cascade components. The encoded protein regulates inflammatory signaling and is involved in interleukin-1 receptor trafficking and in the turnover of IL1R-associated kinase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

GeneCards Summary for TOLLIP Gene

TOLLIP (Toll Interacting Protein) is a Protein Coding gene. Diseases associated with TOLLIP include lymphoproliferative syndrome, x-linked, 1. Among its related pathways are Immune System and Interleukin-3, 5 and GM-CSF signaling. GO annotations related to this gene include signal transducer activity and kinase binding.

UniProtKB/Swiss-Prot for TOLLIP Gene

  • Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity (PubMed:11751856). Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851).

Gene Wiki entry for TOLLIP Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TOLLIP Gene

Genomics for TOLLIP Gene

Regulatory Elements for TOLLIP Gene

Promoters for TOLLIP Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TOLLIP on UCSC Golden Path with GeneCards custom track

Genomic Location for TOLLIP Gene

Chromosome:
11
Start:
1,274,368 bp from pter
End:
1,309,662 bp from pter
Size:
35,295 bases
Orientation:
Minus strand

Genomic View for TOLLIP Gene

Genes around TOLLIP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TOLLIP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TOLLIP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TOLLIP Gene

Proteins for TOLLIP Gene

  • Protein details for TOLLIP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H0E2-TOLIP_HUMAN
    Recommended name:
    Toll-interacting protein
    Protein Accession:
    Q9H0E2
    Secondary Accessions:
    • B3KXC6
    • Q9H9E6
    • Q9UJ69

    Protein attributes for TOLLIP Gene

    Size:
    274 amino acids
    Molecular mass:
    30282 Da
    Quaternary structure:
    • Oligomerizes. Binds to TLR2 and the TLR4-MD2 complex via its C-terminus. Exists as complex with IRAK1 in unstimulated cells. Upon IL-1 signaling, Tollip binds to the activated IL-1 receptor complex containing IL-1RI, IL-1RacP and the adapter protein MyD88, where it interacts with the TIR domain of IL-1RacP. MyD88 then triggers IRAK1 autophosphorylation, which in turn leads to the dissociation of IRAK1 from Tollip and IL-1RAcP. Interacts with TOM1L2. Interacts with ATG8 family proteins (via AIM motifs), and ubiquitin (via CUE domain).
    SequenceCaution:
    • Sequence=BAB14283.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TOLLIP Gene

    Alternative splice isoforms for TOLLIP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TOLLIP Gene

Proteomics data for TOLLIP Gene at MOPED

Post-translational modifications for TOLLIP Gene

  • Phosphorylated by IRAK1 upon stimulation by IL-1 or microbial products.
  • Ubiquitination at Lys 63, Lys 66, Lys 96, Lys 102, Lys 146, and Lys 150
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for TOLLIP (TOLLIP)

No data available for DME Specific Peptides for TOLLIP Gene

Domains & Families for TOLLIP Gene

Gene Families for TOLLIP Gene

Protein Domains for TOLLIP Gene

Graphical View of Domain Structure for InterPro Entry

Q9H0E2

UniProtKB/Swiss-Prot:

TOLIP_HUMAN :
  • Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.
  • Belongs to the tollip family.
Domain:
  • Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.
  • Contains 1 C2 domain.
  • Contains 1 CUE domain.
Family:
  • Belongs to the tollip family.
genes like me logo Genes that share domains with TOLLIP: view

Function for TOLLIP Gene

Molecular function for TOLLIP Gene

UniProtKB/Swiss-Prot Function:
Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity (PubMed:11751856). Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851).

Gene Ontology (GO) - Molecular Function for TOLLIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0035325 Toll-like receptor binding IPI 10854325
genes like me logo Genes that share ontologies with TOLLIP: view
genes like me logo Genes that share phenotypes with TOLLIP: view

Animal Models for TOLLIP Gene

MGI Knock Outs for TOLLIP:

Animal Model Products

miRNA for TOLLIP Gene

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TOLLIP Gene

Localization for TOLLIP Gene

Subcellular locations from UniProtKB/Swiss-Prot for TOLLIP Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TOLLIP Gene COMPARTMENTS Subcellular localization image for TOLLIP gene
Compartment Confidence
cytosol 5
extracellular 5
plasma membrane 5
nucleus 4
endosome 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for TOLLIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0048471 perinuclear region of cytoplasm IEA --
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with TOLLIP: view

Pathways & Interactions for TOLLIP Gene

genes like me logo Genes that share pathways with TOLLIP: view

Gene Ontology (GO) - Biological Process for TOLLIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007267 cell-cell signaling TAS 10854325
GO:0016310 phosphorylation IDA 1085432
GO:0030855 epithelial cell differentiation IEP 21492153
genes like me logo Genes that share ontologies with TOLLIP: view

No data available for SIGNOR curated interactions for TOLLIP Gene

Drugs & Compounds for TOLLIP Gene

(15) Drugs for TOLLIP Gene - From: Novoseek and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Acetylcysteine Approved Pharma Antioxidant;mucolytic agent 293

(16) Additional Compounds for TOLLIP Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TOLLIP: view

Transcripts for TOLLIP Gene

Unigene Clusters for TOLLIP Gene

Toll interacting protein:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TOLLIP Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8a · 8b ^ 9a · 9b · 9c ^ 10 ^ 11a · 11b · 11c ^ 12a · 12b · 12c · 12d · 12e ·
SP1: - - - - - - - - - -
SP2: - - - - - - -
SP3: - - - - - - - - - - - -
SP4: - - - - - - - - - - -
SP5: - - - - - - - - -
SP6: - - - - -
SP7: - -
SP8: - - - - - - - - - - - - - - -
SP9: - - - - -
SP10: - - - - - -
SP11:
SP12: - - -
SP13: - -

ExUns: 12f
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for TOLLIP Gene

GeneLoc Exon Structure for
TOLLIP
ECgene alternative splicing isoforms for
TOLLIP

Expression for TOLLIP Gene

mRNA expression in normal human tissues for TOLLIP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TOLLIP Gene

This gene is overexpressed in Nasopharynx (10.6), Brain (6.6), and Peripheral blood mononuclear cells (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TOLLIP Gene



SOURCE GeneReport for Unigene cluster for TOLLIP Gene Hs.368527

genes like me logo Genes that share expression patterns with TOLLIP: view

Protein tissue co-expression partners for TOLLIP Gene

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for TOLLIP Gene

Orthologs for TOLLIP Gene

This gene was present in the common ancestor of animals.

Orthologs for TOLLIP Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TOLLIP 35
  • 88.6 (n)
  • 92.28 (a)
TOLLIP 36
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TOLLIP 35
  • 87.79 (n)
  • 92.31 (a)
TOLLIP 36
  • 82 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tollip 35
  • 86.08 (n)
  • 93.04 (a)
Tollip 16
Tollip 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TOLLIP 35
  • 87.75 (n)
  • 85.61 (a)
rat
(Rattus norvegicus)
Mammalia Tollip 35
  • 85.84 (n)
  • 93.41 (a)
oppossum
(Monodelphis domestica)
Mammalia TOLLIP 36
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TOLLIP 36
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves TOLLIP 35
  • 78.51 (n)
  • 89.38 (a)
TOLLIP 36
  • 88 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TOLLIP 36
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tollip 35
  • 74.63 (n)
  • 81.72 (a)
zebrafish
(Danio rerio)
Actinopterygii Dr.8875 35
tollip 35
  • 76.47 (n)
  • 83.82 (a)
tollip 36
  • 81 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003615 35
  • 59.21 (n)
  • 52.03 (a)
worm
(Caenorhabditis elegans)
Secernentea F25H2.1 37
  • 36 (a)
tli-1 35
  • 49.34 (n)
  • 44.1 (a)
tli-1 36
  • 40 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6903 36
  • 37 (a)
OneToOne
Species with no ortholog for TOLLIP:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TOLLIP Gene

ENSEMBL:
Gene Tree for TOLLIP (if available)
TreeFam:
Gene Tree for TOLLIP (if available)

Paralogs for TOLLIP Gene

No data available for Paralogs for TOLLIP Gene

Variants for TOLLIP Gene

Sequence variations from dbSNP and Humsavar for TOLLIP Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs5744015 - 1,277,200(-) CGGCC(A/G/T)CCGTG reference, missense
rs908225 -- 1,291,999(+) TCTAA(C/T)CAAAG intron-variant
rs2292635 -- 1,289,915(+) TGTCC(C/T)TGGAA intron-variant
rs3168046 -- 1,275,419(-) TCAGG(C/T)GGGAC utr-variant-3-prime
rs3793962 -- 1,278,274(+) AGCAG(C/G)AGCTG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TOLLIP Gene

Variant ID Type Subtype PubMed ID
nsv469923 CNV Loss 18288195
esv2743878 CNV Deletion 23290073
esv2669189 CNV Deletion 23128226
essv22587 CNV CNV 17122850
nsv896644 CNV Loss 21882294
dgv963n71 CNV Loss 21882294
dgv966n71 CNV Loss 21882294
dgv967n71 CNV Loss 21882294
dgv968n71 CNV Loss 21882294
dgv969n71 CNV Loss 21882294
dgv970n71 CNV Loss 21882294
nsv467637 CNV Loss 19166990
dgv971n71 CNV Loss 21882294
dgv972n71 CNV Loss 21882294
nsv825693 CNV Gain 20364138
nsv825694 CNV Gain 20364138
nsv896687 CNV Loss 21882294
dgv973n71 CNV Loss 21882294
esv1170595 CNV Insertion 17803354
esv1001632 CNV Deletion 20482838
nsv818794 CNV Loss 17921354
esv21758 CNV Gain 19812545
nsv39591 CNV Loss 16902084
esv1673155 CNV Deletion 17803354
esv1056483 CNV Deletion 17803354
esv2743907 CNV Deletion 23290073

Variation tolerance for TOLLIP Gene

Residual Variation Intolerance Score: 81.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.32; 53.40% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TOLLIP Gene

HapMap Linkage Disequilibrium report
TOLLIP

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TOLLIP Gene

Disorders for TOLLIP Gene

MalaCards: The human disease database

(1) MalaCards diseases for TOLLIP Gene - From: Novoseek

Disorder Aliases PubMed IDs
lymphoproliferative syndrome, x-linked, 1
  • lymphoproliferative syndrome, x-linked
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for TOLLIP

Genetic Association Database (GAD)
TOLLIP
Human Genome Epidemiology (HuGE) Navigator
TOLLIP
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TOLLIP
genes like me logo Genes that share disorders with TOLLIP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TOLLIP Gene

Publications for TOLLIP Gene

  1. Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1 receptor. (PMID: 10854325) Burns K. … Volpe F. (Nat. Cell Biol. 2000) 2 3 4 23 67
  2. Diversification of TOLLIP isoforms in mouse and man. (PMID: 19444506) Lo Y.L. … Wells C.A. (Mamm. Genome 2009) 3 23
  3. Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling. (PMID: 19716405) Lee J.Y. … Chung K.C. (Biochim. Biophys. Acta 2009) 3 23
  4. Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination. (PMID: 18987746) Kimman T.G. … Kerkhof M. (PLoS ONE 2008) 3 23
  5. The death domain of IRAK-1: an oligomerization domain mediating interactions with MyD88, Tollip, IRAK-1, and IRAK-4. (PMID: 17276401) Neumann D. … Martin M.U. (Biochem. Biophys. Res. Commun. 2007) 3 23

Products for TOLLIP Gene

Sources for TOLLIP Gene

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