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Aliases for TOLLIP Gene

Aliases for TOLLIP Gene

  • Toll Interacting Protein 2 3 5
  • Toll-Interacting Protein 3
  • 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 TRAF Pathway and IL-1 signaling pathway. 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 CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TOLLIP Gene

Genomics for TOLLIP Gene

Regulatory Elements for TOLLIP Gene

Enhancers for TOLLIP Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11G001301 1.9 FANTOM5 Ensembl ENCODE dbSUPER 17.4 +2.8 2847 10.7 HDGF HNRNPUL1 PKNOX1 FOXA2 MLX CREB3L1 ARID4B SIN3A DMAP1 ZNF2 TOLLIP BRSK2 TOLLIP-AS1 DUSP8 LOC105376512
GH11G001382 1.5 FANTOM5 Ensembl ENCODE 11.5 -73.5 -73529 1.7 PKNOX1 KLF17 GLIS2 EGR1 RELB CREM EGR2 SP3 ZEB2 ZNF398 TOLLIP-AS1 TOLLIP MOB2 DUSP8 BRSK2 IFITM10 GC11P001384 GC11M001373
GH11G001335 1.5 FANTOM5 Ensembl ENCODE 10.9 -27.0 -26979 2.8 TBP HDAC1 PKNOX1 RB1 E2F7 YBX1 ZBTB40 ZNF48 RAD21 PCBP1 TOLLIP TOLLIP-AS1 BRSK2 LOC105376513 GC11P001310
GH11G001274 1 dbSUPER 12.6 +31.9 31919 5.6 FOXA2 MLX ARID4B DMAP1 ZNF48 YY1 SLC30A9 SP5 ZHX2 MIER2 TOLLIP-AS1 TOLLIP DRD4 ENSG00000255177 MUC5B ENSG00000255142 MOB2 ENSG00000255158 BRSK2 GC11M001275
GH11G001281 0.8 dbSUPER 12.7 +27.9 27936 1.3 CTCF SAP130 ZNF792 MAX SIN3A ZNF48 RAD21 YY1 POLR2A HNF4G TOLLIP TOLLIP-AS1 ENSG00000255177 MUC5B MOB2 PIR51627 GC11M001275 LOC105376512
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around TOLLIP on UCSC Golden Path with GeneCards custom track

Promoters for TOLLIP Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000035770 -38 1801 HDGF HNRNPUL1 CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF143

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

Post-translational modifications for TOLLIP Gene

  • Phosphorylated by IRAK1 upon stimulation by IL-1 or microbial products.
  • Ubiquitination at isoforms=63, Lys66, isoforms=296, isoforms=2102, isoforms=2146, and Lys150
  • Modification sites at PhosphoSitePlus

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.
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:0004871 signal transducer activity NAS 11441107
GO:0005150 interleukin-1, Type I receptor binding IEA --
GO:0005515 protein binding IPI 14563850
GO:0019900 kinase binding IPI 10854325
GO:0031624 ubiquitin conjugating enzyme binding IBA --
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

CRISPR Products

miRNA for TOLLIP Gene

Inhibitory RNA Products

Clone Products

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
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TOLLIP gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 5
lysosome 5
nucleus 3
endosome 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for TOLLIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005737 cytoplasm IC,IEA 11441107
GO:0005829 cytosol TAS --
GO:0016604 nuclear body IEA --
GO:0035578 azurophil granule lumen TAS --
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:0006511 ubiquitin-dependent protein catabolic process IBA --
GO:0006914 autophagy IEA --
GO:0006954 inflammatory response NAS 10854325
GO:0007165 signal transduction IPI 11441107
GO:0007267 cell-cell signaling TAS 10854325
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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Acetylcysteine Approved, Investigational Pharma Antioxidant;mucolytic agent 330

(13) 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:

CRISPR Products

Inhibitory RNA Products

Clone Products

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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, MaxQB, and MOPED for TOLLIP Gene



Protein tissue co-expression partners for TOLLIP Gene

NURSA nuclear receptor signaling pathways regulating expression of TOLLIP Gene:

TOLLIP

SOURCE GeneReport for Unigene cluster for TOLLIP Gene:

Hs.368527

Evidence on tissue expression from TISSUES for TOLLIP Gene

  • Nervous system(4.8)
  • Eye(4.3)
  • Lung(2.4)
  • Skin(2.4)
  • Intestine(2.1)
  • Blood(2)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with TOLLIP: view

Primer Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer 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 34 35
  • 88.6 (n)
dog
(Canis familiaris)
Mammalia TOLLIP 34 35
  • 87.79 (n)
chimpanzee
(Pan troglodytes)
Mammalia TOLLIP 34
  • 87.75 (n)
oppossum
(Monodelphis domestica)
Mammalia TOLLIP 35
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tollip 34 16 35
  • 86.08 (n)
rat
(Rattus norvegicus)
Mammalia Tollip 34
  • 85.84 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TOLLIP 35
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves TOLLIP 34 35
  • 78.51 (n)
lizard
(Anolis carolinensis)
Reptilia TOLLIP 35
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tollip 34
  • 74.63 (n)
zebrafish
(Danio rerio)
Actinopterygii tollip 34 35
  • 76.47 (n)
Dr.8875 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003615 34
  • 59.21 (n)
worm
(Caenorhabditis elegans)
Secernentea tli-1 34 35
  • 49.34 (n)
F25H2.1 36
  • 36 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6903 35
  • 37 (a)
OneToOne
Species where no ortholog for TOLLIP was found in the sources mined by GeneCards:
  • 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
rs1000040467 -- 1,308,036(+) AGCAT(C/T)GTGAA intron-variant, upstream-variant-2KB
rs1000114589 -- 1,288,949(+) CGATC(A/G)TATAT intron-variant, nc-transcript-variant, utr-variant-5-prime
rs1000128779 -- 1,295,876(+) ATTCC(C/T)GCGGC intron-variant
rs1000212007 -- 1,284,791(+) AAGTG(A/C)GGGCG intron-variant
rs1000254715 -- 1,299,157(+) CAATT(C/T)GTCAT intron-variant

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

Variant ID Type Subtype PubMed ID
dgv1014n100 CNV gain 25217958
dgv1537n54 CNV loss 21841781
dgv1538n54 CNV gain 21841781
esv1001632 CNV deletion 20482838
esv1056483 CNV deletion 17803354
esv1170595 CNV insertion 17803354
esv1673155 CNV deletion 17803354
esv21758 CNV gain 19812545
esv2669189 CNV deletion 23128226
esv2743878 CNV deletion 23290073
esv2743907 CNV deletion 23290073
esv2759794 CNV loss 17122850
esv3395781 CNV duplication 20981092
esv3625107 CNV gain 21293372
esv3625108 CNV loss 21293372
nsv1053427 CNV gain 25217958
nsv1069542 CNV deletion 25765185
nsv1137981 CNV deletion 24896259
nsv39591 CNV deletion 16902084
nsv467637 CNV loss 19166990
nsv469923 CNV loss 18288195
nsv552927 CNV loss 21841781
nsv818794 CNV loss 17921354
nsv825693 CNV gain 20364138
nsv825694 CNV gain 20364138
nsv951278 CNV deletion 24416366

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

Human Gene Mutation Database (HGMD)
TOLLIP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
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 and GeneCards

Disorder Aliases PubMed IDs
lymphoproliferative syndrome, x-linked, 1
  • x-linked lymphoproliferative syndrome 1
- 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 22 64
  2. 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 22 46 64
  3. Association of toll-interacting protein gene polymorphisms with atopic dermatitis. (PMID: 17362526) Schimming T.T. … Hoffjan S. (BMC Dermatol. 2007) 3 22 46 64
  4. Recruitment of clathrin onto endosomes by the Tom1-Tollip complex. (PMID: 16412388) Katoh Y. … Nakayama K. (Biochem. Biophys. Res. Commun. 2006) 3 4 22 64
  5. Negative regulation of Toll-like receptor-mediated signaling by Tollip. (PMID: 11751856) Zhang G. … Ghosh S. (J. Biol. Chem. 2002) 3 4 22 64

Products for TOLLIP Gene

Sources for TOLLIP Gene

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