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TOLLIP toll interacting protein [ Homo sapiens (human) ]

Gene ID: 54472, updated on 3-Nov-2024

Summary

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Official Symbol
TOLLIPprovided by HGNC
Official Full Name
toll interacting proteinprovided by HGNC
Primary source
HGNC:HGNC:16476
See related
Ensembl:ENSG00000078902 MIM:606277; AllianceGenome:HGNC:16476
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IL-1RAcPIP
Summary
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]
Expression
Ubiquitous expression in brain (RPKM 31.0), testis (RPKM 17.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See TOLLIP in Genome Data Viewer
Location:
11p15.5
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (1274371..1309632, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (1345549..1381261, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (1295601..1330862, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene mucin 5B, oligomeric mucus/gel-forming Neighboring gene MUC5B antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3050 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:1283433-1283938 Neighboring gene microRNA 6744 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4288 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:1319647-1320378 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:1320379-1321110 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:1323133-1323656 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:1323657-1324180 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:1324181-1324704 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3052 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:1331258-1332019 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3053 Neighboring gene TOLLIP divergent transcript Neighboring gene uncharacterized LOC124902606

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Association of toll-interacting protein gene polymorphisms with atopic dermatitis. Schimming TT, et al. BMC Dermatol, 2007 Mar 16. PMID 17362526, Free PMC Article
  2. Tollip Inhibits ST2 Signaling in Airway Epithelial Cells Exposed to Type 2 Cytokines and Rhinovirus. Dakhama A, et al. J Innate Immun, 2020. PMID 30928973, Free PMC Article
  3. Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease. Li X, et al. J Mol Med (Berl), 2021 Jan. PMID 33128579
  4. A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis. Shah JA, et al. Am J Respir Crit Care Med, 2017 Aug 15. PMID 28463648, Free PMC Article
  5. Pharmacogenetics and interstitial lung disease. Oldham JM, et al. Curr Opin Pulm Med, 2016 Sep. PMID 27253772, Free PMC Article

See all (156) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Tollip deficiency exaggerates airway type 2 inflammation in mice exposed to allergen and influenza A virus: role of the ATP/IL-33 signaling axis.
    Title: Tollip deficiency exaggerates airway type 2 inflammation in mice exposed to allergen and influenza A virus: role of the ATP/IL-33 signaling axis.
  2. Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.
    Title: Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.
  3. TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma.
    Title: TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma.
  4. TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide and Mycobacterium tuberculosis.
    Title: TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide and Mycobacterium tuberculosis.
  5. Somatostatin attenuates intestinal epithelial barrier injury during acute intestinal ischemia-reperfusion through Tollip/Myeloiddifferentiationfactor 88/Nuclear factor kappa-B signaling.
    Title: Somatostatin attenuates intestinal epithelial barrier injury during acute intestinal ischemia-reperfusion through Tollip/Myeloiddifferentiationfactor 88/Nuclear factor kappa-B signaling.
  6. Alternative Gene Expression by TOLLIP Variant Is Associated With Lung Function in Chronic Hypersensitivity Pneumonitis.
    Title: Alternative Gene Expression by TOLLIP Variant Is Associated With Lung Function in Chronic Hypersensitivity Pneumonitis.
  7. Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease.
    Title: Toll-interacting protein impacts on inflammation, autophagy, and vacuole trafficking in human disease.
  8. Association of rs3750920 polymorphism in TOLLIP with clinical characteristics of fibrosing interstitial lung diseases in Japanese.
    Title: Association of rs3750920 polymorphism in TOLLIP with clinical characteristics of fibrosing interstitial lung diseases in Japanese.
  9. Toll-interacting protein polymorphisms in viral bronchiolitis outcomes.
    Title: Toll-interacting protein polymorphisms in viral bronchiolitis outcomes.
  10. Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.
    Title: Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.
Submit: New GeneRIF Correction See all GeneRIFs (60)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
HIV-1 JRFL and HXB2 upregulate TOLLIP expression in primary monocyte derived dendritic cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 JRFL and HXB2 Env (gp120) upregulate TOLLIP expression in primary monocyte derived dendritic cells PubMed
Pr55(Gag) gag HIV-1 JRFL Gag (p24) expressing virus like particles upregulates TOLLIP expression in primary monocyte derived macrophages PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ33531

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables SUMO binding IEA
Inferred from Electronic Annotation
more info
  
enables Toll-like receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables interleukin-1, type I receptor binding IEA
Inferred from Electronic Annotation
more info
  
enables kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables molecular adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin conjugating enzyme binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in autophagy IEA
Inferred from Electronic Annotation
more info
  
involved_in epithelial cell differentiation IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in inflammatory response IEA
Inferred from Electronic Annotation
more info
  
involved_in innate immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in interleukin-1-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in leukocyte activation NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of protein sumoylation IEA
Inferred from Electronic Annotation
more info
  
involved_in protein localization to endosome IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction IPI
Inferred from Physical Interaction
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in azurophil granule lumen TAS
Traceable Author Statement
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IC
Inferred by Curator
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in early endosome IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extrinsic component of plasma membrane IC
Inferred by Curator
more info
 PubMed 
located_in nuclear body IEA
Inferred from Electronic Annotation
more info
  
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in specific granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
toll-interacting protein
Names
adapter protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001318512.2 → NP_001305441.1  toll-interacting protein isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC136297, AK090850, AL136835, HY031351
    UniProtKB/TrEMBL
    A0AAG2UV02, B3KR28, E9PQ25
    Related
    ENSP00000434494.1, ENST00000530541.1
    Conserved Domains (2) summary
    cd04016
    Location:12 → 122
    C2_Tollip; C2 domain present in Toll-interacting protein (Tollip)
    cd14363
    Location:180 → 220
    CUE_TOLIP; CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins

  2. NM_001318514.2 → NP_001305443.1  toll-interacting protein isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate first exon compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC136297, AK090850, AK127123, AL136835, DA227912
    Consensus CDS
    CCDS81532.1
    UniProtKB/TrEMBL
    E7EN89
    Related
    ENSP00000434035.1, ENST00000527886.5
    Conserved Domains (2) summary
    cd04016
    Location:1 → 103
    C2_Tollip; C2 domain present in Toll-interacting protein (Tollip)
    cd14363
    Location:161 → 201
    CUE_TOLIP; CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins

  3. NM_001318515.2 → NP_001305444.1  toll-interacting protein isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks three alternate exons compared to variant 1, that causes a frameshift. The resulting isoform (5) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC136297, AK090850, AL136835, DB220293, HY031351
    Consensus CDS
    CCDS81533.1
    UniProtKB/TrEMBL
    E9PNS3
    Related
    ENSP00000432778.1, ENST00000527938.5

  4. NM_001318516.2 → NP_001305445.1  toll-interacting protein isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AC136297, AK090850, AK096693, AL136835, HY031351
    Consensus CDS
    CCDS81534.1
    UniProtKB/TrEMBL
    F2Z2Y8, Q8N8J5
    Related
    ENSP00000432668.1, ENST00000525159.5
    Conserved Domains (2) summary
    cd14363
    Location:169 → 209
    CUE_TOLIP; CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins
    cl14603
    Location:61 → 111
    C2; C2 domain

  5. NM_019009.4 → NP_061882.2  toll-interacting protein isoform 1

    See identical proteins and their annotated locations for NP_061882.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AA861717, AL136835, DB039994
    Consensus CDS
    CCDS7723.1
    UniProtKB/Swiss-Prot
    B3KXC6, Q9H0E2, Q9H9E6, Q9UJ69
    UniProtKB/TrEMBL
    E7EN89, Q6FIE9
    Related
    ENSP00000314733.5, ENST00000317204.11
    Conserved Domains (2) summary
    cd04016
    Location:52 → 172
    C2_Tollip; C2 domain present in Toll-interacting protein (Tollip)
    cd14363
    Location:230 → 270
    CUE_TOLIP; CUE domain found in the C-terminal of toll-interacting protein (Tollip) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    1274371..1309632 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047427134.1 → XP_047283090.1  toll-interacting protein isoform X4

  2. XM_017017931.2 → XP_016873420.1  toll-interacting protein isoform X3

  3. XM_047427135.1 → XP_047283091.1  toll-interacting protein isoform X1

  4. XM_047427136.1 → XP_047283092.1  toll-interacting protein isoform X2

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_025791792.1 Reference GRCh38.p14 PATCHES

    Range
    8637..43898 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054333113.1 → XP_054189088.1  toll-interacting protein isoform X4

  2. XM_054333114.1 → XP_054189089.1  toll-interacting protein isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    1345549..1381261 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054369154.1 → XP_054225129.1  toll-interacting protein isoform X5

  2. XM_054369157.1 → XP_054225132.1  toll-interacting protein isoform X3

  3. XM_054369155.1 → XP_054225130.1  toll-interacting protein isoform X1

  4. XM_054369156.1 → XP_054225131.1  toll-interacting protein isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H0E2.1 GenPept UniProtKB/Swiss-Prot:Q9H0E2

Gene LinkOut

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