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Protein

Toll-interacting protein

Gene

TOLLIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).2 Publications

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • signal transducer activity Source: UniProtKB
  • Toll-like receptor binding Source: UniProtKB
  • ubiquitin binding Source: GO_Central
  • ubiquitin conjugating enzyme binding Source: GO_Central

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • cell-cell signaling Source: ProtInc
  • epithelial cell differentiation Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • intracellular signal transduction Source: UniProtKB
  • leukocyte activation Source: UniProtKB
  • phosphorylation Source: UniProtKB
  • positive regulation of protein sumoylation Source: Ensembl
  • protein localization to endosome Source: UniProtKB
  • signal transduction Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: GO_Central
Complete GO annotation...

Keywords - Biological processi

Autophagy, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000078902-MONOMER.
ReactomeiR-HSA-446652. Interleukin-1 signaling.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiQ9H0E2.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-interacting protein
Gene namesi
Name:TOLLIP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:16476. TOLLIP.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • interleukin-18 receptor complex Source: UniProtKB
  • interleukin-1 receptor complex Source: UniProtKB
  • nuclear body Source: Ensembl
  • perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi54472.
OpenTargetsiENSG00000078902.
PharmGKBiPA134876213.

Polymorphism and mutation databases

BioMutaiTOLLIP.
DMDMi20140803.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000726252 – 274Toll-interacting proteinAdd BLAST273

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Post-translational modificationi

Phosphorylated by IRAK1 upon stimulation by IL-1 or microbial products.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H0E2.
MaxQBiQ9H0E2.
PaxDbiQ9H0E2.
PeptideAtlasiQ9H0E2.
PRIDEiQ9H0E2.

PTM databases

iPTMnetiQ9H0E2.
PhosphoSitePlusiQ9H0E2.

Expressioni

Gene expression databases

BgeeiENSG00000078902.
CleanExiHS_TOLLIP.
ExpressionAtlasiQ9H0E2. baseline and differential.
GenevisibleiQ9H0E2. HS.

Organism-specific databases

HPAiHPA038621.
HPA038622.

Interactioni

Subunit structurei

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).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CSTF1Q050482EBI-74615,EBI-1789619
DAB1O755533EBI-74615,EBI-7875264
DAZAP2Q150388EBI-74615,EBI-724310
DZIP3Q86Y132EBI-74615,EBI-948630
EIF2AK2P195252EBI-74615,EBI-640775
IRAK2O431872EBI-74615,EBI-447733
MAP1LC3AQ9H4923EBI-74615,EBI-720768
PEG10Q86TG72EBI-74615,EBI-2858265
RBPMSQ930624EBI-74615,EBI-740322
TOM1O607844EBI-74615,EBI-74634
TOM1L1O756743EBI-74615,EBI-712991
WDYHV1Q96HA83EBI-74615,EBI-741158
WRNIP1Q96S552EBI-74615,EBI-2513471

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • Toll-like receptor binding Source: UniProtKB
  • ubiquitin binding Source: GO_Central
  • ubiquitin conjugating enzyme binding Source: GO_Central

Protein-protein interaction databases

BioGridi119978. 83 interactors.
DIPiDIP-30845N.
IntActiQ9H0E2. 59 interactors.
MINTiMINT-4539075.
STRINGi9606.ENSP00000314733.

Structurei

Secondary structure

1274
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 7Combined sources4
Beta strandi10 – 13Combined sources4
Helixi231 – 240Combined sources10
Beta strandi242 – 244Combined sources3
Helixi246 – 253Combined sources8
Turni254 – 258Combined sources5
Helixi260 – 269Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WGLNMR-A229-274[»]
2N31NMR-A1-53[»]
ProteinModelPortaliQ9H0E2.
SMRiQ9H0E2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H0E2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 135C2Add BLAST96
Domaini229 – 272CUEPROSITE-ProRule annotationAdd BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 136AIM14
Motifi151 – 154AIM24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi28 – 44Gln-richAdd BLAST17

Domaini

Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.1 Publication

Sequence similaritiesi

Belongs to the tollip family.Curated
Contains 1 C2 domain.Curated
Contains 1 CUE domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IE45. Eukaryota.
ENOG410XQPY. LUCA.
GeneTreeiENSGT00390000013104.
HOGENOMiHOG000293427.
HOVERGENiHBG054213.
InParanoidiQ9H0E2.
KOiK05402.
OMAiHVTIPES.
OrthoDBiEOG091G0JE1.
PhylomeDBiQ9H0E2.
TreeFamiTF324180.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR003892. CUE.
IPR009060. UBA-like.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF02845. CUE. 1 hit.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00546. CUE. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF49562. SSF49562. 1 hit.
PROSITEiPS51140. CUE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H0E2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATTVSTQRG PVYIGELPQD FLRITPTQQQ RQVQLDAQAA QQLQYGGAVG
60 70 80 90 100
TVGRLNITVV QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW
110 120 130 140 150
NKVIHCTVPP GVDSFYLEIF DERAFSMDDR IAWTHITIPE SLRQGKVEDK
160 170 180 190 200
WYSLSGRQGD DKEGMINLVM SYALLPAAMV MPPQPVVLMP TVYQQGVGYV
210 220 230 240 250
PITGMPAVCS PGMVPVALPP AAVNAQPRCS EEDLKAIQDM FPNMDQEVIR
260 270
SVLEAQRGNK DAAINSLLQM GEEP
Length:274
Mass (Da):30,282
Last modified:March 1, 2001 - v1
Checksum:i386E0F284D3837DA
GO
Isoform 2 (identifier: Q9H0E2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.

Note: No experimental confirmation available.
Show »
Length:205
Mass (Da):22,812
Checksum:iDED391C6A30BAE56
GO

Sequence cautioni

The sequence BAB14283 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40Missing in CAB58118 (PubMed:10854325).Curated1
Sequence conflicti150K → E in BAB14283 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034557222A → S.Corresponds to variant rs5744015dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0563011 – 69Missing in isoform 2. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ242972 mRNA. Translation: CAB58118.1.
AL136835 mRNA. Translation: CAB66769.1.
AK022871 mRNA. Translation: BAB14283.1. Different initiation.
AK127123 mRNA. Translation: BAG54438.1.
AC136297 Genomic DNA. No translation available.
BC004420 mRNA. Translation: AAH04420.1.
BC012057 mRNA. Translation: AAH12057.1.
BC018272 mRNA. Translation: AAH18272.1.
CCDSiCCDS7723.1. [Q9H0E2-1]
CCDS81532.1. [Q9H0E2-2]
RefSeqiNP_001305441.1. NM_001318512.1.
NP_001305443.1. NM_001318514.1. [Q9H0E2-2]
NP_001305444.1. NM_001318515.1.
NP_001305445.1. NM_001318516.1.
NP_061882.2. NM_019009.3. [Q9H0E2-1]
UniGeneiHs.368527.

Genome annotation databases

EnsembliENST00000317204; ENSP00000314733; ENSG00000078902. [Q9H0E2-1]
ENST00000527886; ENSP00000434035; ENSG00000078902. [Q9H0E2-2]
GeneIDi54472.
KEGGihsa:54472.
UCSCiuc001ltd.4. human. [Q9H0E2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ242972 mRNA. Translation: CAB58118.1.
AL136835 mRNA. Translation: CAB66769.1.
AK022871 mRNA. Translation: BAB14283.1. Different initiation.
AK127123 mRNA. Translation: BAG54438.1.
AC136297 Genomic DNA. No translation available.
BC004420 mRNA. Translation: AAH04420.1.
BC012057 mRNA. Translation: AAH12057.1.
BC018272 mRNA. Translation: AAH18272.1.
CCDSiCCDS7723.1. [Q9H0E2-1]
CCDS81532.1. [Q9H0E2-2]
RefSeqiNP_001305441.1. NM_001318512.1.
NP_001305443.1. NM_001318514.1. [Q9H0E2-2]
NP_001305444.1. NM_001318515.1.
NP_001305445.1. NM_001318516.1.
NP_061882.2. NM_019009.3. [Q9H0E2-1]
UniGeneiHs.368527.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WGLNMR-A229-274[»]
2N31NMR-A1-53[»]
ProteinModelPortaliQ9H0E2.
SMRiQ9H0E2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119978. 83 interactors.
DIPiDIP-30845N.
IntActiQ9H0E2. 59 interactors.
MINTiMINT-4539075.
STRINGi9606.ENSP00000314733.

PTM databases

iPTMnetiQ9H0E2.
PhosphoSitePlusiQ9H0E2.

Polymorphism and mutation databases

BioMutaiTOLLIP.
DMDMi20140803.

Proteomic databases

EPDiQ9H0E2.
MaxQBiQ9H0E2.
PaxDbiQ9H0E2.
PeptideAtlasiQ9H0E2.
PRIDEiQ9H0E2.

Protocols and materials databases

DNASUi54472.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000317204; ENSP00000314733; ENSG00000078902. [Q9H0E2-1]
ENST00000527886; ENSP00000434035; ENSG00000078902. [Q9H0E2-2]
GeneIDi54472.
KEGGihsa:54472.
UCSCiuc001ltd.4. human. [Q9H0E2-1]

Organism-specific databases

CTDi54472.
DisGeNETi54472.
GeneCardsiTOLLIP.
HGNCiHGNC:16476. TOLLIP.
HPAiHPA038621.
HPA038622.
MIMi606277. gene.
neXtProtiNX_Q9H0E2.
OpenTargetsiENSG00000078902.
PharmGKBiPA134876213.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE45. Eukaryota.
ENOG410XQPY. LUCA.
GeneTreeiENSGT00390000013104.
HOGENOMiHOG000293427.
HOVERGENiHBG054213.
InParanoidiQ9H0E2.
KOiK05402.
OMAiHVTIPES.
OrthoDBiEOG091G0JE1.
PhylomeDBiQ9H0E2.
TreeFamiTF324180.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000078902-MONOMER.
ReactomeiR-HSA-446652. Interleukin-1 signaling.
R-HSA-6798695. Neutrophil degranulation.
SignaLinkiQ9H0E2.

Miscellaneous databases

ChiTaRSiTOLLIP. human.
EvolutionaryTraceiQ9H0E2.
GeneWikiiTOLLIP.
GenomeRNAii54472.
PROiQ9H0E2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078902.
CleanExiHS_TOLLIP.
ExpressionAtlasiQ9H0E2. baseline and differential.
GenevisibleiQ9H0E2. HS.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR003892. CUE.
IPR009060. UBA-like.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF02845. CUE. 1 hit.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00546. CUE. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
SSF49562. SSF49562. 1 hit.
PROSITEiPS51140. CUE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTOLIP_HUMAN
AccessioniPrimary (citable) accession number: Q9H0E2
Secondary accession number(s): B3KXC6, Q9H9E6, Q9UJ69
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 1, 2001
Last modified: November 30, 2016
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.