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Protein

Toll-interacting protein

Gene

Tollip

Organism
Rattus norvegicus (Rat)
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. 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 (By similarity).By similarity

GO - Molecular functioni

  • interleukin-1, Type I receptor binding Source: RGD
  • SUMO binding Source: RGD
  • ubiquitin binding Source: GO_Central
  • ubiquitin conjugating enzyme binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Autophagy, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-RNO-446652. Interleukin-1 signaling.
R-RNO-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-interacting protein
Gene namesi
Name:TollipImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1304676. Tollip.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: Ensembl
  • nuclear body Source: RGD
  • perinuclear region of cytoplasm Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00003081832 – 274Toll-interacting proteinAdd BLAST273

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei274PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiA2RUW1.
PeptideAtlasiA2RUW1.
PRIDEiA2RUW1.

PTM databases

iPTMnetiA2RUW1.
PhosphoSitePlusiA2RUW1.

Expressioni

Gene expression databases

BgeeiENSRNOG00000019861.
GenevisibleiA2RUW1. RN.

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 (By similarity). Interacts with ATG8 family proteins (via the AIM motifs), and ubiquitin (via the CUE domain) (By similarity).By similarity

GO - Molecular functioni

  • interleukin-1, Type I receptor binding Source: RGD
  • SUMO binding Source: RGD
  • ubiquitin binding Source: GO_Central
  • ubiquitin conjugating enzyme binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

Protein-protein interaction databases

BioGridi262870. 15 interactors.
STRINGi10116.ENSRNOP00000049498.

Structurei

3D structure databases

ProteinModelPortaliA2RUW1.
ModBaseiSearch...
MobiDBiSearch...

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-richSequence analysisAdd BLAST17

Domaini

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

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.
InParanoidiA2RUW1.
KOiK05402.
OMAiHVTIPES.
OrthoDBiEOG091G0JE1.
PhylomeDBiA2RUW1.
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]

Sequencei

Sequence statusi: Complete.

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

A2RUW1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATTVSTQRG PVYIGELPQD FLRITPTQQQ QQIQLDAQAA QQLQYGGAVG
60 70 80 90 100
TVGRLSITVV QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW
110 120 130 140 150
NKVIQCTVPP GVDSFYLEIF DERAFSMDDR IAWTHITIPE SLKQGQVEDE
160 170 180 190 200
WYSLSGRQGD DKEGMINLVM SYTSLPAAMM MPPQPVVLMP TVYQQGVGYV
210 220 230 240 250
PIAGMPAVCS PGMVPMAMPP PAVAPQPRCN EEDLKAIQDM FPNMDREVIR
260 270
SVLEAQRGNK DAAINSLLQM GEES
Length:274
Mass (Da):30,315
Last modified:March 6, 2007 - v1
Checksum:i89C8E01F77AD66B1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133067 mRNA. Translation: AAI33068.1.
RefSeqiNP_001103138.1. NM_001109668.1.
UniGeneiRn.137040.

Genome annotation databases

EnsembliENSRNOT00000046344; ENSRNOP00000049498; ENSRNOG00000019861.
GeneIDi361677.
KEGGirno:361677.
UCSCiRGD:1304676. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC133067 mRNA. Translation: AAI33068.1.
RefSeqiNP_001103138.1. NM_001109668.1.
UniGeneiRn.137040.

3D structure databases

ProteinModelPortaliA2RUW1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi262870. 15 interactors.
STRINGi10116.ENSRNOP00000049498.

PTM databases

iPTMnetiA2RUW1.
PhosphoSitePlusiA2RUW1.

Proteomic databases

PaxDbiA2RUW1.
PeptideAtlasiA2RUW1.
PRIDEiA2RUW1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000046344; ENSRNOP00000049498; ENSRNOG00000019861.
GeneIDi361677.
KEGGirno:361677.
UCSCiRGD:1304676. rat.

Organism-specific databases

CTDi54472.
RGDi1304676. Tollip.

Phylogenomic databases

eggNOGiENOG410IE45. Eukaryota.
ENOG410XQPY. LUCA.
GeneTreeiENSGT00390000013104.
HOGENOMiHOG000293427.
HOVERGENiHBG054213.
InParanoidiA2RUW1.
KOiK05402.
OMAiHVTIPES.
OrthoDBiEOG091G0JE1.
PhylomeDBiA2RUW1.
TreeFamiTF324180.

Enzyme and pathway databases

ReactomeiR-RNO-446652. Interleukin-1 signaling.
R-RNO-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiA2RUW1.

Gene expression databases

BgeeiENSRNOG00000019861.
GenevisibleiA2RUW1. RN.

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_RAT
AccessioniPrimary (citable) accession number: A2RUW1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: March 6, 2007
Last modified: November 30, 2016
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.