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Protein

Toll-interacting protein

Gene

Tollip

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Autophagy, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-446652. Interleukin-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-interacting protein
Gene namesi
Name:Tollip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1891808. Tollip.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 274273Toll-interacting proteinPRO_0000072626Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei274 – 2741PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9QZ06.
MaxQBiQ9QZ06.
PaxDbiQ9QZ06.
PeptideAtlasiQ9QZ06.
PRIDEiQ9QZ06.

2D gel databases

REPRODUCTION-2DPAGEIPI00136618.

PTM databases

iPTMnetiQ9QZ06.
PhosphoSiteiQ9QZ06.
SwissPalmiQ9QZ06.

Expressioni

Tissue specificityi

Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney, thymus, pancreas and testis.

Gene expression databases

BgeeiENSMUSG00000025139.
CleanExiMM_TOLLIP.
ExpressionAtlasiQ9QZ06. baseline and differential.
GenevisibleiQ9QZ06. MM.

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

Binary interactionsi

WithEntry#Exp.IntActNotes
Il1rapQ617302EBI-74272,EBI-525035
Irak1Q624062EBI-74272,EBI-448533
Tom1O887462EBI-74272,EBI-74264

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207666. 2 interactions.
IntActiQ9QZ06. 6 interactions.
MINTiMINT-4138189.
STRINGi10090.ENSMUSP00000001950.

Structurei

3D structure databases

ProteinModelPortaliQ9QZ06.
SMRiQ9QZ06. Positions 231-273.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 13596C2Add
BLAST
Domaini229 – 27244CUEPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi133 – 1364AIM1
Motifi151 – 1544AIM2

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi28 – 4417Gln-richAdd
BLAST

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.
InParanoidiQ9QZ06.
KOiK05402.
OMAiHVTIPES.
OrthoDBiEOG091G0JE1.
PhylomeDBiQ9QZ06.
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.

Q9QZ06-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATTVSTQRG PVYIGELPQD FLRITPTQQQ QQIQLDAQAA QQLQYGGTVG
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):30,345
Last modified:May 1, 2000 - v1
Checksum:iC3624DB407B0C17B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ242971 mRNA. Translation: CAB58121.1.
AK015062 mRNA. No translation available.
AK016482 mRNA. Translation: BAB30262.1.
AK045422 mRNA. Translation: BAC32357.1.
AK049263 mRNA. Translation: BAC33643.1.
AK161312 mRNA. Translation: BAE36316.1.
BC062139 mRNA. Translation: AAH62139.1.
CCDSiCCDS22020.1.
RefSeqiNP_076253.1. NM_023764.3.
UniGeneiMm.103551.

Genome annotation databases

EnsembliENSMUST00000001950; ENSMUSP00000001950; ENSMUSG00000025139.
GeneIDi54473.
KEGGimmu:54473.
UCSCiuc009kmd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ242971 mRNA. Translation: CAB58121.1.
AK015062 mRNA. No translation available.
AK016482 mRNA. Translation: BAB30262.1.
AK045422 mRNA. Translation: BAC32357.1.
AK049263 mRNA. Translation: BAC33643.1.
AK161312 mRNA. Translation: BAE36316.1.
BC062139 mRNA. Translation: AAH62139.1.
CCDSiCCDS22020.1.
RefSeqiNP_076253.1. NM_023764.3.
UniGeneiMm.103551.

3D structure databases

ProteinModelPortaliQ9QZ06.
SMRiQ9QZ06. Positions 231-273.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207666. 2 interactions.
IntActiQ9QZ06. 6 interactions.
MINTiMINT-4138189.
STRINGi10090.ENSMUSP00000001950.

PTM databases

iPTMnetiQ9QZ06.
PhosphoSiteiQ9QZ06.
SwissPalmiQ9QZ06.

2D gel databases

REPRODUCTION-2DPAGEIPI00136618.

Proteomic databases

EPDiQ9QZ06.
MaxQBiQ9QZ06.
PaxDbiQ9QZ06.
PeptideAtlasiQ9QZ06.
PRIDEiQ9QZ06.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000001950; ENSMUSP00000001950; ENSMUSG00000025139.
GeneIDi54473.
KEGGimmu:54473.
UCSCiuc009kmd.1. mouse.

Organism-specific databases

CTDi54472.
MGIiMGI:1891808. Tollip.

Phylogenomic databases

eggNOGiENOG410IE45. Eukaryota.
ENOG410XQPY. LUCA.
GeneTreeiENSGT00390000013104.
HOGENOMiHOG000293427.
HOVERGENiHBG054213.
InParanoidiQ9QZ06.
KOiK05402.
OMAiHVTIPES.
OrthoDBiEOG091G0JE1.
PhylomeDBiQ9QZ06.
TreeFamiTF324180.

Enzyme and pathway databases

ReactomeiR-MMU-446652. Interleukin-1 signaling.

Miscellaneous databases

PROiQ9QZ06.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025139.
CleanExiMM_TOLLIP.
ExpressionAtlasiQ9QZ06. baseline and differential.
GenevisibleiQ9QZ06. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q9QZ06
Secondary accession number(s): Q543N1, Q9D5P5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: May 1, 2000
Last modified: September 7, 2016
This is version 124 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.