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Protein

Toll-interacting protein

Gene

Tollip

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

Keywordsi

Biological processAutophagy, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-6798695 Neutrophil degranulation
R-MMU-9020702 Interleukin-1 signaling

Names & Taxonomyi

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

Organism-specific databases

MGIiMGI:1891808 Tollip

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000726262 – 274Toll-interacting proteinAdd BLAST273

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei274PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9QZ06
MaxQBiQ9QZ06
PaxDbiQ9QZ06
PeptideAtlasiQ9QZ06
PRIDEiQ9QZ06

2D gel databases

REPRODUCTION-2DPAGEiIPI00136618

PTM databases

iPTMnetiQ9QZ06
PhosphoSitePlusiQ9QZ06
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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207666, 4 interactors
IntActiQ9QZ06, 6 interactors
MINTiQ9QZ06
STRINGi10090.ENSMUSP00000001950

Structurei

3D structure databases

ProteinModelPortaliQ9QZ06
SMRiQ9QZ06
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-richAdd 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

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

CDDicd04016 C2_Tollip, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR003892 CUE
IPR037301 Tollip_C2
IPR009060 UBA-like_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF02845 CUE, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00546 CUE, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
PROSITEiView protein in PROSITE
PS51140 CUE, 1 hit

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
UCSCiuc009kmd.1 mouse

Similar proteinsi

Entry informationi

Entry nameiTOLIP_MOUSE
AccessioniPrimary (citable) accession number: Q9QZ06
Secondary accession number(s): Q543N1, Q9D5P5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: May 1, 2000
Last modified: March 28, 2018
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health