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Protein

Toll-interacting protein

Gene

TOLLIP

Organism
Homo sapiens (Human)
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 (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

Caution

GO - Molecular functioni

  • interleukin-1, Type I receptor binding Source: Ensembl
  • kinase binding Source: UniProtKB
  • signal transducer activity Source: UniProtKB
  • SUMO binding Source: Ensembl
  • Toll-like receptor binding Source: UniProtKB
  • ubiquitin binding Source: GO_Central
  • ubiquitin conjugating enzyme binding Source: GO_Central
  • ubiquitin protein ligase binding Source: Ensembl

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
  • interleukin-1-mediated signaling pathway Source: Reactome
  • intracellular signal transduction Source: UniProtKB
  • leukocyte activation Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • 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

Keywordsi

Biological processAutophagy, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-9020702 Interleukin-1 signaling
SignaLinkiQ9H0E2
SIGNORiQ9H0E2

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

EuPathDBiHostDB:ENSG00000078902.15
HGNCiHGNC:16476 TOLLIP
MIMi606277 gene
neXtProtiNX_Q9H0E2

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

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi11997887 interactors.
DIPiDIP-30845N
IntActiQ9H0E2 75 interactors.
MINTiQ9H0E2
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

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

CDDicd04016 C2_Tollip, 1 hit
Gene3Di2.60.40.1501 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

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_079499161D → N1 PublicationCorresponds to variant dbSNP:rs1037270334Ensembl.1
Natural variantiVAR_034557222A → S. Corresponds to variant dbSNP:rs5744015Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiTOLIP_HUMAN
AccessioniPrimary (citable) accession number: Q9H0E2
Secondary accession number(s): B3KXC6, Q9H9E6, Q9UJ69
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 1, 2001
Last modified: March 28, 2018
This is version 159 of the entry and version 1 of the sequence. See 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