Q9H0E2 · TOLIP_HUMAN
- ProteinToll-interacting protein
- GeneTOLLIP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids274 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Component of the signaling pathway of IL-1 and Toll-like receptors (PubMed:10854325, PubMed:11751856).
Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex (PubMed:10854325).
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 (PubMed:25042851).
The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851).
In a complex with TOM1, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686).
Binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:26320582).
Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex (PubMed:10854325).
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 (PubMed:25042851).
The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851).
In a complex with TOM1, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686).
Binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:26320582).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameToll-interacting protein
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H0E2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localized to endo/exosomal vesicles.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 9 | Reduced interaction with TOM1; when associated with Ala-12. | ||||
Sequence: R → A | ||||||
Mutagenesis | 12 | Reduced interaction with TOM1; when associated with Ala-9. | ||||
Sequence: V → A | ||||||
Mutagenesis | 20 | Reduced interaction with TOM1; when associated with Ala-23. | ||||
Sequence: D → A | ||||||
Mutagenesis | 21 | Reduced interaction with TOM1. | ||||
Sequence: F → A | ||||||
Mutagenesis | 23 | Reduced interaction with TOM1; when associated with Ala-20. | ||||
Sequence: R → A | ||||||
Natural variant | VAR_079499 | 161 | in dbSNP:rs1037270334 | |||
Sequence: D → N | ||||||
Natural variant | VAR_034557 | 222 | in dbSNP:rs5744015 | |||
Sequence: A → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 307 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000072625 | 2-274 | UniProt | Toll-interacting protein | |||
Sequence: ATTVSTQRGPVYIGELPQDFLRITPTQQQRQVQLDAQAAQQLQYGGAVGTVGRLNITVVQAKLAKNYGMTRMDPYCRLRLGYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSFYLEIFDERAFSMDDRIAWTHITIPESLRQGKVEDKWYSLSGRQGDDKEGMINLVMSYALLPAAMVMPPQPVVLMPTVYQQGVGYVPITGMPAVCSPGMVPVALPPAAVNAQPRCSEEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQMGEEP | |||||||
Modified residue (large scale data) | 25 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 83 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 86 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated by IRAK1 upon stimulation by IL-1 or microbial products.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Oligomerizes (PubMed:11751856).
Interacts (via C-terminus) with TLR2 and the TLR4-MD2 complex (PubMed:11751856).
Exists as complex with IRAK1 in unstimulated cells (PubMed:10854325).
Upon IL-1 signaling, 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 (PubMed:10854325).
MyD88 then triggers IRAK1 autophosphorylation, which in turn leads to the dissociation of IRAK1 from TOLLIP and IL-1RAcP (PubMed:10854325).
Found in a complex with TOM1; interacts (via N-terminus) with TOM1 (via GAT domain); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns3P (PubMed:14563850, PubMed:15047686, PubMed:26320582, PubMed:31263572).
Interacts with TOM1L2 (PubMed:16412388).
Interacts with ATG8 family proteins (via AIM motifs) (PubMed:25042851).
Interacts (via CUE domain) with ubiquitin (PubMed:14563850, PubMed:25042851).
Interacts with LRBA (PubMed:31263572).
Interacts (via C-terminus) with TLR2 and the TLR4-MD2 complex (PubMed:11751856).
Exists as complex with IRAK1 in unstimulated cells (PubMed:10854325).
Upon IL-1 signaling, 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 (PubMed:10854325).
MyD88 then triggers IRAK1 autophosphorylation, which in turn leads to the dissociation of IRAK1 from TOLLIP and IL-1RAcP (PubMed:10854325).
Found in a complex with TOM1; interacts (via N-terminus) with TOM1 (via GAT domain); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns3P (PubMed:14563850, PubMed:15047686, PubMed:26320582, PubMed:31263572).
Interacts with TOM1L2 (PubMed:16412388).
Interacts with ATG8 family proteins (via AIM motifs) (PubMed:25042851).
Interacts (via CUE domain) with ubiquitin (PubMed:14563850, PubMed:25042851).
Interacts with LRBA (PubMed:31263572).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 35-152 | C2 | ||||
Sequence: LDAQAAQQLQYGGAVGTVGRLNITVVQAKLAKNYGMTRMDPYCRLRLGYAVYETPTAHNGAKNPRWNKVIHCTVPPGVDSFYLEIFDERAFSMDDRIAWTHITIPESLRQGKVEDKWY | ||||||
Motif | 133-136 | AIM1 | ||||
Sequence: WTHI | ||||||
Motif | 151-154 | AIM2 | ||||
Sequence: WYSL | ||||||
Domain | 229-272 | CUE | ||||
Sequence: CSEEDLKAIQDMFPNMDQEVIRSVLEAQRGNKDAAINSLLQMGE |
Domain
Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.
The N-terminal TOM1-binding domain (residues 1-53) is a disordered domain that partially folds when bound to the GAT domain of TOM1.
Sequence similarities
Belongs to the tollip family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9H0E2-1
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.
- Name1
- Length274
- Mass (Da)30,282
- Last updated2001-03-01 v1
- Checksum386E0F284D3837DA
Q9H0E2-2
- Name2
- Differences from canonical
- 1-69: Missing
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056301 | 1-69 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 40 | in Ref. 1; CAB58118 | ||||
Sequence: Missing | ||||||
Sequence conflict | 150 | in Ref. 3; BAB14283 | ||||
Sequence: K → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ242972 EMBL· GenBank· DDBJ | CAB58118.1 EMBL· GenBank· DDBJ | mRNA | ||
AL136835 EMBL· GenBank· DDBJ | CAB66769.1 EMBL· GenBank· DDBJ | mRNA | ||
AK022871 EMBL· GenBank· DDBJ | BAB14283.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK127123 EMBL· GenBank· DDBJ | BAG54438.1 EMBL· GenBank· DDBJ | mRNA | ||
AC136297 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC004420 EMBL· GenBank· DDBJ | AAH04420.1 EMBL· GenBank· DDBJ | mRNA | ||
BC012057 EMBL· GenBank· DDBJ | AAH12057.1 EMBL· GenBank· DDBJ | mRNA | ||
BC018272 EMBL· GenBank· DDBJ | AAH18272.1 EMBL· GenBank· DDBJ | mRNA |