Q9HAI6 · TASL_HUMAN
- ProteinTLR adapter interacting with SLC15A4 on the lysosome
- GeneTASL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids301 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Innate immune adapter that mediates the recruitment and activation of IRF5 downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:32433612).
Following recruitment to endolysosome by SLC15A4 downstream of TLR7, TLR8 and TLR9, specifically recruits IRF5 transcription factor via its pLxIS motif, leading to IRF5 activation and subsequent expression of type I interferons (PubMed:32433612).
Plays a role in the regulation of endolysosomal pH in immune cells such as B-cells, dendritic cells and monocytes (PubMed:31001245).
Following recruitment to endolysosome by SLC15A4 downstream of TLR7, TLR8 and TLR9, specifically recruits IRF5 transcription factor via its pLxIS motif, leading to IRF5 activation and subsequent expression of type I interferons (PubMed:32433612).
Plays a role in the regulation of endolysosomal pH in immune cells such as B-cells, dendritic cells and monocytes (PubMed:31001245).
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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Aspect | Term | |
---|---|---|
Cellular Component | endolysosome membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | nucleoplasm | |
Biological Process | innate immune response | |
Biological Process | positive regulation of innate immune response | |
Biological Process | positive regulation of toll-like receptor 7 signaling pathway | |
Biological Process | positive regulation of toll-like receptor 8 signaling pathway | |
Biological Process | regulation of lysosomal lumen pH | |
Biological Process | regulation of toll-like receptor signaling pathway |
Keywords
- Biological process
Enzyme and pathway databases
CXorf21/TASL acts as an innate immune adaptor meditating the activation of IRF5 downstream of endolysosomal TLR7-9 activation. IRF5 recruitment is mediated by a pLxIS motif (where p and x denote hydrophilic and any amino acid, respectively) present in the C-terminal region of CXorf21/TASL. CXorf21/TASL interacts with SLC15A4. Binding to SLC15A4 is required for the recruitment of CXorf21/TASL to endolysosomes.
Names & Taxonomy
Protein names
- Recommended nameTLR adapter interacting with SLC15A4 on the lysosome
Gene names
- Community suggested namesTASL; CXorf21.
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9HAI6
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 294 | Abolished ability to activate IRF5. | ||||
Sequence: S → A | ||||||
Mutagenesis | 294 | Phosphomimetic mutant; retains ability to activate IRF5. | ||||
Sequence: S → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 236 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 chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000251252 | 1-301 | TLR adapter interacting with SLC15A4 on the lysosome | |||
Sequence: MLSEGYLSGLEYWNDIHWSCASYNEQVAGEKEEETNSVATLSYSSVDETQVRSLYVSCKSSGKFISSVHSRESQHSRSQRVTVLQTNPNPVFESPNLAAVEICRDASRETYLVPSSCKSICKNYNDLQIAGGQVMAINSVTTDFPSESSFEYGPLLKSSEIPLPMEDSISTQPSDFPQKPIQRYSSYWRITSIKEKSSLQMQNPISNAVLNEYLEQKVVELYKQYIMDTVFHDSSPTQILASELIMTSVDQISLQVSREKNLETSKARDIVFSRLLQLMSTEITEISTPSLHISQYSNVNP | ||||||
Modified residue | 294 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
The phosphorylated pLxIS motif constitutes an IRF5-binding motif, leading to recruitment of the transcription factor IRF5 to induce type-I interferons and other cytokines.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in immune cell types such as B-cells, neutrophils, dendritic cells and monocytes, the expression levels are two-three-fold higher in female cells compared to male cells (at protein level) (PubMed:31001245, PubMed:31092820).
Expressed at low levels in T-cells and NK cells (PubMed:31001245).
Expressed at low levels in T-cells and NK cells (PubMed:31001245).
Induction
Escape from X chromosome inactivation results in an increased expression in females (PubMed:31001245, PubMed:31092820).
In monocytes and B cells, induced by type I and type II interferons as well as LPS (PubMed:31092820).
In monocytes and B cells, induced by type I and type II interferons as well as LPS (PubMed:31092820).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts (via pLxIS motif) with IRF5; leading to IRF5 activation (PubMed:32433612).
Interacts with SLC15A4; leading to its recruitment to endolysosome (PubMed:32433612).
Interacts with SLC15A4; leading to its recruitment to endolysosome (PubMed:32433612).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9HAI6 | SLC15A4 Q8N697 | 15 | EBI-21895669, EBI-4319594 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 290-294 | pLxIS motif | ||||
Sequence: SLHIS |
Domain
The pLxIS motif constitutes an IRF5-binding motif: following phosphorylation, the phosphorylated pLxIS motif of TASL recruits IRF5.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length301
- Mass (Da)33,894
- Last updated2001-03-01 v1
- Checksum0754B491077927C4
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK021639 EMBL· GenBank· DDBJ | BAB13860.1 EMBL· GenBank· DDBJ | mRNA | ||
BC020611 EMBL· GenBank· DDBJ | AAH20611.1 EMBL· GenBank· DDBJ | mRNA |