Q9HAI6 · TASL_HUMAN

  • Protein
    TLR adapter interacting with SLC15A4 on the lysosome
  • Gene
    TASL
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentendolysosome membrane
Cellular Componentintracellular membrane-bounded organelle
Cellular Componentnucleoplasm
Biological Processinnate immune response
Biological Processpositive regulation of innate immune response
Biological Processpositive regulation of toll-like receptor 7 signaling pathway
Biological Processpositive regulation of toll-like receptor 8 signaling pathway
Biological Processregulation of lysosomal lumen pH
Biological Processregulation of toll-like receptor signaling pathway

Keywords

Enzyme and pathway databases

Community curation (1)

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 name
    TLR adapter interacting with SLC15A4 on the lysosome

Gene names

    • Name
      TASL
    • Synonyms
      CXorf21
Community curation (1)

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q9HAI6

Proteomes

Organism-specific databases

Subcellular Location

Lysosome membrane
Endosome membrane
Nucleus
Cytoplasm
Note: Recruited to endolysosome following interaction with SLC15A4 (PubMed:32433612).
May colocalize with TLR7 in the endosomal pathway (PubMed:31092820).

Keywords

Disease & Variants

Involvement in disease

  • Some alleles may be associated with systemic lupus erythematosus (SLE); a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Because it evades X-chromosome inactivation, its expression is increased in female immune cells which may be involved to SLE striking sex imbalance towards females

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis294Abolished ability to activate IRF5.
Mutagenesis294Phosphomimetic mutant; retains ability to activate IRF5.

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.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00002512521-301TLR adapter interacting with SLC15A4 on the lysosome
Modified residue294Phosphoserine

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

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).

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).

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).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q9HAI6SLC15A4 Q8N69715EBI-21895669, EBI-4319594

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif290-294pLxIS motif

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 status
    Complete
  • Length
    301
  • Mass (Da)
    33,894
  • Last updated
    2001-03-01 v1
  • Checksum
    0754B491077927C4
MLSEGYLSGLEYWNDIHWSCASYNEQVAGEKEEETNSVATLSYSSVDETQVRSLYVSCKSSGKFISSVHSRESQHSRSQRVTVLQTNPNPVFESPNLAAVEICRDASRETYLVPSSCKSICKNYNDLQIAGGQVMAINSVTTDFPSESSFEYGPLLKSSEIPLPMEDSISTQPSDFPQKPIQRYSSYWRITSIKEKSSLQMQNPISNAVLNEYLEQKVVELYKQYIMDTVFHDSSPTQILASELIMTSVDQISLQVSREKNLETSKARDIVFSRLLQLMSTEITEISTPSLHISQYSNVNP

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK021639
EMBL· GenBank· DDBJ
BAB13860.1
EMBL· GenBank· DDBJ
mRNA
BC020611
EMBL· GenBank· DDBJ
AAH20611.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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