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Details on Person UniProt:P58753 TIRAP
| Class:Id | ReferenceGeneProduct:66063 |
|---|---|
| _chainChangeLog | chain:1-221 added on Fri February 6 2015 |
| _displayName | UniProt:P58753 TIRAP |
| _timestamp | 2026-02-20 21:45:20 |
| chain | chain:1-221 |
| checksum | 44A8454D04704540 |
| comment | FUNCTION Adapter involved in TLR2, TLR4 and RAGE signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF (TNF) and interleukin-6 (IL6).SUBUNIT Homodimer (PubMed:17322885). Also forms heterodimers with MYD88 (PubMed:17322885). May interact with PIK3AP1 (By similarity). Interacts with TLR4 and IRAK2 via their respective TIR domains. Interacts with BMX and TBK1. Interacts with EIF2AK2. Does not interact with IRAK1, nor TLR9. Interacts with TLR2 (PubMed:17322885). Interacts with RAGE/AGER (PubMed:21829704).SUBUNIT (Microbial infection) In case of infection, interacts with B.melitensis protein TcpB (AC Q8YF53); TcpB abolishes the TLR4-TIRAP interaction and downstream signaling.INTERACTION Colocalizes with DAB2IP at the plasma membrane.ALTERNATIVE PRODUCTS Highly expressed in liver, kidney, spleen, skeletal muscle and heart. Also detected in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.DOMAIN (Microbial infection) The TIR domain is structurally mimicked by the TIR domain of B.melitensis protein TcpB.PTM Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.PTM Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation.POLYMORPHISM Genetic variations in TIRAP have been proposed to influence susceptibility or resistance to invasive pneumococcal disease, malaria [MIM:611162], and tuberculosis [MIM:607948]. It may define the bacteremia susceptibility locus 1 (BACTS1) [MIM:614382] (PubMed:17322885, PubMed:19602285). Indeed it has been reported that heterozygous carriage of p.Ser180Leu in populations from the U.K., Vietnam, and several African countries may confer protection against invasive pneumococcal disease, bacteremia, malaria, and tuberculosis (PubMed:17322885). However, analyzes of Russian, Ghanaian and Indonesian populations fail to replicate the association between p.Ser180Leu and susceptibility to tuberculosis formerly observed in West African and Algerian populations (PubMed:17322885, PubMed:18305471). |
| description | recommendedName: Toll/interleukin-1 receptor domain-containing adapter protein shortName: TIR domain-containing adapter protein alternativeName: Adaptor protein Wyatt alternativeName: MyD88 adapter-like protein shortName: MyD88-2 |
| geneName | TIRAP MAL |
| identifier | P58753 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell membrane Cytoplasm Disulfide bond Immunity Inflammatory response Innate immunity Membrane Phosphoprotein Proteomics identification Reference proteome Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | TIRAP |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989269] ENSEMBL:ENSG00000150455 TIRAP [Homo sapiens] |
| secondaryIdentifier | TIRAP_HUMAN B3KW65 Q56UH9 Q56UI0 Q8N5E5 |
| sequenceLength | 221 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:154923] UniProt:P58753-2 TIRAP [Homo sapiens] [ReferenceIsoform:251334] UniProt:P58753-3 TIRAP [Homo sapiens] [ReferenceIsoform:404532] UniProt:P58753-1 TIRAP [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:166141] TIRAP [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2201321] p-4Y-TIRAP [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:2201317] O4'-phospho-L-tyrosine at 159 [ModifiedResidue:2201319] O4'-phospho-L-tyrosine at 187 [ModifiedResidue:2201328] O4'-phospho-L-tyrosine at 86 [ModifiedResidue:2201333] O4'-phospho-L-tyrosine at 106 |
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No pathways have been reviewed or authored by UniProt:P58753 TIRAP (66063)
