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Details on Person UniProt:O60603 TLR2
| Class:Id | ReferenceGeneProduct:66103 |
|---|---|
| _chainChangeLog | signal peptide:1-18 added on Fri February 6 2015;chain:19-784 added on Fri February 6 2015;signal peptide:1-18 removed on Fri May 6 2016;chain:19-784 removed on Fri May 6 2016;signal peptide:1-20 added on Fri May 6 2016;chain:21-784 added on Fri May 6 2016 |
| _displayName | UniProt:O60603 TLR2 |
| _timestamp | 2024-11-03 20:12:24 |
| chain | signal peptide:1-20 chain:21-784 |
| checksum | 7DBE6B24CF1FAF8B |
| comment | FUNCTION Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:17889651, PubMed:21078852). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6 (PubMed:11441107). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4 (PubMed:16622205). MAPK activation in response to bacterial peptidoglycan also occurs via this receptor (PubMed:16622205). Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression (PubMed:15809303). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse) (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (PubMed:16880211). Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (By similarity).SUBUNIT Interacts with LY96, TLR1 and TLR6 (via extracellular domain) (PubMed:17889651). TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand. The heterodimers form bigger oligomers in response to their corresponding ligands as well as further heterotypic associations with other receptors such as CD14 and/or CD36 (PubMed:16880211). Binds MYD88 (via TIR domain). Interacts with TICAM1 (PubMed:12471095). Interacts with CNPY3 (By similarity). Interacts with ATG16L1 (PubMed:23376921). Interacts with PPP1R11 (By similarity). Interacts with TICAM2 (PubMed:25385819). Interacts with TIRAP (PubMed:17322885).SUBUNIT (Microbial infection) Interacts with M.tuberculosis EsxA.SUBUNIT (Microbial infection) Interacts with M.bovis MPB83.SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus protein SSL5.INTERACTION Does not reside in lipid rafts before stimulation but accumulates increasingly in the raft upon the presence of the microbial ligand. In response to diacylated lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this recruitment determines the intracellular targeting to the Golgi apparatus. Triacylated lipoproteins induce the same mechanism for TLR2:TLR1 heterodimers.TISSUE SPECIFICITY Highly expressed in peripheral blood leukocytes, in particular in monocytes, in bone marrow, lymph node and in spleen. Also detected in lung and in fetal liver. Levels are low in other tissues.INDUCTION (Microbial infection) In macrophages, induced by SARS-CoV-2 infection.DOMAIN Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12.DOMAIN The ATG16L1-binding motif mediates interaction with ATG16L1.PTM Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2.PTM Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation (PubMed:27805901). Deubiquitinated by USP2 (By similarity).POLYMORPHISM Genetic variations in TLR2 are associated with susceptibility to leprosy [MIM:246300]. Leprosy is a chronic disease associated with depressed cellular (but not humoral) immunity, the bacterium requires a lower temperature than 37 degrees Celsius and thrives particularly in peripheral Schwann cells and macrophages. The Trp-677 polymorphism in the intracellular domain of TLR2 has a role in susceptibility to lepromatous leprosy. Wild-type TLR2 mediates CD14-enhanced Mycobacterium leprae-dependent activation of NFKB1, but TLR2 containing the Trp-677 polymorphism did not. The impaired function of the Trp-677 polymorphism provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy.SIMILARITY Belongs to the Toll-like receptor family.CAUTION In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity. |
| description | recommendedName: fullName evidence="29"Toll-like receptor 2 alternativeName: Toll/interleukin-1 receptor-like protein 4 cdAntigenNameCD282/cdAntigenName |
| geneName | TLR2 TIL4 |
| identifier | O60603 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cytoplasmic vesicle Disulfide bond Glycoprotein Immunity Inflammatory response Innate immunity Isopeptide bond Leucine-rich repeat Membrane NAD Proteomics identification Receptor Reference proteome Repeat Signal Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | TLR2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9001496] ENSEMBL:ENSG00000137462 TLR2 [Homo sapiens] |
| secondaryIdentifier | TLR2_HUMAN B3Y612 D1CS45 D1CS48 D1CS49 O15454 Q8NI00 |
| sequenceLength | 784 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:167992] TLR2 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:6804777] TLR2 [secretory granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:9637646] TLR2 [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:O60603 TLR2 (66103)
