TLR1 (human, Q15399) review notes
Sources: UniProt Q15399, GOA (80 seeded rows; the GOA tsv has 81 lines, two IDA
GO:0035354 rows from PMID:16880211 collapse into one), cached publications, and
TLR1-deep-research-falcon.md (Falcon, completed during this review; consistent with
the primary literature below and used only as background).
Core biology
- TLR1 is the triacyl-lipopeptide-selecting partner of TLR2. Structure:
PMID:17889651;
[PMID:17889651 "Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an \"m\" shaped heterodimer of the TLR1 and TLR2 ectodomains"].
- Partner choice sets TLR2 specificity: PMID:19931471.
- Genetic requirement (mouse): PMID:12077222.
- Cell surface heterodimer, raft recruitment, Golgi trafficking:
PMID:16880211;
PMID:16880211.
- TIR domain: PMID:11081518; TLR1 BB-loop mutants reduce signaling PMID:16893894.
- Phagosome recruitment: PMID:11095740.
Key curation decisions
- GO:0001875 lipopolysaccharide immune receptor activity (IDA, contributes_to,
PMID:16880211) -> MODIFY to GO:0038187 pattern recognition receptor activity.
The definition requires combining with LPS; TLR1:TLR2 binds triacyl lipopeptide.
The same term is used in GO-CAM 5fb9cc0600000727 (TLR1-TLR2 complex); flagged as a
suggested question rather than edited.
- GO:0031663 LPS-mediated signaling pathway (IEA, GO_REF:0000108, inferred from the
GO:0001875 row) -> REMOVE; it is an artefact of the mis-fitting MF term.
- protein binding rows: TLR2 partners -> MODIFY to GO:0035663 Toll-like receptor 2
binding; TLR10 (co-IP, PMID:15728506) -> MODIFY to GO:0035325 Toll-like receptor
binding; isolated-TMD (E. coli ToxR) partners TLR6/TLR10 and BioPlex TLR6 -> REMOVE.
- Cytokine-production regulation terms (IL-6, IL-8, TNF; ISS/IEA/IGI) and positive
regulation of TLR2 signaling (IGI, PMID:22198949) -> KEEP_AS_NON_CORE (downstream
outcomes / co-receptor role). Microglial cell activation (rat IEA) and macrophage
activation (NAS citing an IFN-induction expression paper) -> MARK_AS_OVER_ANNOTATED.
- Core functions: contributes_to GO:0038187 in GO:0035354 at the plasma membrane,
directly in GO:0038123 and GO:0042495; plus GO:0042497 triacyl lipopeptide binding
(structure-based; recorded as a core function, not as a NEW annotation, since
GO:0071723 lipopeptide binding is already accepted).
Relevance to project questions
- There is no TLR-specific MF term; the existing TLR1 MF annotation borrowed the LPS
term. GO:0038187 is the right existing term; a lipopeptide immune receptor term
would be the parallel to GO:0001875 if GO wants ligand-specific MF.