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Toll-like receptor 9; CD289 (TLR9)
Function:
1) innate immune response to microbial agents.
2) detects the unmethylated cytidine-phosphate-guanosine (CpG) motifs present in bacterial DNA
3) acts via MyD88 & TRAF6
a) NF-kappa-B activation
b) cytokine secretion
c) inflammatory response
4) binds MyD88 via their respective TIR domains
Structure:
- belongs to the Toll-like receptor family
- contains 26 LRR repeats (leucine-rich repeats)
- contains 1 TIR domain
Compartment: membrane
Alternative splicing: named isoforms=5
Expression:
- expressed in spleen, lymph node, tonsil & peripheral blood leukocytes, especially in plasmacytoid pre-dendritic cells > monocytes, CD11c+ immature dendritic cells, lung, liver
Pharmacology:
- TLR9 agonist CMP-001 restores response to pembrolizumab in 22% of patients with PD-L1 therapy resistant melanoma [2]
General
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
glycoprotein
leucine-rich repeat-containing protein (LRRC)
toll-like receptor
Properties
SIZE: entity length = 1032 aa
MW = 116 kD
COMPARTMENT: cellular membrane
MOTIF: signal sequence {1-25}
leucine-rich repeat
SITE: 62-85
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N64}
leucine-rich repeat
SITE: 87-110
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 122-147
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N129}
leucine-rich repeat
SITE: 150-166
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 167-190
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 198-221
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N200}
N-glycosylation site {N210}
leucine-rich repeat
SITE: 223-242
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N242}
leucine-rich repeat
SITE: 243-268
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 283-306
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N300}
leucine-rich repeat
SITE: 308-332
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 333-356
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N340}
leucine-rich repeat
SITE: 363-386
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 390-413
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 415-440
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N469}
leucine-rich repeat
SITE: 470-494
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N474}
leucine-rich repeat
SITE: 496-519
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N513}
leucine-rich repeat
SITE: 520-543
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 545-572
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N567}
leucine-rich repeat
SITE: 574-598
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 600-622
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 627-650
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 652-675
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 676-699
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N694}
leucine-rich repeat
SITE: 701-723
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 724-747
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N731}
leucine-rich repeat
SITE: 749-772
MOTIF: leucine residue (SEVERAL)
transmembrane domain {819-839}
TIR domain {868-1016}
Database Correlations
OMIM 605474
UniProt Q9NR96
PFAM correlations
Entrez Gene 54106
Kegg hsa:5410
References
- Entrez Gene :accession 54106
- UniProt :accession Q9NR96
- Bankhead C
Drug May Reverse Anti-PD-1 Resistance in Melanoma.
Responses in 22% of resistant patients with TLR9 agonist.
MedPage Today. April 19, 2018
https://www.medpagetoday.com/meetingcoverage/aacr/72435
- Milhem M, et al
Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001,
in combination with pembrolizumab can reverse resistance to
PD-1 inhibition in a phase Ib trial in subjects with advanced
melanoma.
American Association for Cancer Research (AACR 2018)
Abstract CT144