Tchem TLR2 Toll-like receptor 2

Protein Summary

Description

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:21078852, PubMed:17889651). 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). The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Uniprot Accession IDs

• O60603
• B3Y612
• D1CS45
• D1CS48
• D1CS49
• O15454
• Q8NI00

Gene Name

• TLR2

Ensembl ID

• ENST00000260010
• ENSP00000260010
• ENSG00000137462
• ENST00000642580
• ENSP00000495339
• ENST00000642700
• ENSP00000494425
• ENST00000644308
• ENSP00000496321

Symbol

• TIL4
• TIL4
• CD282

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
virus perturbation	1
protein domain	0.85
disease	0.84

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4935.44   (req: < 5)

Gene RIFs: 1164   (req: <= 3)

Antibodies: 1225   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4935.44   (req: >= 5)

Gene RIFs: 1164   (req: > 3)

Antibodies: 1225   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 68

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 56

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (56)

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1 – 10 of 56

compound 13 [PMID: 23098072]

TLR2Tchem

pKi : 7.6

Diprovocim

TLR2Tchem

pEC50 : 9.96

CHEMBL1923557

TLR2Tchem

pEC50 : 9.59

CHEMBL4552043

TLR2Tchem

pEC50 : 9.55

CHEMBL4442356

TLR2Tchem

pEC50 : 9.52

CHEMBL4546202

TLR2Tchem

pEC50 : 9.42

CHEMBL1923536

TLR2Tchem

pEC50 : 9.35

CHEMBL4560927

TLR2Tchem

pEC50 : 9.33

CHEMBL1923541

TLR2Tchem

pEC50 : 9.25

CHEMBL4461230

TLR2Tchem

pEC50 : 9.21

Protein-Protein Interactions (555)

Explore Interacting Targets

1 – 10 of 555

• See Interactions on String-DB

STAT5A

Tchem

Family:  TF

Novelty:  0.00074026

p_int:  0.99999948

p_ni:  5.2e-7

Score:  0.531

Data Source:  BioPlex,STRINGDB

TMEM214

Tdark

Novelty:  0.32604613

p_int:  0.975242989

p_ni:  0.024757011

Data Source:  BioPlex

ACVR2A

Tchem

Family:  Kinase

Novelty:  0.0063932

p_int:  0.944150669

p_ni:  0.055088187

p_wrong:  0.000761144

Score:  0.247

Data Source:  BioPlex,STRINGDB

BMPR1A

Tchem

Family:  Kinase

Novelty:  0.00343928

p_int:  0.904940777

p_ni:  0.058923062

p_wrong:  0.036136161

Score:  0.25

Data Source:  BioPlex,STRINGDB

ITPRIP

Tdark

Novelty:  0.27051709

p_int:  0.841237631

p_ni:  0.158762369

Score:  0.179

Data Source:  BioPlex,STRINGDB

USP33

Tbio

Family:  Enzyme

Novelty:  0.04411285

p_int:  0.814331969

p_ni:  0.185668003

p_wrong:  2.8e-8

Score:  0.154

Data Source:  BioPlex,STRINGDB

STK11IP

Tdark

Family:  Enzyme

Novelty:  0.2856954

p_int:  0.804157927

p_ni:  0.195842073

Score:  0.188

Data Source:  BioPlex,STRINGDB

LGR4

Tbio

Family:  GPCR

Novelty:  0.01180123

p_int:  0.77703092

p_ni:  0.221896428

p_wrong:  0.001072652

Score:  0.212

Data Source:  BioPlex,STRINGDB

AP1M1

Tbio

Novelty:  0.029282

p_int:  0.762342178

p_ni:  0.237657822

Score:  0.239

Data Source:  BioPlex,STRINGDB

TLR1

Tbio

Novelty:  0.00171909

Score:  0.995

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets (7)

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Downstream (7)

1 – 5 of 7

PIK3CA

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  11

1: PI3K-Akt signaling pathway

2: PD-L1 expression and PD-1 checkpoint pathway in cancer

3: Amoebiasis

4: Chagas disease (American trypanosomiasis)

more:  7 more common pathways

PIK3CD

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  11

1: PI3K-Akt signaling pathway

2: PD-L1 expression and PD-1 checkpoint pathway in cancer

3: Amoebiasis

4: Chagas disease (American trypanosomiasis)

more:  7 more common pathways

IL6

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  13

1: PI3K-Akt signaling pathway

2: Inflammatory bowel disease (IBD)

3: Legionellosis

4: Rheumatoid arthritis

more:  9 more common pathways

IL1B

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  11

1: Inflammatory bowel disease (IBD)

2: Legionellosis

3: Rheumatoid arthritis

4: Amoebiasis

more:  7 more common pathways

IL12B

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  11

1: Inflammatory bowel disease (IBD)

2: Legionellosis

3: Amoebiasis

4: Chagas disease (American trypanosomiasis)

more:  7 more common pathways

Pathways (55)

Reactome (22)

KEGG (19)

PathwayCommons (2)

WikiPathways (12)

Adaptive Immune System (R-HSA-1280218)

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1 – 5 of 22

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing-Cross presentation	169 targets	R-HSA-1236975
Reactome	Antimicrobial peptides	89 targets	R-HSA-6803157
Reactome	Beta defensins	36 targets	R-HSA-1461957
Reactome	Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing-Cross presentation	169 targets	R-HSA-1236975
Antimicrobial peptides	89 targets	R-HSA-6803157
Beta defensins	36 targets	R-HSA-1461957
Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (80)

Functions (11)

Components (12)

Processes (57)

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10

1 – 10 of 11

GO Term	Evidence	Assigned by
amyloid-beta binding	Inferred from Direct Assay (IDA)	ARUK-UCL
lipopolysaccharide binding	Inferred from Direct Assay (IDA)	UniProtKB
peptidoglycan binding	Inferred from Direct Assay (IDA)	UniProtKB
protein heterodimerization activity	Inferred from Direct Assay (IDA)	MGI
signaling pattern recognition receptor activity	Inferred from Direct Assay (IDA)	UniProtKB
triacyl lipopeptide binding	Inferred from Direct Assay (IDA)	MGI
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein-containing complex binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
Toll-like receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
lipopolysaccharide receptor activity	Traceable Author Statement (TAS)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (6)

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1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean reticulocyte volume	EFO_0010701	1	1	1		77.3
mean corpuscular volume	EFO_0004526	1	1	1		61.4
reticulocyte measurement	EFO_0010700	1	1	1		53.7
reticulocyte count	EFO_0007986	1	1	1		50.6
platelet crit	EFO_0007985	1	1	1		49.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean reticulocyte volume	EFO_0010701	1		77.3
mean corpuscular volume	EFO_0004526	1		61.4
reticulocyte measurement	EFO_0010700	1		53.7
reticulocyte count	EFO_0007986	1		50.6
platelet crit	EFO_0007985	1		49.5

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Complete proteome
Cytoplasmic vesicle
Disulfide bond
Glycoprotein
Immunity
Inflammatory response
Innate immunity
Isopeptide bond
Leucine-rich repeat

GWAS Trait Find Similar Targets

No Header	No Header
mean corpuscular volume
mean reticulocyte volume
platelet count
platelet crit
reticulocyte count
reticulocyte measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	toll like receptor 2	VGNC:12860	471325
Macaque	toll like receptor 2		574290
Mouse	toll-like receptor 2	MGI:1346060	24088
Rat	toll-like receptor 2	RGD:735138	310553
Dog	toll like receptor 2		448807

Species	Name	OMA	EggNOG	Inparanoid
Chimp	toll like receptor 2
Macaque	toll like receptor 2
Mouse	toll-like receptor 2
Rat	toll-like receptor 2
Dog	toll like receptor 2

Publication Statistics

PubMed Score 4935.44

PubMed score by year

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PubTator Score 2503.50

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Related Publications

Text Mined References (1334)

GeneRif Annotations (1164)

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PMID	Year	Title