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

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: 4123.96   (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: 4123.96   (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: 6

Tclin

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

Active Drug: 0

Active Ligands (6)

Explore Active Ligands

1 – 6 of 6

CHEMBL2179403

TLR2Tchem

Ki: 7.6

CHEMBL3350702

TLR2Tchem

Ki: 7.96

CHEMBL2179402

TLR2Tchem

Ki: 7.6

diprovocim-1

TLR2Tchem

EC50: 9.96000004

compound 13 [PMID: 23098072]

TLR2Tchem

Ki: 7.5999999

CHEMBL1092429

TLR2Tchem

IC50: 7.32

Protein Data Bank (5)

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (55)

Reactome (22)

KEGG (19)

PathwayCommons (2)

WikiPathways (12)

Adaptive Immune System (R-HSA-1280218)

Click on a row in the table to change the structure displayed.

Items per page:

5

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

Gene Ontology Terms (80)

Functions (11)

Components (12)

Processes (57)

Items per page:

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

Protein-Protein Interactions (555)

Explore Interacting Targets

1 – 10 of 555

• See Interactions on String-DB

STAT5A

Tchem

Family: TF

Novelty: 0.00091229

p_int: 0.99999948

p_ni: 5.2e-7

Score: 0.531

Data Source: BioPlex,STRINGDB

TMEM214

Tdark

Novelty: 1.5

p_int: 0.975242989

p_ni: 0.024757011

Data Source: BioPlex

ACVR2A

Tchem

Family: Kinase

Novelty: 0.007745

p_int: 0.944150669

p_ni: 0.055088187

p_wrong: 0.000761144

Score: 0.247

Data Source: BioPlex,STRINGDB

BMPR1A

Tchem

Family: Kinase

Novelty: 0.00472897

p_int: 0.904940777

p_ni: 0.058923062

p_wrong: 0.036136161

Score: 0.25

Data Source: BioPlex,STRINGDB

ITPRIP

Tdark

Novelty: 0.31547929

p_int: 0.841237631

p_ni: 0.158762369

Score: 0.179

Data Source: BioPlex,STRINGDB

USP33

Tbio

Family: Enzyme

Novelty: 0.06317232

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: 0.50209205

p_int: 0.804157927

p_ni: 0.195842073

Score: 0.188

Data Source: BioPlex,STRINGDB

LGR4

Tbio

Family: GPCR

Novelty: 0.01548681

p_int: 0.77703092

p_ni: 0.221896428

p_wrong: 0.001072652

Score: 0.212

Data Source: BioPlex,STRINGDB

AP1M1

Tbio

Novelty: 0.05716619

p_int: 0.762342178

p_ni: 0.237657822

Score: 0.239

Data Source: BioPlex,STRINGDB

TLR1

Tbio

Novelty: 0.00100796

Score: 0.995

Data Source: Reactome,STRINGDB

Publication Statistics

PubMed Score  4123.96

PubMed score by year

Reset Zoom

PubTator Score  2503.5

PubTator score by year

Reset Zoom

Amino Acid Sequence

Residue Counts

Sequence

MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRITYISNS

1-70

DLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLLGNPYKTLG

70-140

ETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQNVSHLILHMKQH

140-210

ILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLL

210-280

ELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTERVKRITVENSKVFL

280-350

VPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDI

350-420

SKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLKELYISRNKLM

420-490

TLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCEFLSFTQEQQALAKVLIDWPA

490-560

NYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRK

560-630

PRKAPSRNICYDAFVSYSERDAYWVENLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTV

630-700

FVLSENFVKSEWCKYELDFSHFRLFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQ

700-770

REGFWVNLRAAIKS

770-784

MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLSNNRITYISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWFKPLSSLTFLNLLGNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELEIDASDLQSYEPKSLKSIQNVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFSELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLLELEFDDCTLNGVGNFRASDNDRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTERVKRITVENSKVFLVPCLLSQHLKSLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDISKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLKELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCEFLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFLLILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVENLMVQELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFSHFRLFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRAAIKS

Find similar targets by:

Uniprot Keyword

3D-structure
Complete proteome
Cytoplasmic vesicle
Disulfide bond
Glycoprotein
Immunity
Inflammatory response
Innate immunity
Isopeptide bond
Leucine-rich repeat