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Protein

Toll-like receptor 2

Gene

Tlr2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity) (PubMed:15690042). May also promote apoptosis in response to lipoproteins (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 (By similarity). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (PubMed:17486091). Acts as the major receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PhoS1 (pstS1), in conjunction with TLR1 and for some but not all lipoproteins CD14 and/or CD36. The lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Recombinant MPT83 from M.tuberculosis stimulates secretion of cytokines (TNF-alpha, IL-6 and IL-12p40) by mouse macrophage cell lines in a TLR2-dependent fashion, which leads to increased host innate immunity responses against the bacterium (PubMed:22174456). Lung macrophages which express low levels of TLR2 respond poorly to stimulation by M.tuberculosis LpqH (PubMed:19362712). Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (PubMed:27220037).By similarity5 Publications

GO - Molecular functioni

GO - Biological processi

  • cell surface pattern recognition receptor signaling pathway Source: MGI
  • cellular response to bacterial lipopeptide Source: BHF-UCL
  • cellular response to diacyl bacterial lipopeptide Source: UniProtKB
  • cellular response to lipoteichoic acid Source: MGI
  • cellular response to peptidoglycan Source: MGI
  • cellular response to triacyl bacterial lipopeptide Source: UniProtKB
  • chloramphenicol transport Source: MGI
  • cytokine secretion involved in immune response Source: MGI
  • defense response to Gram-positive bacterium Source: MGI
  • detection of diacyl bacterial lipopeptide Source: MGI
  • detection of triacyl bacterial lipopeptide Source: MGI
  • I-kappaB phosphorylation Source: MGI
  • induction by symbiont of defense-related host nitric oxide production Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: BHF-UCL
  • interleukin-10 production Source: MGI
  • MyD88-dependent toll-like receptor signaling pathway Source: MGI
  • negative regulation of growth of symbiont in host Source: MGI
  • negative regulation of interleukin-12 production Source: MGI
  • negative regulation of interleukin-17 production Source: MGI
  • positive regulation of chemokine production Source: MGI
  • positive regulation of cytokine secretion Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of inflammatory response Source: InterPro
  • positive regulation of interferon-beta production Source: BHF-UCL
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of interleukin-18 production Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of interleukin-8 production Source: MGI
  • positive regulation of leukocyte migration Source: MGI
  • positive regulation of macrophage cytokine production Source: MGI
  • positive regulation of NF-kappaB import into nucleus Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of NIK/NF-kappaB signaling Source: MGI
  • positive regulation of nitric oxide biosynthetic process Source: MGI
  • positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  • positive regulation of toll-like receptor signaling pathway Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of tumor necrosis factor biosynthetic process Source: MGI
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • positive regulation of Wnt signaling pathway Source: MGI
  • positive regulation of xenophagy Source: MGI
  • regulation of dendritic cell cytokine production Source: MGI
  • response to bacterium Source: MGI
  • response to molecule of fungal origin Source: MGI
  • response to peptidoglycan Source: MGI
  • toll-like receptor 2 signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 2
Alternative name(s):
CD_antigen: CD282
Gene namesi
Name:Tlr2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1346060. Tlr2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 587ExtracellularSequence analysisAdd BLAST563
Transmembranei588 – 608HelicalSequence analysisAdd BLAST21
Topological domaini609 – 784CytoplasmicSequence analysisAdd BLAST176

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutants succumb to Staphylococcus aureus infection within 5 days.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi681P → H: Abolishes MYD88-binding and response to microbial cell wall components. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1075106.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000003471225 – 784Toll-like receptor 2Add BLAST760

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 36
Glycosylationi147N-linked (GlcNAc...)2 Publications1
Disulfide bondi353 ↔ 382
Glycosylationi414N-linked (GlcNAc...)2 Publications1
Disulfide bondi432 ↔ 454
Glycosylationi442N-linked (GlcNAc...)2 Publications1

Post-translational modificationi

Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9QUN7.
PaxDbiQ9QUN7.
PeptideAtlasiQ9QUN7.
PRIDEiQ9QUN7.

PTM databases

PhosphoSitePlusiQ9QUN7.
SwissPalmiQ9QUN7.

Expressioni

Tissue specificityi

Detected in a macrophage cell line, smooth muscle, lung, spleen, thymus, brain and adipose tissue. Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and at lower levels in lung macrophages (at protein level) (PubMed:19362712).1 Publication

Gene expression databases

CleanExiMM_TLR2.

Interactioni

Subunit structurei

Interacts with LY96, TLR1 and TLR6 (via extracellular domain). TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand (PubMed:19931471). 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 (By similarity). Binds MYD88 (via TIR domain). Interacts with TICAM1 (By similarity). Interacts with CNPY3 (PubMed:18780723). Interacts with ATG16L1 (By similarity). Interacts with non-modified M.tuberculosis protein MPT83 (PubMed:22174456).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei349Interaction with bacterial lipopeptideBy similarity1

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI
  • Toll-like receptor binding Source: MGI

Protein-protein interaction databases

DIPiDIP-61222N.
IntActiQ9QUN7. 4 interactors.
STRINGi10090.ENSMUSP00000029623.

Structurei

Secondary structure

1784
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 37Combined sources4
Beta strandi44 – 46Combined sources3
Beta strandi56 – 58Combined sources3
Beta strandi71 – 74Combined sources4
Beta strandi80 – 82Combined sources3
Turni93 – 98Combined sources6
Beta strandi104 – 106Combined sources3
Helixi117 – 120Combined sources4
Beta strandi128 – 130Combined sources3
Beta strandi137 – 139Combined sources3
Beta strandi153 – 161Combined sources9
Turni167 – 172Combined sources6
Beta strandi175 – 183Combined sources9
Turni191 – 196Combined sources6
Beta strandi198 – 206Combined sources9
Beta strandi208 – 210Combined sources3
Helixi213 – 219Combined sources7
Turni221 – 223Combined sources3
Beta strandi224 – 231Combined sources8
Beta strandi245 – 247Combined sources3
Beta strandi253 – 258Combined sources6
Beta strandi260 – 262Combined sources3
Helixi263 – 270Combined sources8
Helixi271 – 275Combined sources5
Beta strandi281 – 286Combined sources6
Beta strandi288 – 290Combined sources3
Turni299 – 301Combined sources3
Helixi304 – 306Combined sources3
Beta strandi311 – 316Combined sources6
Helixi322 – 324Combined sources3
Helixi330 – 334Combined sources5
Beta strandi340 – 346Combined sources7
Helixi353 – 358Combined sources6
Beta strandi364 – 366Combined sources3
Helixi374 – 380Combined sources7
Beta strandi391 – 393Combined sources3
Helixi402 – 408Combined sources7
Helixi409 – 411Combined sources3
Beta strandi417 – 419Combined sources3
Beta strandi440 – 442Combined sources3
Beta strandi460 – 463Combined sources4
Beta strandi481 – 483Combined sources3
Helixi495 – 497Combined sources3
Beta strandi503 – 505Combined sources3
Helixi516 – 521Combined sources6
Beta strandi527 – 529Combined sources3
Helixi539 – 547Combined sources9
Helixi549 – 553Combined sources5
Turni556 – 561Combined sources6
Beta strandi564 – 567Combined sources4
Turni568 – 572Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z81X-ray1.80A27-506[»]
2Z82X-ray2.60A27-506[»]
3A79X-ray2.90A1-506[»]
3A7BX-ray2.53A1-506[»]
3A7CX-ray2.40A1-506[»]
5D3IX-ray3.20A25-589[»]
ProteinModelPortaliQ9QUN7.
SMRiQ9QUN7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QUN7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati54 – 77LRR 11 PublicationAdd BLAST24
Repeati78 – 101LRR 21 PublicationAdd BLAST24
Repeati102 – 125LRR 31 PublicationAdd BLAST24
Repeati126 – 150LRR 41 PublicationAdd BLAST25
Repeati151 – 175LRR 51 PublicationAdd BLAST25
Repeati176 – 199LRR 61 PublicationAdd BLAST24
Repeati200 – 223LRR 71 PublicationAdd BLAST24
Repeati224 – 250LRR 81 PublicationAdd BLAST27
Repeati251 – 278LRR 91 PublicationAdd BLAST28
Repeati279 – 308LRR 101 PublicationAdd BLAST30
Repeati309 – 337LRR 111 PublicationAdd BLAST29
Repeati338 – 361LRR 121 PublicationAdd BLAST24
Repeati362 – 388LRR 131 PublicationAdd BLAST27
Repeati389 – 414LRR 141 PublicationAdd BLAST26
Repeati415 – 437LRR 151 PublicationAdd BLAST23
Repeati438 – 457LRR 161 PublicationAdd BLAST20
Repeati458 – 478LRR 171 PublicationAdd BLAST21
Repeati479 – 500LRR 181 PublicationAdd BLAST22
Repeati501 – 524LRR 191 PublicationAdd BLAST24
Domaini525 – 576LRRCTAdd BLAST52
Domaini639 – 784TIRPROSITE-ProRule annotationAdd BLAST146

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi761 – 778ATG16L1-binding motifAdd BLAST18

Domaini

Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12.
The ATG16L1-binding motif mediates interaction with ATG16L1.By similarity

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
Contains 19 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 TIR domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000110611.
HOVERGENiHBG108574.
InParanoidiQ9QUN7.
KOiK10159.
PhylomeDBiQ9QUN7.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027185. TLR2.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF17. PTHR24365:SF17. 1 hit.
PfamiPF13516. LRR_6. 1 hit.
PF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 7 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 9 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9QUN7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRALWLFWI LVAITVLFSK RCSAQESLSC DASGVCDGRS RSFTSIPSGL
60 70 80 90 100
TAAMKSLDLS FNKITYIGHG DLRACANLQV LILKSSRINT IEGDAFYSLG
110 120 130 140 150
SLEHLDLSDN HLSSLSSSWF GPLSSLKYLN LMGNPYQTLG VTSLFPNLTN
160 170 180 190 200
LQTLRIGNVE TFSEIRRIDF AGLTSLNELE IKALSLRNYQ SQSLKSIRDI
210 220 230 240 250
HHLTLHLSES AFLLEIFADI LSSVRYLELR DTNLARFQFS PLPVDEVSSP
260 270 280 290 300
MKKLAFRGSV LTDESFNELL KLLRYILELS EVEFDDCTLN GLGDFNPSES
310 320 330 340 350
DVVSELGKVE TVTIRRLHIP QFYLFYDLST VYSLLEKVKR ITVENSKVFL
360 370 380 390 400
VPCSFSQHLK SLEFLDLSEN LMVEEYLKNS ACKGAWPSLQ TLVLSQNHLR
410 420 430 440 450
SMQKTGEILL TLKNLTSLDI SRNTFHPMPD SCQWPEKMRF LNLSSTGIRV
460 470 480 490 500
VKTCIPQTLE VLDVSNNNLD SFSLFLPRLQ ELYISRNKLK TLPDASLFPV
510 520 530 540 550
LLVMKIRENA VSTFSKDQLG SFPKLETLEA GDNHFVCSCE LLSFTMETPA
560 570 580 590 600
LAQILVDWPD SYLCDSPPRL HGHRLQDARP SVLECHQAAL VSGVCCALLL
610 620 630 640 650
LILLVGALCH HFHGLWYLRM MWAWLQAKRK PKKAPCRDVC YDAFVSYSEQ
660 670 680 690 700
DSHWVENLMV QQLENSDPPF KLCLHKRDFV PGKWIIDNII DSIEKSHKTV
710 720 730 740 750
FVLSENFVRS EWCKYELDFS HFRLFDENND AAILVLLEPI ERKAIPQRFC
760 770 780
KLRKIMNTKT YLEWPLDEGQ QEVFWVNLRT AIKS
Length:784
Mass (Da):89,449
Last modified:May 1, 2000 - v1
Checksum:i606D56BF85F320A2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti59L → P in BAB23770 (PubMed:16141072).Curated1
Sequence conflicti82I → M in BAB23770 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF185284 mRNA. Translation: AAF04277.1.
AF124741 mRNA. Translation: AAD46481.1.
AF216289 mRNA. Translation: AAF28345.1.
AF165189 mRNA. Translation: AAD49335.1.
AK005043 mRNA. Translation: BAB23770.1.
AK154504 mRNA. Translation: BAE32635.1.
CCDSiCCDS17435.1.
RefSeqiNP_036035.3. NM_011905.3.
UniGeneiMm.87596.

Genome annotation databases

GeneIDi24088.
KEGGimmu:24088.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF185284 mRNA. Translation: AAF04277.1.
AF124741 mRNA. Translation: AAD46481.1.
AF216289 mRNA. Translation: AAF28345.1.
AF165189 mRNA. Translation: AAD49335.1.
AK005043 mRNA. Translation: BAB23770.1.
AK154504 mRNA. Translation: BAE32635.1.
CCDSiCCDS17435.1.
RefSeqiNP_036035.3. NM_011905.3.
UniGeneiMm.87596.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z81X-ray1.80A27-506[»]
2Z82X-ray2.60A27-506[»]
3A79X-ray2.90A1-506[»]
3A7BX-ray2.53A1-506[»]
3A7CX-ray2.40A1-506[»]
5D3IX-ray3.20A25-589[»]
ProteinModelPortaliQ9QUN7.
SMRiQ9QUN7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61222N.
IntActiQ9QUN7. 4 interactors.
STRINGi10090.ENSMUSP00000029623.

Chemistry databases

ChEMBLiCHEMBL1075106.

PTM databases

PhosphoSitePlusiQ9QUN7.
SwissPalmiQ9QUN7.

Proteomic databases

MaxQBiQ9QUN7.
PaxDbiQ9QUN7.
PeptideAtlasiQ9QUN7.
PRIDEiQ9QUN7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24088.
KEGGimmu:24088.

Organism-specific databases

CTDi7097.
MGIiMGI:1346060. Tlr2.

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000110611.
HOVERGENiHBG108574.
InParanoidiQ9QUN7.
KOiK10159.
PhylomeDBiQ9QUN7.

Miscellaneous databases

EvolutionaryTraceiQ9QUN7.
PROiQ9QUN7.
SOURCEiSearch...

Gene expression databases

CleanExiMM_TLR2.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 3 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027185. TLR2.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF17. PTHR24365:SF17. 1 hit.
PfamiPF13516. LRR_6. 1 hit.
PF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 7 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 9 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLR2_MOUSE
AccessioniPrimary (citable) accession number: Q9QUN7
Secondary accession number(s): Q3U400, Q9DBC4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.