Q9QUN7 (TLR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Toll-like receptor 2

Alternative name(s):
CD_antigen=CD282

Gene names

Name:

Tlr2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	784 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. May also promote apoptosis in response to lipoproteins By similarity. Ref.9
Subunit structure	Interacts with ATG16L1 By similarity. Interacts with LY96, TLR1 and TLR6 (via extracellular domain). Binds MYD88 (via TIR domain). Interacts with TICAM1. Ligand binding induces the formation of a heterodimer with TLR1 or TLR6. Interacts with CNPY3. Ref.7 Ref.9
Subcellular location	Cell membrane; Single-pass type I membrane protein. Cytoplasmic vesicle › phagosome membrane; Single-pass type I membrane protein.
Tissue specificity	Detected in a macrophage cell line, smooth muscle, lung, spleen, thymus, brain and adipose tissue.
Domain	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.
Post-translational modification	Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2 By similarity.
Sequence similarities	Belongs to the Toll-like receptor family. Contains 19 LRR (leucine-rich) repeats. Contains 1 LRRCT domain. Contains 1 TIR domain.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Inferred from genetic interaction PubMed 12719478. Source: MGI cell surface pattern recognition receptor signaling pathway Inferred from mutant phenotype PubMed 12719478. Source: MGI cellular response to bacterial lipopeptide Traceable author statement PubMed 15356140. Source: BHF-UCL cellular response to lipoteichoic acid Inferred from mutant phenotype PubMed 15690042. Source: MGI cellular response to peptidoglycan Inferred from mutant phenotype PubMed 16949315. Source: MGI chloramphenicol transport Inferred from mutant phenotype PubMed 12091878. Source: MGI defense response to Gram-positive bacterium Inferred from mutant phenotype PubMed 11067888PubMed 15690042PubMed 19139201. Source: MGI induction by symbiont of defense-related host nitric oxide production Inferred from mutant phenotype PubMed 16239543. Source: MGI inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement PubMed 15356140. Source: BHF-UCL negative regulation of growth of symbiont in host Inferred from mutant phenotype PubMed 11067888PubMed 15690042. Source: MGI negative regulation of interleukin-12 production Inferred from mutant phenotype PubMed 16949315. Source: MGI negative regulation of interleukin-17 production Inferred from mutant phenotype PubMed 16239543. Source: MGI positive regulation of chemokine production Inferred from mutant phenotype PubMed 16239543. Source: MGI positive regulation of cytokine secretion Inferred from genetic interaction PubMed 19770268. Source: MGI positive regulation of inflammatory response Inferred from electronic annotation. Source: InterPro positive regulation of interferon-beta production Inferred from direct assay PubMed 15356140. Source: BHF-UCL positive regulation of interleukin-12 production Inferred from direct assay PubMed 15356140. Source: BHF-UCL positive regulation of interleukin-18 production Inferred from direct assay PubMed 15356140. Source: BHF-UCL positive regulation of interleukin-6 production Inferred from direct assay PubMed 15356140. Source: BHF-UCL positive regulation of leukocyte migration Inferred from mutant phenotype PubMed 17114491. Source: MGI positive regulation of macrophage cytokine production Inferred from mutant phenotype PubMed 10549626. Source: MGI positive regulation of nitric oxide biosynthetic process Inferred from mutant phenotype PubMed 10549626PubMed 16239543. Source: MGI positive regulation of nitric-oxide synthase biosynthetic process Inferred from direct assay PubMed 15356140. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 15356140. Source: BHF-UCL positive regulation of tumor necrosis factor biosynthetic process Inferred from mutant phenotype PubMed 16239543. Source: MGI positive regulation of tumor necrosis factor production Inferred from direct assay PubMed 15356140. Source: BHF-UCL response to molecule of fungal origin Inferred from mutant phenotype PubMed 12719478. Source: MGI toll-like receptor 2 signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	Toll-like receptor 1-Toll-like receptor 2 protein complex Inferred from sequence orthology Ref.8. Source: MGI Toll-like receptor 2-Toll-like receptor 6 protein complex Inferred from physical interaction Ref.9. Source: MGI external side of plasma membrane Inferred from direct assay PubMed 15220916. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW phagocytic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	diacyl lipopeptide binding Inferred from direct assay Ref.8Ref.9. Source: MGI lipoteichoic acid binding Inferred from direct assay Ref.9. Source: MGI protein heterodimerization activity Inferred from sequence orthology Ref.8. Source: MGI transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro triacyl lipopeptide binding Inferred from direct assay Ref.8. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Chain

25 – 784

760

Toll-like receptor 2

PRO_0000034712

Regions

Topological domain

25 – 587

563

Extracellular Potential

Transmembrane

588 – 608

21

Helical; Potential

Topological domain

609 – 784

176

Cytoplasmic Potential

Repeat

54 – 77

24

LRR 1

Repeat

78 – 101

24

LRR 2

Repeat

102 – 125

24

LRR 3

Repeat

126 – 150

25

LRR 4

Repeat

151 – 175

25

LRR 5

Repeat

176 – 199

24

LRR 6

Repeat

200 – 223

24

LRR 7

Repeat

224 – 250

27

LRR 8

Repeat

251 – 278

28

LRR 9

Repeat

279 – 308

30

LRR 10

Repeat

309 – 337

29

LRR 11

Repeat

338 – 361

24

LRR 12

Repeat

362 – 388

27

LRR 13

Repeat

389 – 414

26

LRR 14

Repeat

415 – 437

23

LRR 15

Repeat

438 – 457

20

LRR 16

Repeat

458 – 478

21

LRR 17

Repeat

479 – 500

22

LRR 18

Repeat

501 – 524

24

LRR 19

Domain

525 – 576

52

LRRCT

Domain

639 – 784

146

TIR

Motif

761 – 778

18

ATG16L1-binding motif

Sites

Site

349

1

Interaction with bacterial lipopeptide By similarity

Amino acid modifications

Glycosylation

147

1

N-linked (GlcNAc...) Ref.8 Ref.9

Glycosylation

414

1

N-linked (GlcNAc...) Ref.8 Ref.9

Glycosylation

442

1

N-linked (GlcNAc...) Ref.8 Ref.9

Disulfide bond

30 ↔ 36

Ref.8 Ref.9

Disulfide bond

353 ↔ 382

Ref.8 Ref.9

Disulfide bond

432 ↔ 454

Ref.8 Ref.9

Experimental info

Mutagenesis

681

1

P → H: Abolishes MYD88-binding and response to microbial cell wall components. Ref.1

Sequence conflict

59

1

L → P in BAB23770. Ref.5

Sequence conflict

82

1

I → M in BAB23770. Ref.5

Secondary structure

1

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784

Helix Strand Turn

Details...

Beta strand

34 – 37

4

Beta strand

44 – 46

3

Beta strand

56 – 58

3

Beta strand

71 – 74

4

Beta strand

80 – 82

3

Turn

93 – 98

6

Beta strand

104 – 106

3

Helix

117 – 120

4

Beta strand

128 – 130

3

Beta strand

137 – 139

3

Beta strand

153 – 161

9

Turn

167 – 172

6

Beta strand

175 – 183

9

Turn

191 – 196

6

Beta strand

198 – 206

9

Beta strand

208 – 210

3

Helix

213 – 219

7

Turn

221 – 223

3

Beta strand

224 – 231

8

Beta strand

245 – 247

3

Beta strand

253 – 258

6

Beta strand

260 – 262

3

Helix

263 – 270

8

Helix

271 – 275

5

Beta strand

281 – 286

6

Beta strand

288 – 290

3

Turn

299 – 301

3

Helix

304 – 306

3

Beta strand

311 – 316

6

Helix

322 – 324

3

Helix

330 – 334

5

Beta strand

340 – 346

7

Helix

353 – 358

6

Beta strand

364 – 366

3

Helix

374 – 380

7

Beta strand

391 – 393

3

Helix

402 – 408

7

Helix

409 – 411

3

Beta strand

417 – 419

3

Beta strand

440 – 442

3

Beta strand

460 – 463

4

Beta strand

481 – 483

3

Helix

495 – 497

3

Beta strand

503 – 505

3

Sequences

	Sequence		Length	Mass (Da)
	Q9QUN7 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 606D56BF85F320A2	FASTA	784	89,449
	10 20 30 40 50 60 MLRALWLFWI LVAITVLFSK RCSAQESLSC DASGVCDGRS RSFTSIPSGL TAAMKSLDLS 70 80 90 100 110 120 FNKITYIGHG DLRACANLQV LILKSSRINT IEGDAFYSLG SLEHLDLSDN HLSSLSSSWF 130 140 150 160 170 180 GPLSSLKYLN LMGNPYQTLG VTSLFPNLTN LQTLRIGNVE TFSEIRRIDF AGLTSLNELE 190 200 210 220 230 240 IKALSLRNYQ SQSLKSIRDI HHLTLHLSES AFLLEIFADI LSSVRYLELR DTNLARFQFS 250 260 270 280 290 300 PLPVDEVSSP MKKLAFRGSV LTDESFNELL KLLRYILELS EVEFDDCTLN GLGDFNPSES 310 320 330 340 350 360 DVVSELGKVE TVTIRRLHIP QFYLFYDLST VYSLLEKVKR ITVENSKVFL VPCSFSQHLK 370 380 390 400 410 420 SLEFLDLSEN LMVEEYLKNS ACKGAWPSLQ TLVLSQNHLR SMQKTGEILL TLKNLTSLDI 430 440 450 460 470 480 SRNTFHPMPD SCQWPEKMRF LNLSSTGIRV VKTCIPQTLE VLDVSNNNLD SFSLFLPRLQ 490 500 510 520 530 540 ELYISRNKLK TLPDASLFPV LLVMKIRENA VSTFSKDQLG SFPKLETLEA GDNHFVCSCE 550 560 570 580 590 600 LLSFTMETPA LAQILVDWPD SYLCDSPPRL HGHRLQDARP SVLECHQAAL VSGVCCALLL 610 620 630 640 650 660 LILLVGALCH HFHGLWYLRM MWAWLQAKRK PKKAPCRDVC YDAFVSYSEQ DSHWVENLMV 670 680 690 700 710 720 QQLENSDPPF KLCLHKRDFV PGKWIIDNII DSIEKSHKTV FVLSENFVRS EWCKYELDFS 730 740 750 760 770 780 HFRLFDENND AAILVLLEPI ERKAIPQRFC KLRKIMNTKT YLEWPLDEGQ QEVFWVNLRT AIKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens." Underhill D.M., Ozinsky A., Hajjar A.M., Stevens A., Wilson C.B., Bassetti M., Aderem A. Nature 401:811-815(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF PRO-681.
[2]	"Cells that carry a null allele for Toll-like receptor 2 are capable of responding to endotoxin." Heine H., Kirschning C.J., Lien E., Monks B.G., Rothe M., Golenbock D.T. J. Immunol. 162:6971-6975(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Macrophage.
[3]	"Gene expressions of lipopolysaccharide receptors, Toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes." Matsuguchi T., Takagi K., Musikacharoen T., Yoshikai Y. Blood 95:1378-1385(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Macrophage.
[4]	"The lipopolysaccharide-activated Toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes." Lin Y., Lee H., Berg A.H., Lisanti M.P., Shapiro L., Scherer P.E. J. Biol. Chem. 275:24255-24263(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adipocyte.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Liver.
[6]	Lubec G., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 405-413 AND 754-759, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain.
[7]	"A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors." Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C., Kuroki Y., Seto Y., Miyake K. Int. Immunol. 20:1407-1415(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CNPY3.
[8]	"Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide." Jin M.S., Kim S.E., Heo J.Y., Lee M.E., Kim H.M., Paik S.-G., Lee H., Lee J.-O. Cell 130:1071-1082(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 27-506, DISULFIDE BONDS, GLYCOSYLATION AT ASN-147; ASN-414 AND ASN-442.
[9]	"Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer." Kang J.Y., Nan X., Jin M.S., Youn S.J., Ryu Y.H., Mah S., Han S.H., Lee H., Paik S.G., Lee J.O. Immunity 31:873-884(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-506 IN COMPLEX WITH TLR6 AND LIPOPEPTIDE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-147; ASN-414 AND ASN-442, FUNCTION, LRR REPEATS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00131898.

RefSeq

NP_036035.3. NM_011905.3.

UniGene

Mm.87596.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Z81	X-ray	1.80	A	27-506	[»]
2Z82	X-ray	2.60	A	27-506	[»]
3A79	X-ray	2.90	A	1-506	[»]
3A7B	X-ray	2.53	A	1-506	[»]
3A7C	X-ray	2.40	A	1-506	[»]

ProteinModelPortal

Q9QUN7.

SMR

Q9QUN7. Positions 27-784.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9QUN7. 1 interaction.

STRING

10090.ENSMUSP00000029623.

PTM databases

PhosphoSite

Q9QUN7.

Proteomic databases

PRIDE

Q9QUN7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

24088.

KEGG

mmu:24088.

Organism-specific databases

CTD

7097.

MGI

MGI:1346060. Tlr2.

Phylogenomic databases

eggNOG

NOG251801.

HOGENOM

HOG000110611.

HOVERGEN

HBG108574.

InParanoid

Q9QUN7.

KO

K10159.

OrthoDB

EOG4SN1N6.

Gene expression databases

CleanEx

MM_TLR2.

Genevestigator

Q9QUN7.

GermOnline

ENSMUSG00000027995. Mus musculus.

Family and domain databases

InterPro

IPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027185. TLR2.
IPR017241. Toll-like_receptor.
[Graphical view]

PANTHER

PTHR24365:SF17. PTHR24365:SF17. 1 hit.

Pfam

PF01582. TIR. 1 hit.
[Graphical view]

PIRSF

PIRSF037595. Toll-like_receptor. 1 hit.

SMART

SM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]

SUPFAM

SSF52200. TIR. 1 hit.

PROSITE

PS51450. LRR. 9 hits.
PS50104. TIR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1075106.

EvolutionaryTrace

Q9QUN7.

NextBio

304101.

SOURCE

Search...

Entry information

Entry name

TLR2_MOUSE

Accession

Primary (citable) accession number: Q9QUN7
Secondary accession number(s): Q3U400, Q9DBC4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program