Toll-like receptor 2

Details

Name
Toll-like receptor 2
Synonyms
  • TIL4
  • Toll/interleukin-1 receptor-like protein 4
Gene Name
TLR2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010812|Toll-like receptor 2
MPHTLWMVWVLGVIISLSKEESSNQASLSCDRNGICKGSSGSLNSIPSGLTEAVKSLDLS
NNRITYISNSDLQRCVNLQALVLTSNGINTIEEDSFSSLGSLEHLDLSYNYLSNLSSSWF
KPLSSLTFLNLLGNPYKTLGETSLFSHLTKLQILRVGNMDTFTKIQRKDFAGLTFLEELE
IDASDLQSYEPKSLKSIQNVSHLILHMKQHILLLEIFVDVTSSVECLELRDTDLDTFHFS
ELSTGETNSLIKKFTFRNVKITDESLFQVMKLLNQISGLLELEFDDCTLNGVGNFRASDN
DRVIDPGKVETLTIRRLHIPRFYLFYDLSTLYSLTERVKRITVENSKVFLVPCLLSQHLK
SLEYLDLSENLMVEEYLKNSACEDAWPSLQTLILRQNHLASLEKTGETLLTLKNLTNIDI
SKNSFHSMPETCQWPEKMKYLNLSSTRIHSVTGCIPKTLEILDVSNNNLNLFSLNLPQLK
ELYISRNKLMTLPDASLLPMLLVLKISRNAITTFSKEQLDSFHTLKTLEAGGNNFICSCE
FLSFTQEQQALAKVLIDWPANYLCDSPSHVRGQQVQDVRLSVSECHRTALVSGMCCALFL
LILLTGVLCHRFHGLWYMKMMWAWLQAKRKPRKAPSRNICYDAFVSYSERDAYWVENLMV
QELENFNPPFKLCLHKRDFIPGKWIIDNIIDSIEKSHKTVFVLSENFVKSEWCKYELDFS
HFRLFDENNDAAILILLEPIEKKAIPQRFCKLRKIMNTKTYLEWPMDEAQREGFWVNLRA
AIKS
Number of residues
784
Molecular Weight
89836.575
Theoretical pI
6.59
GO Classification
Functions
diacyl lipopeptide binding / lipopolysaccharide binding / lipopolysaccharide receptor activity / lipoteichoic acid binding / peptidoglycan binding / protein heterodimerization activity / receptor activity / signaling pattern recognition receptor activity / Toll-like receptor binding / transmembrane signaling receptor activity / triacyl lipopeptide binding
Processes
apoptotic process / cell surface pattern recognition receptor signaling pathway / cellular response to bacterial lipopeptide / cellular response to diacyl bacterial lipopeptide / cellular response to lipoteichoic acid / cellular response to peptidoglycan / cellular response to triacyl bacterial lipopeptide / chloramphenicol transport / cytokine secretion involved in immune response / defense response to Gram-positive bacterium / detection of diacyl bacterial lipopeptide / detection of triacyl bacterial lipopeptide / I-kappaB phosphorylation / immune response / induction by symbiont of defense-related host nitric oxide production / inflammatory response / innate immune response / interleukin-10 production / lipopolysaccharide-mediated signaling pathway / MyD88-dependent toll-like receptor signaling pathway / negative regulation of growth of symbiont in host / negative regulation of interleukin-12 production / negative regulation of interleukin-17 production / positive regulation of chemokine production / positive regulation of cytokine secretion / positive regulation of gene expression / positive regulation of inflammatory response / positive regulation of interferon-beta production / positive regulation of interleukin-12 production / positive regulation of interleukin-18 production / positive regulation of interleukin-6 production / positive regulation of interleukin-8 production / positive regulation of leukocyte migration / positive regulation of macrophage cytokine production / positive regulation of NF-kappaB import into nucleus / positive regulation of NF-kappaB transcription factor activity / positive regulation of nitric oxide biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of toll-like receptor signaling pathway / positive regulation of transcription from RNA polymerase II promoter / positive regulation of tumor necrosis factor biosynthetic process / positive regulation of tumor necrosis factor production / positive regulation of Wnt signaling pathway / regulation of dendritic cell cytokine production / response to molecule of fungal origin / signal transduction / toll-like receptor 2 signaling pathway / toll-like receptor 4 signaling pathway / toll-like receptor signaling pathway / toll-like receptor TLR1 / toll-like receptor TLR6
Components
cell surface / cytoplasm / external side of plasma membrane / Golgi apparatus / integral component of plasma membrane / intrinsic component of plasma membrane / membrane raft / plasma membrane / Toll-like receptor 1-Toll-like receptor 2 protein complex / Toll-like receptor 2-Toll-like receptor 6 protein complex
General Function
Triacyl lipopeptide binding
Specific 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 (PubMed:17889651). 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 (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). Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PhoS1 (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). 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).
Pfam Domain Function
Transmembrane Regions
589-609
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0010813|Toll-like receptor 2 (TLR2)
ATGCCACATACTTTGTGGATGGTGTGGGTCTTGGGGGTCATCATCAGCCTCTCCAAGGAA
GAATCCTCCAATCAGGCTTCTCTGTCTTGTGACCGCAATGGTATCTGCAAGGGCAGCTCA
GGATCTTTAAACTCCATTCCCTCAGGGCTCACAGAAGCTGTAAAAAGCCTTGACCTGTCC
AACAACAGGATCACCTACATTAGCAACAGTGACCTACAGAGGTGTGTGAACCTCCAGGCT
CTGGTGCTGACATCCAATGGAATTAACACAATAGAGGAAGATTCTTTTTCTTCCCTGGGC
AGTCTTGAACATTTAGACTTATCCTATAATTACTTATCTAATTTATCGTCTTCCTGGTTC
AAGCCCCTTTCTTCTTTAACATTCTTAAACTTACTGGGAAATCCTTACAAAACCCTAGGG
GAAACATCTCTTTTTTCTCATCTCACAAAATTGCAAATCCTGAGAGTGGGAAATATGGAC
ACCTTCACTAAGATTCAAAGAAAAGATTTTGCTGGACTTACCTTCCTTGAGGAACTTGAG
ATTGATGCTTCAGATCTACAGAGCTATGAGCCAAAAAGTTTGAAGTCAATTCAGAATGTA
AGTCATCTGATCCTTCATATGAAGCAGCATATTTTACTGCTGGAGATTTTTGTAGATGTT
ACAAGTTCCGTGGAATGTTTGGAACTGCGAGATACTGATTTGGACACTTTCCATTTTTCA
GAACTATCCACTGGTGAAACAAATTCATTGATTAAAAAGTTTACATTTAGAAATGTGAAA
ATCACCGATGAAAGTTTGTTTCAGGTTATGAAACTTTTGAATCAGATTTCTGGATTGTTA
GAATTAGAGTTTGATGACTGTACCCTTAATGGAGTTGGTAATTTTAGAGCATCTGATAAT
GACAGAGTTATAGATCCAGGTAAAGTGGAAACGTTAACAATCCGGAGGCTGCATATTCCA
AGGTTTTACTTATTTTATGATCTGAGCACTTTATATTCACTTACAGAAAGAGTTAAAAGA
ATCACAGTAGAAAACAGTAAAGTTTTTCTGGTTCCTTGTTTACTTTCACAACATTTAAAA
TCATTAGAATACTTGGATCTCAGTGAAAATTTGATGGTTGAAGAATACTTGAAAAATTCA
GCCTGTGAGGATGCCTGGCCCTCTCTACAAACTTTAATTTTAAGGCAAAATCATTTGGCA
TCATTGGAAAAAACCGGAGAGACTTTGCTCACTCTGAAAAACTTGACTAACATTGATATC
AGTAAGAATAGTTTTCATTCTATGCCTGAAACTTGTCAGTGGCCAGAAAAGATGAAATAT
TTGAACTTATCCAGCACACGAATACACAGTGTAACAGGCTGCATTCCCAAGACACTGGAA
ATTTTAGATGTTAGCAACAACAATCTCAATTTATTTTCTTTGAATTTGCCGCAACTCAAA
GAACTTTATATTTCCAGAAATAAGTTGATGACTCTACCAGATGCCTCCCTCTTACCCATG
TTACTAGTATTGAAAATCAGTAGGAATGCAATAACTACGTTTTCTAAGGAGCAACTTGAC
TCATTTCACACACTGAAGACTTTGGAAGCTGGTGGCAATAACTTCATTTGCTCCTGTGAA
TTCCTCTCCTTCACTCAGGAGCAGCAAGCACTGGCCAAAGTCTTGATTGATTGGCCAGCA
AATTACCTGTGTGACTCTCCATCCCATGTGCGTGGCCAGCAGGTTCAGGATGTCCGCCTC
TCGGTGTCGGAATGTCACAGGACAGCACTGGTGTCTGGCATGTGCTGTGCTCTGTTCCTG
CTGATCCTGCTCACGGGGGTCCTGTGCCACCGTTTCCATGGCCTGTGGTATATGAAAATG
ATGTGGGCCTGGCTCCAGGCCAAAAGGAAGCCCAGGAAAGCTCCCAGCAGGAACATCTGC
TATGATGCATTTGTTTCTTACAGTGAGCGGGATGCCTACTGGGTGGAGAACCTTATGGTC
CAGGAGCTGGAGAACTTCAATCCCCCCTTCAAGTTGTGTCTTCATAAGCGGGACTTCATT
CCTGGCAAGTGGATCATTGACAATATCATTGACTCCATTGAAAAGAGCCACAAAACTGTC
TTTGTGCTTTCTGAAAACTTTGTGAAGAGTGAGTGGTGCAAGTATGAACTGGACTTCTCC
CATTTCCGTCTTTTTGATGAGAACAATGATGCTGCCATTCTCATTCTTCTGGAGCCCATT
GAGAAAAAAGCCATTCCCCAGCGCTTCTGCAAGCTGCGGAAGATAATGAACACCAAGACC
TACCTGGAGTGGCCCATGGACGAGGCTCAGCGGGAAGGATTTTGGGTAAATCTGAGAGCT
GCGATAAAGTCCTAG
Chromosome Location
4
Locus
4q32
External Identifiers
ResourceLink
UniProtKB IDO60603
UniProtKB Entry NameTLR2_HUMAN
GenBank Protein ID3132528
GenBank Gene IDAF051152
GenAtlas IDTLR2
HGNC IDHGNC:11848
General References
  1. Chaudhary PM, Ferguson C, Nguyen V, Nguyen O, Massa HF, Eby M, Jasmin A, Trask BJ, Hood L, Nelson PS: Cloning and characterization of two Toll/Interleukin-1 receptor-like genes TIL3 and TIL4: evidence for a multi-gene receptor family in humans. Blood. 1998 Jun 1;91(11):4020-7. [Article]
  2. Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF: A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):588-93. [Article]
  3. Yang RB, Mark MR, Gray A, Huang A, Xie MH, Zhang M, Goddard A, Wood WI, Gurney AL, Godowski PJ: Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature. 1998 Sep 17;395(6699):284-8. [Article]
  4. Nakajima T, Ohtani H, Satta Y, Uno Y, Akari H, Ishida T, Kimura A: Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics. 2008 Dec;60(12):727-35. doi: 10.1007/s00251-008-0332-0. Epub 2008 Sep 23. [Article]
  5. Georgel P, Macquin C, Bahram S: The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes. PLoS One. 2009 Nov 17;4(11):e7803. doi: 10.1371/journal.pone.0007803. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Aliprantis AO, Yang RB, Mark MR, Suggett S, Devaux B, Radolf JD, Klimpel GR, Godowski P, Zychlinsky A: Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science. 1999 Jul 30;285(5428):736-9. [Article]
  8. Bulut Y, Faure E, Thomas L, Equils O, Arditi M: Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J Immunol. 2001 Jul 15;167(2):987-94. [Article]
  9. Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S: Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol. 2002 Dec 15;169(12):6668-72. [Article]
  10. Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K: Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J Biol Chem. 2006 Oct 13;281(41):31002-11. Epub 2006 Jul 31. [Article]
  11. Weber AN, Morse MA, Gay NJ: Four N-linked glycosylation sites in human toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion. J Biol Chem. 2004 Aug 13;279(33):34589-94. Epub 2004 Jun 1. [Article]
  12. Drage MG, Pecora ND, Hise AG, Febbraio M, Silverstein RL, Golenbock DT, Boom WH, Harding CV: TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis. Cell Immunol. 2009;258(1):29-37. doi: 10.1016/j.cellimm.2009.03.008. Epub 2009 Apr 11. [Article]
  13. Boada-Romero E, Letek M, Fleischer A, Pallauf K, Ramon-Barros C, Pimentel-Muinos FX: TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3. EMBO J. 2013 Feb 20;32(4):566-82. doi: 10.1038/emboj.2013.8. Epub 2013 Feb 1. [Article]
  14. Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley JL, Tong L: Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature. 2000 Nov 2;408(6808):111-5. [Article]
  15. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO: Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell. 2007 Sep 21;130(6):1071-82. [Article]
  16. Kang TJ, Chae GT: Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol. 2001 Jul;31(1):53-8. [Article]
  17. Bochud PY, Hawn TR, Aderem A: Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling. J Immunol. 2003 Apr 1;170(7):3451-4. [Article]
  18. Ben-Ali M, Corre B, Manry J, Barreiro LB, Quach H, Boniotto M, Pellegrini S, Quintana-Murci L: Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family. Hum Mutat. 2011 Jun;32(6):643-52. doi: 10.1002/humu.21486. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03963S-(Dimethylarsenic)CysteineexperimentalunknownDetails
DB05475GolotimodinvestigationalunknownDetails
DB00045Lyme disease vaccine (recombinant OspA)approved, withdrawnyesother/unknownDetails
DB11601Tuberculin purified protein derivativeapprovedyesligandDetails
DB00210AdapaleneapprovedyesantagonistDetails