You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NameToll-like receptor 2
Synonyms
  • TIL4
  • Toll/interleukin-1 receptor-like protein 4
Gene NameTLR2
OrganismHuman
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 residues784
Molecular Weight89836.575
Theoretical pI6.59
GO Classification
Functions
  • lipopolysaccharide binding
  • triacyl lipopeptide binding
  • lipopolysaccharide receptor activity
  • transmembrane signaling receptor activity
  • diacyl lipopeptide binding
  • lipoteichoic acid binding
  • protein heterodimerization activity
  • peptidoglycan binding
  • signaling pattern recognition receptor activity
  • Toll-like receptor binding
  • receptor activity
Processes
  • positive regulation of interferon-beta production
  • signal transduction
  • toll-like receptor 2 signaling pathway
  • positive regulation of interleukin-18 production
  • cell surface pattern recognition receptor signaling pathway
  • immune response
  • toll-like receptor 4 signaling pathway
  • positive regulation of macrophage cytokine production
  • lipopolysaccharide-mediated signaling pathway
  • cellular response to bacterial lipopeptide
  • toll-like receptor signaling pathway
  • toll-like receptor TLR1
  • positive regulation of toll-like receptor signaling pathway
  • cellular response to diacyl bacterial lipopeptide
  • inflammatory response
  • toll-like receptor TLR6
  • positive regulation of tumor necrosis factor biosynthetic process
  • positive regulation of interleukin-8 production
  • cellular response to lipoteichoic acid
  • negative regulation of interleukin-17 production
  • regulation of dendritic cell cytokine production
  • positive regulation of chemokine production
  • positive regulation of nitric-oxide synthase biosynthetic process
  • response to molecule of fungal origin
  • positive regulation of gene expression
  • cellular response to peptidoglycan
  • innate immune response
  • positive regulation of NF-kappaB import into nucleus
  • cellular response to triacyl bacterial lipopeptide
  • I-kappaB phosphorylation
  • negative regulation of growth of symbiont in host
  • chloramphenicol transport
  • apoptotic process
  • positive regulation of leukocyte migration
  • cytokine secretion involved in immune response
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of nitric oxide biosynthetic process
  • detection of diacyl bacterial lipopeptide
  • positive regulation of interleukin-6 production
  • positive regulation of interleukin-12 production
  • detection of triacyl bacterial lipopeptide
  • positive regulation of tumor necrosis factor production
  • positive regulation of Wnt signaling pathway
  • induction by symbiont of defense-related host nitric oxide production
  • positive regulation of NF-kappaB transcription factor activity
  • interleukin-10 production
  • positive regulation of inflammatory response
  • defense response to Gram-positive bacterium
  • negative regulation of interleukin-12 production
  • MyD88-dependent toll-like receptor signaling pathway
  • positive regulation of cytokine secretion
Components
  • plasma membrane
  • intrinsic component of plasma membrane
  • cell surface
  • Golgi apparatus
  • external side of plasma membrane
  • integral component of plasma membrane
  • Toll-like receptor 1-Toll-like receptor 2 protein complex
  • Toll-like receptor 2-Toll-like receptor 6 protein complex
  • cytoplasm
  • membrane raft
General FunctionTriacyl lipopeptide binding
Specific FunctionCooperates 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 Regions589-609
GenBank Protein ID3132528
UniProtKB IDO60603
UniProtKB Entry NameTLR2_HUMAN
Cellular LocationMembrane
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
GenBank Gene IDAF051152
GeneCard IDNot Available
GenAtlas IDTLR2
HGNC IDHGNC:11848
Chromosome Location4
Locus4q32
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. 9596645
  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. 9435236
  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. 9751057
  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. 18810425
  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. 19924287
  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. 15489334
  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. 10426996
  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. 11441107
  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. 12471095
  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. 16880211
  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. 15173186
  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. 19362712
  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. 23376921
  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. 11081518
  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. 17889651
  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. 11476982
  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. 12646604
  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. 21618349