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Reviewed, UniProtKB/Swiss-Prot O60603 (TLR2_HUMAN)

Last modified July 22, 2008. Version 91. Feed History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Toll-like receptor 2
Alternative name(s):
    Toll/interleukin-1 receptor-like protein 4
    CD_antigen=CD282
Gene names
Name: TLR2
Synonyms: TIL4
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length784 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR2 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. 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.

Subunit structure

Interacts with LY96, TLR2 and TLR6 via the extracellular domain. Binds MYD88 via their respective TIR domains. Interacts with TICAM1. Ligand binding induces the formation of a heterodimer with TLR1.

Subcellular location

Membrane; Single-pass type I membrane proteinBy similarity.

Tissue specificity

Highly expressed in peripheral blood leukocytes, in particular in monocytes, in bone marrow, lymph node and in spleen. Also detected in lung and in fetal liver. Levels are low in other tissues.

Post-translational modification

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

Polymorphism

Genetic variations in TLR2 are associated with suceptibility to leprosy [MIM:246300]. Leprosy is a chronic disease associated with depressed cellular (but not humoral) immunity, the bacterium requires a lower temperature than 37 degrees Celsius and thrives particularly in peripheral Schwann cells and macrophages. The Trp-677 polymorphism in the intracellular domain of TLR2 has a role in susceptibility to lepromatous leprosy. Wild-type TLR2 mediates CD14-enhanced Mycobacterium leprae-dependent activation of NFKB1, but TLR2 containing the Trp-677 polymorphism did not. The impaired function of the Trp-677 polymorphism provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy.

Sequence similarities

Belongs to the Toll-like receptor family.

Contains 14 LRR (leucine-rich) repeats.

Contains 1 TIR domain.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 784766Toll-like receptor 2

Regions

Topological domain19 – 588570Extracellular Potential
Transmembrane589 – 60921 Potential
Topological domain610 – 784175Cytoplasmic Potential
Repeat51 – 7424LRR 1
Repeat75 – 9824LRR 2
Repeat99 – 12224LRR 3
Repeat124 – 14724LRR 4
Repeat148 – 17225LRR 5
Repeat173 – 19624LRR 6
Repeat221 – 24424LRR 7
Repeat359 – 38426LRR 8
Repeat386 – 41126LRR 9
Repeat412 – 43625LRR 10
Repeat438 – 45619LRR 11
Repeat457 – 47620LRR 12
Repeat477 – 49923LRR 13
Repeat501 – 52121LRR 14
Domain639 – 784146TIR

Sites

Site3491Interaction with bacterial lipopeptide

Amino acid modifications

Glycosylation1141N-linked (GlcNAc...)
Glycosylation1991N-linked (GlcNAc...)
Glycosylation4141N-linked (GlcNAc...)
Glycosylation4421N-linked (GlcNAc...)
Disulfide bond30 ↔ 36
Disulfide bond353 ↔ 382
Disulfide bond432 ↔ 454

Natural variations

Natural variant4111T → I: dbSNP rs5743699.
Natural variant5791R → H: dbSNP rs5743703.
Natural variant6311P → H: dbSNP rs5743704.
Natural variant6771R → W
Natural variant7531R → Q: dbSNP rs5743708.

Experimental info

Mutagenesis1141N → S: Prevents addition of N-glycans. Reduces secretion of the N-terminal ectodomain
Mutagenesis1991N → D: Prevents addition of N-glycans. Reduces secretion of the N-terminal ectodomain
Mutagenesis4161T → A: Prevents addition of N-glycans. Reduces secretion of the N-terminal ectodomain
Mutagenesis4421N → D: Prevents addition of N-glycans. Prevents secretion of the N-terminal ectodomain
Mutagenesis6811P → F: Abolishes the interaction with MYD88. No effect on oligomerization or on the structure of the TIR domain
Sequence conflict591L → Q in AAM23001. Ref.5
Sequence conflict681S → C in AAM23001. Ref.5
Sequence conflict7261D → E in AAC34133. Ref.2

Secondary structure

1 ............................................................................................................. 784
Helix Strand Turn

Details...