Human Gene TLR2 (uc003inq.3) Description and Page Index
  Description: Homo sapiens toll-like receptor 2 (TLR2), mRNA.
RefSeq Summary (NM_003264): The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. This protein is a cell-surface protein that can form heterodimers with other TLR family members to recognize conserved molecules derived from microorganisms known as pathogen-associated molecular patterns (PAMPs). Activation of TLRs by PAMPs leads to an up-regulation of signaling pathways to modulate the host's inflammatory response. This gene is also thought to promote apoptosis in response to bacterial lipoproteins. This gene has been implicated in the pathogenesis of several autoimmune diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016].
Transcript (Including UTRs)
   Position: hg19 chr4:154,605,441-154,627,242 Size: 21,802 Total Exon Count: 3 Strand: +
Coding Region
   Position: hg19 chr4:154,624,060-154,626,414 Size: 2,355 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:154,605,441-154,627,242)mRNA (may differ from genome)Protein (784 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: TLR2_HUMAN
DESCRIPTION: RecName: Full=Toll-like receptor 2; AltName: Full=Toll/interleukin-1 receptor-like protein 4; AltName: CD_antigen=CD282; Flags: Precursor;
FUNCTION: Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 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: 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. Interacts with CNPY3 (By similarity).
INTERACTION: C3PTT6:PAUF; NbExp=3; IntAct=EBI-973722, EBI-3505892;
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (By 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.
PTM: Glycosylation of Asn-442 is critical for secretion of the N- terminal ectodomain of TLR2.
POLYMORPHISM: Genetic variations in TLR2 are associated with susceptibility 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.
SIMILARITY: Belongs to the Toll-like receptor family.
SIMILARITY: Contains 14 LRR (leucine-rich) repeats.
SIMILARITY: Contains 1 TIR domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TLR2
CDC HuGE Published Literature: TLR2
Positive Disease Associations: acute pancreatitis , amyloidosis Familial Mediterranean Fever , Arthritis, Rheumatoid|Rheumatoid Arthritis|Anti-TNF Response , Asthma , asthma; allergic rhinitis; atopic dermatitis , atherosclerosis, coronary , cervical intraepithelial neoplasia grade 3 , colorectal cancer , cytomegalovirus , diabetes, type 1 , IL-12 production from monocyte , rheumatic fever , sarcoidosis , staphylococcal infection , tuberculosis , tuberculosis meningitis
Related Studies:
  1. acute pancreatitis
    Yasuhiko Takagi , et al. Human immunology 2009 Jan, Microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene is associated with susceptibility to acute pancreatitis in Japan., Human immunology 2009 Jan. [PubMed 19480862]
    microsatellite polymorphism in intron 2 of the TLR2 gene was associated with susceptibility to AP and its severity in Japan.
  2. amyloidosis Familial Mediterranean Fever
    Ozen, S. et al. 2006, Arg753Gln TLR-2 Polymorphism in Familial Mediterranean Fever, J Rheumatol 2006. [PubMed 17013994]
    The Arg753Gln polymorphism may affect the severity of this monogenic disease by influencing the innate immune response to pathogens.
  3. Arthritis, Rheumatoid|Rheumatoid Arthritis|Anti-TNF Response
    Potter C et al. 2010, Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways., Annals of the rheumatic diseases 69(7) : 1315-20 2010. [PubMed 20448286]
    Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TLR2
Diseases sorted by gene-association score: leprosy* (609), colorectal cancer* (118), tuberculosis (51), lepromatous leprosy (40), nontuberculous mycobacterial lung disease (19), melioidosis (19), mycobacterium abscessus (18), aspergillosis (18), filariasis (16), suppurative otitis media (16), septic arthritis (16), rosacea (16), chagas disease (16), rheumatic fever (14), mastitis (14), keratitis (14), leptospirosis (13), otitis media (13), leishmaniasis (12), q fever (11), lyme disease (11), bacterial meningitis (11), inflammatory bowel disease (10), mycobacterium chelonae (10), prosthetic joint infection (10), meningitis (10), scrub typhus (10), measles (10), trench fever (10), ileitis (10), paracoccidioidomycosis (9), sebaceous gland disease (9), pelvic inflammatory disease (9), periodontal disease (9), neurosyphilis (9), pulmonary tuberculosis (8), extrapulmonary tuberculosis (8), haemophilus influenzae (8), acne (8), irak4 deficiency (8), anterior uveitis (8), mycobacterium kansasii (8), legionellosis (8), pneumonia (8), peritonitis (8), infective endocarditis (7), bacterial vaginosis (7), acute cervicitis (7), molluscum contagiosum (7), myd88 deficiency (7), tuberculous meningitis (7), visceral leishmaniasis (7), periodontitis (7), congenital cytomegalovirus (7), bronchiectasis (6), alveolar echinococcosis (6), chlamydia (6), tularemia (6), pneumonic tularemia (6), bacteremia (6), cutaneous leishmaniasis (6), rheumatic heart disease (6), malaria (6), penicilliosis (6), genital herpes (6), viral hepatitis (5), middle ear disease (5), invasive aspergillosis (5), myositis fibrosa (5), endocarditis (5), toxoplasmosis (5), primary systemic mycosis (5), primary bacterial infectious disease (5), rheumatoid arthritis (5), globe disease (4), hepatitis b (4), mesenteric lymphadenitis (4), neisseria meningitidis infection (4), obesity (3), trypanosomiasis (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -79.70219-0.364 Picture PostScript Text
3' UTR -215.52828-0.260 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000483 - Cys-rich_flank_reg_C
IPR004075 - IL1_rcpt_1
IPR001611 - Leu-rich_rpt
IPR003591 - Leu-rich_rpt_typical-subtyp
IPR000157 - TIR_dom
IPR017241 - Toll-like_receptor

Pfam Domains:
PF00560 - Leucine Rich Repeat
PF01463 - Leucine rich repeat C-terminal domain
PF01582 - TIR domain
PF13306 - Leucine rich repeats (6 copies)
PF13676 - TIR domain
PF13855 - Leucine rich repeat

SCOP Domains:
52047 - RNI-like
52058 - L domain-like
52075 - Outer arm dynein light chain 1
52200 - Toll/Interleukin receptor TIR domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1FYW
- X-ray MuPIT

1FYX
- X-ray MuPIT

1O77
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2Z7X - X-ray MuPIT 2Z80 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O60603
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001530 lipopolysaccharide binding
GO:0001875 lipopolysaccharide receptor activity
GO:0005515 protein binding
GO:0008329 signaling pattern recognition receptor activity
GO:0035325 Toll-like receptor binding
GO:0038023 signaling receptor activity
GO:0042497 triacyl lipopeptide binding
GO:0042834 peptidoglycan binding
GO:0044877 macromolecular complex binding
GO:0046982 protein heterodimerization activity
GO:0071723 lipopeptide binding

Biological Process:
GO:0001666 response to hypoxia
GO:0001774 microglial cell activation
GO:0001775 cell activation
GO:0002224 toll-like receptor signaling pathway
GO:0002237 response to molecule of bacterial origin
GO:0002374 cytokine secretion involved in immune response
GO:0002376 immune system process
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006691 leukotriene metabolic process
GO:0006915 apoptotic process
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007252 I-kappaB phosphorylation
GO:0007612 learning
GO:0008285 negative regulation of cell proliferation
GO:0009636 response to toxic substance
GO:0010628 positive regulation of gene expression
GO:0014005 microglia development
GO:0030177 positive regulation of Wnt signaling pathway
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032289 central nervous system myelin formation
GO:0032493 response to bacterial lipoprotein
GO:0032496 response to lipopolysaccharide
GO:0032570 response to progesterone
GO:0032613 interleukin-10 production
GO:0032640 tumor necrosis factor production
GO:0032722 positive regulation of chemokine production
GO:0032728 positive regulation of interferon-beta production
GO:0032733 positive regulation of interleukin-10 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032741 positive regulation of interleukin-18 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032757 positive regulation of interleukin-8 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032868 response to insulin
GO:0034123 positive regulation of toll-like receptor signaling pathway
GO:0034134 toll-like receptor 2 signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042495 detection of triacyl bacterial lipopeptide
GO:0042496 detection of diacyl bacterial lipopeptide
GO:0043312 neutrophil degranulation
GO:0045087 innate immune response
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046209 nitric oxide metabolic process
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0050707 regulation of cytokine secretion
GO:0050729 positive regulation of inflammatory response
GO:0050765 negative regulation of phagocytosis
GO:0050830 defense response to Gram-positive bacterium
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0051964 negative regulation of synapse assembly
GO:0070542 response to fatty acid
GO:0071221 cellular response to bacterial lipopeptide
GO:0071223 cellular response to lipoteichoic acid
GO:0071346 cellular response to interferon-gamma
GO:0071726 cellular response to diacyl bacterial lipopeptide
GO:0071727 cellular response to triacyl bacterial lipopeptide
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1903974 positive regulation of cellular response to macrophage colony-stimulating factor stimulus
GO:2000484 positive regulation of interleukin-8 secretion

Cellular Component:
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030667 secretory granule membrane
GO:0030670 phagocytic vesicle membrane
GO:0031226 intrinsic component of plasma membrane
GO:0031410 cytoplasmic vesicle
GO:0035354 Toll-like receptor 1-Toll-like receptor 2 protein complex
GO:0042995 cell projection
GO:0044297 cell body
GO:0045121 membrane raft


-  Descriptions from all associated GenBank mRNAs
  JB406675 - Sequence 1 from Patent WO2012072685.
AF424050 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, 5' untranslated region, splice variant E.
AF424053 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, 5' untranslated region, splice variant C.
AF424049 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, 5' untranslated region, splice variant B.
AF424051 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, 5' untranslated region, splice variant A.
AF424052 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, 5' untranslated region, splice variant D.
HW061240 - JP 2012529430-A/115: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
HW534930 - JP 2014508161-A/1: COMPOSITIONS AND METHODS FOR TREATING LUNG DISEASE AND INJURY.
JA394582 - Sequence 4 from Patent WO2011066475.
JB181736 - Sequence 1 from Patent WO2012118911.
JB202420 - Sequence 1 from Patent WO2012118910.
JB252048 - Sequence 115 from Patent EP2440214.
LP764947 - Sequence 115 from Patent EP3276004.
LP895491 - Sequence 355 from Patent EP3253886.
BC033756 - Homo sapiens toll-like receptor 2, mRNA (cDNA clone MGC:45301 IMAGE:5213439), complete cds.
AF051152 - Homo sapiens Toll/interleukin-1 receptor-like protein 4 (TIL4) mRNA, complete cds.
JD452857 - Sequence 433881 from Patent EP1572962.
AX429250 - Sequence 5 from Patent WO0235236.
U88878 - Homo sapiens Toll-like receptor 2 (TLR2) mRNA, complete cds.
JD136858 - Sequence 117882 from Patent EP1572962.
AK125659 - Homo sapiens cDNA FLJ43671 fis, clone SYNOV4007553, highly similar to Toll-like receptor 2 precursor.
JD283164 - Sequence 264188 from Patent EP1572962.
CU689724 - Synthetic construct Homo sapiens gateway clone IMAGE:100020083 5' read TLR2 mRNA.
AF502291 - Homo sapiens toll-like receptor 2 mRNA, partial cds.
AB590438 - Synthetic construct DNA, clone: pFN21AE1434, Homo sapiens TLR2 gene for toll-like receptor 2, without stop codon, in Flexi system.
KU178364 - Homo sapiens toll-like receptor 2 isoform 1 (TLR2) mRNA, partial cds.
KU178365 - Homo sapiens toll-like receptor 2 isoform 2 (TLR2) mRNA, partial cds, alternatively spliced.
DQ894005 - Synthetic construct Homo sapiens clone IMAGE:100008465; FLH166452.01L; RZPDo839H0185D toll-like receptor 2 (TLR2) gene, encodes complete protein.
KJ897680 - Synthetic construct Homo sapiens clone ccsbBroadEn_07074 TLR2 gene, encodes complete protein.
KR710859 - Synthetic construct Homo sapiens clone CCSBHm_00017694 TLR2 (TLR2) mRNA, encodes complete protein.
KR710860 - Synthetic construct Homo sapiens clone CCSBHm_00017696 TLR2 (TLR2) mRNA, encodes complete protein.
KR710861 - Synthetic construct Homo sapiens clone CCSBHm_00017697 TLR2 (TLR2) mRNA, encodes complete protein.
KR710862 - Synthetic construct Homo sapiens clone CCSBHm_00017699 TLR2 (TLR2) mRNA, encodes complete protein.
AB445624 - Homo sapiens TLR2 mRNA for toll-like receptor 2, complete cds.
DQ012265 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-1 allele, complete cds.
DQ012266 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-2 allele, complete cds.
DQ012267 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-3 allele, complete cds.
DQ012268 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-4 allele, complete cds.
DQ012269 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-5 allele, complete cds.
DQ012270 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-6 allele, complete cds.
DQ012271 - Homo sapiens toll-like receptor 2 (TLR2) mRNA, TLR2-7 allele, complete cds.
EU176198 - Synthetic construct Homo sapiens clone IMAGE:100006347; FLH166459.01X; RZPDo839E04250D toll-like receptor 2 (TLR2) gene, encodes complete protein.
JD130946 - Sequence 111970 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04620 - Toll-like receptor signaling pathway
hsa05140 - Leishmaniasis
hsa05142 - Chagas disease

Reactome (by CSHL, EBI, and GO)

Protein O60603 (Reactome details) participates in the following event(s):

R-HSA-168951 TLR1:TLR2 is recruited to ligand:CD14
R-HSA-1974676 Beta defensin 103 activates TLR1:TLR2
R-HSA-5432814 SFTPA/SFTPD binds TLR2:TLR1
R-HSA-168950 TLR6:TLR2 is recruited to ligand:CD14:CD36
R-HSA-6798743 Exocytosis of secretory granule membrane proteins
R-HSA-2201316 Activated TLR2/4 interacts with MAL(TIRAP)
R-HSA-166072 MyD88 forms a complex with MAL:activated TLR2/4
R-HSA-2201322 MAL is phosphorylated by BTK
R-HSA-2559414 Activated TLR2/4:MAL interacts with BTK
R-HSA-937079 MyD88 oligomerization within the complex of activated TLR:Mal:MyD88
R-HSA-166082 IRAK4 binds to the activated TLR receptor:Mal:MyD88 complex
R-HSA-937022 IRAK4 autophosphorylation in the complex with activated TLR:MyD88:Mal
R-HSA-166091 IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:Mal complex
R-HSA-166362 Dissociation of hp-IRAK1:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex
R-HSA-2262775 Dissociation of p-IRAK2:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex
R-HSA-166286 Multiple IRAK1 autophosphorylation steps
R-HSA-166284 Second phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal
R-HSA-166119 First phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal
R-HSA-166363 TRAF6 binds to hp- IRAK1
R-HSA-937059 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:Mal:activated TLR complex
R-HSA-2262777 TRAF6 binds to p-IRAK2
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-1461957 Beta defensins
R-HSA-5686938 Regulation of TLR by endogenous ligand
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-6798695 Neutrophil degranulation
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-1461973 Defensins
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-168249 Innate Immune System
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-6803157 Antimicrobial peptides
R-HSA-168256 Immune System
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-5602358 Diseases associated with the TLR signaling cascade
R-HSA-5260271 Diseases of Immune System
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: B3Y612, D1CS45, D1CS48, D1CS49, NM_003264, NP_003255, O15454, O60603, Q8NI00, TIL4, TLR2_HUMAN
UCSC ID: uc003inq.3
RefSeq Accession: NM_003264
Protein: O60603 (aka TLR2_HUMAN)
CCDS: CCDS3784.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_003264.3
exon count: 3CDS single in 3' UTR: no RNA size: 3417
ORF size: 2355CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4910.00frame shift in genome: no % Coverage: 99.56
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.