TLR-3 active protein
Human TLR-3
NCBI and Uniprot Product Information
NCBI Description
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. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It may thus play a role in host defense against viruses. Use of alternative polyadenylation sites to generate different length transcripts has been noted for this gene. [provided by RefSeq, Jul 2008]
Uniprot Description
Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.18
Subunit structure: Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes. Interacts with TICAM1 (via the TIR domain); mediates TLR3 signaling. Interacts with SRC; upon binding of double-stranded RNA. Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.18
Subcellular location: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane Ref.12.
Tissue specificity: Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons. Ref.2
Domain: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.
Post-translational modification: Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding. Ref.18 Ref.19TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes.
Polymorphism: The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and Asian ancestry, and confers some natural resistance to HIV-1 infection.
Involvement in disease: Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system. Ref.21
Sequence similarities: Belongs to the Toll-like receptor family.Contains 22 LRR (leucine-rich) repeats.Contains 1 LRRCT domain.Contains 1 LRRNT domain.Contains 1 TIR domain.
Research Articles on TLR-3
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Product Notes
The TLR-3 tlr3 (Catalog #AAA692016) is an Active Protein produced from HEK 293 Cells and is intended for research purposes only. The product is available for immediate purchase. The Human TLR-3 reacts with Human and may cross-react with other species as described in the data sheet. The amino acid sequence is listed below: STTKCTVSHE VADCSHLKLT QVPDDLPTNI TVLNLTHNQL RRLPAA NFTR YSQLTSLDVG FNTISKLEPE LCQKLPMLKV LNLQHNELSQ L SDKTFAFCT NLTELHLMSN SIQKIKNNPF VKQKNLITLD LSHNGLS STK LGTQVQLENL QELLLSNNKI QALKSEELDI FANSSLKKLE LS SNQIKEFS PGCFHAIGRL FGLFLNNVQL GPSLTEKLCL ELANTSIR NL SLSNSQLSTT SNTTFLGLKW TNLTMLDLSY NNLNVVGNDS FAW LPQLEYF FLEYNNIQHL FSHSLHGLFN VRYLNLKRSF TKQSISLAS L PKIDDFSFQW LKCLEHLNME DNDIPGIKSN MFTGLINLKY LSLS NSFTSL RTLTNETFVS LAHSPLHILN LTKNKISKIE SDAFSWLGHL EVLDLGLNEI GQELTGQEWR GLENIFEIYL SYNKYLQLTR NSFAL VPSLQ RLMLRRVALK NVDSSPSPFQ PLRNLTILDL SNNNIANIND DMLEGLEKLE ILDLQHNNLA RLWKHANPGG PIYFLKGLSH LHILNL ESNG FDEIPVEVFK DLFELKIIDL GLNNLNTLPA SVFNNQVSLK S LNLQKNLIT SVEKKVFGPA FRNLTELDMR FNPFDCTCES IAWFVNW INE THTNIPELSS HYLCNTPPHY HGFPVRLFDT SSCKDSAPFE L. It is sometimes possible for the material contained within the vial of "TLR-3, Active Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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