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O15455

- TLR3_HUMAN

UniProt

O15455 - TLR3_HUMAN

Protein

Toll-like receptor 3

Gene

TLR3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    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.9 Publications

    GO - Molecular functioni

    1. double-stranded RNA binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. receptor activity Source: ProtInc
    4. transmembrane signaling receptor activity Source: UniProtKB

    GO - Biological processi

    1. activation of NF-kappaB-inducing kinase activity Source: UniProtKB
    2. cellular response to drug Source: Ensembl
    3. cellular response to exogenous dsRNA Source: Ensembl
    4. cellular response to interferon-beta Source: Ensembl
    5. cellular response to interferon-gamma Source: Ensembl
    6. cellular response to mechanical stimulus Source: UniProtKB
    7. defense response to bacterium Source: ProtInc
    8. defense response to virus Source: BHF-UCL
    9. detection of virus Source: UniProtKB
    10. extrinsic apoptotic signaling pathway Source: UniProtKB
    11. hyperosmotic response Source: UniProtKB
    12. I-kappaB kinase/NF-kappaB signaling Source: Reactome
    13. I-kappaB phosphorylation Source: BHF-UCL
    14. inflammatory response Source: UniProtKB-KW
    15. innate immune response Source: BHF-UCL
    16. male gonad development Source: Ensembl
    17. microglial cell activation involved in immune response Source: Ensembl
    18. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    19. necroptotic signaling pathway Source: UniProtKB
    20. negative regulation of osteoclast differentiation Source: UniProtKB
    21. pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response Source: Ensembl
    22. positive regulation of apoptotic process Source: Ensembl
    23. positive regulation of chemokine biosynthetic process Source: Ensembl
    24. positive regulation of chemokine production Source: BHF-UCL
    25. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
    26. positive regulation of inflammatory response Source: BHF-UCL
    27. positive regulation of interferon-alpha biosynthetic process Source: UniProtKB
    28. positive regulation of interferon-beta biosynthetic process Source: UniProtKB
    29. positive regulation of interferon-beta production Source: BHF-UCL
    30. positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
    31. positive regulation of interleukin-12 production Source: BHF-UCL
    32. positive regulation of interleukin-6 production Source: BHF-UCL
    33. positive regulation of interleukin-8 production Source: BHF-UCL
    34. positive regulation of JNK cascade Source: Ensembl
    35. positive regulation of NF-kappaB import into nucleus Source: BHF-UCL
    36. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
    37. positive regulation of toll-like receptor signaling pathway Source: BHF-UCL
    38. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    39. positive regulation of tumor necrosis factor production Source: BHF-UCL
    40. positive regulation of type III interferon production Source: Ensembl
    41. response to exogenous dsRNA Source: MGI
    42. signal transduction Source: ProtInc
    43. toll-like receptor 3 signaling pathway Source: Reactome
    44. toll-like receptor 4 signaling pathway Source: Reactome
    45. toll-like receptor signaling pathway Source: Reactome
    46. TRIF-dependent toll-like receptor signaling pathway Source: Reactome

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Immunity, Inflammatory response, Innate immunity

    Keywords - Ligandi

    RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_118563. RIP-mediated NFkB activation via ZBP1.
    REACT_118632. Trafficking and processing of endosomal TLR.
    REACT_150361. TRIF-mediated programmed cell death.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_6783. Toll Like Receptor 3 (TLR3) Cascade.
    SignaLinkiO15455.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Toll-like receptor 3
    Alternative name(s):
    CD_antigen: CD283
    Gene namesi
    Name:TLR3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:11849. TLR3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. endolysosome membrane Source: Reactome
    3. endoplasmic reticulum membrane Source: Reactome
    4. endosome membrane Source: Reactome
    5. Golgi membrane Source: Reactome
    6. integral component of plasma membrane Source: ProtInc
    7. lysosomal membrane Source: UniProtKB
    8. membrane Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Endosome, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti554 – 5541P → S in HSE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. 1 Publication
    VAR_054887

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi95 – 951C → A: Reduced response to ds-RNA. 1 Publication
    Mutagenesisi122 – 1221C → A: Reduced response to ds-RNA. 1 Publication
    Mutagenesisi196 – 1961N → G: Reduced expression levels; when associated with R-247. 1 Publication
    Mutagenesisi247 – 2471N → R: Reduced response to ds-RNA. Reduced expression levels; when associated with G-196. 1 Publication
    Mutagenesisi539 – 5391H → A: No effect. 1 Publication
    Mutagenesisi539 – 5391H → E: Loss of RNA binding. Constitutive activation of NF-kappa-B. 1 Publication
    Mutagenesisi541 – 5411N → A: Loss of RNA binding. Abolishes activation of NF-kappa-B. 1 Publication
    Mutagenesisi759 – 7591Y → F: Reduced activation of NF-kappa-B in response to ds-RNA. Reduced induction of IL-8 in response to ds-RNA. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi613002. phenotype.
    Orphaneti1930. Herpetic encephalitis.
    PharmGKBiPA36551.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 23231 PublicationAdd
    BLAST
    Chaini24 – 904881Toll-like receptor 3PRO_0000034715Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi28 ↔ 37
    Glycosylationi52 – 521N-linked (GlcNAc...)3 Publications
    Glycosylationi57 – 571N-linked (GlcNAc...)1 Publication
    Glycosylationi70 – 701N-linked (GlcNAc...)2 Publications
    Disulfide bondi95 ↔ 122
    Glycosylationi124 – 1241N-linked (GlcNAc...)2 Publications
    Glycosylationi196 – 1961N-linked (GlcNAc...)1 Publication
    Glycosylationi247 – 2471N-linked (GlcNAc...)1 Publication
    Glycosylationi252 – 2521N-linked (GlcNAc...)3 Publications
    Glycosylationi265 – 2651N-linked (GlcNAc...)2 Publications
    Glycosylationi275 – 2751N-linked (GlcNAc...)3 Publications
    Glycosylationi291 – 2911N-linked (GlcNAc...)3 Publications
    Glycosylationi398 – 3981N-linked (GlcNAc...)3 Publications
    Glycosylationi413 – 4131N-linked (GlcNAc...)3 Publications
    Glycosylationi507 – 5071N-linked (GlcNAc...)3 Publications
    Glycosylationi636 – 6361N-linked (GlcNAc...)1 Publication
    Disulfide bondi649 ↔ 677
    Disulfide bondi651 ↔ 696
    Glycosylationi662 – 6621N-linked (GlcNAc...)Sequence Analysis
    Modified residuei759 – 7591Phosphotyrosine1 Publication
    Modified residuei858 – 8581Phosphotyrosine1 Publication

    Post-translational modificationi

    Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.4 Publications
    TLR3 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.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiO15455.
    PaxDbiO15455.
    PRIDEiO15455.

    PTM databases

    PhosphoSiteiO15455.

    Expressioni

    Tissue specificityi

    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.1 Publication

    Gene expression databases

    ArrayExpressiO15455.
    BgeeiO15455.
    CleanExiHS_TLR3.
    GenevestigatoriO15455.

    Organism-specific databases

    HPAiCAB025658.

    Interactioni

    Subunit structurei

    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.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PIK3R1P279862EBI-6116630,EBI-79464

    Protein-protein interaction databases

    BioGridi112953. 15 interactions.
    DIPiDIP-29660N.
    IntActiO15455. 6 interactions.
    MINTiMINT-2840066.
    STRINGi9606.ENSP00000296795.

    Structurei

    Secondary structure

    1
    904
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi31 – 366
    Beta strandi47 – 493
    Beta strandi54 – 574
    Helixi68 – 747
    Beta strandi78 – 814
    Helixi94 – 974
    Beta strandi103 – 1053
    Turni118 – 1214
    Beta strandi126 – 1294
    Turni142 – 1454
    Beta strandi151 – 1533
    Beta strandi166 – 1683
    Beta strandi175 – 1773
    Helixi188 – 1914
    Helixi192 – 1943
    Beta strandi198 – 2036
    Helixi216 – 2194
    Beta strandi220 – 2234
    Beta strandi225 – 2273
    Helixi234 – 24512
    Beta strandi252 – 2543
    Turni265 – 2684
    Helixi269 – 2735
    Beta strandi278 – 2803
    Turni291 – 2966
    Beta strandi302 – 3043
    Beta strandi310 – 3134
    Turni315 – 3206
    Beta strandi326 – 3283
    Beta strandi338 – 3403
    Turni348 – 3536
    Beta strandi359 – 3613
    Turni372 – 3776
    Beta strandi383 – 3853
    Turni398 – 4014
    Helixi402 – 4043
    Beta strandi411 – 4133
    Turni424 – 4296
    Beta strandi435 – 4373
    Beta strandi444 – 4463
    Helixi450 – 4523
    Beta strandi460 – 4623
    Beta strandi467 – 4704
    Turni473 – 4786
    Beta strandi484 – 4863
    Turni501 – 5044
    Beta strandi510 – 5123
    Turni523 – 5286
    Beta strandi534 – 5363
    Helixi543 – 5464
    Turni557 – 5604
    Beta strandi566 – 5683
    Turni579 – 5846
    Beta strandi590 – 5923
    Turni603 – 6086
    Beta strandi614 – 6163
    Helixi627 – 6348
    Beta strandi638 – 6414
    Beta strandi655 – 6584
    Helixi671 – 6744
    Beta strandi676 – 6805
    Helixi688 – 6903

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ZIWX-ray2.10A27-700[»]
    2A0ZX-ray2.40A22-703[»]
    3ULUX-ray3.52A22-702[»]
    3ULVX-ray3.52A22-702[»]
    ProteinModelPortaliO15455.
    SMRiO15455. Positions 26-897.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO15455.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 704681LumenalSequence AnalysisAdd
    BLAST
    Topological domaini726 – 904179CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei705 – 72521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini24 – 5128LRRNTAdd
    BLAST
    Repeati52 – 7322LRR 1Add
    BLAST
    Repeati76 – 9722LRR 2Add
    BLAST
    Repeati100 – 12122LRR 3Add
    BLAST
    Repeati124 – 14522LRR 4Add
    BLAST
    Repeati148 – 16821LRR 5Add
    BLAST
    Repeati172 – 19322LRR 6Add
    BLAST
    Repeati198 – 21922LRR 7Add
    BLAST
    Repeati222 – 24423LRR 8Add
    BLAST
    Repeati249 – 27022LRR 9Add
    BLAST
    Repeati275 – 29622LRR 10Add
    BLAST
    Repeati299 – 32022LRR 11Add
    BLAST
    Repeati323 – 34422LRR 12Add
    BLAST
    Repeati356 – 37722LRR 13Add
    BLAST
    Repeati380 – 40021LRR 14Add
    BLAST
    Repeati408 – 42922LRR 15Add
    BLAST
    Repeati432 – 45423LRR 16Add
    BLAST
    Repeati465 – 48622LRR 17Add
    BLAST
    Repeati507 – 52822LRR 18Add
    BLAST
    Repeati531 – 55222LRR 19Add
    BLAST
    Repeati563 – 58422LRR 20Add
    BLAST
    Repeati587 – 60822LRR 21Add
    BLAST
    Repeati611 – 63222LRR 22Add
    BLAST
    Domaini645 – 69854LRRCTAdd
    BLAST
    Domaini754 – 896143TIRPROSITE-ProRule annotationAdd
    BLAST

    Domaini

    ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.

    Sequence similaritiesi

    Belongs to the Toll-like receptor family.Curated
    Contains 22 LRR (leucine-rich) repeats.Curated
    Contains 1 LRRCT domain.Curated
    Contains 1 LRRNT domain.Curated
    Contains 1 TIR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG4886.
    HOGENOMiHOG000251618.
    HOVERGENiHBG023181.
    InParanoidiO15455.
    KOiK05401.
    OMAiIANINDD.
    OrthoDBiEOG79SDZG.
    PhylomeDBiO15455.
    TreeFamiTF325595.

    Family and domain databases

    Gene3Di3.40.50.10140. 1 hit.
    InterProiIPR000483. Cys-rich_flank_reg_C.
    IPR001611. Leu-rich_rpt.
    IPR003591. Leu-rich_rpt_typical-subtyp.
    IPR000372. LRR-contain_N.
    IPR000157. TIR_dom.
    IPR027173. TLR3.
    [Graphical view]
    PANTHERiPTHR24365:SF5. PTHR24365:SF5. 1 hit.
    PfamiPF13855. LRR_8. 6 hits.
    PF01582. TIR. 1 hit.
    [Graphical view]
    SMARTiSM00369. LRR_TYP. 2 hits.
    SM00082. LRRCT. 1 hit.
    SM00013. LRRNT. 1 hit.
    SM00255. TIR. 1 hit.
    [Graphical view]
    SUPFAMiSSF52200. SSF52200. 1 hit.
    PROSITEiPS51450. LRR. 19 hits.
    PS50104. TIR. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O15455-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP    50
    TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM 100
    LKVLNLQHNE LSQLSDKTFA FCTNLTELHL MSNSIQKIKN NPFVKQKNLI 150
    TLDLSHNGLS STKLGTQVQL ENLQELLLSN NKIQALKSEE LDIFANSSLK 200
    KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK LCLELANTSI 250
    RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL 300
    EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS 350
    FQWLKCLEHL NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET 400
    FVSLAHSPLH ILNLTKNKIS KIESDAFSWL GHLEVLDLGL NEIGQELTGQ 450
    EWRGLENIFE IYLSYNKYLQ LTRNSFALVP SLQRLMLRRV ALKNVDSSPS 500
    PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN NLARLWKHAN 550
    PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT 600
    LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT 650
    CESIAWFVNW INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA 700
    PFELFFMINT SILLIFIFIV LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ 750
    TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE DQSLKFCLEE RDFEAGVFEL 800
    EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI EQNLDSIILV 850
    FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK 900
    NSVH 904
    Length:904
    Mass (Da):103,829
    Last modified:January 1, 1998 - v1
    Checksum:i034E05ECA7A4D2F7
    GO
    Isoform 2 (identifier: O15455-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-277: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:627
    Mass (Da):72,937
    Checksum:i0D376D88306EBEFC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti290 – 2901G → R in BAG36884. (PubMed:14702039)Curated
    Sequence conflicti575 – 5751D → N in AAH94737. (PubMed:15489334)Curated
    Sequence conflicti605 – 6051V → A in BAG36884. (PubMed:14702039)Curated
    Sequence conflicti663 – 6631E → G in BAG36884. (PubMed:14702039)Curated

    Polymorphismi

    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.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti284 – 2841N → I.
    Corresponds to variant rs5743316 [ dbSNP | Ensembl ].
    VAR_052361
    Natural varianti307 – 3071Y → D.
    Corresponds to variant rs5743317 [ dbSNP | Ensembl ].
    VAR_052362
    Natural varianti412 – 4121L → F.4 Publications
    Corresponds to variant rs3775291 [ dbSNP | Ensembl ].
    VAR_021976
    Natural varianti554 – 5541P → S in HSE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. 1 Publication
    VAR_054887
    Natural varianti737 – 7371S → T.
    Corresponds to variant rs5743318 [ dbSNP | Ensembl ].
    VAR_024664

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 277277Missing in isoform 2. 1 PublicationVSP_054188Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U88879 mRNA. Translation: AAC34134.1.
    DQ445682 mRNA. Translation: ABE01399.1.
    AB445631 mRNA. Translation: BAG55028.1.
    DQ360814 Genomic DNA. Translation: ABC86908.1.
    DQ360815 Genomic DNA. Translation: ABC86909.1.
    DQ360816 Genomic DNA. Translation: ABC86910.1.
    AK302143 mRNA. Translation: BAH13636.1.
    AK314208 mRNA. Translation: BAG36884.1.
    AC104070 Genomic DNA. No translation available.
    CH471056 Genomic DNA. Translation: EAX04628.1.
    BC094737 mRNA. Translation: AAH94737.1.
    BC096333 mRNA. Translation: AAH96333.1.
    BC096334 mRNA. Translation: AAH96334.1.
    BC096335 mRNA. Translation: AAH96335.1.
    CCDSiCCDS3846.1. [O15455-1]
    RefSeqiNP_003256.1. NM_003265.2. [O15455-1]
    XP_006714357.1. XM_006714294.1. [O15455-1]
    UniGeneiHs.657724.

    Genome annotation databases

    EnsembliENST00000296795; ENSP00000296795; ENSG00000164342. [O15455-1]
    ENST00000504367; ENSP00000423684; ENSG00000164342. [O15455-2]
    GeneIDi7098.
    KEGGihsa:7098.
    UCSCiuc003iyq.3. human. [O15455-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    TLR3base

    TLR3 mutation db

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U88879 mRNA. Translation: AAC34134.1 .
    DQ445682 mRNA. Translation: ABE01399.1 .
    AB445631 mRNA. Translation: BAG55028.1 .
    DQ360814 Genomic DNA. Translation: ABC86908.1 .
    DQ360815 Genomic DNA. Translation: ABC86909.1 .
    DQ360816 Genomic DNA. Translation: ABC86910.1 .
    AK302143 mRNA. Translation: BAH13636.1 .
    AK314208 mRNA. Translation: BAG36884.1 .
    AC104070 Genomic DNA. No translation available.
    CH471056 Genomic DNA. Translation: EAX04628.1 .
    BC094737 mRNA. Translation: AAH94737.1 .
    BC096333 mRNA. Translation: AAH96333.1 .
    BC096334 mRNA. Translation: AAH96334.1 .
    BC096335 mRNA. Translation: AAH96335.1 .
    CCDSi CCDS3846.1. [O15455-1 ]
    RefSeqi NP_003256.1. NM_003265.2. [O15455-1 ]
    XP_006714357.1. XM_006714294.1. [O15455-1 ]
    UniGenei Hs.657724.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1ZIW X-ray 2.10 A 27-700 [» ]
    2A0Z X-ray 2.40 A 22-703 [» ]
    3ULU X-ray 3.52 A 22-702 [» ]
    3ULV X-ray 3.52 A 22-702 [» ]
    ProteinModelPortali O15455.
    SMRi O15455. Positions 26-897.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112953. 15 interactions.
    DIPi DIP-29660N.
    IntActi O15455. 6 interactions.
    MINTi MINT-2840066.
    STRINGi 9606.ENSP00000296795.

    Chemistry

    ChEMBLi CHEMBL1075113.
    GuidetoPHARMACOLOGYi 1753.

    PTM databases

    PhosphoSitei O15455.

    Proteomic databases

    MaxQBi O15455.
    PaxDbi O15455.
    PRIDEi O15455.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296795 ; ENSP00000296795 ; ENSG00000164342 . [O15455-1 ]
    ENST00000504367 ; ENSP00000423684 ; ENSG00000164342 . [O15455-2 ]
    GeneIDi 7098.
    KEGGi hsa:7098.
    UCSCi uc003iyq.3. human. [O15455-1 ]

    Organism-specific databases

    CTDi 7098.
    GeneCardsi GC04P186990.
    HGNCi HGNC:11849. TLR3.
    HPAi CAB025658.
    MIMi 603029. gene.
    613002. phenotype.
    neXtProti NX_O15455.
    Orphaneti 1930. Herpetic encephalitis.
    PharmGKBi PA36551.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG4886.
    HOGENOMi HOG000251618.
    HOVERGENi HBG023181.
    InParanoidi O15455.
    KOi K05401.
    OMAi IANINDD.
    OrthoDBi EOG79SDZG.
    PhylomeDBi O15455.
    TreeFami TF325595.

    Enzyme and pathway databases

    Reactomei REACT_118563. RIP-mediated NFkB activation via ZBP1.
    REACT_118632. Trafficking and processing of endosomal TLR.
    REACT_150361. TRIF-mediated programmed cell death.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_6783. Toll Like Receptor 3 (TLR3) Cascade.
    SignaLinki O15455.

    Miscellaneous databases

    EvolutionaryTracei O15455.
    GeneWikii TLR_3.
    GenomeRNAii 7098.
    NextBioi 27769.
    PROi O15455.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15455.
    Bgeei O15455.
    CleanExi HS_TLR3.
    Genevestigatori O15455.

    Family and domain databases

    Gene3Di 3.40.50.10140. 1 hit.
    InterProi IPR000483. Cys-rich_flank_reg_C.
    IPR001611. Leu-rich_rpt.
    IPR003591. Leu-rich_rpt_typical-subtyp.
    IPR000372. LRR-contain_N.
    IPR000157. TIR_dom.
    IPR027173. TLR3.
    [Graphical view ]
    PANTHERi PTHR24365:SF5. PTHR24365:SF5. 1 hit.
    Pfami PF13855. LRR_8. 6 hits.
    PF01582. TIR. 1 hit.
    [Graphical view ]
    SMARTi SM00369. LRR_TYP. 2 hits.
    SM00082. LRRCT. 1 hit.
    SM00013. LRRNT. 1 hit.
    SM00255. TIR. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52200. SSF52200. 1 hit.
    PROSITEi PS51450. LRR. 19 hits.
    PS50104. TIR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A family of human receptors structurally related to Drosophila Toll."
      Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.
      Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA."
      Lafon M., Megret F., Lafage M., Prehaud C.
      J. Mol. Neurosci. 29:185-194(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
      Tissue: Neuron.
    3. "Natural selection in the TLR-related genes in the course of primate evolution."
      Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
      Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "TLR polymorphism."
      Macquin C., Bahram S.
      Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-412.
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT PHE-412.
      Tissue: Testis and Thymus.
    6. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Placenta.
    9. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 24-38.
    10. "A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling."
      Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., Akira S.
      J. Immunol. 169:6668-6672(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TICAM1.
    11. "TICAM-1, an adapter molecule that participates in Toll-like receptor 3 mediated interferon-beta induction."
      Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T.
      Nat. Immunol. 4:161-167(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TICAM1.
      Tissue: Lung.
    12. "Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH."
      de Bouteiller O., Merck E., Hasan U.A., Hubac S., Benguigui B., Trinchieri G., Bates E.E., Caux C.
      J. Biol. Chem. 280:38133-38145(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-95; CYS-122; ASN-196 AND ASN-247.
    13. "Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling."
      Johnsen I.B., Nguyen T.T., Ringdal M., Tryggestad A.M., Bakke O., Lien E., Espevik T., Anthonsen M.W.
      EMBO J. 25:3335-3346(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SRC.
    14. Cited for: FUNCTION, MUTAGENESIS OF HIS-539 AND ASN-541.
    15. "Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activation."
      Sarkar S.N., Elco C.P., Peters K.L., Chattopadhyay S., Sen G.C.
      J. Biol. Chem. 282:3423-3427(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-759 AND TYR-858, FUNCTION, MUTAGENESIS OF TYR-759.
    16. Cited for: FUNCTION, DOUBLE-STRANDED RNA-BINDING, HOMODIMERIZATION.
    17. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-52 AND ASN-57.
      Tissue: Liver.
    18. Cited for: FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, INTERACTION WITH UNC93B1.
    19. "The molecular structure of the Toll-like receptor 3 ligand-binding domain."
      Bell J.K., Botos I., Hall P.R., Askins J., Shiloach J., Segal D.M., Davies D.R.
      Proc. Natl. Acad. Sci. U.S.A. 102:10976-10980(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 22-703, FUNCTION, DISULFIDE BONDS, SUBUNIT, GLYCOSYLATION AT ASN-52; ASN-70; ASN-196; ASN-252; ASN-265; ASN-275; ASN-291; ASN-398; ASN-413; ASN-507 AND ASN-636, IDENTIFICATION BY MASS SPECTROMETRY.
    20. "Crystal structure of human toll-like receptor 3 (TLR3) ectodomain."
      Choe J., Kelker M.S., Wilson I.A.
      Science 309:581-585(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-700, DISULFIDE BONDS, GLYCOSYLATION AT ASN-124; ASN-252; ASN-275; ASN-291; ASN-398; ASN-413 AND ASN-507.
    21. Cited for: X-RAY CRYSTALLOGRAPHY (3.52 ANGSTROMS) OF 22-702 IN COMPLEX WITH ANTIBODY, DISULFIDE BONDS, SUBUNIT, DS-RNA BINDING REGIONS, GLYCOSYLATION AT ASN-52; ASN-70; ASN-124; ASN-247; ASN-252; ASN-265; ASN-275; ASN-291; ASN-398; ASN-413 AND ASN-507.
    22. Cited for: VARIANT HSE2 SER-554.
    23. Cited for: VARIANT PHE-412.
    24. Cited for: VARIANT PHE-412.

    Entry informationi

    Entry nameiTLR3_HUMAN
    AccessioniPrimary (citable) accession number: O15455
    Secondary accession number(s): B2RAI7
    , B7Z7K0, E6Y0F0, E6Y0F1, E9PGH4, Q4VAL2, Q504W0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 31, 2002
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 148 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3