TLR3_HUMAN » Toll-like receptor 3

TLR3_HUMAN » Toll-like receptor 3
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Topology in Endosome membrane
Topologyendosome lumenal side
cytoplasmic side
TLR3_HUMAN » Toll-like receptor 3 »
Hydrophobic Thickness 34.4 ± 1.0 Å
Tilt Angle 0 ± 0°
ΔGtransfer -55.9 kcal/mol
ΔGfold -22.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology Out
TM Segments 701-726 (701-729)
Pathways

Hepatitis B (KEGG)

Hepatitis C (KEGG)

Herpes simplex infection (KEGG)

Immune System (Reactome)

Influenza A (KEGG)

Toll-like receptor signaling pathway (KEGG)

PDB 2a0z (22-703), 1ziw (27-700), 2mka (A/B/C=698-730), 2mk9 (A/B=698-730), 3ulu (A=22-702), 3ulv (A=22-702)
OPM 2mk9, 2mka
Complexes

TLR3:TLR3_HUMAN

Interactions

TLR3, Complex: Transmembrane homodimer of toll-like receptor 3, PDBID: 2MK9

TMED7, Complex: TLR3:TMED7, PubMed

TRIL, Complex: TRIL:TLR3, PubMed

Domains

AA: 51-111, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine rich repeat

AA: 195-210, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine Rich repeat

AA: 248-302, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine rich repeat

AA: 274-332, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine rich repeat

AA: 504-520, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine Rich repeat

AA: 562-622, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine rich repeat

AA: 586-647, PDBID: 1ZIW, Subunit A, Seq Identity:100%, Leucine rich repeat

AA: 755-897, PDBID: 2J67, Subunit B, Seq Identity:32%, TIR domain

UniProt annotation for TLR3_HUMAN » Toll-like receptor 3
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.

SUBUNIT: 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.

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.

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

DISEASE: Herpes simplex encephalitis 2 (HSE2) OMIM: 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. 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.

UniProt features for TLR3_HUMAN » Toll-like receptor 3
SIGNAL 1 23
CHAIN 24 904 Toll-like receptor 3.
DOMAIN 24 51 LRRNT.
REPEAT 52 73 LRR 1.
REPEAT 76 97 LRR 2.
REPEAT 100 121 LRR 3.
REPEAT 124 145 LRR 4.
REPEAT 148 168 LRR 5.
REPEAT 172 193 LRR 6.
REPEAT 198 219 LRR 7.
REPEAT 222 244 LRR 8.
REPEAT 249 270 LRR 9.
REPEAT 275 296 LRR 10.
REPEAT 299 320 LRR 11.
REPEAT 323 344 LRR 12.
REPEAT 356 377 LRR 13.
REPEAT 380 400 LRR 14.
REPEAT 408 429 LRR 15.
REPEAT 432 454 LRR 16.
REPEAT 465 486 LRR 17.
REPEAT 507 528 LRR 18.
REPEAT 531 552 LRR 19.
REPEAT 563 584 LRR 20.
REPEAT 587 608 LRR 21.
REPEAT 611 632 LRR 22.
DOMAIN 645 698 LRRCT.
DOMAIN 754 896 TIR.
DISULFID 28 37
DISULFID 95 122
DISULFID 649 677
DISULFID 651 696
Amino Acid Sequence for TLR3_HUMAN » Toll-like receptor 3
MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM LKVLNLQHNE LSQLSDKTFA FCTNLTELHL MSNSIQKIKN NPFVKQKNLI TLDLSHNGLS STKLGTQVQL ENLQELLLSN NKIQALKSEE LDIFANSSLK KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK LCLELANTSI RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS FQWLKCLEHL NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET FVSLAHSPLH ILNLTKNKIS KIESDAFSWL GHLEVLDLGL NEIGQELTGQ EWRGLENIFE IYLSYNKYLQ LTRNSFALVP SLQRLMLRRV ALKNVDSSPS PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN NLARLWKHAN PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT CESIAWFVNW INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA PFELFFMINT SILLIFIFIV LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE DQSLKFCLEE RDFEAGVFEL EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI EQNLDSIILV FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK NSVH