ID TLR8_MOUSE Reviewed; 1032 AA.
AC P58682; A2AHI9; Q91XI7;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 24-JAN-2024, entry version 177.
DE RecName: Full=Toll-like receptor 8;
DE AltName: CD_antigen=CD288;
DE Flags: Precursor;
GN Name=Tlr8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RA Heil F.J., Lipford G.B., Wagner H., Bauer S.M.;
RT "Molecular cloning of murine Toll-like receptor 8.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH UNC93B1.
RX PubMed=19451267; DOI=10.1084/jem.20082316;
RA Fukui R., Saitoh S., Matsumoto F., Kozuka-Hata H., Oyama M., Tabeta K.,
RA Beutler B., Miyake K.;
RT "Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic
RT cells toward DNA- but against RNA-sensing.";
RL J. Exp. Med. 206:1339-1350(2009).
RN [5]
RP INTERACTION WITH SMPDL3B.
RX PubMed=26095358; DOI=10.1016/j.celrep.2015.05.006;
RA Heinz L.X., Baumann C.L., Koeberlin M.S., Snijder B., Gawish R., Shui G.,
RA Sharif O., Aspalter I.M., Mueller A.C., Kandasamy R.K., Breitwieser F.P.,
RA Pichlmair A., Bruckner M., Rebsamen M., Blueml S., Karonitsch T.,
RA Fauster A., Colinge J., Bennett K.L., Knapp S., Wenk M.R.,
RA Superti-Furga G.;
RT "The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity.";
RL Cell Rep. 11:1919-1928(2015).
CC -!- FUNCTION: Endosomal receptor that plays a key role in innate and
CC adaptive immunity. Controls host immune response against pathogens
CC through recognition of RNA degradation products specific to
CC microorganisms that are initially processed by RNASET2. Upon binding to
CC agonists, undergoes dimerization that brings TIR domains from the two
CC molecules into direct contact, leading to the recruitment of TIR-
CC containing downstream adapter MYD88 through homotypic interaction. In
CC turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1,
CC TRAF6, TRAF3 leading to activation of downstream transcription factors
CC NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and
CC interferons, respectively. {ECO:0000250|UniProtKB:Q9NR97}.
CC -!- ACTIVITY REGULATION: Activated by RNAs having enough uridines.
CC {ECO:0000250|UniProtKB:Q9NR97}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with MYD88 via their
CC respective TIR domains (Probable). Interacts with UNC93B1
CC (PubMed:19451267). Interacts with BTK (By similarity). Interacts with
CC SMPDL3B (PubMed:26095358). {ECO:0000250|UniProtKB:Q9NR97,
CC ECO:0000269|PubMed:19451267, ECO:0000269|PubMed:26095358, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q9NR97};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q9NR97}.
CC Note=Endosomal localization confers distinctive proteolytic processing.
CC {ECO:0000250|UniProtKB:Q9NR97}.
CC -!- PTM: Ubiquitinated by RNF216; leading to degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q9NR97}.
CC -!- PTM: Proteolytic processing occurs in monocytes and monocyte-derived
CC macrophages by both furin-like proprotein convertase and cathepsins.
CC The cleavage is necessary for dimer formation and subsequent
CC activation. {ECO:0000250|UniProtKB:Q9NR97}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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DR EMBL; AY035890; AAK62677.1; -; mRNA.
DR EMBL; AL731735; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132054; AAI32055.1; -; mRNA.
DR CCDS; CCDS41209.1; -.
DR RefSeq; NP_001300689.1; NM_001313760.1.
DR RefSeq; NP_001300690.1; NM_001313761.1.
DR RefSeq; NP_573475.2; NM_133212.3.
DR AlphaFoldDB; P58682; -.
DR SMR; P58682; -.
DR BioGRID; 228410; 2.
DR IntAct; P58682; 2.
DR STRING; 10090.ENSMUSP00000107793; -.
DR ChEMBL; CHEMBL2146339; -.
DR GlyCosmos; P58682; 21 sites, No reported glycans.
DR GlyGen; P58682; 22 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P58682; -.
DR PhosphoSitePlus; P58682; -.
DR MaxQB; P58682; -.
DR PaxDb; 10090-ENSMUSP00000107793; -.
DR PeptideAtlas; P58682; -.
DR ProteomicsDB; 258896; -.
DR Antibodypedia; 458; 928 antibodies from 43 providers.
DR DNASU; 170744; -.
DR Ensembl; ENSMUST00000049023.3; ENSMUSP00000036762.3; ENSMUSG00000040522.6.
DR Ensembl; ENSMUST00000112170.2; ENSMUSP00000107793.2; ENSMUSG00000040522.6.
DR GeneID; 170744; -.
DR KEGG; mmu:170744; -.
DR UCSC; uc009uwy.1; mouse.
DR AGR; MGI:2176887; -.
DR CTD; 51311; -.
DR MGI; MGI:2176887; Tlr8.
DR VEuPathDB; HostDB:ENSMUSG00000040522; -.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000160879; -.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; P58682; -.
DR OMA; LSWNCYF; -.
DR OrthoDB; 5356114at2759; -.
DR PhylomeDB; P58682; -.
DR TreeFam; TF351113; -.
DR Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR BioGRID-ORCS; 170744; 2 hits in 77 CRISPR screens.
DR ChiTaRS; Tlr8; mouse.
DR PRO; PR:P58682; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P58682; Protein.
DR Bgee; ENSMUSG00000040522; Expressed in granulocyte and 31 other cell types or tissues.
DR ExpressionAtlas; P58682; baseline and differential.
DR Genevisible; P58682; MM.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0038187; F:pattern recognition receptor activity; IBA:GO_Central.
DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; ISO:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; ISO:MGI.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of type II interferon production; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0009615; P:response to virus; ISO:MGI.
DR GO; GO:0034158; P:toll-like receptor 8 signaling pathway; ISS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR026906; LRR_5.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR47410; TOLL-LIKE RECEPTOR 7-RELATED; 1.
DR PANTHER; PTHR47410:SF1; TOLL-LIKE RECEPTOR 8; 1.
DR Pfam; PF13306; LRR_5; 1.
DR Pfam; PF13855; LRR_8; 4.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00365; LRR_SD22; 7.
DR SMART; SM00369; LRR_TYP; 13.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52058; L domain-like; 1.
DR SUPFAM; SSF52047; RNI-like; 1.
DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR PROSITE; PS51450; LRR; 22.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Endosome; Glycoprotein; Immunity; Inflammatory response;
KW Innate immunity; Leucine-rich repeat; Membrane; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1032
FT /note="Toll-like receptor 8"
FT /id="PRO_0000034736"
FT TOPO_DOM 24..818
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 819..839
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 840..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 41..61
FT /note="LRR 1"
FT REPEAT 62..85
FT /note="LRR 2"
FT REPEAT 87..109
FT /note="LRR 3"
FT REPEAT 120..143
FT /note="LRR 4"
FT REPEAT 145..165
FT /note="LRR 5"
FT REPEAT 166..194
FT /note="LRR 6"
FT REPEAT 195..218
FT /note="LRR 7"
FT REPEAT 220..239
FT /note="LRR 8"
FT REPEAT 240..267
FT /note="LRR 9"
FT REPEAT 281..304
FT /note="LRR 10"
FT REPEAT 306..329
FT /note="LRR 11"
FT REPEAT 331..360
FT /note="LRR 12"
FT REPEAT 361..384
FT /note="LRR 13"
FT REPEAT 388..411
FT /note="LRR 14"
FT REPEAT 413..436
FT /note="LRR 15"
FT REPEAT 471..494
FT /note="LRR 16"
FT REPEAT 520..543
FT /note="LRR 17"
FT REPEAT 545..572
FT /note="LRR 18"
FT REPEAT 574..598
FT /note="LRR 19"
FT REPEAT 600..621
FT /note="LRR 20"
FT REPEAT 629..652
FT /note="LRR 21"
FT REPEAT 654..677
FT /note="LRR 22"
FT REPEAT 678..701
FT /note="LRR 23"
FT REPEAT 702..725
FT /note="LRR 24"
FT REPEAT 727..749
FT /note="LRR 25"
FT REPEAT 752..776
FT /note="LRR 26"
FT DOMAIN 869..1013
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 411
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 502
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 581
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 671
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 743
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 754
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 783
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..49
FT /evidence="ECO:0000250"
FT DISULFID 177..181
FT /evidence="ECO:0000250"
FT DISULFID 252..265
FT /evidence="ECO:0000250"
FT DISULFID 255..262
FT /evidence="ECO:0000250"
FT DISULFID 470..500
FT /evidence="ECO:0000250"
FT CONFLICT 613
FT /note="R -> H (in Ref. 1; AAK62677)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1032 AA; 119358 MW; CA192552F08E33EA CRC64;
MENMPPQSWI LTCFCLLSSG TSAIFHKANY SRSYPCDEIR HNSLVIAECN HRQLHEVPQT
IGKYVTNIDL SDNAITHITK ESFQKLQNLT KIDLNHNAKQ QHPNENKNGM NITEGALLSL
RNLTVLLLED NQLYTIPAGL PESLKELSLI QNNIFQVTKN NTFGLRNLER LYLGWNCYFK
CNQTFKVEDG AFKNLIHLKV LSLSFNNLFY VPPKLPSSLR KLFLSNAKIM NITQEDFKGL
ENLTLLDLSG NCPRCYNAPF PCTPCKENSS IHIHPLAFQS LTQLLYLNLS STSLRTIPST
WFENLSNLKE LHLEFNYLVQ EIASGAFLTK LPSLQILDLS FNFQYKEYLQ FINISSNFSK
LRSLKKLHLR GYVFRELKKK HFEHLQSLPN LATINLGINF IEKIDFKAFQ NFSKLDVIYL
SGNRIASVLD GTDYSSWRNR LRKPLSTDDD EFDPHVNFYH STKPLIKPQC TAYGKALDLS
LNNIFIIGKS QFEGFQDIAC LNLSFNANTQ VFNGTEFSSM PHIKYLDLTN NRLDFDDNNA
FSDLHDLEVL DLSHNAHYFS IAGVTHRLGF IQNLINLRVL NLSHNGIYTL TEESELKSIS
LKELVFSGNR LDRLWNANDG KYWSIFKSLQ NLIRLDLSYN NLQQIPNGAF LNLPQSLQEL
LISGNKLRFF NWTLLQYFPH LHLLDLSRNE LYFLPNCLSK FAHSLETLLL SHNHFSHLPS
GFLSEARNLV HLDLSFNTIK MINKSSLQTK MKTNLSILEL HGNYFDCTCD ISDFRSWLDE
NLNITIPKLV NVICSNPGDQ KSKSIMSLDL TTCVSDTTAA VLFFLTFLTT SMVMLAALVH
HLFYWDVWFI YHMCSAKLKG YRTSSTSQTF YDAYISYDTK DASVTDWVIN ELRYHLEESE
DKSVLLCLEE RDWDPGLPII DNLMQSINQS KKTIFVLTKK YAKSWNFKTA FYLALQRLMD
ENMDVIIFIL LEPVLQYSQY LRLRQRICKS SILQWPNNPK AENLFWQSLK NVVLTENDSR
YDDLYIDSIR QY
//
