TLR1_MOUSE
ID TLR1_MOUSE Reviewed; 795 AA.
AC Q9EPQ1; Q9EPW5;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Toll-like receptor 1;
DE AltName: Full=Toll/interleukin-1 receptor-like protein;
DE Short=TIL;
DE AltName: CD_antigen=CD281;
DE Flags: Precursor;
GN Name=Tlr1;
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], AND SUBCELLULAR LOCATION.
RC STRAIN=BALB/cJ; TISSUE=Macrophage;
RX PubMed=11095740; DOI=10.1073/pnas.250476497;
RA Ozinsky A., Underhill D.M., Fontenot J.D., Hajjar A.M., Smith K.D.,
RA Wilson C.B., Schroeder L., Aderem A.;
RT "The repertoire for pattern recognition of pathogens by the innate immune
RT system is defined by cooperation between Toll-like receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13766-13771(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=11123271; DOI=10.4049/jimmunol.166.1.15;
RA Hajjar A.M., O'Mahony D.S., Ozinsky A., Underhill D.M., Aderem A.,
RA Klebanoff S.J., Wilson C.B.;
RT "Functional interactions between Toll-like receptor (TLR) 2 and TLR1 or
RT TLR6 in response to phenol-soluble modulin.";
RL J. Immunol. 166:15-19(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RA Thomson D.P., Campbell C.C., Liew F.Y., Xu D.;
RT "Cloning of Mus musculus Toll-like receptor 1.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 681-692, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP INTERACTION WITH CNPY3, AND SUBCELLULAR LOCATION.
RX PubMed=17998391; DOI=10.1084/jem.20071132;
RA Takahashi K., Shibata T., Akashi-Takamura S., Kiyokawa T., Wakabayashi Y.,
RA Tanimura N., Kobayashi T., Matsumoto F., Fukui R., Kouro T., Nagai Y.,
RA Takatsu K., Saitoh S., Miyake K.;
RT "A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required
RT for TLR-dependent immune responses.";
RL J. Exp. Med. 204:2963-2976(2007).
RN [6]
RP FUNCTION.
RC TISSUE=Macrophage;
RX PubMed=19362712; DOI=10.1016/j.cellimm.2009.03.008;
RA Drage M.G., Pecora N.D., Hise A.G., Febbraio M., Silverstein R.L.,
RA Golenbock D.T., Boom W.H., Harding C.V.;
RT "TLR2 and its co-receptors determine responses of macrophages and dendritic
RT cells to lipoproteins of Mycobacterium tuberculosis.";
RL Cell. Immunol. 258:29-37(2009).
CC -!- FUNCTION: Participates in the innate immune response to microbial
CC agents. Specifically recognizes diacylated and triacylated
CC lipopeptides. Cooperates with TLR2 to mediate the innate immune
CC response to bacterial lipoproteins or lipopeptides. Forms the
CC activation cluster TLR2:TLR1:CD14 in response to triacylated
CC lipopeptides, this cluster triggers signaling from the cell surface and
CC subsequently is targeted to the Golgi in a lipid-raft dependent
CC pathway. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation,
CC cytokine secretion and the inflammatory response (By similarity). Acts
CC as a coreceptor for M.tuberculosis lipoproteins LprG, LpqH and PhoS1
CC (pstS1), in conjunction with TLR2 and for some but not all lipoproteins
CC CD14 and/or CD36. The lipoproteins act as agonists to modulate antigen
CC presenting cell functions in response to the pathogen
CC (PubMed:19362712). {ECO:0000250|UniProtKB:Q15399,
CC ECO:0000269|PubMed:19362712}.
CC -!- SUBUNIT: Interacts (via extracellular domain) with TLR2. TLR2 seems to
CC exist in heterodimers with either TLR1 or TLR6 before stimulation by
CC the ligand. The heterodimers form bigger oligomers in response to their
CC corresponding ligands as well as further heterotypic associations with
CC other receptors such as CD14 and/or CD36 (By similarity). Binds MYD88
CC (via TIR domain). Interacts with CNPY3 (PubMed:17998391).
CC {ECO:0000250|UniProtKB:Q15399, ECO:0000269|PubMed:17998391}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11095740,
CC ECO:0000269|PubMed:17998391}; Single-pass type I membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000269|PubMed:11095740}; Single-pass type I membrane protein
CC {ECO:0000255}. Membrane raft {ECO:0000250|UniProtKB:Q15399}. Golgi
CC apparatus {ECO:0000250|UniProtKB:Q15399}. Note=Does not reside in lipid
CC rafts before stimulation but accumulates increasingly in the raft upon
CC the presence of the microbial ligand. In response to triacylated
CC lipoproteins, TLR2:TLR1 heterodimers are recruited in lipid rafts, this
CC recruitment determine the intracellular targeting to the Golgi
CC apparatus. {ECO:0000250|UniProtKB:Q15399}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
CC -!- CAUTION: In some plant proteins and in human SARM1, the TIR domain has
CC NAD(+) hydrolase (NADase) activity (By similarity). However, despite
CC the presence of the catalytic Asp residue, the isolated TIR domain of
CC human TLR4 lacks NADase activity (By similarity). Based on this, it is
CC unlikely that Toll-like receptors have NADase activity.
CC {ECO:0000250|UniProtKB:O00206, ECO:0000305}.
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DR EMBL; AY009154; AAG37302.1; -; mRNA.
DR EMBL; AF316985; AAG35062.1; -; mRNA.
DR CCDS; CCDS19302.1; -.
DR RefSeq; NP_001263374.1; NM_001276445.1.
DR RefSeq; NP_109607.1; NM_030682.2.
DR RefSeq; XP_006503914.1; XM_006503851.2.
DR RefSeq; XP_006503915.1; XM_006503852.3.
DR RefSeq; XP_006503916.1; XM_006503853.1.
DR RefSeq; XP_006503917.1; XM_006503854.1.
DR RefSeq; XP_006503919.1; XM_006503856.1.
DR RefSeq; XP_011239022.1; XM_011240720.2.
DR AlphaFoldDB; Q9EPQ1; -.
DR SMR; Q9EPQ1; -.
DR BioGRID; 204223; 2.
DR IntAct; Q9EPQ1; 6.
DR STRING; 10090.ENSMUSP00000060793; -.
DR ChEMBL; CHEMBL2146338; -.
DR GlyGen; Q9EPQ1; 9 sites.
DR iPTMnet; Q9EPQ1; -.
DR PhosphoSitePlus; Q9EPQ1; -.
DR MaxQB; Q9EPQ1; -.
DR PaxDb; Q9EPQ1; -.
DR PRIDE; Q9EPQ1; -.
DR ProteomicsDB; 259206; -.
DR Antibodypedia; 10459; 677 antibodies from 43 providers.
DR DNASU; 21897; -.
DR Ensembl; ENSMUST00000059349; ENSMUSP00000060793; ENSMUSG00000044827.
DR Ensembl; ENSMUST00000197315; ENSMUSP00000142500; ENSMUSG00000044827.
DR GeneID; 21897; -.
DR KEGG; mmu:21897; -.
DR UCSC; uc008xmw.2; mouse.
DR CTD; 7096; -.
DR MGI; MGI:1341295; Tlr1.
DR VEuPathDB; HostDB:ENSMUSG00000044827; -.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000162884; -.
DR InParanoid; Q9EPQ1; -.
DR OMA; GTRMIHM; -.
DR OrthoDB; 282372at2759; -.
DR PhylomeDB; Q9EPQ1; -.
DR TreeFam; TF351113; -.
DR Reactome; R-MMU-1461957; Beta defensins.
DR Reactome; R-MMU-5686938; Regulation of TLR by endogenous ligand.
DR BioGRID-ORCS; 21897; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q9EPQ1; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9EPQ1; protein.
DR Bgee; ENSMUSG00000044827; Expressed in peripheral lymph node and 98 other tissues.
DR ExpressionAtlas; Q9EPQ1; baseline and differential.
DR Genevisible; Q9EPQ1; MM.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; NAS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0035354; C:Toll-like receptor 1-Toll-like receptor 2 protein complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0071723; F:lipopeptide binding; IBA:GO_Central.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0035663; F:Toll-like receptor 2 binding; ISO:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:UniProtKB.
DR GO; GO:0042497; F:triacyl lipopeptide binding; NAS:UniProtKB.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; NAS:UniProtKB.
DR GO; GO:0001775; P:cell activation; ISO:MGI.
DR GO; GO:0071221; P:cellular response to bacterial lipopeptide; IBA:GO_Central.
DR GO; GO:0071727; P:cellular response to triacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0006952; P:defense response; IMP:MGI.
DR GO; GO:0042495; P:detection of triacyl bacterial lipopeptide; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0042116; P:macrophage activation; NAS:UniProtKB.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0034130; P:toll-like receptor 1 signaling pathway; IEA:InterPro.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR027190; TLR1.
DR InterPro; IPR017241; Toll-like_receptor.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR24365; PTHR24365; 1.
DR PANTHER; PTHR24365:SF261; PTHR24365:SF261; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR SMART; SM00369; LRR_TYP; 6.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 10.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Immunity;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Membrane; NAD;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..795
FT /note="Toll-like receptor 1"
FT /id="PRO_0000034706"
FT TOPO_DOM 26..582
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 583..603
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 604..795
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 54..77
FT /note="LRR 1"
FT REPEAT 78..101
FT /note="LRR 2"
FT REPEAT 102..125
FT /note="LRR 3"
FT REPEAT 126..150
FT /note="LRR 4"
FT REPEAT 151..175
FT /note="LRR 5"
FT REPEAT 176..199
FT /note="LRR 6"
FT REPEAT 200..223
FT /note="LRR 7"
FT REPEAT 224..250
FT /note="LRR 8"
FT REPEAT 251..278
FT /note="LRR 9"
FT REPEAT 279..308
FT /note="LRR 10"
FT REPEAT 309..337
FT /note="LRR 11"
FT REPEAT 338..361
FT /note="LRR 12"
FT REPEAT 362..388
FT /note="LRR 13"
FT REPEAT 389..414
FT /note="LRR 14"
FT REPEAT 415..437
FT /note="LRR 15"
FT REPEAT 438..457
FT /note="LRR 16"
FT REPEAT 458..478
FT /note="LRR 17"
FT REPEAT 479..500
FT /note="LRR 18"
FT REPEAT 501..524
FT /note="LRR 19"
FT DOMAIN 524..579
FT /note="LRRCT"
FT DOMAIN 638..779
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 316..319
FT /note="Interaction with bacterial lipopeptide"
FT /evidence="ECO:0000250"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
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 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 113..135
FT /evidence="ECO:0000250"
FT DISULFID 226..233
FT /evidence="ECO:0000250"
FT DISULFID 346..371
FT /evidence="ECO:0000250"
FT DISULFID 422..445
FT /evidence="ECO:0000250"
FT CONFLICT 88
FT /note="N -> D (in Ref. 3; AAG35062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 795 AA; 90673 MW; 855356429872D232 CRC64;
MTKPNSLIFY CIIVLGLTLM KIQLSEECEL IIKRPNANLT RVPKDLPLQT TTLDLSQNNI
SELQTSDILS LSKLRVLIMS YNRLQYLNIS VFKFNTELEY LDLSHNELKV ILCHPTVSLK
HLDLSFNAFD ALPICKEFGN MSQLQFLGLS GSRVQSSSVQ LIAHLNISKV LLVLGDAYGE
KEDPESLRHV STETLHIVFP SKREFRFLLD VSVSTTIGLE LSNIKCVLED QGCSYFLRAL
SKLGKNLKLS NLTLNNVETT WNSFINILQI VWHTPVKYFS ISNVKLQGQL AFRMFNYSDT
SLKALSIHQV VTDVFSFPQS YIYSIFANMN IQNFTMSGTH MVHMLCPSQV SPFLHVDFTD
NLLTDMVFKD CRNLVRLKTL SLQKNQLKNL ENIILTSAKM TSLQKLDISQ NSLRYSDGGI
PCAWTQSLLV LNLSSNMLTG SVFRCLPPKV KVLDLHNNRI MSIPKDVTHL QALQELNVAS
NSLTDLPGCG AFSSLSVLVI DHNSVSHPSE DFFQSCQNIR SLTAGNNPFQ CTCELRDFVK
NIGWVAREVV EGWPDSYRCD YPESSRGTAL RDFHMSPLSC DTVLLTVTIG ATMLVLAVTG
AFLCLYFDLP WYVRMLCQWT QTRHRARHIP LEELQRNLQF HAFVSYSGHD SAWVKNELLP
NLEKDDIQIC LHERNFVPGK SIVENIINFI EKSYKSIFVL SPHFIQSEWC HYELYFAHHN
LFHEGSDNLI LILLAPIPQY SIPTNYHKLK TLMSRRTYLE WPTEKNKHGL FWANLRASIN
VKLVNQAEGT CYTQQ
