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   24-JAN-2024, entry version 174.
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.ENSMUSP00000142500; -.
DR   ChEMBL; CHEMBL2146338; -.
DR   GlyCosmos; Q9EPQ1; 9 sites, No reported glycans.
DR   GlyGen; Q9EPQ1; 9 sites.
DR   iPTMnet; Q9EPQ1; -.
DR   PhosphoSitePlus; Q9EPQ1; -.
DR   MaxQB; Q9EPQ1; -.
DR   PaxDb; 10090-ENSMUSP00000060793; -.
DR   ProteomicsDB; 259206; -.
DR   Antibodypedia; 10459; 737 antibodies from 43 providers.
DR   DNASU; 21897; -.
DR   Ensembl; ENSMUST00000059349.6; ENSMUSP00000060793.5; ENSMUSG00000044827.11.
DR   Ensembl; ENSMUST00000197315.5; ENSMUSP00000142500.2; ENSMUSG00000044827.11.
DR   GeneID; 21897; -.
DR   KEGG; mmu:21897; -.
DR   UCSC; uc008xmw.2; mouse.
DR   AGR; MGI:1341295; -.
DR   CTD; 7096; -.
DR   MGI; MGI:1341295; Tlr1.
DR   VEuPathDB; HostDB:ENSMUSG00000044827; -.
DR   eggNOG; KOG4641; Eukaryota.
DR   GeneTree; ENSGT00940000162884; -.
DR   InParanoid; Q9EPQ1; -.
DR   OMA; YKIFSNM; -.
DR   OrthoDB; 21383at2759; -.
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 77 CRISPR screens.
DR   PRO; PR:Q9EPQ1; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q9EPQ1; Protein.
DR   Bgee; ENSMUSG00000044827; Expressed in peripheral lymph node and 99 other cell types or tissues.
DR   ExpressionAtlas; Q9EPQ1; baseline and differential.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
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; ISO:MGI.
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: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:0001774; P:microglial cell activation; ISO:MGI.
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:0032493; P:response to bacterial lipoprotein; ISO:MGI.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI.
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; 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; IPR017241; Toll-like_receptor.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR24365; TOLL-LIKE RECEPTOR; 1.
DR   PANTHER; PTHR24365:SF261; TOLL-LIKE RECEPTOR 1; 1.
DR   Pfam; PF13855; LRR_8; 1.
DR   Pfam; PF01463; LRRCT; 1.
DR   Pfam; PF01582; TIR; 1.
DR   PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR   PRINTS; PR01537; INTRLKN1R1F.
DR   SMART; SM00365; LRR_SD22; 4.
DR   SMART; SM00369; LRR_TYP; 6.
DR   SMART; SM00082; LRRCT; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR   PROSITE; PS51450; LRR; 10.
DR   PROSITE; PS50104; TIR; 1.
DR   Genevisible; Q9EPQ1; MM.
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
//