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Protein

Toll-like receptor 1

Gene

TLR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:21078852). Forms the activation cluster TLR2:TLR1:CD14 in response to triacylated lipopeptides, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (PubMed:16880211). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.2 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • lipopeptide binding Source: GO_Central
  • protein heterodimerization activity Source: MGI
  • signaling receptor activity Source: ProtInc
  • Toll-like receptor 2 binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-1461957 Beta defensins
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-5686938 Regulation of TLR by endogenous ligand

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 1
Alternative name(s):
Toll/interleukin-1 receptor-like protein
Short name:
TIL
CD_antigen: CD281
Gene namesi
Name:TLR1
Synonyms:KIAA0012
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000174125.7
HGNCiHGNC:11847 TLR1
MIMi601194 gene
neXtProtiNX_Q15399

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 580ExtracellularSequence analysisAdd BLAST556
Transmembranei581 – 601HelicalSequence analysisAdd BLAST21
Topological domaini602 – 786CytoplasmicSequence analysisAdd BLAST185

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi7096
MalaCardsiTLR1
MIMi613223 phenotype
OpenTargetsiENSG00000174125
PharmGKBiPA36549

Chemistry databases

ChEMBLiCHEMBL3885643

Polymorphism and mutation databases

BioMutaiTLR1
DMDMi146291086

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 241 PublicationAdd BLAST24
ChainiPRO_000003470525 – 786Toll-like receptor 1Add BLAST762

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi51N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi110 ↔ 1321 Publication
Glycosylationi137N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi163N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi223 ↔ 2301 Publication
Glycosylationi330N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi343 ↔ 3681 Publication
Disulfide bondi419 ↔ 4421 Publication
Glycosylationi429N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi578N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ15399
PaxDbiQ15399
PeptideAtlasiQ15399
PRIDEiQ15399
ProteomicsDBi60569

PTM databases

iPTMnetiQ15399
PhosphoSitePlusiQ15399

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in spleen, ovary, peripheral blood leukocytes, thymus and small intestine.

Gene expression databases

BgeeiENSG00000174125 Expressed in 152 organ(s), highest expression level in leukocyte
CleanExiHS_TLR1
ExpressionAtlasiQ15399 baseline and differential
GenevisibleiQ15399 HS

Interactioni

Subunit structurei

Interacts (via extracellular domain) with TLR2. TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand. The heterodimers form bigger oligomers in response to their corresponding ligands as well as further heterotypic associations with other receptors such as CD14 and/or CD36 (PubMed:16880211, PubMed:17889651). The activation cluster TLR2:TLR1:CD14 forms in response to triacylated lipopeptides (PubMed:16880211). Binds MYD88 (via TIR domain). Interacts with CNPY3 (By similarity).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112951, 13 interactors
IntActiQ15399, 6 interactors
STRINGi9606.ENSP00000354932

Structurei

Secondary structure

1786
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ15399
SMRiQ15399
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15399

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati54 – 77LRR 1Add BLAST24
Repeati78 – 101LRR 2Add BLAST24
Repeati102 – 125LRR 3Add BLAST24
Repeati126 – 150LRR 4Add BLAST25
Repeati151 – 175LRR 5Add BLAST25
Repeati176 – 199LRR 6Add BLAST24
Repeati200 – 223LRR 7Add BLAST24
Repeati224 – 250LRR 8Add BLAST27
Repeati251 – 278LRR 9Add BLAST28
Repeati279 – 308LRR 10Add BLAST30
Repeati309 – 337LRR 11Add BLAST29
Repeati338 – 361LRR 12Add BLAST24
Repeati362 – 388LRR 13Add BLAST27
Repeati389 – 414LRR 14Add BLAST26
Repeati415 – 437LRR 15Add BLAST23
Repeati438 – 457LRR 16Add BLAST20
Repeati458 – 478LRR 17Add BLAST21
Repeati479 – 500LRR 18Add BLAST22
Repeati501 – 524LRR 19Add BLAST24
Domaini525 – 579LRRCTAdd BLAST55
Domaini635 – 779TIRPROSITE-ProRule annotationAdd BLAST145

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni313 – 316Interaction with bacterial lipopeptide4

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119006
HOGENOMiHOG000008676
HOVERGENiHBG023180
InParanoidiQ15399
KOiK05398
OMAiNNIETTW
OrthoDBiEOG091G0356
PhylomeDBiQ15399
TreeFamiTF351113

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027190 TLR1
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR24365:SF261 PTHR24365:SF261, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
PF01463 LRRCT, 1 hit
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 4 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 10 hits
PS50104 TIR, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q15399-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTSIFHFAII FMLILQIRIQ LSEESEFLVD RSKNGLIHVP KDLSQKTTIL
60 70 80 90 100
NISQNYISEL WTSDILSLSK LRILIISHNR IQYLDISVFK FNQELEYLDL
110 120 130 140 150
SHNKLVKISC HPTVNLKHLD LSFNAFDALP ICKEFGNMSQ LKFLGLSTTH
160 170 180 190 200
LEKSSVLPIA HLNISKVLLV LGETYGEKED PEGLQDFNTE SLHIVFPTNK
210 220 230 240 250
EFHFILDVSV KTVANLELSN IKCVLEDNKC SYFLSILAKL QTNPKLSNLT
260 270 280 290 300
LNNIETTWNS FIRILQLVWH TTVWYFSISN VKLQGQLDFR DFDYSGTSLK
310 320 330 340 350
ALSIHQVVSD VFGFPQSYIY EIFSNMNIKN FTVSGTRMVH MLCPSKISPF
360 370 380 390 400
LHLDFSNNLL TDTVFENCGH LTELETLILQ MNQLKELSKI AEMTTQMKSL
410 420 430 440 450
QQLDISQNSV SYDEKKGDCS WTKSLLSLNM SSNILTDTIF RCLPPRIKVL
460 470 480 490 500
DLHSNKIKSI PKQVVKLEAL QELNVAFNSL TDLPGCGSFS SLSVLIIDHN
510 520 530 540 550
SVSHPSADFF QSCQKMRSIK AGDNPFQCTC ELGEFVKNID QVSSEVLEGW
560 570 580 590 600
PDSYKCDYPE SYRGTLLKDF HMSELSCNIT LLIVTIVATM LVLAVTVTSL
610 620 630 640 650
CSYLDLPWYL RMVCQWTQTR RRARNIPLEE LQRNLQFHAF ISYSGHDSFW
660 670 680 690 700
VKNELLPNLE KEGMQICLHE RNFVPGKSIV ENIITCIEKS YKSIFVLSPN
710 720 730 740 750
FVQSEWCHYE LYFAHHNLFH EGSNSLILIL LEPIPQYSIP SSYHKLKSLM
760 770 780
ARRTYLEWPK EKSKRGLFWA NLRAAINIKL TEQAKK
Length:786
Mass (Da):90,291
Last modified:May 1, 2007 - v3
Checksum:i1BFCCC5E42EA5242
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RAP2D6RAP2_HUMAN
Toll-like receptor 1
TLR1
161Annotation score:
D6RA99D6RA99_HUMAN
Toll-like receptor 1
TLR1
90Annotation score:
D6RCE8D6RCE8_HUMAN
Toll-like receptor 1
TLR1
48Annotation score:
D6RF68D6RF68_HUMAN
Toll-like receptor 1
TLR1
23Annotation score:

Sequence cautioni

The sequence BAA02801 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti182E → G in CAB43364 (PubMed:11230166).Curated1
Sequence conflicti228N → S in CAB43364 (PubMed:11230166).Curated1
Sequence conflicti276F → S in CAB43364 (PubMed:11230166).Curated1

Polymorphismi

Genetic variations in TLR1 may influence susceptibility to or protection against contracting leprosy and define the leprosy susceptibility locus 5 [MIMi:613223]. Ser-602 is a common allele in Caucasians. It is associated with impaired cell surface expression and receptor function resulting in protection against leprosy.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06634044S → P1 PublicationCorresponds to variant dbSNP:rs76600635Ensembl.1
Natural variantiVAR_06634175I → T1 PublicationCorresponds to variant dbSNP:rs137853170EnsemblClinVar.1
Natural variantiVAR_03191680R → T3 PublicationsCorresponds to variant dbSNP:rs5743611Ensembl.1
Natural variantiVAR_018474118H → Y1 PublicationCorresponds to variant dbSNP:rs5743612Ensembl.1
Natural variantiVAR_031917248N → S May confer susceptibility to leprosy. 4 PublicationsCorresponds to variant dbSNP:rs4833095EnsemblClinVar.1
Natural variantiVAR_031918305H → L1 PublicationCorresponds to variant dbSNP:rs3923647Ensembl.1
Natural variantiVAR_031919315P → L Severe impairment of activity. 1 PublicationCorresponds to variant dbSNP:rs5743613Ensembl.1
Natural variantiVAR_066342352H → N1 PublicationCorresponds to variant dbSNP:rs76796448Ensembl.1
Natural variantiVAR_066343460I → V1 PublicationCorresponds to variant dbSNP:rs137853171EnsemblClinVar.1
Natural variantiVAR_066344542V → A1 PublicationCorresponds to variant dbSNP:rs137853172EnsemblClinVar.1
Natural variantiVAR_066345554Y → C Severe impairment of activity. 1 PublicationCorresponds to variant dbSNP:rs137853173EnsemblClinVar.1
Natural variantiVAR_031920587V → G1 PublicationCorresponds to variant dbSNP:rs5743617Ensembl.1
Natural variantiVAR_031921602S → I Severe impairment of activity. 5 PublicationsCorresponds to variant dbSNP:rs5743618EnsemblClinVar.1
Natural variantiVAR_052358631L → R. Corresponds to variant dbSNP:rs5743619Ensembl.1
Natural variantiVAR_066346651V → A Severe impairment of activity. 1 PublicationCorresponds to variant dbSNP:rs137853174EnsemblClinVar.1
Natural variantiVAR_066347674V → A1 Publication1
Natural variantiVAR_066348720H → P Severe impairment of activity. 1 PublicationCorresponds to variant dbSNP:rs113706342Ensembl.1
Natural variantiVAR_052359733P → L1 PublicationCorresponds to variant dbSNP:rs5743621Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88540 mRNA Translation: AAC34137.1
AB445617 mRNA Translation: BAG55014.1
DQ012259 mRNA Translation: AAY85638.1
DQ012260 mRNA Translation: AAY85639.1
DQ012261 mRNA Translation: AAY85640.1
D13637 mRNA Translation: BAA02801.2 Different initiation.
AL050262 mRNA Translation: CAB43364.1
BC109093 mRNA Translation: AAI09094.1
BC109094 mRNA Translation: AAI09095.1
CCDSiCCDS33973.1
PIRiT08664
RefSeqiNP_003254.2, NM_003263.3
XP_005262719.1, XM_005262662.4
XP_011512044.1, XM_011513742.2
XP_011512045.1, XM_011513743.2
XP_011512046.1, XM_011513744.2
XP_011512047.1, XM_011513745.2
XP_016864060.1, XM_017008571.1
XP_016864061.1, XM_017008572.1
UniGeneiHs.621817
Hs.654532

Genome annotation databases

EnsembliENST00000308979; ENSP00000354932; ENSG00000174125
ENST00000502213; ENSP00000421259; ENSG00000174125
GeneIDi7096
KEGGihsa:7096
UCSCiuc003gtl.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88540 mRNA Translation: AAC34137.1
AB445617 mRNA Translation: BAG55014.1
DQ012259 mRNA Translation: AAY85638.1
DQ012260 mRNA Translation: AAY85639.1
DQ012261 mRNA Translation: AAY85640.1
D13637 mRNA Translation: BAA02801.2 Different initiation.
AL050262 mRNA Translation: CAB43364.1
BC109093 mRNA Translation: AAI09094.1
BC109094 mRNA Translation: AAI09095.1
CCDSiCCDS33973.1
PIRiT08664
RefSeqiNP_003254.2, NM_003263.3
XP_005262719.1, XM_005262662.4
XP_011512044.1, XM_011513742.2
XP_011512045.1, XM_011513743.2
XP_011512046.1, XM_011513744.2
XP_011512047.1, XM_011513745.2
XP_016864060.1, XM_017008571.1
XP_016864061.1, XM_017008572.1
UniGeneiHs.621817
Hs.654532

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FYVX-ray2.90A625-785[»]
2Z7XX-ray2.10B25-475[»]
ProteinModelPortaliQ15399
SMRiQ15399
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112951, 13 interactors
IntActiQ15399, 6 interactors
STRINGi9606.ENSP00000354932

Chemistry databases

ChEMBLiCHEMBL3885643

PTM databases

iPTMnetiQ15399
PhosphoSitePlusiQ15399

Polymorphism and mutation databases

BioMutaiTLR1
DMDMi146291086

Proteomic databases

EPDiQ15399
PaxDbiQ15399
PeptideAtlasiQ15399
PRIDEiQ15399
ProteomicsDBi60569

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308979; ENSP00000354932; ENSG00000174125
ENST00000502213; ENSP00000421259; ENSG00000174125
GeneIDi7096
KEGGihsa:7096
UCSCiuc003gtl.4 human

Organism-specific databases

CTDi7096
DisGeNETi7096
EuPathDBiHostDB:ENSG00000174125.7
GeneCardsiTLR1
HGNCiHGNC:11847 TLR1
MalaCardsiTLR1
MIMi601194 gene
613223 phenotype
neXtProtiNX_Q15399
OpenTargetsiENSG00000174125
PharmGKBiPA36549
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119006
HOGENOMiHOG000008676
HOVERGENiHBG023180
InParanoidiQ15399
KOiK05398
OMAiNNIETTW
OrthoDBiEOG091G0356
PhylomeDBiQ15399
TreeFamiTF351113

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-1461957 Beta defensins
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-5686938 Regulation of TLR by endogenous ligand

Miscellaneous databases

EvolutionaryTraceiQ15399
GeneWikiiTLR_1
GenomeRNAii7096
PROiPR:Q15399
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000174125 Expressed in 152 organ(s), highest expression level in leukocyte
CleanExiHS_TLR1
ExpressionAtlasiQ15399 baseline and differential
GenevisibleiQ15399 HS

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027190 TLR1
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR24365:SF261 PTHR24365:SF261, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
PF01463 LRRCT, 1 hit
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 4 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 10 hits
PS50104 TIR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTLR1_HUMAN
AccessioniPrimary (citable) accession number: Q15399
Secondary accession number(s): D1CS39
, D1CS41, O15452, Q32MK3, Q32MK4, Q9UG90
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 1, 2007
Last modified: November 7, 2018
This is version 189 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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