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Q15399 (TLR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Toll-like receptor 1
Alternative name(s):
Toll/interleukin-1 receptor-like protein
Short name=TIL
CD_antigen=CD281
Gene names
Name:TLR1
Synonyms:KIAA0012
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length786 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response By similarity.

Subunit structure

Binds MYD88 (via TIR domain). Interacts with CNPY3 By similarity. Interacts (via extracellular domain) with TLR2. Ligand binding induces the formation of a heterodimer with TLR2.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasmic vesiclephagosome membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

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

Polymorphism

Genetic variations in TLR1 may influence susceptibility to or protection against contracting leprosy and define the leprosy susceptibility locus 5 [MIM: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.

Sequence similarities

Belongs to the Toll-like receptor family.

Contains 19 LRR (leucine-rich) repeats.

Contains 1 LRRCT domain.

Contains 1 TIR domain.

Sequence caution

The sequence BAA02801.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasmic vesicle
Membrane
   Coding sequence diversityPolymorphism
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to triacyl bacterial lipopeptide

Inferred from direct assay PubMed 19931471. Source: MGI

detection of triacyl bacterial lipopeptide

Inferred from direct assay PubMed 19931471. Source: MGI

immune response

Traceable author statement PubMed 10426995. Source: ProtInc

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

macrophage activation

Non-traceable author statement PubMed 11607792. Source: UniProtKB

positive regulation of interleukin-6 biosynthetic process

Inferred from sequence or structural similarity PubMed 12077222. Source: UniProtKB

positive regulation of tumor necrosis factor biosynthetic process

Inferred from sequence or structural similarity PubMed 12077222. Source: UniProtKB

signal transduction

Traceable author statement PubMed 10426995Ref.1. Source: ProtInc

toll-like receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentToll-like receptor 1-Toll-like receptor 2 protein complex

Inferred from direct assay Ref.11. Source: MGI

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

membrane

Non-traceable author statement Ref.10. Source: UniProtKB

phagocytic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionprotein heterodimerization activity

Inferred from direct assay Ref.11. Source: MGI

receptor activity

Traceable author statement PubMed 10426995. Source: ProtInc

transmembrane signaling receptor activity

Non-traceable author statement Ref.10. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Ref.7
Chain25 – 786762Toll-like receptor 1
PRO_0000034705

Regions

Topological domain25 – 580556Extracellular Potential
Transmembrane581 – 60121Helical; Potential
Topological domain602 – 786185Cytoplasmic Potential
Repeat54 – 7724LRR 1
Repeat78 – 10124LRR 2
Repeat102 – 12524LRR 3
Repeat126 – 15025LRR 4
Repeat151 – 17525LRR 5
Repeat176 – 19924LRR 6
Repeat200 – 22324LRR 7
Repeat224 – 25027LRR 8
Repeat251 – 27828LRR 9
Repeat279 – 30830LRR 10
Repeat309 – 33729LRR 11
Repeat338 – 36124LRR 12
Repeat362 – 38827LRR 13
Repeat389 – 41426LRR 14
Repeat415 – 43723LRR 15
Repeat438 – 45720LRR 16
Repeat458 – 47821LRR 17
Repeat479 – 50022LRR 18
Repeat501 – 52424LRR 19
Domain525 – 57955LRRCT
Domain635 – 779145TIR
Region313 – 3164Interaction with bacterial lipopeptide

Amino acid modifications

Glycosylation511N-linked (GlcNAc...) Ref.11
Glycosylation1371N-linked (GlcNAc...) Potential
Glycosylation1631N-linked (GlcNAc...) Ref.9 Ref.11
Glycosylation3301N-linked (GlcNAc...) Ref.11
Glycosylation4291N-linked (GlcNAc...) Ref.11
Glycosylation5781N-linked (GlcNAc...) Potential
Disulfide bond110 ↔ 132 Ref.11
Disulfide bond223 ↔ 230 Ref.11
Disulfide bond343 ↔ 368 Ref.11
Disulfide bond419 ↔ 442 Ref.11

Natural variations

Natural variant441S → P. Ref.13
Corresponds to variant rs76600635 [ dbSNP | Ensembl ].
VAR_066340
Natural variant751I → T. Ref.13
Corresponds to variant rs137853170 [ dbSNP | Ensembl ].
VAR_066341
Natural variant801R → T. Ref.3 Ref.4 Ref.13
Corresponds to variant rs5743611 [ dbSNP | Ensembl ].
VAR_031916
Natural variant1181H → Y. Ref.13
Corresponds to variant rs5743612 [ dbSNP | Ensembl ].
VAR_018474
Natural variant2481N → S May confer susceptibility to leprosy. Ref.1 Ref.5 Ref.6 Ref.12 Ref.13
Corresponds to variant rs4833095 [ dbSNP | Ensembl ].
VAR_031917
Natural variant3051H → L. Ref.13
Corresponds to variant rs3923647 [ dbSNP | Ensembl ].
VAR_031918
Natural variant3151P → L Severe impairment of activity. Ref.13
Corresponds to variant rs5743613 [ dbSNP | Ensembl ].
VAR_031919
Natural variant3521H → N. Ref.13
Corresponds to variant rs76796448 [ dbSNP | Ensembl ].
VAR_066342
Natural variant4601I → V. Ref.13
Corresponds to variant rs137853171 [ dbSNP | Ensembl ].
VAR_066343
Natural variant5421V → A. Ref.13
Corresponds to variant rs137853172 [ dbSNP | Ensembl ].
VAR_066344
Natural variant5541Y → C Severe impairment of activity. Ref.13
VAR_066345
Natural variant5871V → G. Ref.13
Corresponds to variant rs5743617 [ dbSNP | Ensembl ].
VAR_031920
Natural variant6021S → I Severe impairment of activity. Ref.1 Ref.3 Ref.5 Ref.6 Ref.13
Corresponds to variant rs5743618 [ dbSNP | Ensembl ].
VAR_031921
Natural variant6311L → R.
Corresponds to variant rs5743619 [ dbSNP | Ensembl ].
VAR_052358
Natural variant6511V → A Severe impairment of activity. Ref.13
VAR_066346
Natural variant6741V → A. Ref.13
VAR_066347
Natural variant7201H → P Severe impairment of activity. Ref.13
Corresponds to variant rs113706342 [ dbSNP | Ensembl ].
VAR_066348
Natural variant7331P → L. Ref.13
Corresponds to variant rs5743621 [ dbSNP | Ensembl ].
VAR_052359

Experimental info

Sequence conflict1821E → G in CAB43364. Ref.5
Sequence conflict2281N → S in CAB43364. Ref.5
Sequence conflict2761F → S in CAB43364. Ref.5

Secondary structure

..................................................................................................... 786
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q15399 [UniParc].

Last modified May 1, 2007. Version 3.
Checksum: 1BFCCC5E42EA5242

FASTA78690,291
        10         20         30         40         50         60 
MTSIFHFAII FMLILQIRIQ LSEESEFLVD RSKNGLIHVP KDLSQKTTIL NISQNYISEL 

        70         80         90        100        110        120 
WTSDILSLSK LRILIISHNR IQYLDISVFK FNQELEYLDL SHNKLVKISC HPTVNLKHLD 

       130        140        150        160        170        180 
LSFNAFDALP ICKEFGNMSQ LKFLGLSTTH LEKSSVLPIA HLNISKVLLV LGETYGEKED 

       190        200        210        220        230        240 
PEGLQDFNTE SLHIVFPTNK EFHFILDVSV KTVANLELSN IKCVLEDNKC SYFLSILAKL 

       250        260        270        280        290        300 
QTNPKLSNLT LNNIETTWNS FIRILQLVWH TTVWYFSISN VKLQGQLDFR DFDYSGTSLK 

       310        320        330        340        350        360 
ALSIHQVVSD VFGFPQSYIY EIFSNMNIKN FTVSGTRMVH MLCPSKISPF LHLDFSNNLL 

       370        380        390        400        410        420 
TDTVFENCGH LTELETLILQ MNQLKELSKI AEMTTQMKSL QQLDISQNSV SYDEKKGDCS 

       430        440        450        460        470        480 
WTKSLLSLNM SSNILTDTIF RCLPPRIKVL DLHSNKIKSI PKQVVKLEAL QELNVAFNSL 

       490        500        510        520        530        540 
TDLPGCGSFS SLSVLIIDHN SVSHPSADFF QSCQKMRSIK AGDNPFQCTC ELGEFVKNID 

       550        560        570        580        590        600 
QVSSEVLEGW PDSYKCDYPE SYRGTLLKDF HMSELSCNIT LLIVTIVATM LVLAVTVTSL 

       610        620        630        640        650        660 
CSYLDLPWYL RMVCQWTQTR RRARNIPLEE LQRNLQFHAF ISYSGHDSFW VKNELLPNLE 

       670        680        690        700        710        720 
KEGMQICLHE RNFVPGKSIV ENIITCIEKS YKSIFVLSPN FVQSEWCHYE LYFAHHNLFH 

       730        740        750        760        770        780 
EGSNSLILIL LEPIPQYSIP SSYHKLKSLM ARRTYLEWPK EKSKRGLFWA NLRAAINIKL 


TEQAKK 

« Hide

References

« Hide 'large scale' references
[1]"A family of human receptors structurally related to Drosophila Toll."
Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.
Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-248 AND ILE-602.
Tissue: Erythroleukemia.
[2]"Natural selection in the TLR-related genes in the course of primate evolution."
Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) genes."
Georgel P., Macquin C., Bahram S.
PLoS ONE 4:E7803-E7803(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-80 AND ILE-602.
[4]"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1."
Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.
DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-80.
Tissue: Bone marrow.
[5]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-248 AND ILE-602.
Tissue: Brain.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-248 AND ILE-602.
[7]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-39.
[8]"Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy."
Johnson C.M., Lyle E.A., Omueti K.O., Stepensky V.A., Yegin O., Alpsoy E., Hamann L., Schumann R.R., Tapping R.I.
J. Immunol. 178:7520-7524(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PROTECTION AGAINST LEPROSY.
[9]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-163.
Tissue: Liver.
[10]"Structural basis for signal transduction by the Toll/interleukin-1 receptor domains."
Xu Y., Tao X., Shen B., Horng T., Medzhitov R., Manley J.L., Tong L.
Nature 408:111-115(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 625-785.
[11]"Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide."
Jin M.S., Kim S.E., Heo J.Y., Lee M.E., Kim H.M., Paik S.-G., Lee H., Lee J.-O.
Cell 130:1071-1082(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-476 IN COMPLEX WITH TLR1 AND BACTERIAL LIPOPEPTIDE ANALOG, DISULFIDE BONDS, GLYCOSYLATION AT ASN-51; ASN-163; ASN-330 AND ASN-429.
[12]"Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosy and leprosy reactions."
Schuring R.P., Hamann L., Faber W.R., Pahan D., Richardus J.H., Schumann R.R., Oskam L.
J. Infect. Dis. 199:1816-1819(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF VARIANT SER-248 WITH SUSCEPTIBILITY TO LEPROSY.
[13]"Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family."
Ben-Ali M., Corre B., Manry J., Barreiro L.B., Quach H., Boniotto M., Pellegrini S., Quintana-Murci L.
Hum. Mutat. 32:643-652(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRO-44; THR-75; THR-80; TYR-118; SER-248; LEU-305; LEU-315; ASN-352; VAL-460; ALA-542; CYS-554; GLY-587; ILE-602; ALA-651; ALA-674; PRO-720 AND LEU-733, CHARACTERIZATION OF VARIANTS LEU-315; CYS-554; ILE-602; ALA-651 AND PRO-720.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS33973.1.
PIRT08664.
RefSeqNP_003254.2. NM_003263.3.
XP_005262719.1. XM_005262662.2.
XP_005262720.1. XM_005262663.2.
XP_005262722.1. XM_005262665.2.
XP_005262723.1. XM_005262666.2.
XP_006714091.1. XM_006714028.1.
UniGeneHs.621817.
Hs.654532.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FYVX-ray2.90A625-785[»]
2Z7XX-ray2.10B25-475[»]
ProteinModelPortalQ15399.
SMRQ15399. Positions 25-578, 625-785.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112951. 2 interactions.
STRING9606.ENSP00000354932.

PTM databases

PhosphoSiteQ15399.

Polymorphism databases

DMDM146291086.

Proteomic databases

PaxDbQ15399.
PRIDEQ15399.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308979; ENSP00000354932; ENSG00000174125.
ENST00000502213; ENSP00000421259; ENSG00000174125.
GeneID7096.
KEGGhsa:7096.
UCSCuc003gtl.3. human.

Organism-specific databases

CTD7096.
GeneCardsGC04M038797.
HGNCHGNC:11847. TLR1.
MIM601194. gene.
613223. phenotype.
neXtProtNX_Q15399.
PharmGKBPA36549.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG272762.
HOGENOMHOG000008676.
HOVERGENHBG023180.
InParanoidQ15399.
KOK05398.
OMAKEFGNMS.
OrthoDBEOG7GN2M5.
PhylomeDBQ15399.
TreeFamTF351113.

Gene expression databases

ArrayExpressQ15399.
BgeeQ15399.
CleanExHS_TLR1.
GenevestigatorQ15399.

Family and domain databases

Gene3D3.40.50.10140. 1 hit.
InterProIPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR000157. TIR_dom.
IPR027190. TLR1.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERPTHR24365:SF261. PTHR24365:SF261. 1 hit.
PfamPF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFPIRSF037595. Toll-like_receptor. 1 hit.
SMARTSM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS51450. LRR. 10 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15399.
GeneWikiTLR_1.
GenomeRNAi7096.
NextBio27759.
PROQ15399.
SOURCESearch...

Entry information

Entry nameTLR1_HUMAN
AccessionPrimary (citable) accession number: Q15399
Secondary accession number(s): D1CS39 expand/collapse secondary AC list , D1CS41, O15452, Q32MK3, Q32MK4, Q9UG90
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 1, 2007
Last modified: July 9, 2014
This is version 151 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries