ID TLR1_HUMAN Reviewed; 786 AA.
AC Q15399; D1CS39; D1CS41; O15452; Q32MK3; Q9UG90;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 3.
DT 01-MAY-2013, entry version 140.
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; Synonyms=KIAA0012;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS SER-248 AND ILE-602.
RC TISSUE=Erythroleukemia;
RX PubMed=9435236; DOI=10.1073/pnas.95.2.588;
RA Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.;
RT "A family of human receptors structurally related to Drosophila
RT Toll.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS THR-80 AND ILE-602.
RX PubMed=19924287; DOI=10.1371/journal.pone.0007803;
RA Georgel P., Macquin C., Bahram S.;
RT "The heterogeneous allelic repertoire of human Toll-Like receptor
RT (TLR) genes.";
RL PLoS ONE 4:E7803-E7803(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-80.
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y.,
RA Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I.
RT The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by
RT analysis of randomly sampled cDNA clones from human immature myeloid
RT cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-248 AND
RP ILE-602.
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-248 AND
RP ILE-602.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 25-39.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP INVOLVEMENT IN PROTECTION AGAINST LEPROSY.
RX PubMed=17548585;
RA Johnson C.M., Lyle E.A., Omueti K.O., Stepensky V.A., Yegin O.,
RA Alpsoy E., Hamann L., Schumann R.R., Tapping R.I.;
RT "Cutting edge: A common polymorphism impairs cell surface trafficking
RT and functional responses of TLR1 but protects against leprosy.";
RL J. Immunol. 178:7520-7524(2007).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-163, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 625-785.
RX PubMed=11081518; DOI=10.1038/35040600;
RA Xu Y., Tao X., Shen B., Horng T., Medzhitov R., Manley J.L., Tong L.;
RT "Structural basis for signal transduction by the Toll/interleukin-1
RT receptor domains.";
RL Nature 408:111-115(2000).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 25-476 IN COMPLEX WITH TLR1
RP AND BACTERIAL LIPOPEPTIDE ANALOG, DISULFIDE BONDS, AND GLYCOSYLATION
RP AT ASN-51; ASN-163; ASN-330 AND ASN-429.
RX PubMed=17889651; DOI=10.1016/j.cell.2007.09.008;
RA Jin M.S., Kim S.E., Heo J.Y., Lee M.E., Kim H.M., Paik S.-G., Lee H.,
RA Lee J.-O.;
RT "Crystal structure of the TLR1-TLR2 heterodimer induced by binding of
RT a tri-acylated lipopeptide.";
RL Cell 130:1071-1082(2007).
RN [11]
RP ASSOCIATION OF VARIANT SER-248 WITH SUSCEPTIBILITY TO LEPROSY.
RX PubMed=19456232; DOI=10.1086/599121;
RA Schuring R.P., Hamann L., Faber W.R., Pahan D., Richardus J.H.,
RA Schumann R.R., Oskam L.;
RT "Polymorphism N248S in the human Toll-like receptor 1 gene is related
RT to leprosy and leprosy reactions.";
RL J. Infect. Dis. 199:1816-1819(2009).
RN [12]
RP VARIANTS PRO-44; THR-75; THR-80; TYR-118; SER-248; LEU-305; LEU-315;
RP ASN-352; VAL-460; ALA-542; CYS-554; GLY-587; ILE-602; ALA-651;
RP ALA-674; PRO-720 AND LEU-733, AND CHARACTERIZATION OF VARIANTS
RP LEU-315; CYS-554; ILE-602; ALA-651 AND PRO-720.
RX PubMed=21618349; DOI=10.1002/humu.21486;
RA Ben-Ali M., Corre B., Manry J., Barreiro L.B., Quach H., Boniotto M.,
RA Pellegrini S., Quintana-Murci L.;
RT "Functional characterization of naturally occurring genetic variants
RT in the human TLR1-2-6 gene family.";
RL Hum. Mutat. 32:643-652(2011).
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. Acts via MYD88
CC and TRAF6, leading to NF-kappa-B activation, cytokine secretion
CC and the inflammatory response (By similarity).
CC -!- SUBUNIT: Binds MYD88 (via TIR domain). Interacts with CNPY3 (By
CC similarity). Interacts (via extracellular domain) with TLR2.
CC Ligand binding induces the formation of a heterodimer with TLR2.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein (By similarity). Cytoplasmic vesicle, phagosome membrane;
CC Single-pass type I membrane protein (By similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in spleen, ovary,
CC peripheral blood leukocytes, thymus and small intestine.
CC -!- POLYMORPHISM: Genetic variations in TLR1 may influence
CC susceptibility to or protection against contracting leprosy and
CC define the leprosy susceptibility locus 5 [MIM:613223]. Ser-602 is
CC a common allele in Caucasians. It is associated with impaired cell
CC surface expression and receptor function resulting in protection
CC against leprosy.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family.
CC -!- SIMILARITY: Contains 19 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 1 LRRCT domain.
CC -!- SIMILARITY: Contains 1 TIR domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02801.2; Type=Erroneous initiation;
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DR EMBL; U88540; AAC34137.1; -; mRNA.
DR EMBL; DQ012259; AAY85638.1; -; mRNA.
DR EMBL; DQ012261; AAY85640.1; -; mRNA.
DR EMBL; D13637; BAA02801.2; ALT_INIT; mRNA.
DR EMBL; AL050262; CAB43364.1; -; mRNA.
DR EMBL; BC109094; AAI09095.1; -; mRNA.
DR IPI; IPI00090764; -.
DR PIR; T08664; T08664.
DR RefSeq; NP_003254.2; NM_003263.3.
DR UniGene; Hs.621817; -.
DR UniGene; Hs.654532; -.
DR PDB; 1FYV; X-ray; 2.90 A; A=625-785.
DR PDB; 2Z7X; X-ray; 2.10 A; B=25-476.
DR PDBsum; 1FYV; -.
DR PDBsum; 2Z7X; -.
DR ProteinModelPortal; Q15399; -.
DR STRING; 9606.ENSP00000354932; -.
DR PhosphoSite; Q15399; -.
DR DMDM; 146291086; -.
DR PaxDb; Q15399; -.
DR PRIDE; Q15399; -.
DR Ensembl; ENST00000308979; ENSP00000354932; ENSG00000174125.
DR Ensembl; ENST00000502213; ENSP00000421259; ENSG00000174125.
DR GeneID; 7096; -.
DR KEGG; hsa:7096; -.
DR UCSC; uc003gtl.3; human.
DR CTD; 7096; -.
DR GeneCards; GC04M038797; -.
DR HGNC; HGNC:11847; TLR1.
DR MIM; 601194; gene.
DR MIM; 613223; phenotype.
DR neXtProt; NX_Q15399; -.
DR PharmGKB; PA36549; -.
DR eggNOG; NOG272762; -.
DR HOGENOM; HOG000008676; -.
DR HOVERGEN; HBG023180; -.
DR InParanoid; Q15399; -.
DR KO; K05398; -.
DR OMA; NNIETTW; -.
DR PhylomeDB; Q15399; -.
DR EvolutionaryTrace; Q15399; -.
DR GenomeRNAi; 7096; -.
DR NextBio; 27759; -.
DR ArrayExpress; Q15399; -.
DR Bgee; Q15399; -.
DR CleanEx; HS_TLR1; -.
DR Genevestigator; Q15399; -.
DR GermOnline; ENSG00000174125; Homo sapiens.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035354; C:Toll-like receptor 1-Toll-like receptor 2 protein complex; IDA:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:UniProtKB.
DR GO; GO:0071727; P:cellular response to triacyl bacterial lipopeptide; IDA:MGI.
DR GO; GO:0042495; P:detection of triacyl bacterial lipopeptide; IDA:MGI.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
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:0045410; P:positive regulation of interleukin-6 biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042535; P:positive regulation of tumor necrosis factor biosynthetic process; ISS:UniProtKB.
DR GO; GO:0050707; P:regulation of cytokine secretion; IEA:InterPro.
DR GO; GO:0034130; P:toll-like receptor 1 signaling pathway; IEA:InterPro.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR027190; TLR1.
DR InterPro; IPR017241; Toll-like_receptor.
DR PANTHER; PTHR24365:SF23; PTHR24365:SF23; 1.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; TIR; 1.
DR PROSITE; PS51450; LRR; 10.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Complete proteome; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Membrane;
KW Polymorphism; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 24
FT CHAIN 25 786 Toll-like receptor 1.
FT /FTId=PRO_0000034705.
FT TOPO_DOM 25 580 Extracellular (Potential).
FT TRANSMEM 581 601 Helical; (Potential).
FT TOPO_DOM 602 786 Cytoplasmic (Potential).
FT REPEAT 54 77 LRR 1.
FT REPEAT 78 101 LRR 2.
FT REPEAT 102 125 LRR 3.
FT REPEAT 126 150 LRR 4.
FT REPEAT 151 175 LRR 5.
FT REPEAT 176 199 LRR 6.
FT REPEAT 200 223 LRR 7.
FT REPEAT 224 250 LRR 8.
FT REPEAT 251 278 LRR 9.
FT REPEAT 279 308 LRR 10.
FT REPEAT 309 337 LRR 11.
FT REPEAT 338 361 LRR 12.
FT REPEAT 362 388 LRR 13.
FT REPEAT 389 414 LRR 14.
FT REPEAT 415 437 LRR 15.
FT REPEAT 438 457 LRR 16.
FT REPEAT 458 478 LRR 17.
FT REPEAT 479 500 LRR 18.
FT REPEAT 501 524 LRR 19.
FT DOMAIN 525 579 LRRCT.
FT DOMAIN 635 779 TIR.
FT REGION 313 316 Interaction with bacterial lipopeptide.
FT CARBOHYD 51 51 N-linked (GlcNAc...).
FT CARBOHYD 137 137 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 163 163 N-linked (GlcNAc...).
FT CARBOHYD 330 330 N-linked (GlcNAc...).
FT CARBOHYD 429 429 N-linked (GlcNAc...).
FT CARBOHYD 578 578 N-linked (GlcNAc...) (Potential).
FT DISULFID 110 132
FT DISULFID 223 230
FT DISULFID 343 368
FT DISULFID 419 442
FT VARIANT 44 44 S -> P (in dbSNP:rs76600635).
FT /FTId=VAR_066340.
FT VARIANT 75 75 I -> T.
FT /FTId=VAR_066341.
FT VARIANT 80 80 R -> T (in dbSNP:rs5743611).
FT /FTId=VAR_031916.
FT VARIANT 118 118 H -> Y (in dbSNP:rs5743612).
FT /FTId=VAR_018474.
FT VARIANT 248 248 N -> S (may confer susceptibility to
FT leprosy).
FT /FTId=VAR_031917.
FT VARIANT 305 305 H -> L (in dbSNP:rs3923647).
FT /FTId=VAR_031918.
FT VARIANT 315 315 P -> L (severe impairment of activity;
FT dbSNP:rs5743613).
FT /FTId=VAR_031919.
FT VARIANT 352 352 H -> N (in dbSNP:rs76796448).
FT /FTId=VAR_066342.
FT VARIANT 460 460 I -> V.
FT /FTId=VAR_066343.
FT VARIANT 542 542 V -> A.
FT /FTId=VAR_066344.
FT VARIANT 554 554 Y -> C (severe impairment of activity).
FT /FTId=VAR_066345.
FT VARIANT 587 587 V -> G (in dbSNP:rs5743617).
FT /FTId=VAR_031920.
FT VARIANT 602 602 S -> I (severe impairment of activity;
FT dbSNP:rs5743618).
FT /FTId=VAR_031921.
FT VARIANT 631 631 L -> R (in dbSNP:rs5743619).
FT /FTId=VAR_052358.
FT VARIANT 651 651 V -> A (severe impairment of activity).
FT /FTId=VAR_066346.
FT VARIANT 674 674 V -> A.
FT /FTId=VAR_066347.
FT VARIANT 720 720 H -> P (severe impairment of activity;
FT dbSNP:rs113706342).
FT /FTId=VAR_066348.
FT VARIANT 733 733 P -> L (in dbSNP:rs5743621).
FT /FTId=VAR_052359.
FT CONFLICT 182 182 E -> G (in Ref. 4; CAB43364).
FT CONFLICT 228 228 N -> S (in Ref. 4; CAB43364).
FT CONFLICT 276 276 F -> S (in Ref. 4; CAB43364).
FT STRAND 28 30
FT STRAND 48 51
FT HELIX 62 65
FT STRAND 73 75
FT STRAND 83 85
FT HELIX 86 89
FT STRAND 97 99
FT STRAND 107 109
FT STRAND 117 120
FT HELIX 133 137
FT STRAND 143 150
FT HELIX 153 159
FT STRAND 164 171
FT HELIX 181 184
FT STRAND 189 195
FT STRAND 198 200
FT STRAND 214 218
FT STRAND 221 223
FT TURN 227 230
FT HELIX 231 238
FT HELIX 239 242
FT STRAND 248 257
FT HELIX 258 269
FT STRAND 274 285
FT STRAND 301 309
FT HELIX 317 324
FT STRAND 329 336
FT STRAND 352 354
FT TURN 362 367
FT STRAND 376 378
FT HELIX 387 394
FT STRAND 402 404
FT HELIX 414 416
FT STRAND 427 429
FT HELIX 437 441
FT STRAND 449 451
FT HELIX 462 466
FT STRAND 472 474
FT STRAND 631 633
FT STRAND 637 642
FT HELIX 645 647
FT HELIX 648 653
FT HELIX 655 660
FT TURN 661 663
FT TURN 669 672
FT HELIX 679 689
FT STRAND 690 698
FT HELIX 699 704
FT HELIX 707 712
FT STRAND 724 732
FT HELIX 736 738
FT HELIX 744 751
FT HELIX 762 764
FT HELIX 767 777
SQ SEQUENCE 786 AA; 90291 MW; 1BFCCC5E42EA5242 CRC64;
MTSIFHFAII FMLILQIRIQ LSEESEFLVD RSKNGLIHVP KDLSQKTTIL NISQNYISEL
WTSDILSLSK LRILIISHNR IQYLDISVFK FNQELEYLDL SHNKLVKISC HPTVNLKHLD
LSFNAFDALP ICKEFGNMSQ LKFLGLSTTH LEKSSVLPIA HLNISKVLLV LGETYGEKED
PEGLQDFNTE SLHIVFPTNK EFHFILDVSV KTVANLELSN IKCVLEDNKC SYFLSILAKL
QTNPKLSNLT LNNIETTWNS FIRILQLVWH TTVWYFSISN VKLQGQLDFR DFDYSGTSLK
ALSIHQVVSD VFGFPQSYIY EIFSNMNIKN FTVSGTRMVH MLCPSKISPF LHLDFSNNLL
TDTVFENCGH LTELETLILQ MNQLKELSKI AEMTTQMKSL QQLDISQNSV SYDEKKGDCS
WTKSLLSLNM SSNILTDTIF RCLPPRIKVL DLHSNKIKSI PKQVVKLEAL QELNVAFNSL
TDLPGCGSFS SLSVLIIDHN SVSHPSADFF QSCQKMRSIK AGDNPFQCTC ELGEFVKNID
QVSSEVLEGW PDSYKCDYPE SYRGTLLKDF HMSELSCNIT LLIVTIVATM LVLAVTVTSL
CSYLDLPWYL RMVCQWTQTR RRARNIPLEE LQRNLQFHAF ISYSGHDSFW VKNELLPNLE
KEGMQICLHE RNFVPGKSIV ENIITCIEKS YKSIFVLSPN FVQSEWCHYE LYFAHHNLFH
EGSNSLILIL LEPIPQYSIP SSYHKLKSLM ARRTYLEWPK EKSKRGLFWA NLRAAINIKL
TEQAKK
//
