Q15399 (TLR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	786 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 vesicle › phagosome 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 process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Inferred from electronic annotation. Source: InterPro cellular 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 regulation of cytokine secretion Inferred from electronic annotation. Source: InterPro toll-like receptor 1 signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	Toll-like receptor 1-Toll-like receptor 2 protein complex Inferred from direct assay Ref.10. Source: MGI integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc phagocytic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein heterodimerization activity Inferred from direct assay Ref.10. Source: MGI transmembrane signaling receptor activity Non-traceable author statement Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Ref.6

Chain

25 – 786

762

Toll-like receptor 1

PRO_0000034705

Regions

Topological domain

25 – 580

556

Extracellular Potential

Transmembrane

581 – 601

21

Helical; Potential

Topological domain

602 – 786

185

Cytoplasmic Potential

Repeat

54 – 77

24

LRR 1

Repeat

78 – 101

24

LRR 2

Repeat

102 – 125

24

LRR 3

Repeat

126 – 150

25

LRR 4

Repeat

151 – 175

25

LRR 5

Repeat

176 – 199

24

LRR 6

Repeat

200 – 223

24

LRR 7

Repeat

224 – 250

27

LRR 8

Repeat

251 – 278

28

LRR 9

Repeat

279 – 308

30

LRR 10

Repeat

309 – 337

29

LRR 11

Repeat

338 – 361

24

LRR 12

Repeat

362 – 388

27

LRR 13

Repeat

389 – 414

26

LRR 14

Repeat

415 – 437

23

LRR 15

Repeat

438 – 457

20

LRR 16

Repeat

458 – 478

21

LRR 17

Repeat

479 – 500

22

LRR 18

Repeat

501 – 524

24

LRR 19

Domain

525 – 579

55

LRRCT

Domain

635 – 779

145

TIR

Region

313 – 316

4

Interaction with bacterial lipopeptide

Amino acid modifications

Glycosylation

51

1

N-linked (GlcNAc...) Ref.10

Glycosylation

137

1

N-linked (GlcNAc...) Potential

Glycosylation

163

1

N-linked (GlcNAc...) Ref.8 Ref.10

Glycosylation

330

1

N-linked (GlcNAc...) Ref.10

Glycosylation

429

1

N-linked (GlcNAc...) Ref.10

Glycosylation

578

1

N-linked (GlcNAc...) Potential

Disulfide bond

110 ↔ 132

Ref.10

Disulfide bond

223 ↔ 230

Ref.10

Disulfide bond

343 ↔ 368

Ref.10

Disulfide bond

419 ↔ 442

Ref.10

Natural variations

Natural variant

44

1

S → P. Ref.12
Corresponds to variant rs76600635 [ dbSNP | Ensembl ].

VAR_066340

Natural variant

75

1

I → T. Ref.12

VAR_066341

Natural variant

80

1

R → T. Ref.2 Ref.3 Ref.12
Corresponds to variant rs5743611 [ dbSNP | Ensembl ].

VAR_031916

Natural variant

118

1

H → Y. Ref.12
Corresponds to variant rs5743612 [ dbSNP | Ensembl ].

VAR_018474

Natural variant

248

1

N → S May confer susceptibility to leprosy. Ref.1 Ref.4 Ref.5 Ref.11 Ref.12

VAR_031917

Natural variant

305

1

H → L. Ref.12
Corresponds to variant rs3923647 [ dbSNP | Ensembl ].

VAR_031918

Natural variant

315

1

P → L Severe impairment of activity. Ref.12
Corresponds to variant rs5743613 [ dbSNP | Ensembl ].

VAR_031919

Natural variant

352

1

H → N. Ref.12
Corresponds to variant rs76796448 [ dbSNP | Ensembl ].

VAR_066342

Natural variant

460

1

I → V. Ref.12

VAR_066343

Natural variant

542

1

V → A. Ref.12

VAR_066344

Natural variant

554

1

Y → C Severe impairment of activity. Ref.12

VAR_066345

Natural variant

587

1

V → G. Ref.12
Corresponds to variant rs5743617 [ dbSNP | Ensembl ].

VAR_031920

Natural variant

602

1

S → I Severe impairment of activity. Ref.1 Ref.2 Ref.4 Ref.5 Ref.12
Corresponds to variant rs5743618 [ dbSNP | Ensembl ].

VAR_031921

Natural variant

631

1

L → R.
Corresponds to variant rs5743619 [ dbSNP | Ensembl ].

VAR_052358

Natural variant

651

1

V → A Severe impairment of activity. Ref.12

VAR_066346

Natural variant

674

1

V → A. Ref.12

VAR_066347

Natural variant

720

1

H → P Severe impairment of activity. Ref.12
Corresponds to variant rs113706342 [ dbSNP | Ensembl ].

VAR_066348

Natural variant

733

1

P → L. Ref.12
Corresponds to variant rs5743621 [ dbSNP | Ensembl ].

VAR_052359

Experimental info

Sequence conflict

182

1

E → G in CAB43364. Ref.4

Sequence conflict

228

1

N → S in CAB43364. Ref.4

Sequence conflict

276

1

F → S in CAB43364. Ref.4

Secondary structure

1

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786

Helix Strand Turn

Details...

Beta strand

28 – 30

3

Beta strand

48 – 51

4

Helix

62 – 65

4

Beta strand

73 – 75

3

Beta strand

83 – 85

3

Helix

86 – 89

4

Beta strand

97 – 99

3

Beta strand

107 – 109

3

Beta strand

117 – 120

4

Helix

133 – 137

5

Beta strand

143 – 150

8

Helix

153 – 159

7

Beta strand

164 – 171

8

Helix

181 – 184

4

Beta strand

189 – 195

7

Beta strand

198 – 200

3

Beta strand

214 – 218

5

Beta strand

221 – 223

3

Turn

227 – 230

4

Helix

231 – 238

8

Helix

239 – 242

4

Beta strand

248 – 257

10

Helix

258 – 269

12

Beta strand

274 – 285

12

Beta strand

301 – 309

9

Helix

317 – 324

8

Beta strand

329 – 336

8

Beta strand

352 – 354

3

Turn

362 – 367

6

Beta strand

376 – 378

3

Helix

387 – 394

8

Beta strand

402 – 404

3

Helix

414 – 416

3

Beta strand

427 – 429

3

Helix

437 – 441

5

Beta strand

449 – 451

3

Helix

462 – 466

5

Beta strand

472 – 474

3

Beta strand

631 – 633

3

Beta strand

637 – 642

6

Helix

645 – 647

3

Helix

648 – 653

6

Helix

655 – 660

6

Turn

661 – 663

3

Turn

669 – 672

4

Helix

679 – 689

11

Beta strand

690 – 698

9

Helix

699 – 704

6

Helix

707 – 712

6

Beta strand

724 – 732

9

Helix

736 – 738

3

Helix

744 – 751

8

Helix

762 – 764

3

Helix

767 – 777

11

Sequences

	Sequence		Length	Mass (Da)
	Q15399 [UniParc]. Last modified May 1, 2007. Version 3. Checksum: 1BFCCC5E42EA5242	FASTA	786	90,291
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[3]	"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.
[4]	"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. , 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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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, MASS SPECTROMETRY. Tissue: Liver.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
DQ012259 mRNA. Translation: AAY85638.1.
DQ012261 mRNA. Translation: AAY85640.1.
D13637 mRNA. Translation: BAA02801.2. Different initiation.
AL050262 mRNA. Translation: CAB43364.1.
BC109094 mRNA. Translation: AAI09095.1.

IPI

IPI00090764.

PIR

T08664.

RefSeq

NP_003254.2. NM_003263.3.

UniGene

Hs.621817.
Hs.654532.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FYV	X-ray	2.90	A	625-785	[»]
2Z7X	X-ray	2.10	B	25-476	[»]

ProteinModelPortal

Q15399.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000354932.

PTM databases

PhosphoSite

Q15399.

Polymorphism databases

DMDM

146291086.

Proteomic databases

PaxDb

Q15399.

PRIDE

Q15399.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000308979; ENSP00000354932; ENSG00000174125.
ENST00000502213; ENSP00000421259; ENSG00000174125.

GeneID

7096.

KEGG

hsa:7096.

UCSC

uc003gtl.3. human.

Organism-specific databases

CTD

7096.

GeneCards

GC04M038797.

HGNC

HGNC:11847. TLR1.

MIM

601194. gene.
613223. phenotype.

neXtProt

NX_Q15399.

PharmGKB

PA36549.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG272762.

HOGENOM

HOG000008676.

HOVERGEN

HBG023180.

InParanoid

Q15399.

KO

K05398.

OMA

NNIETTW.

PhylomeDB

Q15399.

Gene expression databases

ArrayExpress

Q15399.

Bgee

Q15399.

CleanEx

HS_TLR1.

Genevestigator

Q15399.

GermOnline

ENSG00000174125. Homo sapiens.

Family and domain databases

InterPro

IPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR000157. TIR_dom.
IPR027190. TLR1.
IPR017241. Toll-like_receptor.
[Graphical view]

PANTHER

PTHR24365:SF23. PTHR24365:SF23. 1 hit.

Pfam

PF01582. TIR. 1 hit.
[Graphical view]

PIRSF

PIRSF037595. Toll-like_receptor. 1 hit.

SMART

SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]

SUPFAM

SSF52200. TIR. 1 hit.

PROSITE

PS51450. LRR. 10 hits.
PS50104. TIR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q15399.

GenomeRNAi

7096.

NextBio

27759.

SOURCE

Search...

Entry information

Entry name

TLR1_HUMAN

Accession

Primary (citable) accession number: Q15399
Secondary accession number(s): D1CS39 , D1CS41, O15452, Q32MK3, Q9UG90

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.