Toll-like receptor 8 precursor - Homo sapiens (Human)

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Q9NR97 (TLR8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 116. History...

Clusters with 100%, 90%, 50% identity |

Documents (7) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Toll-like receptor 8

Alternative name(s):
CD_antigen=CD288

Gene names

Name:	TLR8
ORF Names:	UNQ249/PRO286

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1041 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	Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Ref.7
Subunit structure	Interacts with MYD88 via their respective TIR domains. Interacts with UNC93B1 By similarity. Interacts with BTK. Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Detected in brain, heart, lung, liver, placenta, in monocytes, and at lower levels in CD11c+ immature dendritic cells.
Sequence similarities	Belongs to the Toll-like receptor family. Contains 23 LRR (leucine-rich) repeats. Contains 1 LRRCT domain. Contains 1 TIR domain.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Inferred from direct assay PubMed 12032557. Source: UniProtKB MyD88-dependent toll-like receptor signaling pathway Inferred from electronic annotation. Source: InterPro cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB defense response to virus Inferred from mutant phenotype PubMed 16188996. Source: UniProtKB immunoglobulin mediated immune response Traceable author statement PubMed 16123302. Source: UniProtKB inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Non-traceable author statement PubMed 12032557. Source: UniProtKB positive regulation of interferon-alpha biosynthetic process Inferred from direct assay PubMed 16286015. Source: UniProtKB positive regulation of interferon-beta biosynthetic process Inferred from direct assay PubMed 16286015. Source: UniProtKB positive regulation of interferon-gamma biosynthetic process Inferred from direct assay PubMed 16286015. Source: UniProtKB positive regulation of interleukin-8 biosynthetic process Inferred from mutant phenotype PubMed 16188996. Source: UniProtKB regulation of cytokine secretion Inferred from electronic annotation. Source: InterPro toll-like receptor 8 signaling pathway Inferred from electronic annotation. Source: InterPro toll-like receptor 9 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome endolysosome membrane Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred by curator PubMed 12032557. Source: UniProtKB
Molecular_function	DNA binding Inferred from direct assay PubMed 16123302. Source: UniProtKB double-stranded RNA binding Inferred from direct assay PubMed 16111635. Source: UniProtKB receptor activity Non-traceable author statement PubMed 12032557. Source: UniProtKB single-stranded RNA binding Inferred from direct assay PubMed 14976262. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

Potential

Chain

27 – 1041

1015

Toll-like receptor 8

PRO_0000034735

Regions

Topological domain

27 – 827

801

Extracellular Potential

Transmembrane

828 – 848

Helical; Potential

Topological domain

849 – 1041

193

Cytoplasmic Potential

Repeat

126 – 147

LRR 1

Repeat

148 – 168

LRR 2

Repeat

171 – 193

LRR 3

Repeat

202 – 223

LRR 4

Repeat

224 – 244

LRR 5

Repeat

247 – 268

LRR 6

Repeat

288 – 309

LRR 7

Repeat

312 – 334

LRR 8

Repeat

338 – 360

LRR 9

Repeat

368 – 389

LRR 10

Repeat

395 – 416

LRR 11

Repeat

419 – 440

LRR 12

Repeat

482 – 503

LRR 13

Repeat

506 – 527

LRR 14

Repeat

531 – 551

LRR 15

Repeat

555 – 577

LRR 16

Repeat

585 – 606

LRR 17

Repeat

609 – 630

LRR 18

Repeat

640 – 661

LRR 19

Repeat

665 – 685

LRR 20

Repeat

689 – 710

LRR 21

Repeat

713 – 734

LRR 22

Repeat

737 – 758

LRR 23

Domain

772 – 824

LRRCT

Domain

878 – 1025

148

TIR

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

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

Glycosylation

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

Glycosylation

115

N-linked (GlcNAc...) Potential

Glycosylation

160

N-linked (GlcNAc...) Potential

Glycosylation

247

N-linked (GlcNAc...) Potential

Glycosylation

285

N-linked (GlcNAc...) Potential

Glycosylation

293

N-linked (GlcNAc...) Potential

Glycosylation

358

N-linked (GlcNAc...) Potential

Glycosylation

362

N-linked (GlcNAc...) Potential

Glycosylation

395

N-linked (GlcNAc...) Potential

Glycosylation

416

N-linked (GlcNAc...) Potential

Glycosylation

443

N-linked (GlcNAc...) Potential

Glycosylation

511

N-linked (GlcNAc...) Potential

Glycosylation

546

N-linked (GlcNAc...) Potential

Glycosylation

582

N-linked (GlcNAc...) Potential

Glycosylation

590

N-linked (GlcNAc...) Potential

Glycosylation

640

N-linked (GlcNAc...) Potential

Glycosylation

680

N-linked (GlcNAc...) Potential

Glycosylation

752

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

M → V.
Corresponds to variant rs5744077 [ dbSNP | Ensembl ].

VAR_024667

Natural variant

715

R → Q.
Corresponds to variant rs5744082 [ dbSNP | Ensembl ].

VAR_052363

Experimental info

Sequence conflict

M → MKESSLQNSSCSLGKETKK Ref.1

Sequence conflict

217

P → S in AAF64061. Ref.1

Sequence conflict

328

A → V in AAQ88663. Ref.4

Sequence conflict

366

L → P in AAF64061. Ref.1

Sequence conflict

867

V → I in AAF64061. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q9NR97 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 39A38B60629291C8
Show »

FASTA

1,041

119,828

        10         20         30         40         50         60 
MENMFLQSSM LTCIFLLISG SCELCAEENF SRSYPCDEKK QNDSVIAECS NRRLQEVPQT 

        70         80         90        100        110        120 
VGKYVTELDL SDNFITHITN ESFQGLQNLT KINLNHNPNV QHQNGNPGIQ SNGLNITDGA 

       130        140        150        160        170        180 
FLNLKNLREL LLEDNQLPQI PSGLPESLTE LSLIQNNIYN ITKEGISRLI NLKNLYLAWN 

       190        200        210        220        230        240 
CYFNKVCEKT NIEDGVFETL TNLELLSLSF NSLSHVPPKL PSSLRKLFLS NTQIKYISEE 

       250        260        270        280        290        300 
DFKGLINLTL LDLSGNCPRC FNAPFPCVPC DGGASINIDR FAFQNLTQLR YLNLSSTSLR 

       310        320        330        340        350        360 
KINAAWFKNM PHLKVLDLEF NYLVGEIASG AFLTMLPRLE ILDLSFNYIK GSYPQHINIS 

       370        380        390        400        410        420 
RNFSKLLSLR ALHLRGYVFQ ELREDDFQPL MQLPNLSTIN LGINFIKQID FKLFQNFSNL 

       430        440        450        460        470        480 
EIIYLSENRI SPLVKDTRQS YANSSSFQRH IRKRRSTDFE FDPHSNFYHF TRPLIKPQCA 

       490        500        510        520        530        540 
AYGKALDLSL NSIFFIGPNQ FENLPDIACL NLSANSNAQV LSGTEFSAIP HVKYLDLTNN 

       550        560        570        580        590        600 
RLDFDNASAL TELSDLEVLD LSYNSHYFRI AGVTHHLEFI QNFTNLKVLN LSHNNIYTLT 

       610        620        630        640        650        660 
DKYNLESKSL VELVFSGNRL DILWNDDDNR YISIFKGLKN LTRLDLSLNR LKHIPNEAFL 

       670        680        690        700        710        720 
NLPASLTELH INDNMLKFFN WTLLQQFPRL ELLDLRGNKL LFLTDSLSDF TSSLRTLLLS 

       730        740        750        760        770        780 
HNRISHLPSG FLSEVSSLKH LDLSSNLLKT INKSALETKT TTKLSMLELH GNPFECTCDI 

       790        800        810        820        830        840 
GDFRRWMDEH LNVKIPRLVD VICASPGDQR GKSIVSLELT TCVSDVTAVI LFFFTFFITT 

       850        860        870        880        890        900 
MVMLAALAHH LFYWDVWFIY NVCLAKVKGY RSLSTSQTFY DAYISYDTKD ASVTDWVINE 

       910        920        930        940        950        960 
LRYHLEESRD KNVLLCLEER DWDPGLAIID NLMQSINQSK KTVFVLTKKY AKSWNFKTAF 

       970        980        990       1000       1010       1020 
YLALQRLMDE NMDVIIFILL EPVLQHSQYL RLRQRICKSS ILQWPDNPKA EGLFWQTLRN 

      1030       1040 
VVLTENDSRY NNMYVDSIKQ Y

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Three novel mammalian Toll-like receptors: gene structure, expression, and evolution." Du X., Poltorak A., Wei Y., Beutler B. Eur. Cytokine Netw. 11:362-371(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Cloning and characterization of a sub-family of human Toll-like receptors: hTLR7, hTLR8 and hTLR9." Chuang T.-H., Ulevitch R.J. Eur. Cytokine Netw. 11:372-378(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"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].
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
[7]	"Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase." Doyle S.L., Jefferies C.A., Feighery C., O'Neill L.A. J. Biol. Chem. 282:36953-36960(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH BTK.
[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-80 AND ASN-88, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF246971 mRNA. Translation: AAF64061.1.
AF245703 mRNA. Translation: AAF78036.1.
AB445666 mRNA. Translation: BAG55063.1.
AY358296 mRNA. Translation: AAQ88663.1.
CH471074 Genomic DNA. Translation: EAW98809.1.
BC101076 mRNA. Translation: AAI01077.1.
BC101077 mRNA. Translation: AAI01078.1.

IPI

IPI00009910.

RefSeq

NP_619542.1. NM_138636.4.

UniGene

Hs.660543.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3W3G	X-ray	2.30	A/B	27-827	[»]
3W3J	X-ray	2.00	A/B	27-827	[»]
3W3K	X-ray	2.30	A/B	27-827	[»]
3W3L	X-ray	2.33	A/B/C/D	27-827	[»]
3W3M	X-ray	2.70	A	27-827	[»]
3W3N	X-ray	2.10	A/B	27-827	[»]

ProteinModelPortal

Q9NR97.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000218032.

PTM databases

PhosphoSite

Q9NR97.

Polymorphism databases

DMDM

20140873.

Proteomic databases

PaxDb

Q9NR97.

PRIDE

Q9NR97.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000218032; ENSP00000218032; ENSG00000101916.

GeneID

51311.

KEGG

hsa:51311.

UCSC

uc004cve.3. human.

Organism-specific databases

CTD

51311.

GeneCards

GC0XP012924.

H-InvDB

HIX0176772.

HGNC

HGNC:15632. TLR8.

HPA

HPA001608.

MIM

300366. gene.

neXtProt

NX_Q9NR97.

PharmGKB

PA38009.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4886.

HOGENOM

HOG000230468.

HOVERGEN

HBG018601.

K10170.

OrthoDB

EOG47SSCZ.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9NR97.

Bgee

Q9NR97.

CleanEx

HS_TLR8.

Genevestigator

Q9NR97.

GermOnline

ENSG00000101916. Homo sapiens.

Family and domain databases

InterPro

IPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027175. TLR8.
[Graphical view]

PANTHER

PTHR24365:SF2. PTHR24365:SF2. 1 hit.

Pfam

PF00560. LRR_1. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]

SMART

SM00369. LRR_TYP. 3 hits.
SM00082. LRRCT. 1 hit.
[Graphical view]

SUPFAM

SSF52200. TIR. 1 hit.

PROSITE

PS51450. LRR. 20 hits.
PS50104. TIR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9NR97.

ChEMBL

CHEMBL5805.

GenomeRNAi

51311.

NextBio

54647.

SOURCE

Search...

Entry information

Entry name

TLR8_HUMAN

Accession

Primary (citable) accession number: Q9NR97
Secondary accession number(s): B3Y654

Q9NYG9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	October 1, 2000
Last modified:	May 29, 2013
This is version 116 of the entry and version 1 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.