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Protein

Toll-like receptor 5

Gene

TLR5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Participates in the innate immune response to microbial agents. Mediates detection of bacterial flagellins. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:G66-32151-MONOMER.
ReactomeiR-HSA-168176. Toll Like Receptor 5 (TLR5) Cascade.
R-HSA-5602680. MyD88 deficiency (TLR5).
R-HSA-5603037. IRAK4 deficiency (TLR5).
R-HSA-975871. MyD88 cascade initiated on plasma membrane.
SIGNORiO60602.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 5
Alternative name(s):
Toll/interleukin-1 receptor-like protein 3
Gene namesi
Name:TLR5
Synonyms:TIL3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:11851. TLR5.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 639ExtracellularSequence analysisAdd BLAST619
Transmembranei640 – 660HelicalSequence analysisAdd BLAST21
Topological domaini661 – 858CytoplasmicSequence analysisAdd BLAST198

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Systemic lupus erythematosus 1 (SLEB1)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
See also OMIM:601744
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018398392 – 858Missing in 10% of the population; abolishes flagellin signaling; associated with resistance to SLEB1. 1 PublicationAdd BLAST467

Keywords - Diseasei

Systemic lupus erythematosus

Organism-specific databases

DisGeNETi7100.
MalaCardsiTLR5.
MIMi109100. phenotype.
601744. phenotype.
608556. phenotype.
615557. phenotype.
PharmGKBiPA36553.

Chemistry databases

ChEMBLiCHEMBL2176839.

Polymorphism and mutation databases

BioMutaiTLR5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000003472921 – 858Toll-like receptor 5Add BLAST838

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi37N-linked (GlcNAc...)1 Publication1
Glycosylationi46N-linked (GlcNAc...)1 Publication1
Glycosylationi245N-linked (GlcNAc...)1 Publication1
Glycosylationi342N-linked (GlcNAc...)1 Publication1
Glycosylationi422N-linked (GlcNAc...)1 Publication1
Disulfide bondi583 ↔ 6101 Publication
Disulfide bondi585 ↔ 6291 Publication
Glycosylationi595N-linked (GlcNAc...)1 Publication1
Glycosylationi598N-linked (GlcNAc...)1 Publication1
Modified residuei798Phosphotyrosine1 Publication1
Modified residuei805Phosphoserine; by PKD/PRKD11 Publication1

Post-translational modificationi

Phosphorylated at Ser-805 by PKD/PRKD1; phosphorylation induces the production of inflammatory cytokines.2 Publications
Phosphorylated at Tyr-798 upon flagellin binding; required for signaling.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO60602.
PeptideAtlasiO60602.
PRIDEiO60602.

PTM databases

iPTMnetiO60602.
PhosphoSitePlusiO60602.

Expressioni

Tissue specificityi

Highly expressed in ovary and in peripheral blood leukocytes, especially in monocytes, less in CD11c+ immature dendritic cells. Also detected in prostate and testis.

Gene expression databases

BgeeiENSG00000187554.
CleanExiHS_TLR5.
ExpressionAtlasiO60602. baseline and differential.
GenevisibleiO60602. HS.

Organism-specific databases

HPAiCAB009013.
HPA015573.

Interactioni

Subunit structurei

Binds MYD88 via their respective TIR domains (By similarity). Homodimer both in the absence and presence of ligand.By similarity1 Publication

GO - Molecular functioni

  • interleukin-1 receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112955. 13 interactors.
IntActiO60602. 2 interactors.
MINTiMINT-4950390.
STRINGi9606.ENSP00000340089.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P95model-B551-560[»]
3J0Aelectron microscopy26.00A/B23-858[»]
ProteinModelPortaliO60602.
SMRiO60602.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati45 – 68LRR 11 PublicationAdd BLAST24
Repeati71 – 93LRR 21 PublicationAdd BLAST23
Repeati95 – 117LRR 31 PublicationAdd BLAST23
Repeati120 – 143LRR 41 PublicationAdd BLAST24
Repeati146 – 166LRR 51 PublicationAdd BLAST21
Repeati171 – 192LRR 61 PublicationAdd BLAST22
Repeati197 – 211LRR 71 PublicationAdd BLAST15
Repeati214 – 229LRR 81 PublicationAdd BLAST16
Repeati234 – 235LRR 91 Publication2
Repeati260 – 284LRR 111 PublicationAdd BLAST25
Repeati289 – 301LRR 121 PublicationAdd BLAST13
Repeati313 – 334LRR 131 PublicationAdd BLAST22
Repeati337 – 355LRR 141 PublicationAdd BLAST19
Repeati385 – 401LRR 161 PublicationAdd BLAST17
Repeati412 – 431LRR 171 PublicationAdd BLAST20
Repeati449 – 470LRR 181 PublicationAdd BLAST22
Repeati474 – 495LRR 191 PublicationAdd BLAST22
Repeati503 – 524LRR 201 PublicationAdd BLAST22
Repeati527 – 546LRR 211 PublicationAdd BLAST20
Repeati549 – 567LRR 221 PublicationAdd BLAST19
Domaini579 – 631LRRCTAdd BLAST53
Domaini691 – 837TIRPROSITE-ProRule annotationAdd BLAST147

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
Contains 22 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 TIR domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000008675.
HOVERGENiHBG023182.
InParanoidiO60602.
KOiK10168.
OrthoDBiEOG091G030N.
PhylomeDBiO60602.
TreeFamiTF351113.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 5 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027176. TLR5.
[Graphical view]
PANTHERiPTHR24365:SF311. PTHR24365:SF311. 1 hit.
PfamiPF13855. LRR_8. 5 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 9 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 12 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O60602-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDHLDLLLG VVLMAGPVFG IPSCSFDGRI AFYRFCNLTQ VPQVLNTTER
60 70 80 90 100
LLLSFNYIRT VTASSFPFLE QLQLLELGSQ YTPLTIDKEA FRNLPNLRIL
110 120 130 140 150
DLGSSKIYFL HPDAFQGLFH LFELRLYFCG LSDAVLKDGY FRNLKALTRL
160 170 180 190 200
DLSKNQIRSL YLHPSFGKLN SLKSIDFSSN QIFLVCEHEL EPLQGKTLSF
210 220 230 240 250
FSLAANSLYS RVSVDWGKCM NPFRNMVLEI LDVSGNGWTV DITGNFSNAI
260 270 280 290 300
SKSQAFSLIL AHHIMGAGFG FHNIKDPDQN TFAGLARSSV RHLDLSHGFV
310 320 330 340 350
FSLNSRVFET LKDLKVLNLA YNKINKIADE AFYGLDNLQV LNLSYNLLGE
360 370 380 390 400
LYSSNFYGLP KVAYIDLQKN HIAIIQDQTF KFLEKLQTLD LRDNALTTIH
410 420 430 440 450
FIPSIPDIFL SGNKLVTLPK INLTANLIHL SENRLENLDI LYFLLRVPHL
460 470 480 490 500
QILILNQNRF SSCSGDQTPS ENPSLEQLFL GENMLQLAWE TELCWDVFEG
510 520 530 540 550
LSHLQVLYLN HNYLNSLPPG VFSHLTALRG LSLNSNRLTV LSHNDLPANL
560 570 580 590 600
EILDISRNQL LAPNPDVFVS LSVLDITHNK FICECELSTF INWLNHTNVT
610 620 630 640 650
IAGPPADIYC VYPDSFSGVS LFSLSTEGCD EEEVLKSLKF SLFIVCTVTL
660 670 680 690 700
TLFLMTILTV TKFRGFCFIC YKTAQRLVFK DHPQGTEPDM YKYDAYLCFS
710 720 730 740 750
SKDFTWVQNA LLKHLDTQYS DQNRFNLCFE ERDFVPGENR IANIQDAIWN
760 770 780 790 800
SRKIVCLVSR HFLRDGWCLE AFSYAQGRCL SDLNSALIMV VVGSLSQYQL
810 820 830 840 850
MKHQSIRGFV QKQQYLRWPE DFQDVGWFLH KLSQQILKKE KEKKKDNNIP

LQTVATIS
Length:858
Mass (Da):97,834
Last modified:November 25, 2008 - v4
Checksum:i9EE0AB6EEFEA9051
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti231L → V in AAC34376 (PubMed:9596645).Curated1
Sequence conflicti352Y → C in AAC34376 (PubMed:9596645).Curated1
Sequence conflicti387Q → R in AAI09120 (PubMed:15489334).Curated1

Polymorphismi

Individuals with a common stop codon polymorphism in position 392 are unable to mediate flagellin signaling. This polymorphism acts in a dominant fashion and is associated with susceptibility to pneumonia caused by Legionella pneumophila [MIMi:608556]. It also provides protection against systemic lupus erythematosus.
A nonsense TLR5 polymorphism, resulting in p.Arg392Ter, confers resistance to melioidosis [MIMi:615557], an infection caused by the Gram-negative, flagellated soil saprophyte Burkholderia pseudomallei. Carriers of this hypofunctional TLR5 variant may generate impaired inflammatory responses during melioidosis infection that result in reduced organ failure and lower mortality.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03245582T → I.Corresponds to variant rs764535dbSNPEnsembl.1
Natural variantiVAR_032456112P → A.Corresponds to variant rs5744166dbSNPEnsembl.1
Natural variantiVAR_061856143N → T.Corresponds to variant rs5744167dbSNPEnsembl.1
Natural variantiVAR_061857181Q → K.Corresponds to variant rs45528236dbSNPEnsembl.1
Natural variantiVAR_018398392 – 858Missing in 10% of the population; abolishes flagellin signaling; associated with resistance to SLEB1. 1 PublicationAdd BLAST467
Natural variantiVAR_018399592N → S.2 PublicationsCorresponds to variant rs2072493dbSNPEnsembl.1
Natural variantiVAR_018400616F → L.3 PublicationsCorresponds to variant rs5744174dbSNPEnsembl.1
Natural variantiVAR_070457644I → F.1 PublicationCorresponds to variant rs5744175dbSNPEnsembl.1
Natural variantiVAR_061858769L → F.Corresponds to variant rs56243703dbSNPEnsembl.1
Natural variantiVAR_047454822F → L.8 PublicationsCorresponds to variant rs7512943dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF051151 mRNA. Translation: AAC34376.1.
AB060695 mRNA. Translation: BAB43955.1.
AB445645 mRNA. Translation: BAG55042.1.
FJ556976 Genomic DNA. Translation: ACM69019.1.
FJ556977 Genomic DNA. Translation: ACM69020.1.
FJ556979 Genomic DNA. Translation: ACM69022.1.
FJ556980 Genomic DNA. Translation: ACM69023.1.
FJ556987 Genomic DNA. Translation: ACM69030.1.
FJ556989 Genomic DNA. Translation: ACM69032.1.
DQ026408 Genomic DNA. Translation: AAZ17463.1.
DQ026409 Genomic DNA. Translation: AAZ17464.1.
DQ026415 Genomic DNA. Translation: AAZ17469.1.
AL929091 Genomic DNA. Translation: CAM28378.1.
CH471100 Genomic DNA. Translation: EAW93262.1.
CH471100 Genomic DNA. Translation: EAW93263.1.
BC109118 mRNA. Translation: AAI09119.1.
BC109119 mRNA. Translation: AAI09120.1.
U88881 mRNA. Translation: AAC34136.1.
CCDSiCCDS31033.1.
RefSeqiNP_003259.2. NM_003268.5.
XP_005273298.2. XM_005273241.4.
XP_005273299.2. XM_005273242.4.
XP_005273300.2. XM_005273243.4.
XP_006711567.1. XM_006711504.3.
XP_006711568.1. XM_006711505.3.
XP_006711569.1. XM_006711506.3.
XP_011508239.1. XM_011509937.2.
XP_016857697.1. XM_017002208.1.
UniGeneiHs.604542.

Genome annotation databases

EnsembliENST00000366881; ENSP00000355846; ENSG00000187554.
ENST00000540964; ENSP00000440643; ENSG00000187554.
GeneIDi7100.
KEGGihsa:7100.
UCSCiuc001hnw.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF051151 mRNA. Translation: AAC34376.1.
AB060695 mRNA. Translation: BAB43955.1.
AB445645 mRNA. Translation: BAG55042.1.
FJ556976 Genomic DNA. Translation: ACM69019.1.
FJ556977 Genomic DNA. Translation: ACM69020.1.
FJ556979 Genomic DNA. Translation: ACM69022.1.
FJ556980 Genomic DNA. Translation: ACM69023.1.
FJ556987 Genomic DNA. Translation: ACM69030.1.
FJ556989 Genomic DNA. Translation: ACM69032.1.
DQ026408 Genomic DNA. Translation: AAZ17463.1.
DQ026409 Genomic DNA. Translation: AAZ17464.1.
DQ026415 Genomic DNA. Translation: AAZ17469.1.
AL929091 Genomic DNA. Translation: CAM28378.1.
CH471100 Genomic DNA. Translation: EAW93262.1.
CH471100 Genomic DNA. Translation: EAW93263.1.
BC109118 mRNA. Translation: AAI09119.1.
BC109119 mRNA. Translation: AAI09120.1.
U88881 mRNA. Translation: AAC34136.1.
CCDSiCCDS31033.1.
RefSeqiNP_003259.2. NM_003268.5.
XP_005273298.2. XM_005273241.4.
XP_005273299.2. XM_005273242.4.
XP_005273300.2. XM_005273243.4.
XP_006711567.1. XM_006711504.3.
XP_006711568.1. XM_006711505.3.
XP_006711569.1. XM_006711506.3.
XP_011508239.1. XM_011509937.2.
XP_016857697.1. XM_017002208.1.
UniGeneiHs.604542.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P95model-B551-560[»]
3J0Aelectron microscopy26.00A/B23-858[»]
ProteinModelPortaliO60602.
SMRiO60602.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112955. 13 interactors.
IntActiO60602. 2 interactors.
MINTiMINT-4950390.
STRINGi9606.ENSP00000340089.

Chemistry databases

ChEMBLiCHEMBL2176839.

PTM databases

iPTMnetiO60602.
PhosphoSitePlusiO60602.

Polymorphism and mutation databases

BioMutaiTLR5.

Proteomic databases

PaxDbiO60602.
PeptideAtlasiO60602.
PRIDEiO60602.

Protocols and materials databases

DNASUi7100.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366881; ENSP00000355846; ENSG00000187554.
ENST00000540964; ENSP00000440643; ENSG00000187554.
GeneIDi7100.
KEGGihsa:7100.
UCSCiuc001hnw.3. human.

Organism-specific databases

CTDi7100.
DisGeNETi7100.
GeneCardsiTLR5.
HGNCiHGNC:11851. TLR5.
HPAiCAB009013.
HPA015573.
MalaCardsiTLR5.
MIMi109100. phenotype.
601744. phenotype.
603031. gene.
608556. phenotype.
615557. phenotype.
neXtProtiNX_O60602.
PharmGKBiPA36553.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOGENOMiHOG000008675.
HOVERGENiHBG023182.
InParanoidiO60602.
KOiK10168.
OrthoDBiEOG091G030N.
PhylomeDBiO60602.
TreeFamiTF351113.

Enzyme and pathway databases

BioCyciZFISH:G66-32151-MONOMER.
ReactomeiR-HSA-168176. Toll Like Receptor 5 (TLR5) Cascade.
R-HSA-5602680. MyD88 deficiency (TLR5).
R-HSA-5603037. IRAK4 deficiency (TLR5).
R-HSA-975871. MyD88 cascade initiated on plasma membrane.
SIGNORiO60602.

Miscellaneous databases

GeneWikiiTLR_5.
GenomeRNAii7100.
PROiO60602.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187554.
CleanExiHS_TLR5.
ExpressionAtlasiO60602. baseline and differential.
GenevisibleiO60602. HS.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 5 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027176. TLR5.
[Graphical view]
PANTHERiPTHR24365:SF311. PTHR24365:SF311. 1 hit.
PfamiPF13855. LRR_8. 5 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 9 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 12 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLR5_HUMAN
AccessioniPrimary (citable) accession number: O60602
Secondary accession number(s): B1AZ05
, B3Y633, B9VJ63, D1CS80, D3DTB8, O15456, Q32MI2, Q32MI3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: November 25, 2008
Last modified: November 2, 2016
This is version 159 of the entry and version 4 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.