UniProtKB - O60602 (TLR5_HUMAN)
Protein
Toll-like receptor 5
Gene
TLR5
Organism
Homo sapiens (Human)
Status
Functioni
Pattern recognition receptor (PRR) located on the cell surface that participates in the activation of innate immunity and inflammatory response (PubMed:11323673, PubMed:18490781). Recognizes small molecular motifs named pathogen-associated molecular pattern (PAMPs) expressed by pathogens and microbe-associated molecular patterns (MAMPs) usually expressed by resident microbiota (PubMed:29934223). Upon ligand binding such as bacterial flagellins, recruits intracellular adapter proteins MYD88 and TRIF leading to NF-kappa-B activation, cytokine secretion and induction of the inflammatory response (PubMed:20855887, PubMed:11489966). Plays thereby an important role in the relationship between the intestinal epithelium and enteric microbes and contributes to the gut microbiota composition throughout life (By similarity).By similarity5 Publications
GO - Molecular functioni
- interleukin-1 receptor binding Source: UniProtKB
- signaling receptor activity Source: GO_Central
- transmembrane signaling receptor activity Source: InterPro
GO - Biological processi
- cellular response to mechanical stimulus Source: UniProtKB
- defense response to bacterium Source: InterPro
- inflammatory response Source: GO_Central
- innate immune response Source: UniProtKB-KW
- MyD88-dependent toll-like receptor signaling pathway Source: Reactome
- positive regulation of interleukin-8 production Source: BHF-UCL
- positive regulation of toll-like receptor signaling pathway Source: BHF-UCL
- regulation of cytokine secretion Source: InterPro
- toll-like receptor 5 signaling pathway Source: Reactome
- toll-like receptor signaling pathway Source: GO_Central
Keywordsi
Molecular function | Receptor |
Biological process | Immunity, Inflammatory response, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | O60602 |
Reactomei | R-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 |
SIGNORi | O60602 |
Names & Taxonomyi
Protein namesi | Recommended name: Toll-like receptor 5Alternative name(s): Toll/interleukin-1 receptor-like protein 3 |
Gene namesi | Name:TLR5 Synonyms:TIL3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000187554.11 |
HGNCi | HGNC:11851, TLR5 |
MIMi | 603031, gene |
neXtProti | NX_O60602 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein Sequence analysis
Plasma Membrane
- integral component of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 21 – 639 | ExtracellularSequence analysisAdd BLAST | 619 | |
Transmembranei | 640 – 660 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 661 – 858 | CytoplasmicSequence analysisAdd BLAST | 198 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & 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.
Related information in OMIMKeywords - Diseasei
Systemic lupus erythematosusOrganism-specific databases
DisGeNETi | 7100 |
MalaCardsi | TLR5 |
MIMi | 109100, phenotype 601744, phenotype 608556, phenotype 615557, phenotype |
PharmGKBi | PA36553 |
Miscellaneous databases
Pharosi | O60602, Tbio |
Chemistry databases
ChEMBLi | CHEMBL2176839 |
Polymorphism and mutation databases
BioMutai | TLR5 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | 1 PublicationAdd BLAST | 20 | |
ChainiPRO_0000034729 | 21 – 858 | Toll-like receptor 5Add BLAST | 838 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 37 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 46 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 245 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 342 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 422 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 583 ↔ 610 | 1 Publication | ||
Disulfide bondi | 585 ↔ 629 | 1 Publication | ||
Glycosylationi | 595 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 598 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Modified residuei | 798 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 805 | Phosphoserine; by PKD/PRKD11 Publication | 1 |
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, PhosphoproteinProteomic databases
jPOSTi | O60602 |
MassIVEi | O60602 |
PaxDbi | O60602 |
PeptideAtlasi | O60602 |
PRIDEi | O60602 |
ProteomicsDBi | 49480 |
PTM databases
GlyGeni | O60602, 7 sites |
iPTMneti | O60602 |
PhosphoSitePlusi | O60602 |
Expressioni
Tissue specificityi
Highly expressed on the basolateral surface of intestinal epithelia (PubMed:11489966). Expressed also in other cells such as lung epithelial cells (PubMed:11489966, PubMed:18490781).2 Publications
Gene expression databases
Bgeei | ENSG00000187554, Expressed in blood and 207 other tissues |
ExpressionAtlasi | O60602, baseline and differential |
Genevisiblei | O60602, HS |
Organism-specific databases
HPAi | ENSG00000187554, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsO60602
With | #Exp. | IntAct |
---|---|---|
Amyloid-beta protein 42 (PRO_0000000092) | 3 | EBI-3505951,EBI-821758 |
Amyloid-beta protein 40 (PRO_0000000093) | 3 | EBI-3505951,EBI-2431589 |
GO - Molecular functioni
- interleukin-1 receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 112955, 13 interactors |
IntActi | O60602, 21 interactors |
MINTi | O60602 |
STRINGi | 9606.ENSP00000440643 |
Chemistry databases
BindingDBi | O60602 |
Miscellaneous databases
RNActi | O60602, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 45 – 68 | LRR 11 PublicationAdd BLAST | 24 | |
Repeati | 71 – 93 | LRR 21 PublicationAdd BLAST | 23 | |
Repeati | 95 – 117 | LRR 31 PublicationAdd BLAST | 23 | |
Repeati | 120 – 143 | LRR 41 PublicationAdd BLAST | 24 | |
Repeati | 146 – 166 | LRR 51 PublicationAdd BLAST | 21 | |
Repeati | 171 – 192 | LRR 61 PublicationAdd BLAST | 22 | |
Repeati | 197 – 211 | LRR 71 PublicationAdd BLAST | 15 | |
Repeati | 214 – 229 | LRR 81 PublicationAdd BLAST | 16 | |
Repeati | 234 – 235 | LRR 91 Publication | 2 | |
Repeati | 260 – 284 | LRR 111 PublicationAdd BLAST | 25 | |
Repeati | 289 – 301 | LRR 121 PublicationAdd BLAST | 13 | |
Repeati | 313 – 334 | LRR 131 PublicationAdd BLAST | 22 | |
Repeati | 337 – 355 | LRR 141 PublicationAdd BLAST | 19 | |
Repeati | 385 – 401 | LRR 161 PublicationAdd BLAST | 17 | |
Repeati | 412 – 431 | LRR 171 PublicationAdd BLAST | 20 | |
Repeati | 449 – 470 | LRR 181 PublicationAdd BLAST | 22 | |
Repeati | 474 – 495 | LRR 191 PublicationAdd BLAST | 22 | |
Repeati | 503 – 524 | LRR 201 PublicationAdd BLAST | 22 | |
Repeati | 527 – 546 | LRR 211 PublicationAdd BLAST | 20 | |
Repeati | 549 – 567 | LRR 221 PublicationAdd BLAST | 19 | |
Domaini | 579 – 631 | LRRCTAdd BLAST | 53 | |
Domaini | 691 – 836 | TIRPROSITE-ProRule annotationAdd BLAST | 146 |
Sequence similaritiesi
Belongs to the Toll-like receptor family.Curated
Keywords - Domaini
Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4641, Eukaryota |
HOGENOMi | CLU_006000_4_1_1 |
InParanoidi | O60602 |
OrthoDBi | 282372at2759 |
PhylomeDBi | O60602 |
TreeFami | TF351113 |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 3 hits |
InterProi | View protein in InterPro IPR000483, Cys-rich_flank_reg_C IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR027176, TLR5 IPR017241, Toll-like_receptor IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR24365, PTHR24365, 1 hit PTHR24365:SF525, PTHR24365:SF525, 1 hit |
Pfami | View protein in Pfam PF13855, LRR_8, 5 hits PF01582, TIR, 1 hit |
PIRSFi | PIRSF037595, Toll-like_receptor, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 9 hits SM00082, LRRCT, 1 hit SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 12 hits PS50104, TIR, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
O60602-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8Y7Z4 | A0A2R8Y7Z4_HUMAN | Toll-like receptor 5 | TLR5 | 858 | Annotation score: | ||
A0A2R8Y4Q2 | A0A2R8Y4Q2_HUMAN | Toll-like receptor 5 | TLR5 | 775 | Annotation score: | ||
B1AZ06 | B1AZ06_HUMAN | Toll-like receptor 5 | TLR5 | 21 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 231 | L → V in AAC34376 (PubMed:9596645).Curated | 1 | |
Sequence conflicti | 352 | Y → C in AAC34376 (PubMed:9596645).Curated | 1 | |
Sequence conflicti | 387 | Q → R in AAI09120 (PubMed:15489334).Curated | 1 |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032455 | 82 | T → I. Corresponds to variant dbSNP:rs764535EnsemblClinVar. | 1 | |
Natural variantiVAR_032456 | 112 | P → A. Corresponds to variant dbSNP:rs5744166EnsemblClinVar. | 1 | |
Natural variantiVAR_061856 | 143 | N → T. Corresponds to variant dbSNP:rs5744167EnsemblClinVar. | 1 | |
Natural variantiVAR_061857 | 181 | Q → K. Corresponds to variant dbSNP:rs45528236Ensembl. | 1 | |
Natural variantiVAR_018398 | 392 – 858 | Missing in 10% of the population; abolishes flagellin signaling; associated with resistance to SLEB1. 1 PublicationAdd BLAST | 467 | |
Natural variantiVAR_018399 | 592 | N → S2 PublicationsCorresponds to variant dbSNP:rs2072493EnsemblClinVar. | 1 | |
Natural variantiVAR_018400 | 616 | F → L3 PublicationsCorresponds to variant dbSNP:rs5744174Ensembl. | 1 | |
Natural variantiVAR_070457 | 644 | I → F1 PublicationCorresponds to variant dbSNP:rs5744175EnsemblClinVar. | 1 | |
Natural variantiVAR_061858 | 769 | L → F. Corresponds to variant dbSNP:rs56243703Ensembl. | 1 | |
Natural variantiVAR_047454 | 822 | F → L8 PublicationsCorresponds to variant dbSNP:rs7512943Ensembl. | 1 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000366881; ENSP00000355846; ENSG00000187554 ENST00000540964; ENSP00000440643; ENSG00000187554 |
GeneIDi | 7100 |
KEGGi | hsa:7100 |
UCSCi | uc001hnw.3, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1P95 | model | - | B | 551-560 | [»] | |
3J0A | electron microscopy | 26.00 | A/B | 23-858 | [»] | |
SMRi | O60602 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112955, 13 interactors |
IntActi | O60602, 21 interactors |
MINTi | O60602 |
STRINGi | 9606.ENSP00000440643 |
Chemistry databases
BindingDBi | O60602 |
ChEMBLi | CHEMBL2176839 |
PTM databases
GlyGeni | O60602, 7 sites |
iPTMneti | O60602 |
PhosphoSitePlusi | O60602 |
Polymorphism and mutation databases
BioMutai | TLR5 |
Proteomic databases
jPOSTi | O60602 |
MassIVEi | O60602 |
PaxDbi | O60602 |
PeptideAtlasi | O60602 |
PRIDEi | O60602 |
ProteomicsDBi | 49480 |
Protocols and materials databases
Antibodypediai | 2711, 922 antibodies |
DNASUi | 7100 |
Genome annotation databases
Ensembli | ENST00000366881; ENSP00000355846; ENSG00000187554 ENST00000540964; ENSP00000440643; ENSG00000187554 |
GeneIDi | 7100 |
KEGGi | hsa:7100 |
UCSCi | uc001hnw.3, human |
Organism-specific databases
CTDi | 7100 |
DisGeNETi | 7100 |
EuPathDBi | HostDB:ENSG00000187554.11 |
GeneCardsi | TLR5 |
HGNCi | HGNC:11851, TLR5 |
HPAi | ENSG00000187554, Low tissue specificity |
MalaCardsi | TLR5 |
MIMi | 109100, phenotype 601744, phenotype 603031, gene 608556, phenotype 615557, phenotype |
neXtProti | NX_O60602 |
PharmGKBi | PA36553 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4641, Eukaryota |
HOGENOMi | CLU_006000_4_1_1 |
InParanoidi | O60602 |
OrthoDBi | 282372at2759 |
PhylomeDBi | O60602 |
TreeFami | TF351113 |
Enzyme and pathway databases
PathwayCommonsi | O60602 |
Reactomei | R-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 |
SIGNORi | O60602 |
Miscellaneous databases
BioGRID-ORCSi | 7100, 3 hits in 822 CRISPR screens |
GeneWikii | TLR_5 |
GenomeRNAii | 7100 |
Pharosi | O60602, Tbio |
PROi | PR:O60602 |
RNActi | O60602, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000187554, Expressed in blood and 207 other tissues |
ExpressionAtlasi | O60602, baseline and differential |
Genevisiblei | O60602, HS |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 3 hits |
InterProi | View protein in InterPro IPR000483, Cys-rich_flank_reg_C IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR027176, TLR5 IPR017241, Toll-like_receptor IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR24365, PTHR24365, 1 hit PTHR24365:SF525, PTHR24365:SF525, 1 hit |
Pfami | View protein in Pfam PF13855, LRR_8, 5 hits PF01582, TIR, 1 hit |
PIRSFi | PIRSF037595, Toll-like_receptor, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 9 hits SM00082, LRRCT, 1 hit SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 12 hits PS50104, TIR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TLR5_HUMAN | |
Accessioni | O60602Primary (citable) accession number: O60602 Secondary accession number(s): B1AZ05 Q32MI3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 31, 2002 |
Last sequence update: | November 25, 2008 | |
Last modified: | December 2, 2020 | |
This is version 184 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations