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Protein

Toll-like receptor 5

Gene

TLR5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • interleukin-1 receptor binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000187554.11
HGNCiHGNC:11851 TLR5
MIMi603031 gene
neXtProtiNX_O60602

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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

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...) asparagine1 Publication1
Glycosylationi46N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi245N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi342N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi422N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi583 ↔ 6101 Publication
Disulfide bondi585 ↔ 6291 Publication
Glycosylationi595N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi598N-linked (GlcNAc...) asparagine1 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
ProteomicsDBi49480

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 Expressed in 188 organ(s), highest expression level in blood
CleanExiHS_TLR5
ExpressionAtlasiO60602 baseline and differential
GenevisibleiO60602 HS

Organism-specific databases

HPAiCAB009013

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

Protein-protein interaction databases

BioGridi112955, 13 interactors
IntActiO60602, 9 interactors
MINTiO60602
STRINGi9606.ENSP00000340089

Structurei

3D structure databases

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

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, 3 hits
InterProiView 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
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44698:SF2 PTHR44698:SF2, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 5 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 9 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 12 hits
PS50104 TIR, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y7Z4A0A2R8Y7Z4_HUMAN
Toll-like receptor 5
TLR5
858Annotation score:
A0A2R8Y4Q2A0A2R8Y4Q2_HUMAN
Toll-like receptor 5
TLR5
775Annotation score:
B1AZ06B1AZ06_HUMAN
Toll-like receptor 5
TLR5
21Annotation score:

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 dbSNP:rs764535Ensembl.1
Natural variantiVAR_032456112P → A. Corresponds to variant dbSNP:rs5744166Ensembl.1
Natural variantiVAR_061856143N → T. Corresponds to variant dbSNP:rs5744167Ensembl.1
Natural variantiVAR_061857181Q → K. Corresponds to variant dbSNP:rs45528236Ensembl.1
Natural variantiVAR_018398392 – 858Missing in 10% of the population; abolishes flagellin signaling; associated with resistance to SLEB1. 1 PublicationAdd BLAST467
Natural variantiVAR_018399592N → S2 PublicationsCorresponds to variant dbSNP:rs2072493EnsemblClinVar.1
Natural variantiVAR_018400616F → L3 PublicationsCorresponds to variant dbSNP:rs5744174Ensembl.1
Natural variantiVAR_070457644I → F1 PublicationCorresponds to variant dbSNP:rs5744175EnsemblClinVar.1
Natural variantiVAR_061858769L → F. Corresponds to variant dbSNP:rs56243703Ensembl.1
Natural variantiVAR_047454822F → L8 PublicationsCorresponds to variant dbSNP:rs7512943Ensembl.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 No translation available.
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

Similar proteinsi

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 No translation available.
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, 9 interactors
MINTiO60602
STRINGi9606.ENSP00000340089

Chemistry databases

ChEMBLiCHEMBL2176839

PTM databases

iPTMnetiO60602
PhosphoSitePlusiO60602

Polymorphism and mutation databases

BioMutaiTLR5

Proteomic databases

PaxDbiO60602
PeptideAtlasiO60602
PRIDEiO60602
ProteomicsDBi49480

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
EuPathDBiHostDB:ENSG00000187554.11
GeneCardsiTLR5
HGNCiHGNC:11851 TLR5
HPAiCAB009013
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

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

ChiTaRSiTLR5 human
GeneWikiiTLR_5
GenomeRNAii7100
PROiPR:O60602
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000187554 Expressed in 188 organ(s), highest expression level in blood
CleanExiHS_TLR5
ExpressionAtlasiO60602 baseline and differential
GenevisibleiO60602 HS

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 3 hits
InterProiView 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
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44698:SF2 PTHR44698:SF2, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 5 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 9 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 12 hits
PS50104 TIR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTLR5_HUMAN
AccessioniPrimary (citable) accession number: O60602
Secondary accession number(s): B1AZ05
, B3Y633, B9VJ63, D1CS80, D3DTB8, O15456, Q32MI2, Q32MI3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: November 25, 2008
Last modified: September 12, 2018
This is version 171 of the entry and version 4 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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