TLR5

Protein identityUniProt · HPA

UniProt accession

O60602

Gene

TLR5

Ensembl

ENSG00000187554

Chromosome

1

Canonical length

858 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Golgi apparatus,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immune responses. These receptors recognize distinct pathogen-associated molecular patterns that are expressed on infectious agents. The protein encoded by this gene recognizes bacterial flagellin, the principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-kappaB, which in turn activates a host of inflammatory-related target genes. Mutations in this gene have been associated with both resistance and susceptibility to systemic lupus erythematosus, and susceptibility to Legionnaire disease.[provided by RefSeq, Dec 2009]

Canonical amino-acid sequenceUniProt

858 residues, UniProt reviewed canonical sequence.

>O60602|TLR5
     1  MGDHLDLLLG VVLMAGPVFG IPSCSFDGRI AFYRFCNLTQ VPQVLNTTER LLLSFNYIRT
    61  VTASSFPFLE QLQLLELGSQ YTPLTIDKEA FRNLPNLRIL DLGSSKIYFL HPDAFQGLFH
   121  LFELRLYFCG LSDAVLKDGY FRNLKALTRL DLSKNQIRSL YLHPSFGKLN SLKSIDFSSN
   181  QIFLVCEHEL EPLQGKTLSF FSLAANSLYS RVSVDWGKCM NPFRNMVLEI LDVSGNGWTV
   241  DITGNFSNAI SKSQAFSLIL AHHIMGAGFG FHNIKDPDQN TFAGLARSSV RHLDLSHGFV
   301  FSLNSRVFET LKDLKVLNLA YNKINKIADE AFYGLDNLQV LNLSYNLLGE LYSSNFYGLP
   361  KVAYIDLQKN HIAIIQDQTF KFLEKLQTLD LRDNALTTIH FIPSIPDIFL SGNKLVTLPK
   421  INLTANLIHL SENRLENLDI LYFLLRVPHL QILILNQNRF SSCSGDQTPS ENPSLEQLFL
   481  GENMLQLAWE TELCWDVFEG LSHLQVLYLN HNYLNSLPPG VFSHLTALRG LSLNSNRLTV
   541  LSHNDLPANL EILDISRNQL LAPNPDVFVS LSVLDITHNK FICECELSTF INWLNHTNVT
   601  IAGPPADIYC VYPDSFSGVS LFSLSTEGCD EEEVLKSLKF SLFIVCTVTL TLFLMTILTV
   661  TKFRGFCFIC YKTAQRLVFK DHPQGTEPDM YKYDAYLCFS SKDFTWVQNA LLKHLDTQYS
   721  DQNRFNLCFE ERDFVPGENR IANIQDAIWN SRKIVCLVSR HFLRDGWCLE AFSYAQGRCL
   781  SDLNSALIMV VVGSLSQYQL MKHQSIRGFV QKQQYLRWPE DLQDVGWFLH KLSQQILKKE
   841  KEKKKDNNIP LQTVATIS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TLR5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TLR5.

Disease | AllUniProt

Conditions TLR5 is implicated in, by any mechanism.

• Systemic lupus erythematosus 1 (SLEB1) MIM:601744

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 131 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Systemic lupus erythematosus, susceptibility to, 1

Disease | ImmuneIEDB

Conditions an epitope on TLR5 was assayed in.

• influenza T cell

ReferencesPubMed · IEDB

Publications for TLR5 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.38

gnomAD pLI

0

gnomAD missense Z

0.39

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to lipopolysaccharide
• cellular response to mechanical stimulus
• inflammatory response
• innate immune response
• male gonad development
• positive regulation of interleukin-8 production
• positive regulation of nitric oxide biosynthetic process
• toll-like receptor 5 signaling pathway
• toll-like receptor signaling pathway

Molecular functions

• interleukin-1 receptor binding
• pattern recognition receptor activity
• signaling receptor activity
• transmembrane signaling receptor activity

Cellular components

• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Toll/interleukin-1 receptor homology (TIR) domain
• Cysteine-rich flanking region, C-terminal
• Leucine-rich repeat
• Leucine-rich repeat, typical subtype
• Toll-like receptor
• Leucine-rich repeat domain superfamily
• Toll/interleukin-1 receptor homology (TIR) domain superfamily
• Leucine Rich Repeat
• TIR domain
• Leucine rich repeat

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunity
• Inflammatory response
• Innate immunity
• Leucine-rich repeat
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Systemic lupus erythematosus
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of TLR5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MYD88
• TICAM1
• UNC93B1
• SIGIRR
• RNF216