Seroatlas · Human Serome Atlas

TLR4

Toll-like receptor 4

Also known as: ARMD10, CD284, hToll, TLR-4, TLR4_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O00206
Gene
TLR4
Ensembl
ENSG00000136869
Chromosome
9
Canonical length
839 aa
Protein class
CD markers, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters
Subcellular location
Golgi apparatus,Plasma membrane
Secretome location
Intracellular and membrane
Quaternary structure
Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. In silico studies have found a particularly strong binding of surface TLR4 with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease-2019 (COVID-19). This receptor has also been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness, and with susceptibility to age-related macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

839 residues, UniProt reviewed canonical sequence.

>O00206|TLR4
     1  MMSASRLAGT LIPAMAFLSC VRPESWEPCV EVVPNITYQC MELNFYKIPD NLPFSTKNLD
    61  LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS LSHLSTLILT GNPIQSLALG
   121  AFSGLSSLQK LVAVETNLAS LENFPIGHLK TLKELNVAHN LIQSFKLPEY FSNLTNLEHL
   181  DLSSNKIQSI YCTDLRVLHQ MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL
   241  NVMKTCIQGL AGLEVHRLVL GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI
   301  IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC KFGQFPTLKL KSLKRLTFTS
   361  NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS LKYLDLSFNG VITMSSNFLG
   421  LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI YLDISHTHTR VAFNGIFNGL SSLEVLKMAG
   481  NSFQENFLPD IFTELRNLTF LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY
   541  KCLNSLQVLD YSLNHIMTSK KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL
   601  LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS VLVVSVVAVL VYKFYFHLML
   661  LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV PPFQLCLHYR DFIPGVAIAA
   721  NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR
   781  QQVELYRLLS RNTYLEWEDS VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TLR4 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
31 nTPM

Expression across tissuesHPA

Tissue

  • spleen: 31 nTPM
  • adipose tissue: 29 nTPM
  • appendix: 24 nTPM
  • placenta: 23 nTPM
  • bone marrow: 21 nTPM
  • liver: 16 nTPM

Single-cell type

  • neutrophils: 4.4 nCPM
  • monocytes: 1.3 nCPM
  • astrocytes: 1 nCPM
  • foveolar cells: 1 nCPM
  • lymphatic endothelial cells: 0.9 nCPM
  • cdc: 0.7 nCPM

Immune cell

  • neutrophil: 87 nTPM
  • non-classical monocyte: 66 nTPM
  • classical monocyte: 65 nTPM
  • basophil: 64 nTPM
  • intermediate monocyte: 58 nTPM
  • total PBMC: 26 nTPM

Brain region

  • hypothalamus: 46 nTPM
  • basal ganglia: 40 nTPM
  • spinal cord: 40 nTPM
  • midbrain: 38 nTPM
  • thalamus: 37 nTPM
  • medulla oblongata: 33 nTPM

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)
0.99
gnomAD pLI
0
gnomAD missense Z
0.65
DepMap mean gene effect
0.04
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of TLR4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads TLR4 as an antibody target. Whether an autoantibody or antibody against TLR4 could matter depends on whether native TLR4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TLR4 is annotated at the cell surface, where native TLR4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label TLR4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/TLR4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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