Seroatlas · Human Serome Atlas

TLR3

Toll-like receptor 3

Also known as: CD283, TLR3_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: O15455
Gene: TLR3
Ensembl: ENSG00000164342
Chromosome: 4
Canonical length: 904 aa
Protein class: CD markers, Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters
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 (PAMPs) 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. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It thus plays a role in host defense against multiple viruses. [provided by RefSeq, Jul 2021]

Canonical amino-acid sequenceUniProt

904 residues, UniProt reviewed canonical sequence.

>O15455|TLR3
     1  MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP TNITVLNLTH
    61  NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM LKVLNLQHNE LSQLSDKTFA
   121  FCTNLTELHL MSNSIQKIKN NPFVKQKNLI TLDLSHNGLS STKLGTQVQL ENLQELLLSN
   181  NKIQALKSEE LDIFANSSLK KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK
   241  LCLELANTSI RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL
   301  EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS FQWLKCLEHL
   361  NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET FVSLAHSPLH ILNLTKNKIS
   421  KIESDAFSWL GHLEVLDLGL NEIGQELTGQ EWRGLENIFE IYLSYNKYLQ LTRNSFALVP
   481  SLQRLMLRRV ALKNVDSSPS PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN
   541  NLARLWKHAN PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT
   601  LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT CESIAWFVNW
   661  INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA PFELFFMINT SILLIFIFIV
   721  LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE
   781  DQSLKFCLEE RDFEAGVFEL EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI
   841  EQNLDSIILV FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK
   901  NSVH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TLR3 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: Other membrane
Secreted: No
Transmembrane segments: 1
Mean surface accessibility (rSASA): 0.26
Highest tissue expression: 12 nTPM

Expression across tissuesHPA

Tissue

duodenum: 12 nTPM
placenta: 11 nTPM
small intestine: 11 nTPM
liver: 10 nTPM
colon: 8.3 nTPM
seminal vesicle: 8.2 nTPM

Single-cell type

early spermatids: 102 nCPM
foveolar cells: 30 nCPM
microglia: 29 nCPM
syncytiotrophoblasts: 29 nCPM
alveolar cells type 1: 28 nCPM
endometrial glandular cells: 26 nCPM

Immune cell

memory CD8 T-cell: 3.1 nTPM
gdT-cell: 2.9 nTPM
MAIT T-cell: 1.6 nTPM
naive CD8 T-cell: 1.5 nTPM
myeloid DC: 0.9 nTPM
memory CD4 T-cell: 0.6 nTPM

Brain region

medulla oblongata: 4.2 nTPM
white matter: 4 nTPM
spinal cord: 3.1 nTPM
pons: 2.7 nTPM
hypothalamus: 2.2 nTPM
choroid plexus: 2.1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TLR3.

Disease | AllUniProt

Conditions TLR3 is implicated in, by any mechanism.

Immunodeficiency 83, susceptibility to viral infections (IMD83) MIM:613002

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): 0.8
gnomAD pLI: 0
gnomAD missense Z: 0.51
DepMap mean gene effect: 0.23
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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

Toll/interleukin-1 receptor homology (TIR) domain
Cysteine-rich flanking region, C-terminal
Leucine-rich repeat
Leucine-rich repeat, typical subtype
Leucine-rich repeat domain superfamily
Toll/interleukin-1 receptor homology (TIR) domain superfamily
TIR domain
Leucine Rich repeat
Leucine rich repeat
Toll-like receptor 3 trans-membrane domain
Toll-like receptor 3 trans-membrane domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of TLR3 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 TLR3 as an antibody target. Whether an autoantibody or antibody against TLR3 could matter depends on whether native TLR3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

TLR3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label TLR3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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