TLR3 (toll like receptor 3)

Gene

• Entrez ID: 7098
• Gene name: Toll like receptor 3
• Gene symbol: TLR3
• Synonyms: CD283, IIAE2, IMD83
• Chromosome: 4
• Chromosome location: 4q35.1
• Summary: 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 func

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs35311343	C>G	Likely-benign, risk-factor	Missense variant, coding sequence variant
rs121434431	C>T	Risk-factor, uncertain-significance	Missense variant, coding sequence variant
rs199768900	G>A	Risk-factor	Coding sequence variant, missense variant
rs768091235	T>C	Risk-factor	Coding sequence variant, missense variant
rs1244010954	G>A,T	Risk-factor	Missense variant, coding sequence variant
rs1280549921	G>A	Risk-factor, uncertain-significance	Coding sequence variant, missense variant
rs1554064929	G>T	Risk-factor	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022528	hsa-miR-124-3p	Microarray	18668037
MIRT438603	hsa-miR-758-3p	Luciferase reporter assay, Western blot, qRT-PCR	25008898
MIRT438603	hsa-miR-758-3p	Luciferase reporter assay, Western blot, qRT-PCR	25008898
MIRT564104	hsa-miR-548e-5p	PAR-CLIP	20371350
MIRT564103	hsa-miR-3662	PAR-CLIP	20371350
MIRT564102	hsa-miR-365a-3p	PAR-CLIP	20371350
MIRT564101	hsa-miR-365b-3p	PAR-CLIP	20371350
MIRT564100	hsa-miR-3163	PAR-CLIP	20371350
MIRT564099	hsa-miR-25-3p	PAR-CLIP	20371350
MIRT564098	hsa-miR-32-5p	PAR-CLIP	20371350
MIRT564097	hsa-miR-363-3p	PAR-CLIP	20371350
MIRT564096	hsa-miR-367-3p	PAR-CLIP	20371350
MIRT564095	hsa-miR-92a-3p	PAR-CLIP	20371350
MIRT564094	hsa-miR-92b-3p	PAR-CLIP	20371350
MIRT564093	hsa-miR-137	PAR-CLIP	20371350
MIRT734999	hsa-miR-148a-5p	Luciferase reporter assay, Western blotting, qRT-PCR, ELISA	31947624
MIRT736439	hsa-miR-491-3p	qRT-PCR, Flow cytometry	33679688
MIRT736873	hsa-miR-155-3p	Microarray, Immunofluorescence, qRT-PCR	33291448
MIRT564104	hsa-miR-548e-5p	PAR-CLIP	20371350
MIRT564103	hsa-miR-3662	PAR-CLIP	20371350
MIRT564102	hsa-miR-365a-3p	PAR-CLIP	20371350
MIRT564101	hsa-miR-365b-3p	PAR-CLIP	20371350
MIRT564100	hsa-miR-3163	PAR-CLIP	20371350
MIRT564099	hsa-miR-25-3p	PAR-CLIP	20371350
MIRT564098	hsa-miR-32-5p	PAR-CLIP	20371350
MIRT564097	hsa-miR-363-3p	PAR-CLIP	20371350
MIRT564096	hsa-miR-367-3p	PAR-CLIP	20371350
MIRT564095	hsa-miR-92a-3p	PAR-CLIP	20371350
MIRT564094	hsa-miR-92b-3p	PAR-CLIP	20371350
MIRT564093	hsa-miR-137	PAR-CLIP	20371350

Transcription factors

Transcription factor	Regulation	Reference
E2F1	Repression	22310660
IRF3	Unknown	22208359
IRF8	Repression	21220691
NFKB1	Activation	20658750
NFKB1	Repression	16423052
RELA	Activation	20658750
RELA	Repression	16423052
STAT1	Activation	16628196

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	TAS
GO:0001774	Process	Microglial cell activation	IEA
GO:0002224	Process	Toll-like receptor signaling pathway	TAS
GO:0002730	Process	Regulation of dendritic cell cytokine production	IEA
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	TAS
GO:0003725	Function	Double-stranded RNA binding	IBA	21873635
GO:0003725	Function	Double-stranded RNA binding	IDA	16111635
GO:0003725	Function	Double-stranded RNA binding	NAS	12054664
GO:0004888	Function	Transmembrane signaling receptor activity	NAS	12054664
GO:0005515	Function	Protein binding	IPI	16858407, 25736436
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	19740627
GO:0005765	Component	Lysosomal membrane	HDA	17897319
GO:0005769	Component	Early endosome	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	9435236
GO:0006954	Process	Inflammatory response	IEA
GO:0006972	Process	Hyperosmotic response	NAS	12054664
GO:0007165	Process	Signal transduction	TAS	9435236, 10426995
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS
GO:0007250	Process	Activation of NF-kappaB-inducing kinase activity	NAS	12054664
GO:0007252	Process	I-kappaB phosphorylation	IDA	19740627
GO:0008584	Process	Male gonad development	IEA
GO:0009597	Process	Detection of virus	NAS	12054664
GO:0009986	Component	Cell surface	IDA	19740627
GO:0010008	Component	Endosome membrane	TAS
GO:0010628	Process	Positive regulation of gene expression	IMP	23817958, 25754930
GO:0016020	Component	Membrane	NAS	12054664
GO:0031012	Component	Extracellular matrix	IBA	21873635
GO:0032722	Process	Positive regulation of chemokine production	IDA	19740627
GO:0032727	Process	Positive regulation of interferon-alpha production	IDA	16286015
GO:0032728	Process	Positive regulation of interferon-beta production	IDA	16286015
GO:0032728	Process	Positive regulation of interferon-beta production	IMP	12054664
GO:0032728	Process	Positive regulation of interferon-beta production	ISS
GO:0032729	Process	Positive regulation of interferon-gamma production	IDA	16286015
GO:0032735	Process	Positive regulation of interleukin-12 production	ISS
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	19740627
GO:0032757	Process	Positive regulation of interleukin-8 production	IDA	17128265
GO:0032760	Process	Positive regulation of tumor necrosis factor production	ISS
GO:0034123	Process	Positive regulation of toll-like receptor signaling pathway	IDA	17128265
GO:0034128	Process	Negative regulation of MyD88-independent toll-like receptor signaling pathway	TAS
GO:0034138	Process	Toll-like receptor 3 signaling pathway	TAS
GO:0034346	Process	Positive regulation of type III interferon production	IEA
GO:0035458	Process	Cellular response to interferon-beta	IEA
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0035690	Process	Cellular response to drug	IEA
GO:0036020	Component	Endolysosome membrane	TAS
GO:0038023	Function	Signaling receptor activity	TAS	10426995
GO:0042742	Process	Defense response to bacterium	TAS	10426995
GO:0042802	Function	Identical protein binding	IPI	18172197, 23155421, 25217833
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEA
GO:0043330	Process	Response to exogenous dsRNA	IDA	21266579
GO:0043331	Process	Response to dsRNA	IBA	21873635
GO:0045087	Process	Innate immune response	TAS	15356140
GO:0045671	Process	Negative regulation of osteoclast differentiation	NAS	12133979
GO:0045766	Process	Positive regulation of angiogenesis	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046330	Process	Positive regulation of JNK cascade	IEA
GO:0050729	Process	Positive regulation of inflammatory response	IC	19740627
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IEA
GO:0051607	Process	Defense response to virus	TAS	15356140
GO:0070266	Process	Necroptotic process	TAS
GO:0071260	Process	Cellular response to mechanical stimulus	IEP	19593445
GO:0071346	Process	Cellular response to interferon-gamma	IEA
GO:0071360	Process	Cellular response to exogenous dsRNA	IEA
GO:0097190	Process	Apoptotic signaling pathway	TAS
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IDA	21737330
GO:0097527	Process	Necroptotic signaling pathway	IDA	21737330
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IDA	19740627

Other IDs

• MIM: 603029
• HGNC: 11849
• e!Ensembl: ENSG00000164342

Protein

• UniProt ID: O15455
• Protein name: Toll-like receptor 3 (CD antigen CD283)
• Protein function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by
• PDB: 1ZIW, 2A0Z, 2MK9, 2MKA, 3ULU, 3ULV, 5GS0, 7C76, 7WV3, 7WV4, 7WV5, 7WVE, 7WVF, 7WVJ, 8AR1, 8YHT, 8YHU, 9LSH, 9LSI, 9LSJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13855	LRR_8	51 → 111	Leucine rich repeat	Repeat
  PF13516	LRR_6	195 → 210	Leucine Rich repeat	Repeat
  PF13855	LRR_8	248 → 302	Leucine rich repeat	Repeat
  PF13855	LRR_8	274 → 332	Leucine rich repeat	Repeat
  PF13855	LRR_8	562 → 620	Leucine rich repeat	Repeat
  PF13855	LRR_8	586 → 647	Leucine rich repeat	Repeat
  PF17968	Tlr3_TMD	698 → 730	Toll-like receptor 3 trans-membrane domain	Domain
  PF01582	TIR	755 → 897	TIR domain	Family

• Sequence:

  MRQTLPCIYFWGGLLPFGMLCASSTTKCTVSHEVADCSHLKLTQVPDDLPTNITVLNLTH
  NQLRRLPAANFTRYSQLTSLDVGFNTISKLEPELCQKLPMLKVLNLQHNELSQLSDKTFA
  FCTNLTELHLMSNSIQKIKNNPFVKQKNLITLDLSHNGLSSTKLGTQVQLENLQELLLSN
  NKIQALKSEELDIFANSSLKKLELSSNQIKEFSPGCFHAIGRLFGLFLNNVQLGPSLTEK
  LCLELANTSIRNLSLSNSQLSTTSNTTFLGLKWTNLTMLDLSYNNLNVVGNDSFAWLPQL
  EYFFLEYNNIQHLFSHSLHGLFNVRYLNLKRSFTKQSISLASLPKIDDFSFQWLKCLEHL
  NMEDNDIPGIKSNMFTGLINLKYLSLSNSFTSLRTLTNETFVSLAHSPLHILNLTKNKIS
  KIESDAFSWLGHLEVLDLGLNEIGQELTGQEWRGLENIFEIYLSYNKYLQLTRNSFALVP
  SLQRLMLRRVALKNVDSSPSPFQPLRNLTILDLSNNNIANINDDMLEGLEKLEILDLQHN
  NLARLWKHANPGGPIYFLKGLSHLHILNLESNGFDEIPVEVFKDLFELKIIDLGLNNLNT
  LPASVFNNQVSLKSLNLQKNLITSVEKKVFGPAFRNLTELDMRFNPFDCTCESIAWFVNW
  INETHTNIPELSSHYLCNTPPHYHGFPVRLFDTSSCKDSAPFELFFMINTSILLIFIFIV
  LLIHFEGWRISFYWNVSVHRVLGFKEIDRQTEQFEYAAYIIHAYKDKDWVWEHFSSMEKE
  DQSLKFCLEERDFEAGVFELEAIVNSIKRSRKIIFVITHHLLKDPLCKRFKVHHAVQQAI
  EQNLDSIILVFLEEIPDYKLNHALCLRRGMFKSHCILNWPVQKERIGAFRHKLQVALGSK
  NSVH

• Sequence length: 904

Pathways

KEGG:

Necroptosis
Toll-like receptor signaling pathway
Hepatitis C
Hepatitis B
Influenza A
Human papillomavirus infection
Kaposi sarcoma-associated herpesvirus infection
Herpes simplex virus 1 infection
Coronavirus disease - COVID-19

Reactome:

Trafficking and processing of endosomal TLR
Toll Like Receptor 3 (TLR3) Cascade
TICAM1, RIP1-mediated IKK complex recruitment
RIP-mediated NFkB activation via ZBP1
TLR3 deficiency - HSE
UNC93B1 deficiency - HSE
TICAM1 deficiency - HSE
TRAF3 deficiency - HSE
TLR3-mediated TICAM1-dependent programmed cell death
TICAM1-dependent activation of IRF3/IRF7
TICAM1,TRAF6-dependent induction of TAK1 complex

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	23587629