TLR4 toll like receptor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TLR4provided by HGNC
Official Full Name: toll like receptor 4provided by HGNC
Primary source: HGNC:HGNC:11850
See related: Ensembl:ENSG00000136869 MIM:603030; AllianceGenome:HGNC:11850
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TOLL; CD284; TLR-4; ARMD10
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 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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for COVID-19 treatment.
Expression: Broad expression in spleen (RPKM 17.1), appendix (RPKM 15.6) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q33.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (117704403..117724735)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (129898286..129918621)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (120466681..120487013)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells.
Title: TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells.
Hepatitis B surface antigen impairs TLR4 signaling by upregulating A20 expression in monocytes.
Title: Hepatitis B surface antigen impairs TLR4 signaling by upregulating A20 expression in monocytes.
Growth inhibition of subcutaneous tumor with glioma cells in nude mice by silencing TLR4.
Title: Growth inhibition of subcutaneous tumor with glioma cells in nude mice by silencing TLR4.
Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.
Title: Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.
S100A9 and HMGB1 orchestrate MDSC-mediated immunosuppression in melanoma through TLR4 signaling.
Title: S100A9 and HMGB1 orchestrate MDSC-mediated immunosuppression in melanoma through TLR4 signaling.
TNFAIP3 Overexpression Inhibits Diffuse Large B-Cell Lymphoma Progression by Promoting Autophagy through TLR4/MyD88/NF-kappaB Signaling Pathway.
Title: TNFAIP3 Overexpression Inhibits Diffuse Large B-Cell Lymphoma Progression by Promoting Autophagy through TLR4/MyD88/NF-κB Signaling Pathway.
Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma.
Title: Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma.
The relationship between Toll-like receptor-4 genes and preeclampsia outcomes.
Title: The relationship between Toll-like receptor-4 genes and preeclampsia outcomes.
Association of TLR4 gene rs4986790 and rs4986791 polymorphisms with asthma susceptibility: meta-analysis and trial sequential analysis.
Title: Association of TLR4 gene rs4986790 and rs4986791 polymorphisms with asthma susceptibility: meta-analysis and trial sequential analysis.
Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning.
Title: Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning.

Submit: New GeneRIF Correction See all GeneRIFs (2445)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 CN54, JRFL, and Ada Env (gp120) upregulates IL-6, CCL2, CCL4, CXCL8, and IL-1b through TLR4 and CCR5 induction in monocyte derived macrophages and hepatic stellate cells because treatment with an anti-TLR4 antibody mitigated the response	PubMed
	env	The binding of soluble HIV-1 gp120 to TLR2 or TLR4 results in upregulation of the TNF-alpha and IL-8 production through NF-kappaB activation	PubMed
	env	Human primary astrocytes exposed to HIV-1 gp120 has a significant increase in TLR4 protein expression	PubMed
Tat	tat	HIV-1 Tat engages TLR4, which induces production of TNF and IL10 in human monocytes	PubMed
	tat	HIV-1 Tat downregulates TLR4 by specific dynamin endocytosis as a result of Tat-TLR4 interaction	PubMed
	tat	HIV-1 Tat engages TLR4 resulting in RELA (NK-kappaB) activation and IL6 and CXCL8 (IL8) protein expression	PubMed
	tat	HIV-1 Tat-induced release of TNF-alpha and IL-10 is TLR4-dependent in monocytes	PubMed
	tat	HIV-1 Tat-mediated regulation of MSRV and Syncytin-1 involves TLR-4 in primary astrocytes	PubMed
	tat	HIV-1 Tat upregulates the expression of CCR2, CD16, and TLR4 in monocyte-derived macrophages	PubMed
	tat	HIV-1 Tat interacts physically with the TLR4-MD2 complex and the N-terminal region (residues 1-29) of Tat is involved in the interation with TLR4-MD2	PubMed
	tat	HIV-1 Tat-induced upregulation of PD-L1 on monocyte-derived dendritic cells involves a TNF-alpha-mediated mechanism through the TLR4 pathway	PubMed
	tat	HIV-1 Tat protein decreases TLR4 protein levels and suppresses C. parvum-induced TLR4 protein expression	PubMed
Vpr	vpr	HIV-1 Vpr-induced IL-6 production depends on the activation of NFkappaB and the involvement of C/EBP-beta, TLR4, and MyD88	PubMed
	vpr	HIV-1 Vpr potentiates the suppression of Toll-like receptor 4 by glucocorticoids via the glucocorticoid receptor pathway	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC98129P2 (e-PCR)
- UniSTS:273666

PMC98226P2 (e-PCR)
- UniSTS:273668

PMC98510P2 (e-PCR)
- UniSTS:273672

PMC201071P2 (e-PCR)
- UniSTS:271881

PMC201071P3 (e-PCR)
- UniSTS:271882

PMC98826P3 (e-PCR)
- UniSTS:273682

G32954 (e-PCR)
- UniSTS:117532

PMC289161P2 (e-PCR)
- UniSTS:272413

TLR4_1086 (e-PCR)
- UniSTS:277820

A009X32 (e-PCR)
- UniSTS:20859

TLR4 (e-PCR)
- UniSTS:480158

PMC55404P3 (e-PCR)
- UniSTS:273342

PMC31919P1 (e-PCR)
- UniSTS:273097

PMC128073P5 (e-PCR)
- UniSTS:270567

D9S1060E (e-PCR)
- UniSTS:151277

PMC97668P2 (e-PCR)
- UniSTS:273657

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NAD+ nucleotidase, cyclic ADP-ribose generating	IEA Inferred from Electronic Annotation more info
enables amyloid-beta binding	IC Inferred by Curator more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables lipopolysaccharide binding	IBA Inferred from Biological aspect of Ancestor more info
enables lipopolysaccharide binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables lipopolysaccharide binding	NAS Non-traceable Author Statement more info	PubMed
enables lipopolysaccharide immune receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables lipopolysaccharide immune receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables lipopolysaccharide immune receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane signaling receptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell proliferation involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in I-kappaB phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in MHC class II biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in MyD88-dependent toll-like receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in MyD88-dependent toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in MyD88-dependent toll-like receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in T-helper 1 type immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in TRIF-dependent toll-like receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in astrocyte development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amyloid-beta	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amyloid-beta	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to lipopolysaccharide	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to lipopolysaccharide	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to lipoteichoic acid	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to oxidised low-density lipoprotein particle stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to oxidised low-density lipoprotein particle stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to platelet-derived growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to type II interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to Gram-negative bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to Gram-negative bacterium	IC Inferred by Curator more info	PubMed
involved_in defense response to bacterium	IGI Inferred from Genetic Interaction more info	PubMed
involved_in defense response to bacterium	TAS Traceable Author Statement more info	PubMed
involved_in detection of fungus	NAS Non-traceable Author Statement more info	PubMed
involved_in detection of lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in detection of lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in intestinal epithelial structure maintenance	ISS Inferred from Sequence or Structural Similarity more info
NOT acts_upstream_of_or_within lipopolysaccharide-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within lipopolysaccharide-mediated signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in macrophage activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microglia differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of interleukin-17 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-23 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of osteoclast differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of type II interferon production	ISS Inferred from Sequence or Structural Similarity more info
involved_in nitric oxide biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in nitric oxide production involved in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in nucleotide-binding oligomerization domain containing 1 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in phagocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of MAP kinase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of MHC class II biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NLRP3 inflammasome complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cellular response to macrophage colony-stimulating factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of chemokine (C-X-C motif) ligand 2 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytokine production involved in inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cytokine production involved in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of extrinsic apoptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in positive regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interferon-alpha production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interferon-beta production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-1 beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-1 beta production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-1 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-10 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-12 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macrophage cytokine production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of matrix metallopeptidase secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nitric oxide biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of platelet activation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of reactive oxygen species biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of smooth muscle cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type II interferon production	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of dendritic cell cytokine production	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IC Inferred by Curator more info	PubMed
acts_upstream_of_or_within response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in toll-like receptor 4 signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in wound healing involved in inflammatory response	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IPI Inferred from Physical Interaction more info	PubMed
located_in early endosome	IEA Inferred from Electronic Annotation more info
is_active_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of lipopolysaccharide receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of lipopolysaccharide receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in phagocytic cup	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IPI Inferred from Physical Interaction more info	PubMed
located_in ruffle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: toll-like receptor 4

Names: hToll; homolog of Drosophila toll; toll like receptor 4 protein

NP_003257.1

EC 3.2.2.6

NP_612564.1

EC 3.2.2.6

NP_612567.1

EC 3.2.2.6

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011475.2 RefSeqGene

Range

5001..25333

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_320

mRNA and Protein(s)

NM_003266.4 → NP_003257.1 toll-like receptor 4 isoform C

See identical proteins and their annotated locations for NP_003257.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an additional internal exon compared to transcript variant 1. This variant represents translation initiation at a downstream AUG compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a weak Kozak sequence and a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG, which results in an isoform (C) with a shorter N-terminus compared to isoform A.

Source sequence(s)

AK226155, AL160272, BC025294, BC143841, BG622357, DA187988, DA218006

UniProtKB/TrEMBL

D1CS55

Related

ENSP00000377997.4, ENST00000394487.5

Conserved Domains (6) summary

smart00082
Location:539 → 585

LRRCT; Leucine rich repeat C-terminal domain

smart00255
Location:634 → 775

TIR; Toll - interleukin 1 - resistance

cd00116
Location:112 → 416

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

sd00031
Location:16 → 39

LRR_1; leucine-rich repeat [structural motif]

sd00033
Location:335 → 360

LRR_RI; leucine-rich repeat [structural motif]

pfam13855
Location:17 → 74

LRR_8; Leucine rich repeat
NM_138554.5 → NP_612564.1 toll-like receptor 4 isoform A precursor

See identical proteins and their annotated locations for NP_612564.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (A).

Source sequence(s)

AK226155, AL160272, BC117422, BG622357, DA187988, DA218006

Consensus CDS

CCDS6818.1

UniProtKB/Swiss-Prot

A8K1Y8, A9XLP9, A9XLQ0, A9XLQ1, B4E194, D1CS52, D1CS53, O00206, Q5VZI8, Q5VZI9, Q9UK78, Q9UM57

UniProtKB/TrEMBL

D1CS55

Related

ENSP00000363089.5, ENST00000355622.8

Conserved Domains (6) summary

smart00082
Location:579 → 625

LRRCT; Leucine rich repeat C-terminal domain

smart00255
Location:674 → 815

TIR; Toll - interleukin 1 - resistance

cd00116
Location:152 → 456

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

sd00031
Location:56 → 79

LRR_1; leucine-rich repeat [structural motif]

sd00033
Location:353 → 374

LRR_RI; leucine-rich repeat [structural motif]

pfam13855
Location:57 → 114

LRR_8; Leucine rich repeat
NM_138557.3 → NP_612567.1 toll-like receptor 4 isoform D

See identical proteins and their annotated locations for NP_612567.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an internal exon compared to transcript variant 1. This variant represents translation initiation at a downstream AUG compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a weak Kozak sequence and a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG, which results in an isoform (D) with a shorter N-terminus compared to isoform A.

Source sequence(s)

AK226155, AL160272, BC025294, BG622357, DA218006

UniProtKB/Swiss-Prot

O00206

Conserved Domains (5) summary

smart00082
Location:379 → 425

LRRCT; Leucine rich repeat C-terminal domain

smart00255
Location:474 → 615

TIR; Toll - interleukin 1 - resistance

cd00116
Location:27 → 256

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

sd00033
Location:175 → 200

LRR_RI; leucine-rich repeat [structural motif]

pfam13855
Location:247 → 308

LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

117704403..117724735

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

129898286..129918621

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_138556.1: Suppressed sequence

Description

NM_138556.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein is not supported by current protein homology data.