TLR4 Gene Summary [Human]
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]
Details
| Type | Protein Coding |
| Official Symbol | TLR4 |
| Official Name | toll like receptor 4 [Source:HGNC Symbol;Acc:HGNC:11850] |
| Ensembl ID | ENSG00000136869 |
| Bio databases IDs | |
| Aliases | toll like receptor 4 |
| Synonyms | ARMD10, CD284, HTOLL, Ly87, Ran/M1, Rasl2-8, Tlrp4, TOLL, toll-like receptor 4, TOLL receptor |
| Species | Human, Homo sapiens |
| Orthologies |
Protein Domains
A protein domain is a distinct structural or functional region within a protein that can evolve, function, and exist independently of the rest of the protein chain. These domains in human TLR4 often fold into stable, three-dimensional structures and are associated with specific biological functions, such as binding to DNA, other proteins, or small molecules.
- Leucine rich repeat
- SEFIR domain
- intracellular signaling domain
- Leucine Rich repeats (2 copies)
- TIR domain
- identical protein binding
- Toll IL-1 receptor domain beta strand B
- leucine-rich repeat
- N-linked glycosylation site
- cytoplasmic domain
- BB loop
- intracellular domain
- Toll IL-1 receptor domain helix B
- transmembrane receptor
- extracellular domain
- leucine rich domain
- protein phosphatase 1 regulatory subunit 42
- signaling receptor activity
- AB loop
- ectodomain
- Leucine rich repeat C-terminal domain
- protein binding
- receptor binding
- lipopolysaccharide binding
- D helix
- phosphoinositide 3-kinase binding
- toll IL-1 receptor domain helix E
- transmembrane domain
- protein heterodimerization
Pathways
Biological processes and signaling networks where the TLR4 gene in human plays a role, providing insight into its function and relevance in health or disease.
- Autophagy
- Crosstalk between Dendritic Cells and Natural Killer Cells
- Dendritic Cell Maturation
- Hepatic Fibrosis / Hepatic Stellate Cell Activation
- IL-10 Signaling
- Inflammasome pathway
- iNOS Signaling
- LPS-stimulated MAPK Signaling
- LPS/IL-1 Mediated Inhibition of RXR Function
- LXR/RXR Activation
- MIF Regulation of Innate Immunity
- MIF-mediated Glucocorticoid Regulation
- MSP-RON Signaling Pathway
- NF-κB Signaling
- Osteoarthritis Pathway
- PI3K Signaling in B Lymphocytes
- Role of Hypercytokinemia/hyperchemokinemia in the Pathogenesis of Influenza
- Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses
- Role of PKR in Interferon Induction and Antiviral Response
- Toll-like Receptor Signaling
- TREM1 Signaling
Top Findings
The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
disease
- edema
- renal clear cell cancer
- renal cell cancer
- epithelial cancer
- cancer
- metastasis
- renal clear cell adenocarcinoma
- atopic dermatitis
- neoplasia
- rheumatoid arthritis
role in cell
- proliferation
- cell viability
- oxidative stress response
- injury
- cell death
- necrosis
- internalization in
- phosphorylation in
- molecular cleavage in
- survival
Subcellular Expression
Locations within the cell where the protein is known or predicted to be active, providing insight into its function and cellular context.
- Plasma Membrane
- intracellular compartment
- Cytoplasm
- cell surface
- cell periphery
- intracellular space
- apical compartment
- basal compartment
- perinuclear region
- intracellular membranes
- membrane surface
- cellular membrane
- endosomes
- Golgi Apparatus
- membrane compartment
- apical cell surfaces
- plasma membrane extracellular face
- endosomal membrane
- cytoplasmic vesicles
- membrane rafts
- brush border
- pseudopodia
- filopodia
- cell membrane leading edge
- perikaryon
- lamellipodia
- phagocytic cups
Gene Ontology Annotations
Describes the biological processes, cellular components, and molecular functions associated with the human TLR4 gene, providing context for its role in the cell.
Biological Process
Functions and activities the gene product is involved in
- I-kappaB phosphorylation
- JNK cascade
- positive regulation of cytokine production involved in inflammatory response
- positive regulation of NF-kappaB transcription factor activity
- B cell proliferation involved in immune response
- positive regulation of interferon-alpha production
- inflammatory response
- MyD88-dependent toll-like receptor signaling pathway
- immune response
- intestinal epithelial structure maintenance
- positive regulation of interferon-beta production
- positive regulation of interferon-gamma production
- positive regulation of macrophage activation
- positive regulation of tumor necrosis factor production
- positive regulation of chemokine production
- negative regulation of interferon-gamma production
- negative regulation of tumor necrosis factor production
- stress-activated MAPK cascade
- cellular response to platelet-derived growth factor stimulus
- toll-like receptor 4 signaling pathway
- positive regulation of inflammatory response
- positive regulation of NLRP3 inflammasome complex assembly
- defense response to bacterium
- wound healing involved in inflammatory response
- negative regulation of interleukin-6 production
- positive regulation of interleukin-8 production
- positive regulation of nitric-oxide synthase biosynthetic process
- positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
- MHC class II biosynthetic process
- nucleotide-binding oligomerization domain containing 2 signaling pathway
- positive regulation of gene expression
- positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
- gene expression
- lipopolysaccharide-mediated signaling pathway
- positive regulation of B cell proliferation
- nitric oxide biosynthetic process
- detection of fungus
- positive regulation of interleukin-6 production
- positive regulation of stress-activated MAPK cascade
- TRIF-dependent toll-like receptor signaling pathway
- positive regulation of MAP kinase activity
- microglia differentiation
- positive regulation of nitric oxide biosynthetic process
- astrocyte development
- positive regulation of I-kappaB kinase/NF-kappaB cascade
- positive regulation of transcription from RNA polymerase II promoter
- positive regulation of MHC class II biosynthetic process
- macrophage activation
- regulation of dendritic cell cytokine production
- positive regulation of smooth muscle cell proliferation
- positive regulation of macrophage cytokine production
- nitric oxide production involved in inflammatory response
- negative regulation of interleukin-23 production
- negative regulation of osteoclast differentiation
- positive regulation of smooth muscle cell migration
- negative regulation of interleukin-17 production
- nucleotide-binding oligomerization domain containing 1 signaling pathway
- positive regulation of platelet activation
- defense response to Gram-negative bacterium
- T-helper 1 type immune response
- toll-like receptor signaling pathway
- ERK1 and ERK2 cascade
- cellular response to mechanical stimulus
- positive regulation of interleukin-12 production
- cellular response to lipopolysaccharide
- cellular response to lipoteichoic acid
- positive regulation of JNK cascade
- negative regulation of ERK1 and ERK2 cascade
- innate immune response
- positive regulation of ERK1 and ERK2 cascade
- phagocytosis
- positive regulation of chemokine (C-X-C motif) ligand 2 production
- positive regulation of extrinsic apoptotic signaling pathway
- response to lipopolysaccharide
- detection of lipopolysaccharide
- cellular response to interferon-gamma
- positive regulation of interleukin-10 production
- positive regulation of interleukin-1 beta production
- positive regulation of interleukin-1 production
Cellular Component
Where in the cell the gene product is active
- early endosome
- perinuclear region of cytoplasm
- cytoplasm
- lipopolysaccharide receptor complex
- ruffle
- external side of plasma membrane
- receptor complex
- endosome membrane
- phagocytic cup
- plasma membrane
- cell surface
Molecular Function
What the gene product does at the molecular level
- identical protein binding
- protein binding
- transmembrane signaling receptor activity
- lipopolysaccharide receptor activity
- protein heterodimerization activity
- signaling receptor activity
- receptor binding
- beta-amyloid binding
- lipopolysaccharide binding