Tlr4 Gene Summary [Mouse]

This gene belongs to the evolutionarily-conserved Toll-like receptor family, whose members are type-1 transmembrane proteins that are involved in innate immunity. Toll-like receptors are characterized by an extracellular leucine-rich repeat domain that functions in ligand recognition and an intracellular toll/interleukin-1 receptor-like domain that is crucial for signal transduction. The receptor encoded by this gene mediates the innate immune response to bacterial lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria, through synthesis of pro-inflammatory cytokines and chemokines. In addition, this protein can recognize other pathogens from Gram-negative and Gram-positive bacteria as well as viral components. Mice deficient in this gene display a number of immune response-related phenotypes including hyporesponsiveness to bacterial lipopolysaccharide and increased levels of respiratory syncytial virus compared to controls. [provided by RefSeq, Sep 2015]

Details

Type
Protein Coding
Official Symbol
Tlr4
Official Name
toll-like receptor 4 [Source:MGI Symbol;Acc:MGI:96824]
Ensembl ID
ENSMUSG00000039005
Bio databases IDs NCBI: 21898 Ensembl: ENSMUSG00000039005
Aliases toll-like receptor 4
Synonyms ARMD10, CD284, HTOLL, Ly87, Ran/M1, Rasl2-8, Tlrp4, TOLL, toll-like receptor 4, TOLL receptor
Species
Mouse, Mus musculus
OrthologiesHumanRat

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 mouse 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

Top Findings

The most significant associations for this gene, including commonly observed domains, pathway involvement, and functional highlights based on current data.
regulates
regulated by
  • empagliflozin
  • IFNG
  • lipopolysaccharide
  • CYP2E1
  • interferon alpha
  • magnolol
  • E. coli B4 lipopolysaccharide
  • ozone
  • E. coli B5 lipopolysaccharide
  • PTEN
disease
  • edema
  • renal clear cell cancer
  • renal cell cancer
  • epithelial cancer
  • cancer
  • metastasis
  • renal clear cell adenocarcinoma
  • atopic dermatitis
  • neoplasia
  • rheumatoid arthritis
phenotypes
  • abnormal cecum morphology
  • decreased heart weight
  • enlarged cecum
  • enlarged uterus
  • small superior vagus ganglion
  • abnormal T-helper 2 physiology
  • abnormal acute inflammation
  • abnormal airway responsiveness
  • abnormal artery morphology
  • abnormal bile salt level
  • abnormal bone structure
  • abnormal circulating enzyme level
  • abnormal circulating glucose level
  • abnormal circulating leptin level
  • abnormal cytokine level
  • abnormal cytokine secretion
  • abnormal enterocyte differentiation
  • abnormal enterocyte proliferation
  • abnormal fatty acid level
  • abnormal fibroblast proliferation
  • abnormal gas homeostasis
  • abnormal glial cell apoptosis
  • abnormal glial cell physiology
  • abnormal glucose homeostasis
  • abnormal hepatocyte morphology
  • abnormal inflammatory response
  • abnormal interleukin level
  • abnormal intestinal goblet cell morphology
  • abnormal level of surface class II molecules
  • abnormal lipid level
  • abnormal liver physiology
  • abnormal locomotor behavior
  • abnormal macrophage chemotaxis
  • abnormal macrophage physiology
  • abnormal microglial cell physiology
  • abnormal motor coordination/ balance
  • abnormal muscle cell glucose uptake
  • abnormal myelin sheath morphology
  • abnormal nephron morphology
  • abnormal nervous system morphology
  • abnormal neuron differentiation
  • abnormal osteoclast differentiation
  • abnormal phagocyte morphology
  • abnormal proximal convoluted tubule brush border morphology
  • abnormal pulmonary alveolar duct morphology
  • abnormal pulmonary alveolus morphology
  • abnormal pulmonary elastic fiber morphology
  • abnormal renal tubule epithelium morphology
  • abnormal renal tubule morphology
  • abnormal respiratory system morphology
  • abnormal respiratory system physiology
  • abnormal retinal layer morphology
  • abnormal retinal pigment epithelium morphology
  • abnormal retinal progenitor cell morphology
  • abnormal retinal rod bipolar cell morphology
  • abnormal retinal rod cell morphology
  • abnormal spleen weight
  • abnormal tumor necrosis factor level
  • abnormal vascular wound healing
  • altered susceptibility to infection
  • atherosclerotic lesions
  • brain ischemia
  • cellular necrosis
  • decreased B cell number
  • decreased B cell proliferation
  • decreased acute inflammation
  • decreased angiogenesis
  • decreased body size
  • decreased body temperature
  • decreased body weight
  • decreased cerebral infarction size
  • decreased circulating alanine transaminase level
  • decreased circulating insulin level
  • decreased circulating interleukin-6 level
  • decreased epididymal fat pad weight
  • decreased fat cell size
  • decreased hemoglobin content
  • decreased hepatocyte apoptosis
  • decreased incidence of tumors by chemical induction
  • decreased interferon-beta secretion
  • decreased interleukin-1 beta secretion
  • decreased interleukin-10 secretion
  • decreased interleukin-6 secretion
  • decreased liver triglyceride level
  • decreased macrophage apoptosis
  • decreased macrophage cytokine production
  • decreased memory B cell number
  • decreased neuron apoptosis
  • decreased percent body fat/body weight
  • decreased respiratory quotient
  • decreased response of heart to induced stress
  • decreased sensitivity to induced morbidity/mortality
  • decreased susceptibility to Orthomyxoviridae infection
  • decreased susceptibility to bacterial infection
  • decreased susceptibility to bone fracture
  • decreased susceptibility to endotoxin shock
  • decreased susceptibility to induced arthritis
  • decreased susceptibility to injury
  • decreased susceptibility to ischemic brain injury
  • decreased susceptibility to kidney reperfusion injury
  • decreased susceptibility to weight loss
  • decreased tumor necrosis factor secretion
  • dilated pulmonary alveolar ducts
  • dilated renal tubules
  • enlarged lung
  • enlarged mesenteric lymph nodes
  • focal hepatic necrosis
  • hyporesponsive to tactile stimuli
  • impaired neutrophil chemotaxis
  • improved glucose tolerance
  • increased adiponectin level
  • increased bone mass
  • increased bone mineral content
  • increased bone mineral density
  • increased cell death
  • increased circulating interleukin-6 level
  • increased lung compliance
  • increased oxygen consumption
  • increased spleen weight
  • increased susceptibility to Poxviridae infection induced morbidity/mortality
  • increased susceptibility to bacterial infection
  • increased susceptibility to induced arthritis
  • increased thermal nociceptive threshold
  • liver inflammation
  • lung inflammation
  • no abnormal phenotype detected
  • pulmonary edema
  • rectal hemorrhage
  • renal cast
  • renal tubular necrosis
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 mouse 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

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