The TLR4 gene and its putative association with human ageing

Cell Types

Lung microvascular endothelial

Cell Lines

HLMVEC

Cancer Cell?

No

Method

Knockdown

Type of senescence

Unclear

Senescence Effect

Inhibits

Primary Reference

Kim et al. (2020) Endothelial toll-like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a. Aging Cell 18(3)e12914 (PubMed)

HGNC symbol

TLR4

Aliases

ARMD10; CD284; hToll; TLR-4

Common name

toll like receptor 4

Entrez Id

7099

Description

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].

Gene Ontology

Process:

GO:50729; positive regulation of inflammatory response
GO:7165; signal transduction
GO:2376; immune system process
GO:45087; innate immune response
GO:6955; immune response
GO:6954; inflammatory response
GO:2224; toll-like receptor signaling pathway
GO:42742; defense response to bacterium
GO:6909; phagocytosis
GO:71222; cellular response to lipopolysaccharide
GO:10628; positive regulation of gene expression
GO:32731; positive regulation of interleukin-1 beta production
GO:32760; positive regulation of tumor necrosis factor production
GO:71346; cellular response to interferon-gamma
GO:71260; cellular response to mechanical stimulus
GO:1900227; positive regulation of NLRP3 inflammasome complex assembly
GO:45944; positive regulation of transcription by RNA polymerase II
GO:32735; positive regulation of interleukin-12 production
GO:32757; positive regulation of interleukin-8 production
GO:51092; positive regulation of NF-kappaB transcription factor activity
GO:43406; positive regulation of MAP kinase activity
GO:31663; lipopolysaccharide-mediated signaling pathway
GO:32496; response to lipopolysaccharide
GO:2755; MyD88-dependent toll-like receptor signaling pathway
GO:7252; I-kappaB phosphorylation
GO:10572; positive regulation of platelet activation
GO:16046; detection of fungus
GO:32497; detection of lipopolysaccharide
GO:32689; negative regulation of interferon-gamma production
GO:32700; negative regulation of interleukin-17 production
GO:32707; negative regulation of interleukin-23 production
GO:32715; negative regulation of interleukin-6 production
GO:32720; negative regulation of tumor necrosis factor production
GO:32722; positive regulation of chemokine production
GO:32727; positive regulation of interferon-alpha production
GO:32728; positive regulation of interferon-beta production
GO:32729; positive regulation of interferon-gamma production
GO:32732; positive regulation of interleukin-1 production
GO:32733; positive regulation of interleukin-10 production
GO:32755; positive regulation of interleukin-6 production
GO:35666; TRIF-dependent toll-like receptor signaling pathway
GO:42088; T-helper 1 type immune response
GO:42116; macrophage activation
GO:43032; positive regulation of macrophage activation
GO:45429; positive regulation of nitric oxide biosynthetic process
GO:45671; negative regulation of osteoclast differentiation
GO:50829; defense response to Gram-negative bacterium
GO:51770; positive regulation of nitric-oxide synthase biosynthetic process
GO:60729; intestinal epithelial structure maintenance
GO:70373; negative regulation of ERK1 and ERK2 cascade
GO:120163; negative regulation of cold-induced thermogenesis
GO:140052; cellular response to oxidised low-density lipoprotein particle stimulus
GO:1900017; positive regulation of cytokine production involved in inflammatory response
GO:1901224; positive regulation of NIK/NF-kappaB signaling
GO:1903223; positive regulation of oxidative stress-induced neuron death
GO:1903428; positive regulation of reactive oxygen species biosynthetic process
GO:1903974; positive regulation of cellular response to macrophage colony-stimulating factor stimulus
GO:1904466; positive regulation of matrix metallopeptidase secretion
GO:1904646; cellular response to amyloid-beta
GO:2000343; positive regulation of chemokine (C-X-C motif) ligand 2 production
GO:2218; activation of innate immune response
GO:2246; wound healing involved in inflammatory response
GO:2322; B cell proliferation involved in immune response
GO:2537; nitric oxide production involved in inflammatory response
GO:2730; regulation of dendritic cell cytokine production
GO:9617; response to bacterium
GO:14002; astrocyte development
GO:14911; positive regulation of smooth muscle cell migration
GO:30890; positive regulation of B cell proliferation
GO:32874; positive regulation of stress-activated MAPK cascade
GO:34142; toll-like receptor 4 signaling pathway
GO:36120; cellular response to platelet-derived growth factor stimulus
GO:43123; positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:45348; positive regulation of MHC class II biosynthetic process
GO:46330; positive regulation of JNK cascade
GO:48661; positive regulation of smooth muscle cell proliferation
GO:50671; positive regulation of lymphocyte proliferation
GO:50727; regulation of inflammatory response
GO:60907; positive regulation of macrophage cytokine production
GO:70374; positive regulation of ERK1 and ERK2 cascade
GO:70430; positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:70434; positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:71223; cellular response to lipoteichoic acid

Cellular component:

GO:5737; cytoplasm
GO:16020; membrane
GO:16021; integral component of membrane
GO:5794; Golgi apparatus
GO:5886; plasma membrane
GO:5768; endosome
GO:42995; cell projection
GO:48471; perinuclear region of cytoplasm
GO:5769; early endosome
GO:9986; cell surface
GO:1726; ruffle
GO:5887; integral component of plasma membrane
GO:1891; phagocytic cup
GO:10008; endosome membrane
GO:43235; receptor complex
GO:9897; external side of plasma membrane
GO:31226; intrinsic component of plasma membrane
GO:46696; lipopolysaccharide receptor complex

Function:

GO:5515; protein binding
GO:16787; hydrolase activity
GO:4888; transmembrane signaling receptor activity
GO:3953; NAD+ nucleosidase activity
GO:42802; identical protein binding
GO:50135; NAD(P)+ nucleosidase activity
GO:61809; NAD+ nucleotidase, cyclic ADP-ribose generating
GO:38023; signaling receptor activity
GO:1530; lipopolysaccharide binding
GO:1540; amyloid-beta binding
GO:1875; lipopolysaccharide immune receptor activity
GO:5102; signaling receptor binding
GO:46982; protein heterodimerization activity

Hide GO terms

Danio rerio

tlr4bb

Mus musculus

Tlr4

Rattus norvegicus

Tlr4

LongevityMap