InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TLR4

Summary

InnateDB Protein

IDBP-82746.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TLR4

Protein Name

toll-like receptor 4

Synonyms

ARMD10; CD284; TLR-4; TOLL;

Species

Homo sapiens

Ensembl Protein

ENSP00000363089

InnateDB Gene

IDBG-82738 (TLR4)

Protein Structure

UniProt Annotation

Function

Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS- independent inflammatory responses triggered by free fatty acids such as palmitate and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species- specific. {ECO:0000269PubMed:17478729, ECO:0000269PubMed:20711192}.

Subcellular Localization

Membrane; Single-pass type I membrane protein.

Disease Associations

Macular degeneration, age-related, 10 (ARMD10) [MIM:611488]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Tissue Specificity

Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 91 experimentally validated interaction(s) in this database.
They are also associated with 38 interaction(s) predicted by orthology.

Experimentally validated
Total	91 [view]
Protein-Protein	81 [view]
Protein-DNA	4 [view]
Protein-RNA	1 [view]
DNA-DNA	3 [view]
RNA-RNA	2 [view]
DNA-RNA	0

Predicted by orthology
Total	38 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001530	lipopolysaccharide binding
GO:0001875	lipopolysaccharide receptor activity
GO:0004872	receptor activity
GO:0004888	transmembrane signaling receptor activity
GO:0005515	protein binding

Biological Process

GO:0000187	activation of MAPK activity
GO:0002218	activation of innate immune response
GO:0002224	toll-like receptor signaling pathway
GO:0002322	B cell proliferation involved in immune response
GO:0002537	nitric oxide production involved in inflammatory response
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006955	immune response
GO:0007165	signal transduction
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0007252	I-kappaB phosphorylation
GO:0009617	response to bacterium
GO:0010572	positive regulation of platelet activation
GO:0016046	detection of fungus
GO:0030890	positive regulation of B cell proliferation
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032496	response to lipopolysaccharide
GO:0032497	detection of lipopolysaccharide
GO:0032609	interferon-gamma production
GO:0032689	negative regulation of interferon-gamma production
GO:0032700	negative regulation of interleukin-17 production
GO:0032707	negative regulation of interleukin-23 production
GO:0032715	negative regulation of interleukin-6 production
GO:0032720	negative regulation of tumor necrosis factor production
GO:0032722	positive regulation of chemokine production
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0032729	positive regulation of interferon-gamma production
GO:0032732	positive regulation of interleukin-1 production
GO:0032733	positive regulation of interleukin-10 production
GO:0032735	positive regulation of interleukin-12 production
GO:0032755	positive regulation of interleukin-6 production
GO:0032757	positive regulation of interleukin-8 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0032874	positive regulation of stress-activated MAPK cascade
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0042088	T-helper 1 type immune response
GO:0042116	macrophage activation
GO:0042346	positive regulation of NF-kappaB import into nucleus
GO:0042535	positive regulation of tumor necrosis factor biosynthetic process
GO:0042742	defense response to bacterium
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045084	positive regulation of interleukin-12 biosynthetic process
GO:0045087	innate immune response (InnateDB)
GO:0045348	positive regulation of MHC class II biosynthetic process
GO:0045359	positive regulation of interferon-beta biosynthetic process
GO:0045416	positive regulation of interleukin-8 biosynthetic process
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0045671	negative regulation of osteoclast differentiation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046330	positive regulation of JNK cascade
GO:0050671	positive regulation of lymphocyte proliferation
GO:0050707	regulation of cytokine secretion
GO:0050727	regulation of inflammatory response
GO:0050729	positive regulation of inflammatory response
GO:0050829	defense response to Gram-negative bacterium
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
GO:0060729	intestinal epithelial structure maintenance
GO:0060907	positive regulation of macrophage cytokine production
GO:0070373	negative regulation of ERK1 and ERK2 cascade
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070430	positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070434	positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0071222	cellular response to lipopolysaccharide
GO:0071223	cellular response to lipoteichoic acid
GO:0071260	cellular response to mechanical stimulus

Cellular Component

GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009897	external side of plasma membrane
GO:0010008	endosome membrane
GO:0016021	integral component of membrane
GO:0046696	lipopolysaccharide receptor complex
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000157 Toll/interleukin-1 receptor homology (TIR) domain
IPR000483 Cysteine-rich flanking region, C-terminal
IPR001611 Leucine-rich repeat
IPR003591 Leucine-rich repeat, typical subtype
IPR017241 Toll-like receptor

PFAM

PF01582
PF13676
PF01463
PF00560
PF13504
PF13855

PRINTS

PIRSF

PIRSF037595

SMART

SM00255
SM00082
SM00369

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt