MultifacetedProtDB - Bologna Biocomputing Group

Structure

PDB	Resolution (Å)	PDB name
2Z62	1.7	Crystal structure of the TV3 hybrid of human TLR4 and hagfish VLRB.61
2Z63	2.0	Crystal structure of the TV8 hybrid of human TLR4 and hagfish VLRB.61
2Z65	2.7	Crystal structure of the human TLR4 TV3 hybrid-MD-2-Eritoran complex
2Z66	1.9	Crystal structure of the VT3 hybrid of human TLR4 and hagfish VLRB.61
3FXI	3.1	Crystal structure of the human TLR4-human MD-2-E.coli LPS Ra complex
3UL7	2.37	Crystal structure of the TV3 mutant F63W
3UL8	2.5	Crystal structure of the TV3 mutant V134L
3UL9	2.45	structure of the TV3 mutant M41E
3ULA	3.6	Crystal structure of the TV3 mutant F63W-MD-2-Eritoran complex
4G8A	2.4	Crystal structure of human TLR4 polymorphic variant D299G and T399I in complex with MD-2 and LPS
5NAM		NMR structure of TLR4 transmembrane domain (624-670) in DMPG/DHPC bicelles
5NAO		NMR structure of TLR4 transmembrane domain (624-657) in DPC micelles

GO term

GO ontology	GO term	GO description
Biological Process	GO:0002322	B cell proliferation involved in immune response
Biological Process	GO:0070371	ERK1 and ERK2 cascade
Biological Process	GO:0007252	I-kappaB phosphorylation
Biological Process	GO:0007254	JNK cascade
Biological Process	GO:0045342	MHC class II biosynthetic process
Biological Process	GO:0002755	MyD88-dependent toll-like receptor signaling pathway
Biological Process	GO:0042088	T-helper 1 type immune response
Biological Process	GO:0035666	TRIF-dependent toll-like receptor signaling pathway
Biological Process	GO:0014002	astrocyte development
Biological Process	GO:1904646	cellular response to amyloid-beta
Biological Process	GO:0071222	cellular response to lipopolysaccharide
Biological Process	GO:0071223	cellular response to lipoteichoic acid
Biological Process	GO:0071260	cellular response to mechanical stimulus
Biological Process	GO:0140052	cellular response to oxidised low-density lipoprotein particle stimulus
Biological Process	GO:0036120	cellular response to platelet-derived growth factor stimulus
Biological Process	GO:0071346	cellular response to type II interferon
Biological Process	GO:0050829	defense response to Gram-negative bacterium
Biological Process	GO:0042742	defense response to bacterium
Biological Process	GO:0016046	detection of fungus
Biological Process	GO:0032497	detection of lipopolysaccharide
Biological Process	GO:0010467	gene expression
Biological Process	GO:0006955	immune response
Biological Process	GO:0006954	inflammatory response
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0060729	intestinal epithelial structure maintenance
Biological Process	GO:0031663	lipopolysaccharide-mediated signaling pathway
Biological Process	GO:0042116	macrophage activation
Biological Process	GO:0014004	microglia differentiation
Biological Process	GO:0070373	negative regulation of ERK1 and ERK2 cascade
Biological Process	GO:0120163	negative regulation of cold-induced thermogenesis
Biological Process	GO:0032700	negative regulation of interleukin-17 production
Biological Process	GO:0032707	negative regulation of interleukin-23 production
Biological Process	GO:0032715	negative regulation of interleukin-6 production
Biological Process	GO:0045671	negative regulation of osteoclast differentiation
Biological Process	GO:0032720	negative regulation of tumor necrosis factor production
Biological Process	GO:0032689	negative regulation of type II interferon production
Biological Process	GO:0006809	nitric oxide biosynthetic process
Biological Process	GO:0002537	nitric oxide production involved in inflammatory response
Biological Process	GO:0070427	nucleotide-binding oligomerization domain containing 1 signaling pathway
Biological Process	GO:0070431	nucleotide-binding oligomerization domain containing 2 signaling pathway
Biological Process	GO:0006909	phagocytosis
Biological Process	GO:0030890	positive regulation of B cell proliferation
Biological Process	GO:0070374	positive regulation of ERK1 and ERK2 cascade
Biological Process	GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
Biological Process	GO:0046330	positive regulation of JNK cascade
Biological Process	GO:0043406	positive regulation of MAP kinase activity
Biological Process	GO:0045348	positive regulation of MHC class II biosynthetic process
Biological Process	GO:0051092	positive regulation of NF-kappaB transcription factor activity
Biological Process	GO:1901224	positive regulation of NIK/NF-kappaB signaling
Biological Process	GO:1900227	positive regulation of NLRP3 inflammasome complex assembly
Biological Process	GO:1903974	positive regulation of cellular response to macrophage colony-stimulating factor stimulus
Biological Process	GO:2000343	positive regulation of chemokine (C-X-C motif) ligand 2 production
Biological Process	GO:0032722	positive regulation of chemokine production
Biological Process	GO:1900017	positive regulation of cytokine production involved in inflammatory response
Biological Process	GO:2001238	positive regulation of extrinsic apoptotic signaling pathway
Biological Process	GO:0010628	positive regulation of gene expression
Biological Process	GO:0050729	positive regulation of inflammatory response
Biological Process	GO:0032727	positive regulation of interferon-alpha production
Biological Process	GO:0032728	positive regulation of interferon-beta production
Biological Process	GO:0032731	positive regulation of interleukin-1 beta production
Biological Process	GO:0032732	positive regulation of interleukin-1 production
Biological Process	GO:0032733	positive regulation of interleukin-10 production
Biological Process	GO:0032735	positive regulation of interleukin-12 production
Biological Process	GO:0032755	positive regulation of interleukin-6 production
Biological Process	GO:0032757	positive regulation of interleukin-8 production
Biological Process	GO:0043032	positive regulation of macrophage activation
Biological Process	GO:0060907	positive regulation of macrophage cytokine production
Biological Process	GO:1904466	positive regulation of matrix metallopeptidase secretion
Biological Process	GO:0045429	positive regulation of nitric oxide biosynthetic process
Biological Process	GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process
Biological Process	GO:0070430	positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
Biological Process	GO:0070434	positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
Biological Process	GO:0010572	positive regulation of platelet activation
Biological Process	GO:1903428	positive regulation of reactive oxygen species biosynthetic process
Biological Process	GO:0014911	positive regulation of smooth muscle cell migration
Biological Process	GO:0048661	positive regulation of smooth muscle cell proliferation
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0032760	positive regulation of tumor necrosis factor production
Biological Process	GO:0032729	positive regulation of type II interferon production
Biological Process	GO:0002730	regulation of dendritic cell cytokine production
Biological Process	GO:0032496	response to lipopolysaccharide
Biological Process	GO:0034142	toll-like receptor 4 signaling pathway
Biological Process	GO:0002224	toll-like receptor signaling pathway
Biological Process	GO:0002246	wound healing involved in inflammatory response
Molecular Function	GO:0050135	NAD(P)+ nucleosidase activity
Molecular Function	GO:0061809	NAD+ nucleotidase, cyclic ADP-ribose generating
Molecular Function	GO:0001540	amyloid-beta binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0001530	lipopolysaccharide binding
Molecular Function	GO:0001875	lipopolysaccharide immune receptor activity
Molecular Function	GO:0046982	protein heterodimerization activity
Molecular Function	GO:0038023	signaling receptor activity
Molecular Function	GO:0005102	signaling receptor binding
Molecular Function	GO:0004888	transmembrane signaling receptor activity
Cellular Component	GO:0005794	Golgi apparatus
Cellular Component	GO:0009986	cell surface
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005769	early endosome
Cellular Component	GO:0010008	endosome membrane
Cellular Component	GO:0009897	external side of plasma membrane
Cellular Component	GO:0046696	lipopolysaccharide receptor complex
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Cellular Component	GO:0001891	phagocytic cup
Cellular Component	GO:0005886	plasma membrane
Cellular Component	GO:0043235	receptor complex
Cellular Component	GO:0001726	ruffle

InterPro / Pfam

InterPro	InterPro name
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
IPR032675	Leucine-rich repeat domain superfamily
IPR035897	Toll/interleukin-1 receptor homology (TIR) domain superfamily

Pfam	Pfam name
PF01582	TIR domain
PF13855	Leucine rich repeat

Reactome

Reactome	Reactome Name	Node type	Reactome Root	Reactome Root Name
R-HSA-1236974	ER-Phagosome pathway	Leaf	R-HSA-168256	Immune System
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand	Internal node	R-HSA-5357801	Programmed Cell Death
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade	Internal node	R-HSA-168256	Immune System
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane	Internal node	R-HSA-168256	Immune System
R-HSA-166166	MyD88-independent TLR4 cascade	Internal node	R-HSA-168256	Immune System
R-HSA-2562578	TRIF-mediated programmed cell death	Leaf	R-HSA-168256	Immune System
R-HSA-5602498	MyD88 deficiency (TLR2/4)	Leaf	R-HSA-1643685	Disease
R-HSA-5603041	IRAK4 deficiency (TLR2/4)	Leaf	R-HSA-1643685	Disease
R-HSA-5686938	Regulation of TLR by endogenous ligand	Leaf	R-HSA-168256	Immune System
R-HSA-936964	Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon	Leaf	R-HSA-168256	Immune System
R-HSA-937041	IKK complex recruitment mediated by RIP1	Leaf	R-HSA-168256	Immune System
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex	Leaf	R-HSA-168256	Immune System
R-HSA-9707616	Heme signaling	Leaf	R-HSA-8953897	Cellular responses to stimuli
R-HSA-975163	IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation	Leaf	R-HSA-168256	Immune System

Subcellular location

Location	ECO term	Pubmed
Cell membrane	ECO:0000269	PubMed:11274165
Cell membrane	ECO:0000269	PubMed:17098818
Cell membrane	ECO:0000269	PubMed:20037584
Cell membrane	ECO:0000269	PubMed:21393102
Cell membrane	ECO:0000269	PubMed:27022195
Cell membrane	ECO:0000269	PubMed:9237759
Cell projection, ruffle	ECO:0000250
Early endosome	ECO:0000269	PubMed:27022195

Interactor | Variant | Drug

Phenotype

HPO ID	HPO name
HP:0000083	Renal insufficiency
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000518	Cataract
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0001061	Acne
HP:0001097	Keratoconjunctivitis sicca
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001269	Hemiparesis
HP:0001287	Meningitis
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001347	Hyperreflexia
HP:0001369	Arthritis
HP:0001482	Subcutaneous nodule
HP:0001637	Abnormal myocardium morphology
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001701	Pericarditis
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001945	Fever
HP:0002017	Nausea and vomiting
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002076	Migraine
HP:0002102	Pleuritis
HP:0002105	Hemoptysis
HP:0002113	Pulmonary infiltrates
HP:0002202	Pleural effusion
HP:0002204	Pulmonary embolism
HP:0002239	Gastrointestinal hemorrhage
HP:0002321	Vertigo
HP:0002354	Memory impairment
HP:0002376	Developmental regression
HP:0002383	Infectious encephalitis
HP:0002516	Increased intracranial pressure
HP:0002633	Vasculitis
HP:0002637	Cerebral ischemia
HP:0002716	Lymphadenopathy
HP:0002829	Arthralgia
HP:0003326	Myalgia
HP:0003401	Paresthesia
HP:0004420	Arterial thrombosis
HP:0004936	Venous thrombosis
HP:0006824	Cranial nerve paralysis
HP:0007256	Abnormal pyramidal sign
HP:0008066	Abnormal blistering of the skin
HP:0010885	Avascular necrosis
HP:0011107	Recurrent aphthous stomatitis
HP:0012378	Fatigue
HP:0012649	Increased inflammatory response
HP:0100326	Immunologic hypersensitivity
HP:0100584	Endocarditis
HP:0100614	Myositis
HP:0100653	Optic neuritis
HP:0100654	Retrobulbar optic neuritis
HP:0100758	Gangrene
HP:0100796	Orchitis
HP:0100820	Glomerulopathy
HP:0200034	Papule

Tissue and cell type

Tissue	Cell type	Expression level	Reliability
adrenal gland	glandular cells	Low	Approved
bone marrow	hematopoietic cells	High	Approved
cerebral cortex	neuronal cells	Low	Approved
esophagus	squamous epithelial cells	Low	Approved
lymph node	non-germinal center cells	Medium	Approved
salivary gland	glandular cells	Low	Approved
spleen	cells in red pulp	Medium	Approved
tonsil	squamous epithelial cells	Low	Approved

Summary of O00206

Gene: TLR4
Protein: Toll-like receptor 4

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Summary of O00206

Gene: TLR4 Protein: Toll-like receptor 4

Structure

GO term

InterPro / Pfam

Reactome

Subcellular location

Interactor | Variant | Drug

Phenotype

Tissue and cell type

Disease

Gene: TLR4
Protein: Toll-like receptor 4