Toll-like receptor 4; hToll; CD284 (TLR4)

Function: 1) cooperates with LY96 & CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) or lipid A 2) acts via MyD88, TIRAP & TRAF6 3) NF-kappa-B activation 4) cytokine secretion 5) inflammatory response 6) may attenuate allergic response [2] - TLR4 stimulation reduces allergen induced IL-13 7) component of lipopolysaccharide receptor (LPS receptor) 8) interacts with MyD88, TIRAP, NOX4 9) interacts with LY96 via the extracellular domain Structure: - N-glycosylated a) glycosylation of Asn-526 & Asn-575 appears to be necessary for the expression of TLR4 on the cell surface & the LPS-response b) mutants lacking 2 or more other N-glycosylation sites are deficient in interaction with LPS - TIR domain mediates interaction with NOX4 - belongs to the Toll-like receptor family - contains 21 LRR repeats (leucine-rich repeats) - contains 1 TIR domain Compartment: membrane Alternative splicing: named isoforms=3 Expression: - expressed in placenta, spleen, peripheral blood leukocytes > monocytes, macrophages, dendritic cells, T-cells Polymorphism: - allele TLR4*B (Gly-299, Ile-399) associated with blunted response to inhaled LPS Pathology: - genetic variation in TLR4 is associated with age-related macular degeneration type 10 Pharmacology: - ibudilast inhibits Toll-like receptor 4 allegedly targeting neuroinflammation - ApToll is a DNA oligonucleotide antagonist at toll-like receptor 4 & an investigational agent for treatment of ischemic stroke in combination with endovascular thrombectomy

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein leucine-rich repeat-containing protein (LRRC) toll-like receptor

Properties

SIZE: entity length = 839 aa MW = 96 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-23} cysteine residue {C29} MODIFICATION: cysteine residue {C40} N-glycosylation site {N35} cysteine residue {C40} MODIFICATION: cysteine residue {C29} leucine-rich repeat SITE: 52-76 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 77-100 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 101-124 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 128-149 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 150-173 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N173} leucine-rich repeat SITE: 174-197 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 203-225 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N205} leucine-rich repeat SITE: 228-252 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 277-303 MOTIF: leucine residue (SEVERAL) cysteine residue {C281} MODIFICATION: cysteine residue {C306} N-glycosylation site {N282} cysteine residue {C306} MODIFICATION: cysteine residue {C281} leucine-rich repeat SITE: 307-330 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N309} leucine-rich repeat SITE: 332-350 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 351-372 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 373-398 MOTIF: leucine residue (SEVERAL) cysteine residue {C390} MODIFICATION: cysteine residue {C391} cysteine residue {C391} MODIFICATION: cysteine residue {C390} leucine-rich repeat SITE: 400-421 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 422-445 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 447-469 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 470-494 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 495-518 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N497} leucine-rich repeat SITE: 520-541 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N526} leucine-rich repeat SITE: 543-566 MOTIF: leucine residue (SEVERAL) leucine-rich repeat SITE: 568-592 MOTIF: leucine residue (SEVERAL) N-glycosylation site {N575} cysteine residue {C583} MODIFICATION: cysteine residue {C609} cysteine residue {C585} MODIFICATION: cysteine residue {C627} cysteine residue {C609} MODIFICATION: cysteine residue {C583} N-glycosylation site {N624} cysteine residue {C627} MODIFICATION: cysteine residue {C585} N-glycosylation site {N630} transmembrane domain {632-652} TIR domain {672-818}

Database Correlations

OMIM correlations MORBIDMAP 603030 UniProt O00206 PFAM correlations Entrez Gene 7099 Kegg hsa:7099