Tlr4
entrez
21898
canonical
uniprot
Q9QUK6
canonical
ensembl
ENSMUSG00000039005
resolver
ensp
ENSMUSP00000045770
resolver
enst
ENSMUST00000048096
resolver
genesymbol
Tlr4
resolver
genesymbol_syn
Lps
resolver
uniprot
L0CL36
resolver
uniprot
Q9D691
resolver
uniprot
Q9QZF5
resolver
uniprot
Q9Z203
resolver
uniprot_entry
L0CL36_MOUSE
resolver
uniprot_entry
TLR4_MOUSE
resolver
uniprot_sec
Q9D691
resolver
uniprot_sec
Q9QZF5
resolver
uniprot_sec
Q9Z203
resolver
amino_acid_sequence
MMPPWLLARTLIMALFFSCLTPGSLNPCIEVVPNITYQCMDQKLSKVPDDIPSSTKNIDLSFNPLKILKSYSFSNFSELQWLDLSRCEIETIEDKAWHGLHHLSNLILTGNPIQSFSPGSFSGLTSLENLVAVETKLASLESFPIGQLITLKKLNVAHNFIHSCKLPAYFSNLTNLVHVDLSYNYIQTITVNDLQFLRENPQVNLSLDMSLNPIDFIQDQAFQGIKLHELTLRGNFNSSNIMKTCLQNLAGLHVHRLILGEFKDERNLEIFEPSIMEGLCDVTIDEFRLTYTNDFSDDIVKFHCLANVSAMSLAGVSIKYLEDVPKHFKWQSLSIIRCQLKQFPTLDLPFLKSLTLTMNKGSISFKKVALPSLSYLDLSRNALSFSGCCSYSDLGTNSLRHLDLSFNGAIIMSANFMGLEELQHLDFQHSTLKRVTEFSAFLSLEKLLYLDISYTNTKIDFDGIFLGLTSLNTLKMAGNSFKDNTLSNVFANTTNLTFLDLSKCQLEQISWGVFDTLHRLQLLNMSHNNLLFLDSSHYNQLYSLSTLDCSFNRIETSKGILQHFPKSLAFFNLTNNSVACICEHQKFLQWVKEQKQFLVNVEQMTCATPVEMNTSLVLDFNNSTCYMYKTIISVSVVSVIVVSTVAFLIYHFYFHLILIAGCKKYSRGESIYDAFVIYSSQNEDWVRNELVKNLEEGVPRFHLCLHYRDFIPGVAIAANIIQEGFHKSRKVIVVVSRHFIQSRWCIFEYEIAQTWQFLSSRSGIIFIVLEKVEKSLLRQQVELYRLLSRNTYLEWEDNPLGRHIFWRRLKNALLDGKASNPEQTAEEEQETATWT
uniprot
proteins
disease_involvement
DISEASE: Note=The protein is encoded by the Lps locus, an important susceptibility locus, influencing the propensity to develop a disseminated Gram-negative infection. {ECO:0000269|PubMed:9851930, ECO:0000269|PubMed:9989976}.
uniprot
proteins
function
FUNCTION: Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways (PubMed:20133493, PubMed:9851930, PubMed:9989976). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:20133493, PubMed:9851930, PubMed:9989976). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:24380872). Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production. In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade. In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86. Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway. In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner (By similarity). {ECO:0000250|UniProtKB:O00206, ECO:0000269|PubMed:10952994, ECO:0000269|PubMed:17478729, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20133493, ECO:0000269|PubMed:23812099, ECO:0000269|PubMed:24380872, ECO:0000269|PubMed:9851930, ECO:0000269|PubMed:9989976}.; FUNCTION: (Microbial infection) Required for the virulence of fungus C.neoformans var. grubii serotype A (strain KN99) CPL1 (PubMed:35896747). Independently of Ly96/Md2, activated by CPL1 which results in a type 2 inflammation response characterized by Arg1/arginase-1 induction in interstitial macrophages (PubMed:35896747). {ECO:0000269|PubMed:35896747}.; FUNCTION: (Microbial infection) Mediates activation of bone marrow-derived dendritic cells and macrophages, and production of pro-inflammatory cytokines, such as IL12 (IL12B/IL12A), triggered by Toxoplasma gondii micronemal protein 4 (MIC4) and micronemal protein 1 (MIC1) (PubMed:31226171). Mediates production of anti-inflammatory cytokine IL10 triggered by Toxoplasma gondii micronemal protein 4 (MIC4) and micronemal protein 1 (MIC1) in murine bone marrow-derived macrophages (PubMed:33912181). {ECO:0000269|PubMed:31226171, ECO:0000269|PubMed:33912181}.
uniprot
proteins
mass_dalton
95519
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues by LYN after binding lipopolysaccharide. {ECO:0000269|PubMed:28098138}.; PTM: Ubiquitinated by RNF128 via 'Lys-28'-linked polyubiquitin chains, leading to proteasomal degradation. {ECO:0000250|UniProtKB:O00206}.
uniprot
proteins
protein_family
Toll-like receptor family
uniprot
proteins
pubmed
10087992
uniprot
proteins
pubmed
10548109
uniprot
proteins
pubmed
10952994
uniprot
proteins
pubmed
11104518
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17478729
uniprot
proteins
pubmed
17803912
uniprot
proteins
pubmed
18780723
uniprot
proteins
pubmed
20037584
uniprot
proteins
pubmed
20133493
uniprot
proteins
pubmed
20865800
uniprot
proteins
pubmed
22496641
uniprot
proteins
pubmed
22532668
uniprot
proteins
pubmed
23812099
uniprot
proteins
pubmed
24380872
uniprot
proteins
pubmed
25736436
uniprot
proteins
pubmed
26095358
uniprot
proteins
pubmed
28098138
uniprot
proteins
pubmed
31226171
uniprot
proteins
pubmed
33912181
uniprot
proteins
pubmed
34675215
uniprot
proteins
pubmed
35896747
uniprot
proteins
pubmed
38378891
uniprot
proteins
pubmed
9851930
uniprot
proteins
pubmed
9989976
uniprot
proteins
sequence_length
835
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20133493, ECO:0000269|PubMed:28098138, ECO:0000269|PubMed:35896747}; Single-pass type I membrane protein {ECO:0000269|PubMed:20133493}. Early endosome {ECO:0000250|UniProtKB:O00206}. Cell projection, ruffle {ECO:0000269|PubMed:28098138}. Note=Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis. Colocalizes with RFTN1 at cell membrane and then together with RFTN1 moves to endosomes, upon lipopolysaccharide stimulation. {ECO:0000250|UniProtKB:O00206}.; SUBCELLULAR LOCATION: Note=(Microbial infection) Endocytosed upon interaction with fungus C.neoformans var. grubii serotype A (strain KN99) CPL1 at the macrophage cell surface. {ECO:0000269|PubMed:35896747}.
uniprot
proteins
transmembrane_region
TRANSMEM 639..659; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins