TLR4
entrez
7099
canonical
uniprot
O00206
canonical
ensembl
ENSG00000136869
resolver
ensp
ENSP00000363089
resolver
ensp
ENSP00000377997
resolver
genesymbol
TLR4
resolver
hgnc
HGNC:11850
resolver
uniprot
A8K1Y8
resolver
uniprot
A9XLP9
resolver
uniprot
A9XLQ0
resolver
uniprot
A9XLQ1
resolver
uniprot
B4E194
resolver
uniprot
D1CS52
resolver
uniprot
D1CS53
resolver
uniprot
Q5VZI8
resolver
uniprot
Q5VZI9
resolver
uniprot
Q9UK78
resolver
uniprot
Q9UM57
resolver
uniprot_entry
TLR4_HUMAN
resolver
uniprot_sec
A8K1Y8
resolver
uniprot_sec
A9XLP9
resolver
uniprot_sec
A9XLQ0
resolver
uniprot_sec
A9XLQ1
resolver
uniprot_sec
B4E194
resolver
uniprot_sec
D1CS52
resolver
uniprot_sec
D1CS53
resolver
uniprot_sec
Q5VZI8
resolver
uniprot_sec
Q5VZI9
resolver
uniprot_sec
Q9UK78
resolver
uniprot_sec
Q9UM57
resolver
amino_acid_sequence
MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
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:10835634, PubMed:15809303, PubMed:16622205, PubMed:17292937, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:29038465, PubMed:17803912, PubMed:15852007). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) (PubMed:20711192). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:10835634, PubMed:21393102, PubMed:27022195, PubMed:36945827, PubMed:9237759). 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 (PubMed:14517278). 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 (PubMed:32894580). In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 (PubMed:23880187). 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 (PubMed:23880187). 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 (PubMed:15265881, PubMed:23880187). Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells. {ECO:0000269|PubMed:10835634, ECO:0000269|PubMed:14517278, ECO:0000269|PubMed:15265881, ECO:0000269|PubMed:15809303, ECO:0000269|PubMed:15852007, ECO:0000269|PubMed:16622205, ECO:0000269|PubMed:17292937, ECO:0000269|PubMed:17478729, ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20711192, ECO:0000269|PubMed:23880187, ECO:0000269|PubMed:27022195, ECO:0000269|PubMed:29038465, ECO:0000269|PubMed:36945827, ECO:0000269|PubMed:9237759}.
uniprot
proteins
mass_dalton
95680
uniprot
proteins
mutagenesis
MUTAGEN 431; /note="H->A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-456 or A-458."; /evidence="ECO:0000269|PubMed:20711192"; MUTAGEN 456; /note="H->A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-431. Suppresses NF-kappa-B activation induced by Ni(2+); when associated with A-458."; /evidence="ECO:0000269|PubMed:20711192"; MUTAGEN 458; /note="H->A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-431. Suppresses NF-kappa-B activation induced by Ni(2+); when associated with A-456."; /evidence="ECO:0000269|PubMed:20711192"; MUTAGEN 526; /note="N->A: Abolishes LPS-response and prevents the cell surface expression."; /evidence="ECO:0000269|PubMed:11706042"; MUTAGEN 575; /note="N->A: Abolishes LPS-response and prevents the cell surface expression."; /evidence="ECO:0000269|PubMed:11706042"; MUTAGEN 697; /note="E->R: Abolishes LPS-response."; /evidence="ECO:0000269|PubMed:11081518"; MUTAGEN 710; /note="R->E: Abolishes LPS-response."; /evidence="ECO:0000269|PubMed:11081518"; MUTAGEN 711; /note="D->K: Abolishes LPS-response."; /evidence="ECO:0000269|PubMed:11081518"; MUTAGEN 714; /note="P->H,R,E: Abolishes MYD88-binding and LPS-response."; /evidence="ECO:0000269|PubMed:11081518
uniprot
proteins
post_translational_modification
PTM: N-Glycosylation of Asn-526 and Asn-575 by STT3A-containing OST-A complex is necessary for the expression of TLR4 on the cell surface and the LPS-response (PubMed:11706042, PubMed:38670073). Likewise, mutants lacking two or more of the other N-glycosylation sites were deficient in interaction with LPS (PubMed:11706042, PubMed:38670073). {ECO:0000269|PubMed:11706042, ECO:0000269|PubMed:38670073}.; PTM: Phosphorylated on tyrosine residues by LYN after binding lipopolysaccharide. {ECO:0000250|UniProtKB:Q9QUK6}.; PTM: Ubiquitinated by RNF128 via 'Lys-28'-linked polyubiquitin chains, leading to proteasomal degradation. {ECO:0000269|PubMed:37344492}.
uniprot
proteins
protein_family
Toll-like receptor family
uniprot
proteins
pubmed
10835634
uniprot
proteins
pubmed
11081518
uniprot
proteins
pubmed
11104518
uniprot
proteins
pubmed
11274165
uniprot
proteins
pubmed
11514453
uniprot
proteins
pubmed
11706042
uniprot
proteins
pubmed
14517278
uniprot
proteins
pubmed
14519765
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15265881
uniprot
proteins
pubmed
15340161
uniprot
proteins
pubmed
15356101
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15809303
uniprot
proteins
pubmed
15829498
uniprot
proteins
pubmed
15852007
uniprot
proteins
pubmed
16622205
uniprot
proteins
pubmed
17098818
uniprot
proteins
pubmed
17292937
uniprot
proteins
pubmed
17478729
uniprot
proteins
pubmed
17803912
uniprot
proteins
pubmed
18810425
uniprot
proteins
pubmed
19252480
uniprot
proteins
pubmed
19846529
uniprot
proteins
pubmed
19924287
uniprot
proteins
pubmed
20037584
uniprot
proteins
pubmed
20711192
uniprot
proteins
pubmed
20865800
uniprot
proteins
pubmed
21393102
uniprot
proteins
pubmed
21602844
uniprot
proteins
pubmed
22363519
uniprot
proteins
pubmed
23569230
uniprot
proteins
pubmed
23880187
uniprot
proteins
pubmed
24265315
uniprot
proteins
pubmed
25736436
uniprot
proteins
pubmed
25787250
uniprot
proteins
pubmed
27022195
uniprot
proteins
pubmed
28334607
uniprot
proteins
pubmed
29038465
uniprot
proteins
pubmed
30573680
uniprot
proteins
pubmed
32894580
uniprot
proteins
pubmed
36232715
uniprot
proteins
pubmed
36945827
uniprot
proteins
pubmed
37344492
uniprot
proteins
pubmed
38378891
uniprot
proteins
pubmed
38670073
uniprot
proteins
pubmed
9237759
uniprot
proteins
pubmed
9435236
uniprot
proteins
sequence_length
839
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11274165, ECO:0000269|PubMed:17098818, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:21393102, ECO:0000269|PubMed:27022195, ECO:0000269|PubMed:36232715, ECO:0000269|PubMed:36945827, ECO:0000269|PubMed:38670073, ECO:0000269|PubMed:9237759}; Single-pass type I membrane protein {ECO:0000269|PubMed:11274165}. Early endosome {ECO:0000269|PubMed:27022195}. Cell projection, ruffle {ECO:0000250|UniProtKB:Q9QUK6}. Note=Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis (PubMed:20037584). Colocalizes with RFTN1 at cell membrane and then together with RFTN1 moves to endosomes, upon lipopolysaccharide stimulation. Co-localizes with ZG16B/PAUF at the cell membrane of pancreatic cancer cells (PubMed:36232715). {ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:36232715}.
uniprot
proteins
transmembrane_region
TRANSMEM 632..652; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins