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NameToll-like receptor 4
Synonyms
  • hToll
Gene NameTLR4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004795|Toll-like receptor 4
MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLD
LSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALG
AFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHL
DLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSL
NVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDI
IDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTS
NKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLG
LEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAG
NSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPY
KCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQL
LVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLML
LAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAA
NIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLR
QQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTGCNWQEATSI
Number of residues839
Molecular Weight95679.19
Theoretical pI6.26
GO Classification
Functions
  • transmembrane signaling receptor activity
  • receptor activity
  • lipopolysaccharide binding
  • lipopolysaccharide receptor activity
Processes
  • positive regulation of ERK1 and ERK2 cascade
  • positive regulation of interferon-alpha production
  • cellular response to mechanical stimulus
  • positive regulation of interleukin-12 production
  • TRIF-dependent toll-like receptor signaling pathway
  • negative regulation of interleukin-6 production
  • defense response to Gram-negative bacterium
  • positive regulation of interferon-beta biosynthetic process
  • apoptotic process
  • positive regulation of NF-kappaB transcription factor activity
  • extrinsic apoptotic signaling pathway
  • positive regulation of interleukin-8 production
  • T-helper 1 type immune response
  • positive regulation of transcription from RNA polymerase II promoter
  • negative regulation of ERK1 and ERK2 cascade
  • negative regulation of interleukin-17 production
  • activation of MAPK activity
  • positive regulation of platelet activation
  • defense response to bacterium
  • negative regulation of tumor necrosis factor production
  • positive regulation of interleukin-12 biosynthetic process
  • positive regulation of chemokine production
  • positive regulation of interleukin-1 production
  • positive regulation of interleukin-10 production
  • positive regulation of B cell proliferation
  • positive regulation of MHC class II biosynthetic process
  • positive regulation of gene expression
  • regulation of cytokine secretion
  • positive regulation of interleukin-6 production
  • negative regulation of osteoclast differentiation
  • MyD88-dependent toll-like receptor signaling pathway
  • positive regulation of nitric-oxide synthase biosynthetic process
  • negative regulation of interleukin-23 production
  • positive regulation of tumor necrosis factor production
  • MyD88-independent toll-like receptor signaling pathway
  • positive regulation of NF-kappaB import into nucleus
  • positive regulation of interferon-gamma production
  • positive regulation of inflammatory response
  • toll-like receptor 2 signaling pathway
  • I-kappaB phosphorylation
  • immune response
  • I-kappaB kinase/NF-kappaB signaling
  • B cell proliferation involved in immune response
  • response to lipopolysaccharide
  • toll-like receptor 3 signaling pathway
  • cellular response to lipoteichoic acid
  • programmed cell death
  • interferon-gamma production
  • detection of fungus
  • cellular response to lipopolysaccharide
  • interleukin-1 beta secretion
  • toll-like receptor 4 signaling pathway
  • positive regulation of interferon-beta production
  • positive regulation of JNK cascade
  • intestinal epithelial structure maintenance
  • toll-like receptor signaling pathway
  • positive regulation of macrophage cytokine production
  • positive regulation of interleukin-8 biosynthetic process
  • positive regulation of NLRP3 inflammasome complex assembly
  • toll-like receptor TLR1
  • positive regulation of tumor necrosis factor biosynthetic process
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
  • detection of lipopolysaccharide
  • regulation of dendritic cell cytokine production
  • innate immune response
  • macrophage activation
  • lipopolysaccharide-mediated signaling pathway
  • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
  • nitric oxide production involved in inflammatory response
  • negative regulation of interferon-gamma production
  • positive regulation of nitric oxide biosynthetic process
  • toll-like receptor TLR6
Components
  • cytoplasm
  • lipopolysaccharide receptor complex
  • plasma membrane
  • cell surface
  • perinuclear region of cytoplasm
  • endosome membrane
  • external side of plasma membrane
  • intrinsic component of plasma membrane
  • integral component of plasma membrane
General FunctionTransmembrane signaling receptor activity
Specific FunctionCooperates 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 (PubMed:9237759, PubMed:10835634). 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 (PubMed:20711192). In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (PubMed:23880187).
Pfam Domain Function
Transmembrane Regions632-652
GenBank Protein IDNot Available
UniProtKB IDO00206
UniProtKB Entry NameTLR4_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0020616|Toll-like receptor 4 (TLR4)
ATGGAGCTGAATTTCTACAAAATCCCCGACAACCTCCCCTTCTCAACCAAGAACCTGGAC
CTGAGCTTTAATCCCCTGAGGCATTTAGGCAGCTATAGCTTCTTCAGTTTCCCAGAACTG
CAGGTGCTGGATTTATCCAGGTGTGAAATCCAGACAATTGAAGATGGGGCATATCAGAGC
CTAAGCCACCTCTCTACCTTAATATTGACAGGAAACCCCATCCAGAGTTTAGCCCTGGGA
GCCTTTTCTGGACTATCAAGTTTACAGAAGCTGGTGGCTGTGGAGACAAATCTAGCATCT
CTAGAGAACTTCCCCATTGGACATCTCAAAACTTTGAAAGAACTTAATGTGGCTCACAAT
CTTATCCAATCTTTCAAATTACCTGAGTATTTTTCTAATCTGACCAATCTAGAGCACTTG
GACCTTTCCAGCAACAAGATTCAAAGTATTTATTGCACAGACTTGCGGGTTCTACATCAA
ATGCCCCTACTCAATCTCTCTTTAGACCTGTCCCTGAACCCTATGAACTTTATCCAACCA
GGTGCATTTAAAGAAATTAGGCTTCATAAGCTGACTTTAAGAAATAATTTTGATAGTTTA
AATGTAATGAAAACTTGTATTCAAGGTCTGGCTGGTTTAGAAGTCCATCGTTTGGTTCTG
GGAGAATTTAGAAATGAAGGAAACTTGGAAAAGTTTGACAAATCTGCTCTAGAGGGCCTG
TGCAATTTGACCATTGAAGAATTCCGATTAGCATACTTAGACTACTACCTCGATGATATT
ATTGACTTATTTAATTGTTTGACAAATGTTTCTTCATTTTCCCTGGTGAGTGTGACTATT
GAAAGGGTAAAAGACTTTTCTTATAATTTCGGATGGCAACATTTAGAATTAGTTAACTGT
AAATTTGGACAGTTTCCCACATTGAAACTCAAATCTCTCAAAAGGCTTACTTTCACTTCC
AACAAAGGTGGGAATGCTTTTTCAGAAGTTGATCTACCAAGCCTTGAGTTTCTAGATCTC
AGTAGAAATGGCTTGAGTTTCAAAGGTTGCTGTTCTCAAAGTGATTTTGGGACAACCAGC
CTAAAGTATTTAGATCTGAGCTTCAATGGTGTTATTACCATGAGTTCAAACTTCTTGGGC
TTAGAACAACTAGAACATCTGGATTTCCAGCATTCCAATTTGAAACAAATGAGTGAGTTT
TCAGTATTCCTATCACTCAGAAACCTCATTTACCTTGACATTTCTCATACTCACACCAGA
GTTGCTTTCAATGGCATCTTCAATGGCTTGTCCAGTCTCGAAGTCTTGAAAATGGCTGGC
AATTCTTTCCAGGAAAACTTCCTTCCAGATATCTTCACAGAGCTGAGAAACTTGACCTTC
CTGGACCTCTCTCAGTGTCAACTGGAGCAGTTGTCTCCAACAGCATTTAACTCACTCTCC
AGTCTTCAGGTACTAAATATGAGCCACAACAACTTCTTTTCATTGGATACGTTTCCTTAT
AAGTGTCTGAACTCCCTCCAGGTTCTTGATTACAGTCTCAATCACATAATGACTTCCAAA
AAACAGGAACTACAGCATTTTCCAAGTAGTCTAGCTTTCTTAAATCTTACTCAGAATGAC
TTTGCTTGTACTTGTGAACACCAGAGTTTCCTGCAATGGATCAAGGACCAGAGGCAGCTC
TTGGTGGAAGTTGAACGAATGGAATGTGCAACACCTTCAGATAAGCAGGGCATGCCTGTG
CTGAGTTTGAATATCACCTGTCAGATGAATAAGACCATCATTGGTGTGTCGGTCCTCAGT
GTGCTTGTAGTATCTGTTGTAGCAGTTCTGGTCTATAAGTTCTATTTTCACCTGATGCTT
CTTGCTGGCTGCATAAAGTATGGTAGAGGTGAAAACATCTATGATGCCTTTGTTATCTAC
TCAAGCCAGGATGAGGACTGGGTAAGGAATGAGCTAGTAAAGAATTTAGAAGAAGGGGTG
CCTCCATTTCAGCTCTGCCTTCACTACAGAGACTTTATTCCCGGTGTGGCCATTGCTGCC
AACATCATCCATGAAGGTTTCCATAAAAGCCGAAAGGTGATTGTTGTGGTGTCCCAGCAC
TTCATCCAGAGCCGCTGGTGTATCTTTGAATATGAGATTGCTCAGACCTGGCAGTTTCTG
AGCAGTCGTGCTGGTATCATCTTCATTGTCCTGCAGAAGGTGGAGAAGACCCTGCTCAGG
CAGCAGGTGGAGCTGTACCGCCTTCTCAGCAGGAACACTTACCTGGAGTGGGAGGACAGT
GTCCTGGGGCGGCACATCTTCTGGAGACGACTCAGAAAAGCCCTGCTGGATGGTAAATCA
TGGAATCCAGAAGGAACAGTGGGTACAGGATGCAATTGGCAGGAAGCAACATCTATCTGA
GenBank Gene IDU93091
GeneCard IDNot Available
GenAtlas IDTLR4
HGNC IDHGNC:11850
Chromosome Location9
Locus9q32-q33
References
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