Toll-like receptor 4

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
  • regulation of cytokine secretion
  • cellular response to mechanical stimulus
  • positive regulation of MHC class II biosynthetic process
  • positive regulation of interleukin-12 production
  • defense response to Gram-negative bacterium
  • negative regulation of interleukin-23 production
  • apoptotic process
  • positive regulation of nitric-oxide synthase biosynthetic process
  • positive regulation of NF-kappaB transcription factor activity
  • positive regulation of interleukin-8 production
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of NF-kappaB import into nucleus
  • negative regulation of ERK1 and ERK2 cascade
  • activation of MAPK activity
  • B cell proliferation involved in immune response
  • defense response to bacterium
  • I-kappaB phosphorylation
  • negative regulation of tumor necrosis factor production
  • positive regulation of chemokine production
  • detection of fungus
  • positive regulation of interleukin-10 production
  • cellular response to lipoteichoic acid
  • positive regulation of B cell proliferation
  • positive regulation of gene expression
  • intestinal epithelial structure maintenance
  • positive regulation of interleukin-6 production
  • positive regulation of interferon-beta production
  • negative regulation of osteoclast differentiation
  • MyD88-dependent toll-like receptor signaling pathway
  • positive regulation of NLRP3 inflammasome complex assembly
  • positive regulation of tumor necrosis factor production
  • positive regulation of macrophage cytokine production
  • MyD88-independent toll-like receptor signaling pathway
  • positive regulation of interferon-gamma production
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway
  • positive regulation of inflammatory response
  • positive regulation of tumor necrosis factor biosynthetic process
  • toll-like receptor 2 signaling pathway
  • immune response
  • I-kappaB kinase/NF-kappaB signaling
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
  • response to lipopolysaccharide
  • regulation of dendritic cell cytokine production
  • toll-like receptor 3 signaling pathway
  • programmed cell death
  • interferon-gamma production
  • cellular response to lipopolysaccharide
  • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
  • interleukin-1 beta secretion
  • negative regulation of interferon-gamma production
  • toll-like receptor 4 signaling pathway
  • toll-like receptor TLR6
  • positive regulation of JNK cascade
  • positive regulation of interferon-alpha production
  • toll-like receptor signaling pathway
  • TRIF-dependent toll-like receptor signaling pathway
  • positive regulation of interleukin-8 biosynthetic process
  • positive regulation of interferon-beta biosynthetic process
  • toll-like receptor TLR1
  • negative regulation of interleukin-6 production
  • detection of lipopolysaccharide
  • T-helper 1 type immune response
  • innate immune response
  • extrinsic apoptotic signaling pathway
  • macrophage activation
  • lipopolysaccharide-mediated signaling pathway
  • positive regulation of platelet activation
  • negative regulation of interleukin-17 production
  • nitric oxide production involved in inflammatory response
  • positive regulation of interleukin-1 production
  • positive regulation of interleukin-12 biosynthetic process
  • positive regulation of nitric oxide biosynthetic process
Components
  • lipopolysaccharide receptor complex
  • cytoplasm
  • 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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