Protein:TLR4 |
Protein Summary |
 Gene summary |
| Gene name: TLR4 | ASpdb.0 ID: 7099 | Gene | Gene symbol | TLR4 | Gene ID | 7099 |
| Gene name | toll like receptor 4 |
| Synonyms | ARMD10|CD284|TLR-4|TOLL |
| Cytomap | 9q33.1 |
| Type of gene | protein-coding |
| Description | toll-like receptor 4hTollhomolog of Drosophila tolltoll like receptor 4 protein |
| Modification date | 20240416 |
| UniProtAcc | O00206 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TLR4 | GO:0001875 | lipopolysaccharide immune receptor activity | 19252480 |
| Gene | TLR4 | GO:0001891 | phagocytic cup | 30883606 |
| Gene | TLR4 | GO:0002224 | toll-like receptor signaling pathway | 14607928 |
| Gene | TLR4 | GO:0002755 | MyD88-dependent toll-like receptor signaling pathway | 20037584 |
| Gene | TLR4 | GO:0005737 | cytoplasm | 19740627 |
| Gene | TLR4 | GO:0005886 | plasma membrane | 12055629 |
| Gene | TLR4 | GO:0005886 | plasma membrane | 11274165|15027902|16338228|19740627|36232715 |
| Gene | TLR4 | GO:0006909 | phagocytosis | 30883606 |
| Gene | TLR4 | GO:0007252 | I-kappaB phosphorylation | 19740627 |
| Gene | TLR4 | GO:0009897 | external side of plasma membrane | 16514062 |
| Gene | TLR4 | GO:0009986 | cell surface | 25204797 |
| Gene | TLR4 | GO:0010008 | endosome membrane | 18222170 |
| Gene | TLR4 | GO:0031663 | lipopolysaccharide-mediated signaling pathway | 10880523 |
| Gene | TLR4 | GO:0032496 | response to lipopolysaccharide | 12594207 |
| Gene | TLR4 | GO:0032496 | response to lipopolysaccharide | 14607928 |
| Gene | TLR4 | GO:0032497 | detection of lipopolysaccharide | 19252480 |
| Gene | TLR4 | GO:0032722 | positive regulation of chemokine production | 19740627 |
| Gene | TLR4 | GO:0032731 | positive regulation of interleukin-1 beta production | 11432859 |
| Gene | TLR4 | GO:0032735 | positive regulation of interleukin-12 production | 15027902 |
| Gene | TLR4 | GO:0032755 | positive regulation of interleukin-6 production | 19740627 |
| Gene | TLR4 | GO:0032757 | positive regulation of interleukin-8 production | 17951129|19740627|21329689 |
| Gene | TLR4 | GO:0032760 | positive regulation of tumor necrosis factor production | 17951129 |
| Gene | TLR4 | GO:0034142 | toll-like receptor 4 signaling pathway | 10196138|15618008|18222170 |
| Gene | TLR4 | GO:0038023 | signaling receptor activity | 15618008|16751103|18222170 |
| Gene | TLR4 | GO:0046696 | lipopolysaccharide receptor complex | 11274165|19252480 |
| Gene | TLR4 | GO:0048471 | perinuclear region of cytoplasm | 15027902 |
| Gene | TLR4 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 12594207 |
| Gene | TLR4 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 29038465 |
| Gene | TLR4 | GO:0071222 | cellular response to lipopolysaccharide | 11432859 |
| Gene | TLR4 | GO:0071346 | cellular response to type II interferon | 11672593 |
| Gene | TLR4 | GO:0140052 | cellular response to oxidised low-density lipoprotein particle stimulus | 20037584 |
| Gene | TLR4 | GO:1901224 | positive regulation of non-canonical NF-kappaB signal transduction | 19740627 |
| Gene | TLR4 | GO:1903974 | positive regulation of cellular response to macrophage colony-stimulating factor stimulus | 11672593 |
| Gene | TLR4 | GO:1904646 | cellular response to amyloid-beta | 20037584 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| O00206-1 | O00206-1_4g8a_B.pdb | 4G8A | X-ray | 2.4 | B | 23 | 627 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| O00206 | TLR4 | O00206-1 | O00206-2 | 839 | 799 | 1 | 40 | Deletion | none | none | 0 | 0 |
| O00206 | TLR4 | O00206-1 | O00206-3 | 839 | 639 | 1 | 200 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced TLR4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TLR4 |
| UniProt-id | ENSG | ENST | ENSP |
| O00206-1 | ENSG00000136869.16 | ENST00000355622.8 | ENSP00000363089.5 |
| O00206-2 | ENSG00000136869.16 | ENST00000394487.5 | ENSP00000377997.4 |
| UniProt-id | NM ID | NP ID |
| O00206-1 | NM_138554.4 | NP_612564.1 |
| O00206-2 | NM_003266.3 | NP_003257.1 |
| O00206-3 | NM_138557.2 | NP_612567.1 |
| Amino acid sequences of our canonical and alternatively spliced TLR4 |
| accession_id | Protein sequence |
| O00206-1 | MMSASRLAGTLIPAMAFLSCVRPESWEPCVEVVPNITYQCMELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEI QTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQKLVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHL DLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLE KFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTS NKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLI YLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPY KCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMN KTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAA NIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRR |
| O00206-2 | MELNFYKIPDNLPFSTKNLDLSFNPLRHLGSYSFFSFPELQVLDLSRCEIQTIEDGAYQSLSHLSTLILTGNPIQSLALGAFSGLSSLQK LVAVETNLASLENFPIGHLKTLKELNVAHNLIQSFKLPEYFSNLTNLEHLDLSSNKIQSIYCTDLRVLHQMPLLNLSLDLSLNPMNFIQP GAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRLAYLDYYLDDIIDLFNCLTNV SSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDLSRNGLSFKGCCSQSDFGTTS LKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGLSSLEVLKMAGNSFQENFLPD IFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSKKQELQHFPSSLAFLNLTQND FACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVLVYKFYFHLMLLAGCIKYGRG ENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQHFIQSRWCIFEYEIAQTWQFL |
| O00206-3 | MPLLNLSLDLSLNPMNFIQPGAFKEIRLHKLTLRNNFDSLNVMKTCIQGLAGLEVHRLVLGEFRNEGNLEKFDKSALEGLCNLTIEEFRL AYLDYYLDDIIDLFNCLTNVSSFSLVSVTIERVKDFSYNFGWQHLELVNCKFGQFPTLKLKSLKRLTFTSNKGGNAFSEVDLPSLEFLDL SRNGLSFKGCCSQSDFGTTSLKYLDLSFNGVITMSSNFLGLEQLEHLDFQHSNLKQMSEFSVFLSLRNLIYLDISHTHTRVAFNGIFNGL SSLEVLKMAGNSFQENFLPDIFTELRNLTFLDLSQCQLEQLSPTAFNSLSSLQVLNMSHNNFFSLDTFPYKCLNSLQVLDYSLNHIMTSK KQELQHFPSSLAFLNLTQNDFACTCEHQSFLQWIKDQRQLLVEVERMECATPSDKQGMPVLSLNITCQMNKTIIGVSVLSVLVVSVVAVL VYKFYFHLMLLAGCIKYGRGENIYDAFVIYSSQDEDWVRNELVKNLEEGVPPFQLCLHYRDFIPGVAIAANIIHEGFHKSRKVIVVVSQH FIQSRWCIFEYEIAQTWQFLSSRAGIIFIVLQKVEKTLLRQQVELYRLLSRNTYLEWEDSVLGRHIFWRRLRKALLDGKSWNPEGTVGTG |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TLR4 (go to UniProt):O00206 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| O00206 | Topological domain | 24 | 631 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=40 |
| O00206 | Topological domain | 24 | 631 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=200 |
| O00206 | Repeat | 55 | 76 | Note=LRR 1 | Type=Deletion;Start=1;End=200 |
| O00206 | Repeat | 79 | 100 | Note=LRR 2 | Type=Deletion;Start=1;End=200 |
| O00206 | Repeat | 103 | 124 | Note=LRR 3 | Type=Deletion;Start=1;End=200 |
| O00206 | Repeat | 127 | 148 | Note=LRR 4 | Type=Deletion;Start=1;End=200 |
| O00206 | Repeat | 151 | 172 | Note=LRR 5 | Type=Deletion;Start=1;End=200 |
| O00206 | Repeat | 176 | 199 | Note=LRR 6 | Type=Deletion;Start=1;End=200 |
Gene Isoform Structures and Expression Levels for TLR4 |
| Gene structures of our canonical and alternative spliced genes of TLR4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of O00206-1 |
| 3D view using mol* of O00206-2 |
| 3D view using mol* of O00206-3 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of O00206-1 |
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| pLDDT distribution across the protein length of O00206-2 |
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| pLDDT distribution across the protein length of O00206-3 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of O00206-1 |
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| Ramachandran plot of O00206-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| O00206-1 | 0.981 | 101 | 1.017 | 225.351 | 0.598 | 0.64 | 0.841 | 0.465 | 0.942 | 0.494 | 1.814 | 664,667,668,669,670,671,672,724,727,728,729,730,73 1,732,733,757,760,761,763,764 |
| O00206-2 | 0.928 | 77 | 0.945 | 262.738 | 0.567 | 0.678 | 0.944 | 0.743 | 0.879 | 0.845 | 1.559 | 624,627,628,629,630,632,684,687,688,689,690,691,71 7,721,723,724 |
| O00206-3 | 0.979 | 93 | 1.041 | 222.95 | 0.622 | 0.611 | 0.808 | 0.581 | 0.714 | 0.814 | 1.696 | 464,465,467,468,469,470,472,524,528,529,530,531,55 7,560,561,563,564 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of O00206-1_O00206-1_4g8a_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O00206-1_4g8a_B_O00206-2.pdb |
| 3D view using mol* of O00206-1_4g8a_B_O00206-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O00206-1_O00206-2.pdb |
| 3D view using mol* of O00206-1_O00206-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O00206-1_vs_O00206-2.png |
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| ./stats/secondary_structure/figure/O00206-1_vs_O00206-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O00206-1_vs_O00206-2.png |
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| ./stats/relative_asa/O00206-1_vs_O00206-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to TLR4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| O00206 | TLR4 | DB01183 | Naloxone | approved, vet_approved | inhibitor |
| O00206 | TLR4 | DB06447 | E5531 | investigational | |
| O00206 | TLR4 | DB04933 | Eritoran | investigational | |
| O00206 | TLR4 | DB13615 | Mifamurtide | approved, experimental | ligand |
| O00206 | TLR4 | DB05475 | Golotimod | investigational | |
| O00206 | TLR4 | DB08231 | Myristic acid | experimental | |
| O00206 | TLR4 | DB00924 | Cyclobenzaprine | approved | inhibitor |
| O00206 | TLR4 | DB02767 | (R)-3-hydroxytetradecanoic acid | experimental | |
| O00206 | TLR4 | DB11193 | Papain | approved | activator |
| O00206 | TLR4 | DB03017 | Lauric acid | approved, experimental |
Related Diseases to TLR4 |
| Previous studies relating to the alternative splicing of TLR4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
Clinically important variants in TLR4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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