Protein:IRF3 |
Protein Summary |
 Gene summary |
| Gene name: IRF3 | ASpdb.0 ID: 3661 | Gene | Gene symbol | IRF3 | Gene ID | 3661 |
| Gene name | interferon regulatory factor 3 |
| Synonyms | IIAE7 |
| Cytomap | 19q13.33 |
| Type of gene | protein-coding |
| Description | interferon regulatory factor 3 |
| Modification date | 20240413 |
| UniProtAcc | Q14653 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | IRF3 | GO:0000785 | chromatin | 8524823 |
| Gene | IRF3 | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | 8524823 |
| Gene | IRF3 | GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | 8524823 |
| Gene | IRF3 | GO:0001216 | DNA-binding transcription activator activity | 8524823|36603579 |
| Gene | IRF3 | GO:0002753 | cytoplasmic pattern recognition receptor signaling pathway | 8524823 |
| Gene | IRF3 | GO:0003700 | DNA-binding transcription factor activity | 8524823 |
| Gene | IRF3 | GO:0005515 | protein binding | 10920266 |
| Gene | IRF3 | GO:0005634 | nucleus | 10805757|25636800|36603579 |
| Gene | IRF3 | GO:0005634 | nucleus | 17079289|18818105 |
| Gene | IRF3 | GO:0005737 | cytoplasm | 9566918 |
| Gene | IRF3 | GO:0005737 | cytoplasm | 17079289|18818105 |
| Gene | IRF3 | GO:0005739 | mitochondrion | 25609812 |
| Gene | IRF3 | GO:0005829 | cytosol | - |
| Gene | IRF3 | GO:0032481 | positive regulation of type I interferon production | 18636090|25636800|36603579 |
| Gene | IRF3 | GO:0034142 | toll-like receptor 4 signaling pathway | 25636800 |
| Gene | IRF3 | GO:0035666 | TRIF-dependent toll-like receptor signaling pathway | 25636800 |
| Gene | IRF3 | GO:0042803 | protein homodimerization activity | 22394562|30699354 |
| Gene | IRF3 | GO:0042981 | regulation of apoptotic process | 25609812 |
| Gene | IRF3 | GO:0043565 | sequence-specific DNA binding | 17574024|23332764 |
| Gene | IRF3 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 8524823|9660935 |
| Gene | IRF3 | GO:0098586 | cellular response to virus | 25609812 |
| Gene | IRF3 | GO:1990837 | sequence-specific double-stranded DNA binding | 28473536 |
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 |
| Q14653-1 | Q14653-1_3a77_A.pdb | 3A77 | X-ray | 1.8 | A | 189 | 427 |
| 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 |
| Q14653 | IRF3 | Q14653-1 | Q14653-2 | 427 | 300 | 201 | 327 | Deletion | none | none | 200 | 200 |
| Q14653 | IRF3 | Q14653-1 | Q14653-3 | 427 | 154 | 1 | 146 | Deletion | none | none | 0 | 0 |
| Q14653 | IRF3 | Q14653-1 | Q14653-3 | 427 | 154 | 201 | 327 | Deletion | none | none | 54 | 54 |
| Q14653 | IRF3 | Q14653-1 | Q14653-4 | 427 | 452 | 328 | 427 | Substitution | DLITFTEGSGRSPRYALWFCVGESWPQDQPWTKRLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISNSHPLSLTSDQYKAYLQDLVEGMDFQGPGES | GSWAPRSDYLHGRKRTLTTLCPLVLCGGVMAPGPAVDQEARDGQGCAHVPQGLGRNGPGRGCLLPGEYCGPAHFQQPPTLPHLRPVQGLPAGLGGGHGFPGPWGELSPRSSWCASNPPVPHHLNQ | 328 | 452 |
| Q14653 | IRF3 | Q14653-1 | Q14653-5 | 427 | 104 | 56 | 104 | Substitution | AWAEATGAYVPGRDKPDLPTWKRNFRSALNRKEGLRLAEDRSKDPHDPH | ELGTFPSQTPLRTPMVEAVLLIPRKTFWMSYWVTWCWPHSQIRDPQAWL | 56 | 104 |
| Q14653 | IRF3 | Q14653-1 | Q14653-5 | 427 | 104 | 105 | 427 | Deletion | none | none | 104 | 104 |
| Multiple sequence alignment of our canonical and alternatively spliced IRF3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of IRF3 |
| UniProt-id | ENSG | ENST | ENSP |
| Q14653-1 | ENSG00000126456.16 | ENST00000309877.11 | ENSP00000310127.6 |
| Q14653-1 | ENSG00000126456.16 | ENST00000377139.8 | ENSP00000366344.3 |
| Q14653-1 | ENSG00000126456.16 | ENST00000597198.5 | ENSP00000469113.1 |
| Q14653-2 | ENSG00000126456.16 | ENST00000599223.5 | ENSP00000471358.1 |
| Q14653-3 | ENSG00000126456.16 | ENST00000596765.5 | ENSP00000470512.1 |
| Q14653-3 | ENSG00000126456.16 | ENST00000600022.5 | ENSP00000472700.1 |
| Q14653-4 | ENSG00000126456.16 | ENST00000601291.5 | ENSP00000471896.1 |
| Q14653-5 | ENSG00000126456.16 | ENST00000442265.2 | ENSP00000400378.2 |
| UniProt-id | NM ID | NP ID |
| Q14653-1 | NM_001571.5 | NP_001562.1 |
| Q14653-1 | XM_017026766.1 | XP_016882255.1 |
| Q14653-1 | XM_017026767.1 | XP_016882256.1 |
| Q14653-2 | NM_001197124.1 | NP_001184053.1 |
| Q14653-3 | NM_001197127.1 | NP_001184056.1 |
| Q14653-3 | NM_001197128.1 | NP_001184057.1 |
| Q14653-4 | NM_001197122.1 | NP_001184051.1 |
| Q14653-4 | XM_006723197.1 | XP_006723260.1 |
| Q14653-4 | XM_006723198.1 | XP_006723261.1 |
| Amino acid sequences of our canonical and alternatively spliced IRF3 |
| accession_id | Protein sequence |
| Q14653-1 | MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEATGAYVPGRDKPDLPTWKRNFRSALNRKEGL RLAEDRSKDPHDPHKIYEFVNSGVGDFSQPDTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPT PFPNLGPSENPLKRLLVPGEEWEFEVTAFYRGRQVFQQTISCPEGLRLVGSEVGDRTLPGWPVTLPDPGMSLTDRGVMSYVRHVLSCLGG GLALWRAGQWLWAQRLGHCHTYWAVSEELLPNSGHGPDGEVPKDKEGGVFDLGPFIVDLITFTEGSGRSPRYALWFCVGESWPQDQPWTK |
| Q14653-2 | MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEATGAYVPGRDKPDLPTWKRNFRSALNRKEGL RLAEDRSKDPHDPHKIYEFVNSGVGDFSQPDTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPT PFPNLGPSENPLKRLLVPGEDLITFTEGSGRSPRYALWFCVGESWPQDQPWTKRLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISN |
| Q14653-3 | MVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPTPFPNLGPSENPLKRLLVPGEDLITFTEGSGRSPRYALWFCVGESWPQDQPWTKRLV |
| Q14653-4 | MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEATGAYVPGRDKPDLPTWKRNFRSALNRKEGL RLAEDRSKDPHDPHKIYEFVNSGVGDFSQPDTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPT PFPNLGPSENPLKRLLVPGEEWEFEVTAFYRGRQVFQQTISCPEGLRLVGSEVGDRTLPGWPVTLPDPGMSLTDRGVMSYVRHVLSCLGG GLALWRAGQWLWAQRLGHCHTYWAVSEELLPNSGHGPDGEVPKDKEGGVFDLGPFIVGSWAPRSDYLHGRKRTLTTLCPLVLCGGVMAPG PAVDQEARDGQGCAHVPQGLGRNGPGRGCLLPGEYCGPAHFQQPPTLPHLRPVQGLPAGLGGGHGFPGPWGELSPRSSWCASNPPVPHHL |
| Q14653-5 | MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQELGTFPSQTPLRTPMVEAVLLIPRKTFWMSYWVTW |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| IRF3 (go to UniProt):Q14653 |
| 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 |
| Q14653 | DNA binding | 5 | 111 | Note=IRF tryptophan pentad repeat;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00840 | Type=Deletion;Start=1;End=146 |
| Q14653 | DNA binding | 5 | 111 | Note=IRF tryptophan pentad repeat;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00840 | Type=Substitution;Start=56;End=104 |
| Q14653 | DNA binding | 5 | 111 | Note=IRF tryptophan pentad repeat;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00840 | Type=Deletion;Start=105;End=427 |
| Q14653 | Region | 91 | 136 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=146 |
| Q14653 | Region | 91 | 136 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=56;End=104 |
| Q14653 | Region | 91 | 136 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=105;End=427 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=1;End=146 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Substitution;Start=328;End=427 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=105;End=427 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Substitution;Start=328;End=427 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Deletion;Start=105;End=427 |
| Q14653 | Motif | 139 | 149 | Note=Nuclear export signal | Type=Deletion;Start=1;End=146 |
| Q14653 | Motif | 139 | 149 | Note=Nuclear export signal | Type=Deletion;Start=105;End=427 |
| Q14653 | Compositional bias | 91 | 106 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=146 |
| Q14653 | Compositional bias | 91 | 106 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=56;End=104 |
| Q14653 | Compositional bias | 91 | 106 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=105;End=427 |
| Q14653 | Compositional bias | 115 | 136 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=146 |
| Q14653 | Compositional bias | 115 | 136 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=105;End=427 |
Gene Isoform Structures and Expression Levels for IRF3 |
| Gene structures of our canonical and alternative spliced genes of IRF3 * 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 Q14653-1 |
| 3D view using mol* of Q14653-2 |
| 3D view using mol* of Q14653-3 |
| 3D view using mol* of Q14653-4 |
| 3D view using mol* of Q14653-5 |
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 Q14653-1 |
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| pLDDT distribution across the protein length of Q14653-2 |
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| pLDDT distribution across the protein length of Q14653-3 |
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| pLDDT distribution across the protein length of Q14653-4 |
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| pLDDT distribution across the protein length of Q14653-5 |
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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 Q14653-1 |
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| Ramachandran plot of Q14653-2 |
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| Ramachandran plot of Q14653-3 |
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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 |
| Q14653-1 | 1.043 | 146 | 0.998 | 420.518 | 0.447 | 0.763 | 1.017 | 0.398 | 1.227 | 0.324 | 1.443 | 21,22,23,24,35,37,39,43,45,47,49,50,52,53,100,101, 102,103,210,211,213,214,215,246,247,248,249,251,25 3,254,256,257,258 |
| Q14653-2 | 1.045 | 45 | 1.064 | 88.151 | 0.458 | 0.946 | 1.199 | 4.039 | 0.414 | 9.76 | 2.681 | 140,144,196,244,245,248,251,274,276,281,284,285,28 8 |
| Q14653-3 | 0.986 | 123 | 1.012 | 400.624 | 0.633 | 0.666 | 0.863 | 0.314 | 1.005 | 0.313 | 0.82 | 27,29,30,34,35,36,37,48,49,51,52,55,59,65,66,67,68 ,69,71,100,101,103,104,105,107,108,117,118,119 |
| Q14653-4 | 1.108 | 159 | 1.154 | 332.367 | 0.45 | 0.789 | 1.028 | 1.902 | 0.795 | 2.392 | 1.068 | 208,209,210,211,228,245,257,260,261,264,265,268,27 2,291,292,301,302,306,307,347,348,349,350,351,352, 392,393,394,395,396,397,398,399 |
| Q14653-5 | 1.048 | 198 | 1.102 | 514.5 | 0.509 | 0.694 | 0.95 | 1.116 | 0.779 | 1.432 | 0.93 | 8,9,11,12,13,16,26,27,31,32,33,34,35,36,38,39,40,4 1,42,43,51,53,54,57,74,75,77,78,79,81,82,84,85,88, 89,90,91,92,93 |
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 Q14653-1_Q14653-1_3a77_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q14653-1_3a77_A_Q14653-2.pdb |
| 3D view using mol* of Q14653-1_3a77_A_Q14653-3.pdb |
| 3D view using mol* of Q14653-1_3a77_A_Q14653-4.pdb |
| 3D view using mol* of Q14653-1_3a77_A_Q14653-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q14653-1_Q14653-2.pdb |
| 3D view using mol* of Q14653-1_Q14653-3.pdb |
| 3D view using mol* of Q14653-1_Q14653-4.pdb |
| 3D view using mol* of Q14653-1_Q14653-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q14653-1_vs_Q14653-2.png |
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| ./stats/secondary_structure/figure/Q14653-1_vs_Q14653-3.png |
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| ./stats/secondary_structure/figure/Q14653-1_vs_Q14653-4.png |
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| ./stats/secondary_structure/figure/Q14653-1_vs_Q14653-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q14653-1_vs_Q14653-2.png |
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| ./stats/relative_asa/Q14653-1_vs_Q14653-3.png |
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| ./stats/relative_asa/Q14653-1_vs_Q14653-4.png |
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| ./stats/relative_asa/Q14653-1_vs_Q14653-5.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=1;End=146 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Substitution;Start=328;End=427 |
| Q14653 | Region | 141 | 427 | Note=Mediates interaction with ZDHHC11;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28331227;Dbxref=PMID:28331227 | Type=Deletion;Start=105;End=427 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Deletion;Start=201;End=327 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Substitution;Start=328;End=427 |
| Q14653 | Region | 200 | 360 | Note=Interaction with HERC5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20308324;Dbxref=PMID:20308324 | Type=Deletion;Start=105;End=427 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to IRF3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to IRF3 |
| Previous studies relating to the alternative splicing of IRF3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| IRF3 | 21120614 | The characterization of two novel IRF-3 transcripts starting from intron 2 of the wild type of IRF-3. | Interferon regulatory factor 3 (IRF-3) is one of the master transcription factors involved in the stringent regulation of interferon production following virus infection. The aim of our study was to explore new isoforms of IRF-3 and further characterize transcriptional regulation. Two new TSSs of IRF-3 were identified by 5' RACE experiments. The expression profiles of new isoforms were tested using RT-PCR. Additionally, the promoter activity and potential transcription factor binding sites of the promoter regions were analyzed. Here we report two novel spliced variants of IRF-3 starting from intron 2 of the wild type of IRF-3, Int2V1 and Int2V2. We localized the transcription start sites (TSS) in the second intron of IRF-3 in pheochromocytoma tissue and thus identified two distinct transcripts. RT-PCR results showed they were expressed in most of tissues and cell lines tested. The expressions levels of them are varying in different tissues and cells. Furthermore, Int2V2 were expressed higher than Int2V1 in all tissues. Luciferase analysis in Hela and 293T cell line defined the promoter regions of the new transcripts had higher promoter activities. Both of the relative luciferase activities were over 100 times higher than that of pGL3-Basic vector. Bioinformatics analysis demonstrated that it contains Sp1, GATA-1/2, IRF-1/2 and Lyf-1 transcription factor binding sites in the promoter regions. The discovery of new transcripts of IRF-3 provides a further insight into the alternative splicing of IRF-3. The novel isoforms expanded the splice variants numbers of IRF-3. | D000310 | Adrenal Gland Neoplasms |
| IRF3 | 21120614 | The characterization of two novel IRF-3 transcripts starting from intron 2 of the wild type of IRF-3. | Interferon regulatory factor 3 (IRF-3) is one of the master transcription factors involved in the stringent regulation of interferon production following virus infection. The aim of our study was to explore new isoforms of IRF-3 and further characterize transcriptional regulation. Two new TSSs of IRF-3 were identified by 5' RACE experiments. The expression profiles of new isoforms were tested using RT-PCR. Additionally, the promoter activity and potential transcription factor binding sites of the promoter regions were analyzed. Here we report two novel spliced variants of IRF-3 starting from intron 2 of the wild type of IRF-3, Int2V1 and Int2V2. We localized the transcription start sites (TSS) in the second intron of IRF-3 in pheochromocytoma tissue and thus identified two distinct transcripts. RT-PCR results showed they were expressed in most of tissues and cell lines tested. The expressions levels of them are varying in different tissues and cells. Furthermore, Int2V2 were expressed higher than Int2V1 in all tissues. Luciferase analysis in Hela and 293T cell line defined the promoter regions of the new transcripts had higher promoter activities. Both of the relative luciferase activities were over 100 times higher than that of pGL3-Basic vector. Bioinformatics analysis demonstrated that it contains Sp1, GATA-1/2, IRF-1/2 and Lyf-1 transcription factor binding sites in the promoter regions. The discovery of new transcripts of IRF-3 provides a further insight into the alternative splicing of IRF-3. The novel isoforms expanded the splice variants numbers of IRF-3. | D010673 | Pheochromocytoma |
| IRF3 | 21182093 | Novel splice variants of human IKKε negatively regulate IKKε-induced IRF3 and NF-kB activation. | The inhibitor of κB kinase ε (IKKε) is pivotal for an efficient innate immune response to viral infections and has been recognized as breast cancer oncogene. The antiviral function of IKKε involves activation of the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB, thus inducing the expression of type I IFN. Here, we have identified two novel splice variants of human IKKε, designated IKKε-sv1 and IKKε-sv2, respectively. Interestingly, RT-PCR revealed quantitatively different isoform expression in PBMC from different individuals. Moreover, we found cell type- and stimulus-specific protein expression of the various splice variants. Overexpression of full-length wt IKKε (IKKε-wt) leads to the activation of NF-κB- as well as IRF3-driven luciferase reporter genes. Although none of the splice variants activates IRF3, IKKε-sv1 still activates NF-κB, whereas IKKε-sv2 is also defective in NF-κB activation. Both splice variants form dimers with IKKε-wt and inhibit IKKε-wt-induced IRF3 signaling including the antiviral activity in a dominant-negative manner. The lack of IRF3 activation is likely caused by the failure of the splice variants to interact with the adapter proteins TANK, NAP1, and/or SINTBAD. Taken together, our data suggest alternative splicing as a novel regulatory mechanism suitable to shift the balance between different functions of IKKε. | D014777 | Virus Diseases |
Clinically important variants in IRF3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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