Protein: Interferon regulatory factor 1 (IRF-1) (P10914)
Organism: Homo sapiens (Human)
Function: Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Competes with the transcriptional repressor ZBED2 for binding to a common consensus sequence in gene promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, RIGI, TNFSF10/TRAIL, ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1/IRG1. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.
Subcellular location: Nucleus {ECO:0000269|PubMed:37622993}. Cytoplasm {ECO:0000250|UniProtKB:P15314}. Note=MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1. {ECO:0000250|UniProtKB:P15314}.
Sequence: MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAIHTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTKNQRKERKSKSSRDAKSKAKRKSCGDSSPDTFSDGLSSSTLPDDHSSYTVPGYMQDLEVEQALTPALSPCAVSSTLPDWHIPVEVVPDSTSDLYNFQVSPMPSTSEATTDEDEEGKLPEDIMKLLEQSEWQPTNVDGKGYLLNEPGVQPTSVYGDFSCKEEPEIDSPGGDIGLSLQRVFTDLKNMDATWLDSLLTPVRLPSIQAIPCAP
InterPro domains: - IPR036390: Winged helix DNA-binding domain superfamily (homologous_superfamily) [4-113]
- IPR017431: Interferon regulatory factor-1/2 (family) [1-310]
- IPR019817: Interferon regulatory factor, conserved site (conserved_site) [26-59]
- IPR001346: Interferon regulatory factor, DNA-binding domain (domain) [1-114]
- IPR036388: Winged helix-like DNA-binding domain superfamily (homologous_superfamily) [1-113]
Interaction partners: - Signal transducer and activator of transcription 1-alpha/beta
- Histone deacetylase 1
- Histone acetyltransferase p300
- Interferon regulatory factor 8
- Interferon regulatory factor 2
- Transcription factor PU.1
- E3 ubiquitin-protein ligase Mdm2
- Myeloid differentiation primary response protein MyD88
- Signal transducer and activator of transcription 2
- Interferon beta
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:1901363 (heterocyclic compound binding), GO:0003700 (DNA-binding transcription factor activity), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0001216 (DNA-binding transcription activator activity), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0001228 (DNA-binding transcription activator activity, RNA polymerase II-specific), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0042221 (response to chemical), GO:0006955 (immune response), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0002683 (negative regulation of immune system process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0007165 (signal transduction), GO:0009058 (biosynthetic process), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0002682 (regulation of immune system process), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0006950 (response to stress), GO:0051094 (positive regulation of developmental process), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050777 (negative regulation of immune response), GO:0002695 (negative regulation of leukocyte activation), GO:0043207 (response to external biotic stimulus), GO:0030155 (regulation of cell adhesion), GO:0060255 (regulation of macromolecule metabolic process), GO:0002694 (regulation of leukocyte activation), GO:0006725 (cellular aromatic compound metabolic process), GO:1903706 (regulation of hemopoiesis), GO:0001817 (regulation of cytokine production), GO:1903707 (negative regulation of hemopoiesis), GO:1901360 (organic cyclic compound metabolic process), GO:0050866 (negative regulation of cell activation), GO:0007162 (negative regulation of cell adhesion), GO:0002697 (regulation of immune effector process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0050778 (positive regulation of immune response), GO:0045595 (regulation of cell differentiation), GO:0001819 (positive regulation of cytokine production), GO:1903708 (positive regulation of hemopoiesis), GO:0007166 (cell surface receptor signaling pathway), GO:0002698 (negative regulation of immune effector process), GO:0009615 (response to virus), GO:0050865 (regulation of cell activation), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0045597 (positive regulation of cell differentiation), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0006952 (defense response), GO:0044249 (cellular biosynthetic process), GO:0045785 (positive regulation of cell adhesion), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0009891 (positive regulation of biosynthetic process), GO:0050867 (positive regulation of cell activation), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0002696 (positive regulation of leukocyte activation), GO:2000026 (regulation of multicellular organismal development), GO:0050776 (regulation of immune response), GO:0042127 (regulation of cell population proliferation), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0045596 (negative regulation of cell differentiation), GO:0009889 (regulation of biosynthetic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0002699 (positive regulation of immune effector process), GO:0080090 (regulation of primary metabolic process), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0022409 (positive regulation of cell-cell adhesion), GO:0022407 (regulation of cell-cell adhesion), GO:0032655 (regulation of interleukin-12 production), GO:0032735 (positive regulation of interleukin-12 production), GO:0070663 (regulation of leukocyte proliferation), GO:0051250 (negative regulation of lymphocyte activation), GO:0010468 (regulation of gene expression), GO:0032479 (regulation of type I interferon production), GO:0051250 (negative regulation of lymphocyte activation), GO:0045622 (regulation of T-helper cell differentiation), GO:0051251 (positive regulation of lymphocyte activation), GO:0090304 (nucleic acid metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:1902105 (regulation of leukocyte differentiation), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0022408 (negative regulation of cell-cell adhesion), GO:0019221 (cytokine-mediated signaling pathway), GO:0002828 (regulation of type 2 immune response), GO:0010467 (gene expression), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0002819 (regulation of adaptive immune response), GO:0051249 (regulation of lymphocyte activation), GO:1902106 (negative regulation of leukocyte differentiation), GO:0071310 (cellular response to organic substance), GO:0019438 (aromatic compound biosynthetic process), GO:0060284 (regulation of cell development), GO:0010720 (positive regulation of cell development), GO:0062207 (regulation of pattern recognition receptor signaling pathway), GO:0010628 (positive regulation of gene expression), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0140546 (defense response to symbiont), GO:0032481 (positive regulation of type I interferon production), GO:0031326 (regulation of cellular biosynthetic process), GO:0070664 (negative regulation of leukocyte proliferation), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0034341 (response to type II interferon), GO:0010721 (negative regulation of cell development), GO:0051253 (negative regulation of RNA metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0016070 (RNA metabolic process), GO:0045619 (regulation of lymphocyte differentiation), GO:0050670 (regulation of lymphocyte proliferation), GO:0002822 (regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains), GO:0050863 (regulation of T cell activation), GO:0032944 (regulation of mononuclear cell proliferation), GO:2001141 (regulation of RNA biosynthetic process), GO:0045621 (positive regulation of lymphocyte differentiation), GO:0032945 (negative regulation of mononuclear cell proliferation), GO:0071345 (cellular response to cytokine stimulus), GO:0140888 (interferon-mediated signaling pathway), GO:0050672 (negative regulation of lymphocyte proliferation), GO:1902680 (positive regulation of RNA biosynthetic process), GO:1903038 (negative regulation of leukocyte cell-cell adhesion), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0050870 (positive regulation of T cell activation), GO:0006355 (regulation of DNA-templated transcription), GO:0045620 (negative regulation of lymphocyte differentiation), GO:0032816 (positive regulation of natural killer cell activation), GO:0032814 (regulation of natural killer cell activation), GO:1903037 (regulation of leukocyte cell-cell adhesion), GO:1903039 (positive regulation of leukocyte cell-cell adhesion), GO:0050868 (negative regulation of T cell activation), GO:0032774 (RNA biosynthetic process), GO:0034121 (regulation of toll-like receptor signaling pathway), GO:0045582 (positive regulation of T cell differentiation), GO:0045892 (negative regulation of DNA-templated transcription), GO:0046634 (regulation of alpha-beta T cell activation), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045581 (negative regulation of T cell differentiation), GO:0006351 (DNA-templated transcription), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0042130 (negative regulation of T cell proliferation), GO:0045893 (positive regulation of DNA-templated transcription), GO:0046635 (positive regulation of alpha-beta T cell activation), GO:0046636 (negative regulation of alpha-beta T cell activation), GO:0002825 (regulation of T-helper 1 type immune response), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0042129 (regulation of T cell proliferation), GO:0045580 (regulation of T cell differentiation), GO:0045944 (positive regulation of transcription by RNA polymerase II), GO:0046639 (negative regulation of alpha-beta T cell differentiation), GO:2000516 (positive regulation of CD4-positive, alpha-beta T cell activation), GO:2000514 (regulation of CD4-positive, alpha-beta T cell activation), GO:0006366 (transcription by RNA polymerase II), GO:0046637 (regulation of alpha-beta T cell differentiation), GO:0046638 (positive regulation of alpha-beta T cell differentiation), GO:0043370 (regulation of CD4-positive, alpha-beta T cell differentiation), GO:0043372 (positive regulation of CD4-positive, alpha-beta T cell differentiation), GO:0043371 (negative regulation of CD4-positive, alpha-beta T cell differentiation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043229 (intracellular organelle), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)