P15314 · IRF1_MOUSE
- ProteinInterferon regulatory factor 1
- GeneIrf1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids329 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431, PubMed:25774715).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
Has an essentail role in IFNG-dependent immunity to mycobacteria (By similarity).
Binds to a consensus sequence in gene promoters (By similarity).
Its target genes for transcriptional activation activity are: 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 GBP2, GBP5, IRGB10 and 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 (PubMed:12387893, PubMed:17018642, PubMed:18955028, PubMed:20308629, PubMed:21909274, PubMed:25774715, PubMed:27693356, PubMed:29321274, PubMed:30635240).
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 (PubMed:18641303).
Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53 (By similarity).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
Has an essentail role in IFNG-dependent immunity to mycobacteria (By similarity).
Binds to a consensus sequence in gene promoters (By similarity).
Its target genes for transcriptional activation activity are: 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 GBP2, GBP5, IRGB10 and 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 (PubMed:12387893, PubMed:17018642, PubMed:18955028, PubMed:20308629, PubMed:21909274, PubMed:25774715, PubMed:27693356, PubMed:29321274, PubMed:30635240).
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 (PubMed:18641303).
Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53 (By similarity).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
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 (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).
Activity regulation
Activated by MYD88.
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 5-113 | IRF tryptophan pentad repeat | ||||
Sequence: RMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAIHTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLP |
GO annotations
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameInterferon regulatory factor 1
- Short namesIRF-1
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP15314
Proteomes
Organism-specific databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000154546 | 1-329 | Interferon regulatory factor 1 | |||
Sequence: MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAIHTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTRNQRKERKSKSSRDTKSKTKRKLCGDVSPDTFSDGLSSSTLPDDHSSYTTQGYLGQDLDMERDITPALSPCVVSSSLSEWHMQMDIIPDSTTDLYNLQVSPMPSTSEAATDEDEEGKIAEDLMKLFEQSEWQPTHIDGKGYLLNEPGTQLSSVYGDFSCKEEPEIDSPRGDIGIGIQHVFTEMKNMDSIMWMDSLLGNSVRLPPSIQAIPCAP | ||||||
Modified residue | 78 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 276 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | ||||||
Cross-link | 300 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K |
Post-translational modification
Phosphorylated by CK2 and this positively regulates its activity.
Ubiquitinated in a SPOP-depedent manner. Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation (PubMed:12387893, PubMed:18955028).
Sumolyated by UBE2I/UBC9 and SUMO1 (PubMed:18955028).
Inactivates the tumor suppressor activity (By similarity).
Elevated levels in tumor cells (By similarity).
Major site is Lys-276 (By similarity).
Sumoylation is enhanced by PIAS3 (PubMed:12387893).
Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (By similarity).
Sumolyated by UBE2I/UBC9 and SUMO1 (PubMed:18955028).
Inactivates the tumor suppressor activity (By similarity).
Elevated levels in tumor cells (By similarity).
Major site is Lys-276 (By similarity).
Sumoylation is enhanced by PIAS3 (PubMed:12387893).
Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (By similarity).
Ubiquitinated. Appears to compete with sumoylation on C-terminal sites (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Monomer (PubMed:9422515).
Homodimer (PubMed:9422515).
Interacts with EP300 (By similarity).
Interacts with MYD88 (PubMed:17018642).
Interacts with PIAS3 (PubMed:12387893).
Interacts with SPOP (By similarity).
Homodimer (PubMed:9422515).
Interacts with EP300 (By similarity).
Interacts with MYD88 (PubMed:17018642).
Interacts with PIAS3 (PubMed:12387893).
Interacts with SPOP (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P15314 | KEAP1 Q14145 | 2 | EBI-6115486, EBI-751001 | |
XENO | P15314 | TRAF3 Q13114 | 2 | EBI-6115486, EBI-357631 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 93-166 | Disordered | ||||
Sequence: EVKDQSRNKGSSAVRVYRMLPPLTRNQRKERKSKSSRDTKSKTKRKLCGDVSPDTFSDGLSSSTLPDDHSSYTT | ||||||
Compositional bias | 116-143 | Basic and acidic residues | ||||
Sequence: TRNQRKERKSKSSRDTKSKTKRKLCGDV | ||||||
Compositional bias | 147-166 | Polar residues | ||||
Sequence: TFSDGLSSSTLPDDHSSYTT |
Sequence similarities
Belongs to the IRF family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length329
- Mass (Da)37,319
- Last updated1990-04-01 v1
- Checksum0E5DD23C0D977B34
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 116-143 | Basic and acidic residues | ||||
Sequence: TRNQRKERKSKSSRDTKSKTKRKLCGDV | ||||||
Compositional bias | 147-166 | Polar residues | ||||
Sequence: TFSDGLSSSTLPDDHSSYTT |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M21065 EMBL· GenBank· DDBJ | AAA39334.1 EMBL· GenBank· DDBJ | mRNA | ||
BC003821 EMBL· GenBank· DDBJ | AAH03821.1 EMBL· GenBank· DDBJ | mRNA |