| IED ID | IndEnz0002004663 |
| Enzyme Type ID | protease004663 |
| Protein Name |
Interferon regulatory factor 7 IRF-7 |
| Gene Name | IRF7 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MALAPERAAPRVLFGEWLLGEISSGCYEGLQWLDEARTCFRVPWKHFARKDLSEADARIFKAWAVARGRWPPSSRGGGPPPEAETAERAGWKTNFRCALRSTRRFVMLRDNSGDPADPHKVYALSRELCWREGPGTDQTEAEAPAAVPPPQGGPPGPFLAHTHAGLQAPGPLPAPAGDKGDLLLQAVQQSCLADHLLTASWGADPVPTKAPGEGQEGLPLTGACAGGPGLPAGELYGWAVETTPSPGPQPAALTTGEAAAPESPHQAEPYLSPSPSACTAVQEPSPGALDVTIMYKGRTVLQKVVGHPSCTFLYGPPDPAVRATDPQQVAFPSPAELPDQKQLRYTEELLRHVAPGLHLELRGPQLWARRMGKCKVYWEVGGPPGSASPSTPACLLPRNCDTPIFDFRVFFQELVEFRARQRRGSPRYTIYLGFGQDLSAGRPKEKSLVLVKLEPWLCRVHLEGTQREGVSSLDSSSLSLCLSSANSLYDDIECFLMELEQPA |
| Enzyme Length | 503 |
| Uniprot Accession Number | Q92985 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | DNA_BIND 11..126; /note=IRF tryptophan pentad repeat; /evidence=ECO:0000255|PROSITE-ProRule:PRU00840 |
| EC Number | |
| Enzyme Function | FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:17574024, PubMed:32972995). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner (By similarity). Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages (By similarity) (PubMed:11073981, PubMed:12374802, PubMed:15361868, PubMed:17404045). {ECO:0000250|UniProtKB:P70434, ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:17404045, ECO:0000269|PubMed:17574024, ECO:0000269|PubMed:32972995}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (4); Beta strand (4); Chain (1); Cross-link (2); DNA binding (1); Helix (4); Modified residue (9); Mutagenesis (12); Natural variant (15); Region (4); Site (2) |
| Keywords | 3D-structure;Acetylation;Activator;Alternative splicing;Antiviral defense;Cytoplasm;DNA-binding;Disease variant;Host-virus interaction;Immunity;Innate immunity;Isopeptide bond;Nucleus;Phosphoprotein;Reference proteome;Transcription;Transcription regulation;Ubl conjugation |
| Interact With | O00170; P10398; Q96A33; O15111; P51617; O94822; Q9ULE6; Q9UHD2; Q86UE8; Q9BVS5; P29128; F5HDE4; Q77M19; P03230 |
| Induction | INDUCTION: By type I interferon (IFN) and viruses. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The phosphorylated and active form accumulates selectively in the nucleus. |
| Modified Residue | MOD_RES 92; /note=N6-acetyllysine; by KAT2A and KAT2B; /evidence=ECO:0000269|PubMed:12374802; MOD_RES 471; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70434; MOD_RES 472; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70434; MOD_RES 475; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70434; MOD_RES 477; /note=Phosphoserine; by TBK1 and IKKE; /evidence=ECO:0000269|PubMed:15367631; MOD_RES 479; /note=Phosphoserine; by TBK1 and IKKE; /evidence=ECO:0000269|PubMed:15367631; MOD_RES 483; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70434; MOD_RES 484; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70434; MOD_RES 487; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P70434 |
| Post Translational Modification | PTM: Acetylation inhibits its DNA-binding ability and activity. {ECO:0000269|PubMed:12374802}.; PTM: In response to a viral infection, phosphorylated on Ser-477 and Ser-479 by TBK1 and IKBKE1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling pathway, phosphorylated by IRAK1. {ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15767370}.; PTM: TRAF6-mediated ubiquitination is required for IRF7 activation (By similarity). TRIM35 mediates IRF7 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation (PubMed:25907537). Ubiquitinated by UBE3C, leading to its degradation (PubMed:21167755). {ECO:0000250|UniProtKB:P70434, ECO:0000269|PubMed:21167755, ECO:0000269|PubMed:25907537}.; PTM: Sumoylated by TRIM28, which inhibits its transactivation activity. {ECO:0000269|PubMed:21940674}.; PTM: (Microbial infection) Cleaved and inactivated by the protease 3C of enterovirus 71 allowing the virus to disrupt the host type I interferon production. {ECO:0000269|PubMed:23175366}.; PTM: (Microbial infection) Cleaved and inactivated by the protease 3C of human enterovirus 68D (EV68) allowing the virus to disrupt the host type I interferon production. {ECO:0000269|PubMed:26608321}.; PTM: 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation is NMI-dependent in response to Sendai virus infection. {ECO:0000250|UniProtKB:P70434}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 2O61; |
| Mapped Pubmed ID | 10893229; 11092454; 11337497; 11404376; 12029096; 12604599; 12692549; 14555995; 14703513; 14769151; 14968112; 15047845; 1508672; 15210742; 15251447; 16009940; 16153868; 16914100; 17157040; 1730654; 17526488; 17599067; 18362138; 18710948; 18922877; 19153231; 19176627; 19479062; 19549727; 20043992; 20467438; 20581830; 20627800; 20696886; 21743479; 21903422; 21988832; 2211721; 22787218; 23121362; 28367002; 28768858; 30485383; 6162102; 6548414; 7530745; 8176225; 8483949; 8530158; 9096384; 9143706; 9463386; 9566918; 9660935; 9822609; 9861020; |
| Motif | |
| Gene Encoded By | |
| Mass | 54,278 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |