Protein: ZBP1_MOUSE
Sequence: MAEAPVDLSTGDNLEQKILQVLSDDGGPVKIGQLVKKCQVPKKTLNQVLYRLKKEDRVSSPEPATWSIGGAASGDGAPAIPENSSAQPSLDERILRFLEANGPHRALHIAKALGMTTAKEVNPLLYSMRNKHLLSYDGQTWKIYHSRQEGQDIAHSGVTQESPAIICQHNPVNMICQQGANSHISIANSNAIQIGHGNVIVREKACGEPGPRTSHPLPLAWDASAQDMPPVAHGAQYIYMDKSLLQQVQLGHHNEMSLVGDAGKHPSYSFSDSPPEVSTTTADPGASFNMQTFEPGPHPEGDTVQTVHIKSCFLEDATIGNGNKMTIHLRSKGEVMESGDSEEPKKEDTGTSSEATPPRSCQHTPSDSMLPTSELRAMALGDSSPQTTEPVLREHEVQDIESSQDTGLSKQ
What is the function of this protein?
Key innate sensor that recognizes and binds Z-RNA structures, which are produced by a number of viruses, such as herpesvirus, orthomyxovirus or flavivirus, and triggers different forms of cell death (PubMed:17618271, PubMed:18375758, PubMed:19590578, PubMed:23283962, PubMed:27746097, PubMed:27917412, PubMed:27819681, PubMed:28716805, PubMed:28607035, PubMed:30050136, PubMed:31358656, PubMed:32200799, PubMed:32296175, PubMed:30498077, PubMed:29073079).  ZBP1 acts as an essential mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, by activating RIPK3, caspase-8 (CASP8), and the NLRP3 inflammasome (PubMed:27746097, PubMed:27917412, PubMed:28607035, PubMed:32200799, PubMed:32298652, PubMed:32350114, PubMed:32296175).  Key activator of necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, via its ability to bind Z-RNA: once activated upon Z-RNA-binding, ZBP1 interacts and stimulates RIPK3 kinase, which phosphorylates and activates MLKL, triggering execution of programmed necrosis (PubMed:22423968, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:28716805, PubMed:32200799, PubMed:32350114, PubMed:32315377, PubMed:32296175).  In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: ZBP1 recognizes and binds Z-RNA structures that are produced in infected nuclei by orthomyxoviruses, such as the influenza A virus (IAV), leading to ZBP1 activation, RIPK3 stimulation and subsequent MLKL phosphorylation, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (PubMed:32200799, PubMed:32296175).  ZBP1-dependent cell death in response to IAV infection promotes interleukin-1 alpha (IL1A) induction in an NLRP3-inflammasome-independent manner: IL1A expression is required for the optimal interleukin-1 beta (IL1B) production, and together, these cytokines promote infiltration of inflammatory neutrophils to the lung, leading to the formation of neutrophil extracellular traps (PubMed:31630209).  In addition to its direct role in driving necroptosis via its ability to sense Z-RNAs, also involved in PANoptosis triggered in response to bacterial infection: component of the AIM2 PANoptosome complex, a multiprotein complex that triggers PANoptosis (PubMed:34471287).  Also acts as the apical sensor of fungal infection responsible for activating PANoptosis (PubMed:33109609).  Involved in CASP8-mediated cell death via its interaction with RIPK1 but independently of its ability to sense Z-RNAs (PubMed:33397971).  In some cell types, also able to restrict viral replication by promoting cell death-independent responses (PubMed:30635240).  In response to flavivirus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with RIPK3, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate (PubMed:30635240).  Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed:30635240).
What are the official names of this protein?
Z-DNA-binding protein 1, DNA-dependent activator of IFN-regulatory factors, DAI, Tumor stroma and activated macrophage protein DLM-1.
What are the subcellular locations of this protein?
Cytoplasm. Nucleus. Note=Mainly cytoplasmic (PubMed:32200799). Accumulates in the nucleus in response to influenza A virus (IAV) infection: senses IAV defective viral genomes RNA in the nucleus (PubMed:32200799).