Recombinant Human Z-DNA-binding protein 1 (ZBP1)

Uniprot Id

Q9H171

Target Species

Human

Target Name

ZBP1

Target Full Name

Z-DNA-binding protein 1

Target Function

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. Once activated upon Z-RNA-binding, ZBP1 interacts with RIPK3, inducing the complementary pathways of apoptosis, necroptosis and pyroptosis. Acts as a key activator of necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members: ZBP1-dependent necroptosis involves RIPK3 stimulation, which phosphorylates and activates MLKL, triggering execution of programmed necrosis. 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. 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. In some cell types, also able to restrict viral replication by promoting cell death-independent responses. In response to Zika virus 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. Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes.; (Microbial infection) In case of herpes simplex virus 1/HHV-1 infection, forms hetero-amyloid structures with HHV-1 protein RIR1/ICP6 which may inhibit ZBP1-mediated necroptosis, thereby preventing host cell death pathway and allowing viral evasion.

Target Subcellular Location

Cytoplasm. Nucleus.; [Isoform 7]: Cytoplasm. Nucleus.

Target Tissue Specificity

Highly expressed in lymphatic tissues including lymph node, leukocytes, tonsil, bone marrow and spleen. Expressed to a lesser extent in thymus, lung and liver.

Target Research Area

Others

Target Synonyms

C20orf183; DAI; DLM 1; DLM1; DNA-dependent activator of interferon regulatory factors; DNA-dependent activator of IRFs; OTTHUMP00000031373; OTTHUMP00000174290; OTTHUMP00000237854; Tumor stroma and activated macrophage protein DLM 1; Tumor stroma and activated macrophage protein DLM-1; Z-DNA-binding protein 1; ZBP 1; Zbp1; ZBP1_HUMAN; ZDBP1

Target Background

This gene encodes a Z-DNA binding protein. The encoded protein plays a role in the innate immune response by binding to foreign DNA and inducing type-I interferon production. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.