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Description

ORF7a protein (UniProt: P59635, also known as Accessory protein 7a, Protein U122, Protein X4) is encoded by the 7a gene (Gene ID: 1489674) in Severe acute respiratory syndrome coronavirus (SARS-CoV). ORF7a protein is expressed by the severe acute respiratory syndrome coronavirus (SARS-CoV) and is not found in other known coronaviruses. It is synthesized with a signal peptide (aa 1-15), which is subsequently cleaved off. Its presence is detected in the mitochondria and the endoplasmic reticulum-Golgi intermediate compartments. The C-terminal region of ORF7a contains a transmembrane domain (aa 97-117) and a short cytoplasmic tail (118 to 122 aa). The transmembrane domain is shown to be important for the insertion of ORF7a into intracellular membranes. The cytoplasmic tail has an endoplasmic reticulum retrieval motif that mediates the transport of ORF7a between the Golgi and the endoplasmic reticulum. ORF7 can induce apoptosis in various cell lines, however, overexpression of Bcl-XL can block ORF-7a induced apoptosis. It is not shown to react with any pro-apoptotic proteins of theBcl-2 family. Its transmembrane domain is also important for its interaction with Bcl-XL and for the induction of apoptosis. Two residues (aa 224, 225) within the transmembrane domain of Bcl-XL are essential for its interaction with ORF7a. SARS-CoV-2 ORF7a is considered as an immunomodulating factor for immune cell binding and can trigger inflammatory responses. It can interact with CD14+ monocytes with high efficiency, compared to the SARS-CoV ORF7a. (Ref.: Zhou, Z., et al. (2021). iScience 24(3), 102187, Tan, YX., et al. (2007). J. Virol. 81(12), 6346-6355).