Ly6E, or Lymphocyte antigen 6E, is a GPI-anchored cell surface protein that plays a role in cell signaling and adhesion, signal transduction, immune regulation, and drug resistance. It has been found to be over-expressed in several human malignancies, including head and neck, lung, gastric, and oesophageal cancers. Recently, Ly6E was shown to enhance infectivity of several RNA flaviviruses including West Nile virus, Dengue virus, and Zika virus, as well as HIV-1 and influenza A viruses. Recently, Ly6E was found to have an inhibitory effect on coronavirus entry into cells. The proposed mechanism is that Ly6E interferes with the Coronavirus spike protein and inhibits membrane fusion. This effect was observed in several coronaviruses, including SARS-CoV-2, SARS-CoV, and MERS-CoV.
Ly6E is also known as Stem cell antigen 2 (SCA-2) and Thymic shared antigen-1 (TSA-1). The Ly6E gene encodes a 131 amino acid peptide containing an N-terminal signal peptide followed by the 81 amino acid mature protein and a 30 amino acid propeptide. Within the mature protein, there are 5 disulfide bonds, an N-linked glycosylation site, and a GPI-anchored serine residue. Ly6E is widely expressed with highest expression levels observed in liver, kidney, ovary, spleen, and peripheral blood leukocytes.