Lymphocyte antigen 6 family member E (LY6E)

Lymphocyte antigen 6 family member E (LY6E) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the LY6/uPAR superfamily[1][2][3][4]. It is expressed in multiple tissues, especially in immune cells, and is inducible by type I interferons[2]. LY6E regulates T cell activation, proliferation, differentiation, and immune signaling, including modulation of T cell receptor (TCR) signaling through interaction with CD3ζ[1][2]. It has a dual role in viral infection: while it can enhance the entry and uncoating of several enveloped RNA viruses (including HIV-1, influenza, yellow fever, West Nile, dengue, and Zika) in certain cell contexts, it can also restrict entry of human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2, possibly by interfering with spike-mediated fusion[1][2][3][4]. LY6E is additionally required for placental development, functioning as a main receptor for syncytin-A, crucial in trophoblast cell fusion. In cancer, LY6E has been implicated in tumor progression and metastasis via modulation of PI3K/Akt signaling and immune checkpoint expression. Variability in its function is observed across cell types and viruses, reflecting complex regulatory roles in both immune defense and disease pathogenesis[1][2][3].

Other names

Lymphocyte antigen 6ERIGESCA2TSA1Ly-6ERIG-ESCA-2TSA-1Retinoic acid-induced gene E proteinStem cell antigen 2Thymic shared antigen 1retinoic acid induced gene Elymphocyte antigen 6 complex, locus E

Modulation of cell membrane fusion (in viral cell entry); Regulation of immune signaling (impact on TCR/CD3–zeta chain, PTEN/PI3K/Akt/HIF-1 axis, TGFβ-dependent pathways); Downregulation of CD4 expression affecting HIV entry; Direct/indirect modulation of viral infectivity (virus- and cell-type dependent)