Recombinant Human ULBP-6/RAET1L Protein, CF

RAET1L (retinoic acid early transcript 1L), also called ULBP‑6 (cytomegalovirus glycoprotein UL16 binding protein 6), is an approximately 31 kDa glycophosphatidylinositol (GPI)‑linked member of a family of human cell‑surface proteins that are ligands for human NKG2D (1‑3). When engaged on effector cells that express it, such as NK cells and CD8⁺ T cells, NKG2D cooperates with other cell surface receptors to activate cytolytic activity and/or cytokine production (3). Human RAET1L mRNA encodes a 25 amino acid (aa) signal sequence, a 193 aa extracellular domain, and a 28 aa C‑terminal propeptide that is removed during GPI linkage. Single nucleotide polymorphisms of RAET1L that potentially affect its function have been described (3). Mature RAET1L shares high aa sequence identity with extracellular regions of ULBP‑2/RAET1H (97%) and ULBP‑5/RAET1G (92%), and 35‑60% aa identity with remaining family members (1, 3). Most family members, like ULBP‑6, are GPI anchored membrane proteins, although ULBP‑5/RAET1G and ULBP4/RAET1E express a transmembrane form (1‑3). Rodent NKG2D ligands Rae‑1 alpha‑ epsilon are, like ULBP proteins, distantly related to MHC class I proteins, but ULBP and Rae‑1 family proteins do not share significant sequence identity (2). RAET1L mRNA shows restricted expression in the trachea and some HPV‑positive cervical carcinoma and colorectal carcinoma cell lines (3). It is induced upon cytomegalovirus (CMV) infection in primary human fibroblasts but, like several other CMV‑induced family members, is sequestered from the cell surface by UL16 (3). RAET1L shows stronger binding to NKG2D molecules and UL16 than ULBP‑5/RAET1G (3, 4).