Recombinant Human ULBP-5 Protein, CF

ULBP‑5 (cytomegalovirus glycoprotein UL16 binding protein 5), also called RAET1G (retinoic acid early transcript 1G), is a 37 kDa member of a family of cell‑surface proteins that function as ligands for human NKG2D (1‑3). When engaged, NKG2D activates cytolytic activity and/or cytokine production by effector cells that express it, such as NK cells, NKT cells, gamma delta T cells, and CD8⁺ alpha beta T cells (3‑5). Human ULBP‑5 mRNA encodes a 25 amino acid (aa) signal sequence, a 198 aa extracellular domain (ECD), a 20 aa transmembrane domain, and a 91 aa cytoplasmic sequence. Transmembrane, predicted soluble (RAET1G2), and glycosylphosphatidylinositol (GPI)‑anchored isoforms are identical through aa 210, while a shorter soluble form (RAET1G3) lacks aa 118‑154 (3‑5). Secreted, cell surface and intracellular ULBP‑5 have been described (3‑8). While most family members are GPI‑anchored, only ULBP‑5 and ULBP‑4/RAET1E express a transmembrane form (4, 5). Within the ECD, ULBP‑5 possesses two MHC Class I alpha domains and shares ~93% aa sequence identity with ULBP‑2/RAET1H plus ULBP‑6/RAET1L, and 30‑60% aa identity with remaining family members (1, 5). 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). ULBP‑5 mRNA expression is low or undetected in many tissues, but increased expression is reported in epithelial tissues and human decidua (5‑8). ULBP‑5 is expressed on some breast, epithelial and hematopoietic tumor cells and has been implicated in tumor surveillance (4‑6).