Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity. Interacts with KLRK1/NKG2D. (Microbial infection) In CMV-infected cells, interacts with the viral glycoprotein UL16; this interaction causes relocalization from the cell surface to the cytoplasm and prevents binding to and activation of KLRK1/NKG2D, providing CMV with an immune evasion mechanism. In CMV-infected fibroblasts, detected intracellularly. Widely expressed (PubMed:11827464). Expressed in trachea (PubMed:19658097). Constitutively expressed in peripheral blood mononuclear cells, including B-cells and natural killer cells, as well as CD4+ and CD8+ T-cells and monocytes. Tends to be up-regulated in various lymphoid malignancies, including chronic lymphocytic leukemia (PubMed:28559451). 4 alleles have been identified in 32 Caucasian individuals: ULBP6*01 (frequency 0.483), ULBP6*02 (frequency 0.424), ULBP6*03 (frequency 0.069) and ULBP6*04 (frequency 0.024). The sequence shown is that of ULBP6*03 (PubMed:19658097). Allele ULBP6*02 has a much higher affinity for KLRK1/NKG2D than allele ULBP6*01, but elicits less-efficient cytotoxicity. This high binding affinity and limited functional potency may depend upon the presence of the Leu residue at position 106 (PubMed:28559451). UL16-binding proteins (ULBPs) are unusual members of the extended MHC class I superfamily. They do not contain the alpha 3 domain and lack a transmembrane domain. Belongs to the MHC class I family.