PRAME

PRAME/MAPE/OIP4 is a germinal tissue-specific gene that is also expressed at high levels in haematological malignancies and solid tumors. The physiological functions of PRAME in normal and tumor cells are unknown, although a role in the regulation of retinoic acid signaling has been proposed. Sequence homology and structural predictions suggest that PRAME is related to the Leucine-rich repeat (LRR) family of proteins, which have diverse functions. PRAME, or „preferentially expressed antigen in melanoma”, was originally identified as a gene encoding a HLA-A24 restricted antigenic peptide presented to autologous tumor-specific cytotoxic T lymphocytes derived from a patient with melanoma. PRAME is synonymous with MAPE (melanoma antigen preferentially expressed in tumors) and OIP4 (OPA-interacting protein 4), and its expression profile defines it as a cancer-testis antigen. Cancer-testis antigens (CTAs) are encoded by non-mutated genes expressed at high levels in germinal tissues and tumors, but which are absent from or detected at low levels in other tissues. PRAME may be somewhat different to other cancer-testis antigens in that it shows some expression in normal tissues such as ovary, adrenal, placenta and endometrium. The C-terminus of human PRAME (amino acids 453-509) was also identified to bind Neisseria gonorrhoeae opacity factors, in this case the OPA-P protein. Thus PRAME is also known as OIP4 (OPA interacting protein), although the functional implications of the interaction are unknown.