Human endogenous retrovirus K envelope glycoprotein (HERV-K Env)

Human endogenous retrovirus K (HERV-K) envelope glycoprotein is a protein encoded by the HML-2 subfamily of endogenous retroviruses, which are remnants of ancient germline infections integrated into the human genome millions of years ago (UniProt P61566). While typically silenced in healthy adult tissues through epigenetic mechanisms, the HERV-K Env protein is frequently reactivated and expressed on the cell surface in various malignancies, such as melanoma, breast cancer, and germ cell tumors, as well as in the central nervous system of patients with amyotrophic lateral sclerosis (ALS) (PMID: 26416744, 29330113). Structurally, it consists of a surface (SU) subunit and a transmembrane (TM) subunit that can mediate cell-cell fusion and trigger oncogenic signaling pathways, including the MAPK/ERK cascade. Due to its restricted expression in normal tissues and high prevalence in specific diseases, it serves as a promising therapeutic target for monoclonal antibodies, CAR-T cell therapies, and vaccines. Current clinical and preclinical efforts aim to neutralize its neurotoxic effects in ALS or exploit its surface presence to induce targeted destruction of cancer cells (NCT03354390, GeNeuro).

Other names

HERV-K(HML-2) envelope proteinEnvKK-EnvHERV-K113 EnvEnvelope polyprotein

Targeted cell lysis via CAR-T cells, antibody-dependent cellular cytotoxicity (ADCC), and neutralization of pathogenic signaling or neurotoxic effects.