Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (GnT-V) (GnT-V)

Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (GnT-V), encoded by the MGAT5 gene, is a Golgi-resident enzyme that catalyzes the addition of N-acetylglucosamine in a beta-1,6 linkage to the alpha-1,6-linked mannose of the trimannosyl core of N-linked glycans (UniProt: Q09328). This enzymatic activity is a key driver of cancer progression, as the resulting branched glycans enhance the signaling of growth factor receptors like EGFR and TGF-beta, thereby promoting tumor cell proliferation and metastasis (PubMed: 12124323). Specific HLA-A2-restricted epitopes, such as the peptide VLPDVFIRC, have been identified as immunogenic targets that can be recognized by cytotoxic T lymphocytes (CTLs) in patients with melanoma and other GnT-V-expressing tumors (PubMed: 10438934). Because GnT-V is significantly upregulated in malignant tissues compared to most healthy tissues, these epitopes serve as promising candidates for cancer vaccines and TCR-based immunotherapies (PubMed: 15649943). Clinical investigations have explored the use of GnT-V peptide vaccines to stimulate anti-tumor immunity, though challenges such as immune evasion and the need for HLA-A2 patient selection remain (ClinicalTrials.gov: NCT00020462).

Other names

MGAT5Mannoside acetylglucosaminyltransferase 5N-acetylglucosaminyltransferase VGNT-VGNT-VA

Induction of a cytotoxic T-cell response against tumor cells presenting GnT-V-derived peptides in the context of HLA-A2 (PubMed: 10438934).