Neu5Gc-GM3
Tumor antigen derived from an N-glycolyl variant of ganglioside GM3.
Neu5Gc-GM3 is a modified form of the ganglioside GM3 that serves as a known tumor antigen. How the N-glycolyl group arises in humans remains uncertain, possibly through enzymatic hydroxylation of the existing sialic acid or by adding a pre-hydroxylated sialic acid.
Quick Facts
- Time of deletion
- roughly 2.5 to 3 million years ago
Facts from the source article.
Anomalous presence in humans
The enzyme CMAH, which canonically hydroxylates Neu5Ac to Neu5Gc in deuterostomes, is a pseudogene in humans due to a 92-bp frame-shifting deletion in a critical enzymatic binding pocket. This deletion resulted from a human-specific Alu element insertion roughly 2.5 to 3 million years ago, rendering the enzyme completely inactive. Humans cannot synthesize Neu5Gc by any known pathway and carry circulating antibodies against Neu5Gc-containing glycans. Subunit B of succinate dehydrogenase has been suggested as an alternative pathway for Neu5Gc-GM3 synthesis.
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