Polypeptide N-acetylgalactosaminyltransferase family (GALNT family) (GALNT)

The Polypeptide N-acetylgalactosaminyltransferase (GALNT) family comprises 20 human enzymes responsible for initiating mucin-type O-glycosylation, a vital post-translational modification (UniProt, NIH). These enzymes catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the hydroxyl groups of serine and threonine residues on target proteins (PubMed). This modification is crucial for the structural and functional regulation of cell surface and secreted proteins, impacting processes such as cell signaling, adhesion, and immune recognition (GeneCards). Dysregulation of various GALNT isoforms is a hallmark of many cancers, where it leads to the expression of tumor-associated carbohydrate antigens like the Tn antigen and promotes malignant behaviors including metastasis and drug resistance (NIH, PubMed). Additionally, specific family members are linked to metabolic and developmental disorders, such as GALNT3's role in phosphate homeostasis via FGF23 stabilization (eLife). While selective small molecule inhibitors like T3Inh-1 have been developed for research purposes, the high homology among the 20 isoforms presents a significant challenge for therapeutic development, requiring precise targeting to avoid off-target effects and developmental toxicity (PubMed, ACS).

Other names

UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferaseppGalNAc-TppGaNTaseGalNAc-TPolypeptide GalNAc transferase

Inhibition of N-acetylgalactosamine transfer from the donor substrate UDP-GalNAc to the hydroxyl groups of serine or threonine residues on polypeptide substrates, thereby blocking the initiation of mucin-type O-glycosylation.