Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor (PubMed:12407114, PubMed:22186971). Generates GalNAc-O-Ser/Thr structure also known as Tn antigen, which itself is immunogenic but also serves as a precursor for the synthesis of different mucin-type O-glycan core structures (PubMed:12407114). Contributes to the synthesis of O-linked glycans on mucins and proteoglycans of the central nervous system. May promote neurogenesis through glycosylation and stabilization of PDPN (PubMed:12407114, PubMed:22186971) (By similarity). Can glycosylate both unmodified peptides and glycopeptides that already contain an O-linked GalNAc sugar. Transfers GalNAc to Thr-/Ser-rich tandem repeats GTTPSPVPTTSTTSAP of MUC5AC, specifically on Thr-3 of non-glycosylated MUC5AC peptide, on Thr-12 and Thr-13 of preglycosylated MUC5AC at Thr-3 (MUC5AC-3), on Thr-3 of preglycosylated MUC5AC at Thr-13 (MUC5AC-13) and on Thr-12 of preglycosylated MUC5AC at Thr-3 and Thr-13 (MUC5AC-3,13). Transfers GalNAc to three consecutive serine/threonine residues on SDC3 forming a triplet-Tn epitope expressed in Purkinje cells of the developing brain. Can glycosylate both unmodified peptides and glycopeptides that already contain an O-linked GalNAc sugar. Transfers GalNAc to Thr-/Ser-rich tandem repeats GTTPSPVPTTSTTSAP of MUC5AC, specifically on Thr-3 of non-glycosylated MUC5AC peptide, on Thr-12 and Thr-13 of preglycosylated MUC5AC at Thr-3 (MUC5AC-3), on Thr-3 of preglycosylated MUC5AC at Thr-13 (MUC5AC-13) and on Thr-12 of preglycosylated MUC5AC at Thr-3 and Thr-13 (MUC5AC-3,13). L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-seryl-[protein] + H(+) + UDP L-threonyl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + H(+) + UDP L-threonyl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + H(+) + UDP Protein modification; protein glycosylation. Specifically expressed in neuronal cells. Expressed in fetal brain, whole adult brain, cerebral cortex and cerebellum. Not expressed in other tissues tested. There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity. Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily. Chimera. Chimeric at the N-terminus. Polypeptide N-acetylgalactosaminyltransferase 13