Molecular cloning and expression of the pituitary glycoprotein hormone N-acetylgalactosamine-4-O-sulfotransferase

N-Linked oligosaccharides terminating with the sequence SO4-4-GalNAc beta1,4GlcNAc beta1,2Man alpha are present on the pituitary hormones lutropin (LH), thyrotropin, and pro-opiomelanocortin. The sulfated structures on LII are essential for expression of its biologic function in vivo. We have cloned the N-acetglgalactosamine-4-sulfo-transferase (GalNac-4-ST1, GenBank(TM) accession number AF300612), which mediates sulfate addition to the N-linked oligosaccharides on LH and other pituitary glycoproteins with terminal (beta1,4-linked GalNAc based on its homology to HNK-1 sulfotransferase (HNK-1 ST). GalNAc-4-ST1 displays 23% identity to HNK-1 ST and 28% to chondroitin 4-sulfotransferase I (C4ST-1) and 26% to chondroitin 4-sulfotransferase 2 (C4ST-2), The cDNA predicts a type II transmembrane protein of 424 amino acids with four potential N-linked glycosylation sites and a single membrane-spanning domain. GalNAc-4-ST1 has putative 5'-phosphosulfonate and S'-phosphate binding sites, Three more carboxyl-terminal regions of unknown function also show a high degree of identity with HNK-1 ST, C4ST-1, and C4ST-2. The membrane-bound form of GalNAc-4-ST1 transfers sulfate to GalNAc beta1,4GlcNAc beta -R but not to chondroitin, whereas truncated forms of GalNAc-4-ST1 that are released into the medium transfer sulfate to both GalNAc beta1, 4GlcNAc beta -R and chondroitin, The first 118 amino acids of GalNAc-4-ST1 appear to contribute to both its activity and specificity for terminal beta1,4-linked GalNAc. GalNAc-4-ST1 also efficiently transfers sulfate to N-linked oligosaccharides on native LH and other glycoproteins terminating with beta1,4-linked GalNAc. A single transcript of 2.4 kilobases is most highly expressed in the pituitary and other regions of the central nervous system. The GalNAc-4-ST1 gene is located on human chromosome 19q13.1.