Molecular cloning and expression of two distinct human N-acetylgalactosamine 4-O-sulfotransferases that transfer sulfate to GalNAc beta 1-->4GlcNAc beta 1-->R in both N- and O-glycans.
Recently, cDNAs encoding human chondroitin 4-O-sulfotransferase-1 and -2 (C4ST-1 and C4ST-2) were cloned based on their similarity to HNK-1 sulfotransferase (HNK-1ST) (Hiraoka, N., Nakagawa, H., Ong, E., Akama, T.O., Fukuda, M.N., and Fukuda, M. [2000] Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family. J. Biol. Chem., 275, 20188--20196). In the present study, we identified two additional novel sulfotransferases by searching the expression sequence tag and genomic DNA database for enzymes similar to C4ST-1 and C4ST-2. These newly cloned enzymes, termed GalNAc4ST-1 and GalNAc4ST-2, belong to the HNK-1ST gene family having 40--42% identity with C4ST-1. GalNAc4ST-1 and -2 do not add sulfate to HNK-1 precursor glycans, chondroitin, or desulfated dermatan sulfate. Instead, both enzymes can transfer sulfate to the 4-position of GalNAc in the context of GalNAc beta 1-->4GlcNAc beta 1-->R attached to both N-linked and core 2 branched O-linked oligosaccharides. GalNAc4ST-1 and -2 transcripts are highly expressed in the pituitary gland and trachea, respectively, and GalNAc4ST-1 and -2 transcripts are reciprocally expressed in other tissues as well. Moreover, both enzymes can transfer sulfate to lutropin, a pituitary glycoprotein hormone. These combined results indicate that GalNAc4ST-1 and -2 play critical roles in forming sulfo-->4GalNAc beta 1-->4GlcNAc beta 1-->R in both N-glycans and O-glycans in a tissue-specific manner.
Hiraoka
N
N
Glycobiology Program, Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 USA.
Misra
A
A
Belot
F
F
Hindsgaul
O
O
Fukuda
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
D013431:Sulfates; D007986:Luteinizing Hormone; C498300:CHST9 protein, human; C092527:N-acetylgalactosamine-4-sulfotransferase; D015238:Sulfotransferases