Abstract
Tyrosine O-sulfation, a common post-translational modification in eukaryotes, is mediated by Golgi enzymes that catalyze the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate to tyrosine residues in polypeptides. We recently isolated cDNAs encoding human and mouse tyrosylprotein sulfotransferase-1 (Ouyang, Y. B., Lane, W. S., and Moore, K. L. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 2896-2901). Here we report the isolation of cDNAs encoding a second tyrosylprotein sulfotransferase (TPST), designated TPST-2. The human and mouse TPST-2 cDNAs predict type II transmembrane proteins of 377 and 376 amino acid residues, respectively. The cDNAs encode functional N-glycosylated enzymes when expressed in mammalian cells. In addition, preliminary analysis indicates that TPST-1 and TPST-2 have distinct specificities toward peptide substrates. The human TPST-2 gene is on chromosome 22q12.1, and the mouse gene is in the central region of chromosome 5. We have also identified a cDNA that encodes a TPST in the nematode Caenorhabditis elegans that maps to the right arm of chromosome III. Thus, we have identified two new members of a class of membrane-bound sulfotransferases that catalyze tyrosine O-sulfation. These enzymes may catalyze tyrosine O-sulfation of a variety of protein substrates involved in diverse physiologic functions.
Highlights
Tyrosine O-sulfation is a post-translation modification of membrane and secretory proteins that occurs in all eukaryotic organisms [1,2,3]
Tyrosine O-sulfation is mediated by tyrosylprotein sulfotransferase (TPST),1 which catalyzes the transfer of the sulfuryl group from 3Ј-phosphoadenosine 5Ј-phosphosulfate (PAPS) to tyrosine residue(s) within highly acidic motifs of polypeptides [2, 21]
Excluding ESTs that aligned with TPST-1, 17 human and 23 mouse ESTs were identified that were aligned into separate contigs
Summary
Tyrosine O-sulfation is a post-translation modification of membrane and secretory proteins that occurs in all eukaryotic organisms [1,2,3]. We recently purified a TPST from rat liver microsomes and cloned human and mouse cDNAs that encode this enzyme activity, which we designate TPST-1 [24]. The human and mouse TPST-1 cDNAs encode N-glycosylated proteins of 370 amino acids with type II transmembrane topology and are broadly expressed in mammalian tissues as assessed by Northern blotting.
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