ST6GalNAc-I

Abstract

ST6GalNAc-I is a CMP-sialic acid: N-acetylgalactosaminide α2-6-sialyltransferase (GalNAc α2-6-sialyltransferase), and a member of the ST6GalNAc subfamily that exhibits activity toward GalNAc-O-Ser/Thr, Galβ1-3GalNAc-O-Ser/Thr, and NeuAcα2- 3Galβ1-3GalNAc-O-Ser/Thr (Kurosawa et al. 1994, 2000; Ikehara et al. 1999; Kono et al. 2000). Like other sialyltransferases, ST6GalNAc-I exhibits type II membrane protein topology and has characteristic motifs for sialyltransferases called sialylmotifs L, S, and VS. ST6GalNAc-I also has the Kurosawa motif (Cys-Xaa75-in82-Cys-Xaa-Cys- Ala-Xaa-Va1-Xaa150-160-Cys; Xaa denotes any amino acid residue) as seen in the ST3Gal family and two members of the ST6GalNAc family (Kurosawa et al. 1996; Tsuji 1999). ST6GalNAc-I is a relatively large sialyltransferase (600 amino acids in length in Homo sapiens, 526 in Mus musculus, and 566 in Gallus gallus) compared with other sialyltransferases characterized to date. This structural character is attributed to its long stem domain. The putative active domain of mouse ST6GalNAc-I (250 amino acid residues from the C-terminal end) showed a high identity to the corresponding region of human ST6GalNAc-I (85%) and to the chick enzyme (67%), but showed low identity to other members of the mouse ST6GalNAc family: ST6GalNAc-II 48%, ST6GalNAc-III 41%, ST6GalNAc-IV 23%, and ST6GalNAc-V 16%. Human ST6GalNAc-I cDNA has two isoforms (2.46 and 2.23 kb). The former encodes an active enzyme with a predicted 600 amino acid sequence. The latter, a splice-variant of the long form, encodes an inactive enzyme (Ikehara et al. 1999).