TABLE 4.

Outstanding questions and perspectives for functions of glycosyltransferases, sulfotransferases, and epimerase involving CS/DS-biosynthesis.

Questions	Related enzymes	Related references
How XYLTs recognize serine residues on core proteins?	XYLT1, XYLT2	Götting et al. (2000), Pönighaus et al. (2007)
What sorting mechanism of CS/DS and HS?	CSGALNACT1, CSGALNACT2, EXTL2, EXTL3	Izumikawa and Kitagawa (2015), Izumikawa et al. (2015), Koike et al. (2009), Koike et al. (2014), Sugahara and Kitagawa, (2000)
Which GalTs compensate GalT-I and GalT-II-deficiencies?	B4GALTs, B3GALTs	Almeida et al. (1999), Okajima et al. (1999), Bai et al. (2001), Mizumoto and Yamada (2021)
How three dimensional structures of glycosyltransferases and sulfotransferases?	CHSY1, CHPF, DSE, CHST14	Kitagawa et al. (2001a), Kitagawa et al. (2003), Maccarana et al. (2006), Evers et al. (2001), Mikami et al. (2003)
What is the differential roles of the respective isoforms?	XYLTs, CHSYs, CHPFs, CSGALNACTs, C4STs, DSEs	Götting et al. (2000), Kitagawa et al. (2001b), Kitagawa et al., 2003, Uyama et al. (2002), Hiraoka et al. (2000), Maccarana et al. (2006)
What is the roles of 2-O-sulfation in CS/DS?	UST	Kobayashi et al. (1999)
What is the roles of CS/DS in tumor metastasis and development?	All CS/DS-biosynthetic enzymes	ten Dam et al. (2007), Bi et al., (2008), Li et al. (2008), Sugahara et al. (2008), Mizumoto et al. (2012)
Which golgin(s) regurate GAG biosynthesis?	All CS/DS-biosynthetic enzymes	Chan et al. (2018), Ferreira et al. (2018)
Regulation of gene expression and related transcriptional factors	All genes encoding CS/DS-biosynthetic enzymes	Kitagawa et al. (2001a)