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Core2GlcNAcT-I is an enzyme belonging to the β1, 6N-acetylglucosaminyltransferase gene family [Fukuda et al, 2002] and three of them form GlcNAcβ1→6 GalNAc linkage on the Galβ1→3GalNAcα1→Thr/Ser sequence present on O-linked mucin-type glycoproteins [Bierhuizen and Fukuda, 1992; Yeh et al, 1999; Schwientek et al, 2000]. The fourth enzyme utilizes GlcNAcβ1→3Galβ→sequence as an acceptor and forms GlcNAcβ1→6 Gal sequence, resulting in the synthesis of I- antigen Galβ1→4GlcNAcβ1→6(Galβ1→4GlcNAcβ1→3)Gal [Bierhuizen et al, 1993]. These four enzymes are highly related to each other at amino acid sequence levels and indeed, Core2GlcNAcT-II has I-antigen synthesizing activity as well.
Core2GlcNAcT-I acts on Galβ1→3GalNAc→R but not on NeuAcα2→3Galβ1→3GalNAc→R. Consistent with this acceptor specificity, Core2GlcNAcT-I resides in cis to medial Golgi apparatus, presumably earlier Golgi compartments than ST3Gal-I that adds sialic acid to Galβ1→3GalNAc [Skrincosky et al, 1997]. However, those two enzymes are not segregated well and gene inactivation of ST3Gal-I resulted in overexpession of core 2 branched O-glycans in T lymphocytes [Priatel et al, 2000]. Such an overexpression leads to apoptisis of CD8 lymphocytes. Core2GlcNAcT-1 contains 4 disulfide bonds [Yen et al, 2003]. No structural information, however, is available from x-ray crystallography or NMR studies.
The product of Core2GlcNAcT-I, Galβ1→4GlcNAcβ→6(Gal β1→3)GalNAcα1→R is called core 2 branched O-glycans. In blood and other cells, core 2 branched O-glycans provide a backbone for sialyl Lewis X capping structure, NeuAcα2→3Galβ1→4(Fucα1→3)GlcNAc and this capping structure serve as selectin ligands [Hemmerich et al, 1995; Wilkins et al, 1996; Yeh et al, 2001]. Indeed, in vivo functional study using Core2GlcNAcT-I deficient mice indicates that sialyl Lewis X capping structure on core 2 branched O-glycans plays a major role in recruiting leukocytes to inflammatory sites [Ellies et al, 1998]. The amount of core 2 branched O-glycans is upregulated in many cancer cells, suggesting that core 2 branched O-glycans or its sialyl Lewis X version is recognized by adhestion molecules on endothelial cells [Machida et al, 2001]. Alternatively, overexpression of core 2 branched O-glycans on immune cells attenuates immune cell-immune cell interaction, leading to hypo-immune responses [Tsuboi and Fukuda, 1997].
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