ST6GalNAc I gene is located on chromosome 17, at location 72,132,442-72,151,489, spans 19.05 kb and contains 9 exons. The start of this gene is located in Contig AC005837.1.1.163218.

Northern blot analysis has shown that ST6GalNAc I gene is expressed in pyloric mucosa as a single 2.5 kb transcript, but it is not expressed in spleen, brain, or pancreas. ST6GalNAc I transcripts were also detected in intestinal metaplasia and duodenal mucosa. In situ hybridization demonstrated that the localization of transcripts correlated well with that of STn antigen in gastric cancer cells and Goblet cells in intestinal metaplastic glands (Ikehara et al., 1999).
RT-PCR analysis shows that ST6GalNAc I gene is expressed only in a limited number of cultured cancer cells, including HT29 and Dami cells (Figure 2). ST6GalNAc I ESTs have been obtained in bone marrow, cervix, esophagus, intestine, skeletal muscle, prostate, spleen, stomach, tongue and trachea, and in several cancer tissues, including cervical, esophageal, prostate, stomach and uterine cancers.
Two cDNA of about 2.5 and 2.3 kp have been isolated. The longer cDNA encodes a 600 amino acids protein (DDBJ/EMBL/GenBank # Y11339). The shorter cDNA shows a nucleotide sequence identical to that of the longer form except for the lack of a 234 bp segment at nucleotide positions 652-885 (relative to the ATG of the long-form (# Y11339)). The short-form cDNA would encode a protein that lacks a 78 amino acid fragment at positions 218-295 in the catalytic region (Ikehara et al., 1999).

No ST6GalNAc I pseudogene has been identified in the human genome.

CMP-NeuAc: N-acetyl-galactosaminide-alpha1-O-Ser/Thr alpha2,6-sialyltransferase 1; synonyms: SIAT7A, HSY11339, hSTYI, ST6GalNAc I

The human ST6GalNAc I (EC 2.4.99.3, CAZy Family GT29, CMP-NeuAc R-GalNAc-alpha1-O-Ser/Thr alpha2,6-sialyltransferase, with R = H, Gal-beta1-3, or NeuAc-alpha2-3Gal-beta1-3) is a 600 AA type II membrane-bound sialyltransferase. It shares the same typical organization with other Golgi glycosyltransferases with a short N-terminal domain in the cytoplasm of the cell, a trans-membrane domain (TMD), an unusually long stem region and a catalytic domain oriented in the lumen of Golgi cisternae. The enzyme possess the 4 signature motifs (sialylmotifs L, S, VS and motif III) of mammalian sialyltransferases (Harduin-Lepers et al., 2005; Jeanneau et al., 2004) and the ST6GalNAc A family-motifs (Patel & Balaji, 2006). No 3D structure is available. The enzyme transfers a sialic acid (N-acetylneuraminic acid) from CMP-NeuAc in the 6-position of a GalNAc residue linked to a serine or a threonine residue of a mucin-type glycopeptide or glycoprotein. The human ST6GalNAc I accepts the following structures as acceptor substrate: GalNAc-alpha-O-Ser/Thr, Gal-beta1-3GalNAc-alpha-O-Ser/Thr and Neu5Ac-alpha2-3Gal-beta1-3GalNAc-alpha-O-Ser/Thr (Ikehara et al., 1999).

The stable transfection of MDA-MB-231 or T47D breast cancer cells with an expression vector encoding ST6GalNAc I induces the expression of STn antigen at the cell surface, which is carried by several high molecular weight membrane bound O-glycoproteins, including MUC1 (Julien et al., 2001; Julien et al., 2005). Sialyl-Tn expression is associated with morphological changes, decreased growth and adhesion, and increased cell migration of sialyl-Tn positive clones. STn positive MDA-MB-231 breast cancer cells exhibit an increased tumor growth in SCID mice (Julien et al., 2006). The MKN45 gastric cell line stably transfected with the full length ST6GalNAc-I also showed high expression of Sialyl-Tn antigen (Marcos et al., 2004). In breast carcinomas, a complete correlation between the expression of ST6GalNAc-I and the expression of sialyl-Tn has been shown (Sewell et al., 2006).

ST6GalNAc I is a Golgi-resident glycosyltransferase.

The Human ST6GalNAc I is a sialyltransferase involved in the biosynthesis of the carbohydrate moiety of mucin-type O-linked glycan chains, transferring a sialic acid residue in 6-position of the first GalNAc residue linked to the peptide aglycone. ST6GalNAc I is particularly involved in the biosynthesis of the sialyl-Tn antigen (STn, NeuAc-alpha2-6GalNAc-alpha1-O-Ser/Thr) and also participates to the biosynthesis of sialyl-6-T (Gal-beta1-3[NeuAc-alpha2-6]GalNAc-alpha1-O-Ser/Thr) and disialyl-T antigens (NeuAc-alpha2-3Gal-beta1-3[NeuAc-alpha2-6]GalNAc-alpha1-O-Ser/Thr) (Figure 4).
ST6GalNAc I compete with O-glycans elongating glycosyltransferases and prevent cancer cells to exhibit longer O-glycans. While fetal and normal adult tissues weakly express STn, the antigen is over-expressed in a wide range of epithelial cancers and is considered as a good maker of tumor. The prognostic value of STn expression has been widely studied, especially in gastric, colorectal, ovarian and breast cancers, and is correlated to a decreased survival of the patients.

ST6GalNAc I is a sialyltransferase (GT-family #29 in the CAZy classification) belonging to the ST6GalNAc family . The amino acid sequence in the catalytic region of human ST6GalNAc I (250 amino acid residues from the C-terminal end) shows sequence identity to mouse ST6GalNAc I (85%), chick ST6GalNAc I (67.2%), 62% homology to human ST6GalNAc II, 36.4% to human ST6GalNAc III, 35.5% to human ST6GalNAc IV, 37.6% to human ST6GalNAc V, and 36.6% to human ST6GalNAc VI.

Mutation analysis showed a heterozygous transition (g.136T→C) leading to p.V80A with a frequency of 9.3% in 32 unrelated control individuals. No other exonic sequence variations were found. In addition, one intronic (g.IVS8 24G→A) and one 3UTR SNP (g.1653A→G) were found (Meuleman et al., 2001).