Alternative titles; symbols
HGNC Approved Gene Symbol: ST6GALNAC4
Cytogenetic location: 9q34.11 Genomic coordinates (GRCh38): 9:127,907,886-127,917,041 (from NCBI)
Members of the GalNAc-alpha-2,6-sialyltransferase family catalyze the transfer of sialic acid from CMP-Neu5Ac forming an alpha-2,6 linkage. ST6GalNAc IV shows restricted substrate specificity, utilizing only the trisaccharide sequence Neu5Ac-alpha-2,3-Gal-beta-1,3-GalNAc, suggesting that it does not discriminate between alpha- and beta-linked GalNAc (Harduin-Lepers et al., 2000).
By database searching for sequences homologous to rat N-acetylgalactosamine alpha-2,6-sialyltransferase (ST6GalNAc) III, Harduin-Lepers et al. (2000) identified a novel member of the human ST6GalNAc family, which they named ST6GalNAc IV. They assembled the cDNA sequence using a combination of database searches and PCR techniques. The ST6GalNAc IV cDNA encodes a deduced 302-amino acid type II membrane protein containing the sialyl motifs L, S, and VS. Using SDS/PAGE and Western blotting analysis of recombinant protein, Harduin-Lepers et al. (2000) detected a protein with a 35-kD molecular mass. They confirmed the identity of the ST6GalNAc IV cDNA by transiently expressing an active recombinant enzyme capable of transferring a sialic acid residue to an alpha-2,6 position of the GalNAc residue. The ST6GalNAc IV protein shares 46.6% and 88.1% sequence identity with the rat St6GalNAc III and the mouse ST6GalNAc IV proteins, respectively. Harduin-Lepers et al. (2000) concluded that ST6GalNAc IV is the human ortholog of the Fugu rubripes SIAT3C gene.
By Northern blot analysis, Harduin-Lepers et al. (2000) detected constitutive expression of a 2.2-kb ST6GalNAc IV transcript in various adult tissues and lower levels of expression of an additional 2.5-kb transcript in brain, heart, and skeletal muscle. By RT-PCR analysis, they detected ST6GalNAc IV expression in a wide variety of cultured human cancer cells.
By 5-prime RACE-PCR, Kim et al. (2003) cloned a ST6GalNAc IV splice variant in addition to the full-length ST6GalNAc IV transcript from human fetal brain. The variant was not found in fetal liver or adult brain or liver. It lacks exon 2, which contains the in-frame start codon. Northern blot analysis of fetal tissues detected highest ST6GalNAc IV expression in liver. Expression was very low in kidney and lung and was undetectable in fetal brain.
Lee et al. (1999) cloned mouse St6GalNAc IV from a brain cDNA library. The deduced 302-amino acid protein contains a short N-terminal tail, followed by a transmembrane region, a central sialyl motif L, and a C-terminal sialyl motif S.
Lee et al. (1999) assayed the ability of a soluble form of mouse St6GalNAc IV to transfer radiolabeled N-acetylneuraminic acid (NeuAc) from CMP-NeuAc to several glycolipid, glycoprotein, and free oligosaccharide substrates. Only fetuin (AHSG; 138680) and the unconjugated NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc residue found in fetuin were good acceptor substrates. The glycolipid GM1b, which contains the same carbohydrate residue, was a much weaker substrate. The incorporated sialic acids contained an alpha-2,6 linkage, confirming that the enzyme belongs to the ST6GalNAc family.
Harduin-Lepers et al. (2000) determined that the SIAT3C gene contains 7 exons and spans at least 10 kb of genomic DNA.
Kim et al. (2003) determined that the 5-prime region of ST6GalNAc IV lacks canonical TATA and CAAT boxes, but contains several putative binding sites for transcription factors.
Gilley and Fried (1999) mapped the human ortholog of the Fugu rubripes SIAT3C gene to chromosome 9q31 by FISH and radiation hybrid analysis. Harduin-Lepers et al. (2000) mapped the human SIAT3C gene to 9q31 by sequence analysis.
Gilley, J., Fried, M. Extensive gene order differences within regions of conserved synteny between the Fugu and human genomes: implications for chromosomal evolution and the cloning of disease genes. Hum. Molec. Genet. 8: 1313-1320, 1999. [PubMed: 10369878] [Full Text: https://doi.org/10.1093/hmg/8.7.1313]
Harduin-Lepers, A., Stokes, D. C., Steelant, W. F. A., Samyn-Petit, B., Krzewinski-Recchi, M.-A., Vallejo-Ruiz, V., Zanetta, J.-P., Auge, C., Delannoy, P. Cloning, expression and gene organization of a human Neu5Ac-alpha-2-3Gal-beta-1-3GalNAc alpha-2,6-sialyltransferase: hST6GalNAc IV. Biochem. J. 352: 37-48, 2000. [PubMed: 11062056]
Kim, S.-W., Kang, N.-Y., Lee, S.-H., Kim, K.-W., Kim, K.-S., Lee, J.-H., Kim, C.-H., Lee, Y.-C. Genomic structure and promoter analysis of human NeuAc alpha-2,3Gal beta-1,3GalNAc alpha-2,6-sialyltransferase (hST6GalNAc IV) gene. Gene 305: 113-120, 2003. [PubMed: 12594047] [Full Text: https://doi.org/10.1016/s0378-1119(02)01234-9]
Lee, Y.-C., Kaufmann, M., Kitazume-Kawaguchi, S., Kono, M., Takashima, S., Kurosawa, N., Liu, H., Pircher, H., Tsuji, S. Molecular cloning and functional expression of two members of mouse NeuAc-alpha-2,3Gal-beta-1,3GalNAc GalNAc-alpha-2,6-sialyltransferase family, ST6GalNAc III and IV. J. Biol. Chem. 274: 11958-11967, 1999. [PubMed: 10207017] [Full Text: https://doi.org/10.1074/jbc.274.17.11958]