Disease relevance of GALNAC4S-6ST

• To identify the gene in this region responsible for endometrial cancer, we further characterized this region and localized the hBRAG gene [1].
• During the turning process, expression of GalNAc4S-6ST gene is detected in the forebrain, branchial arches, across the gut tube (hindgut, midgut and foregut diverticulum), in the vitelline veins and artery and in the splanchnopleure layer [2].

High impact information on GALNAC4S-6ST

• We have shown previously that a highly sulfated sequence, GalNAc(4,6-SO(4))-GlcA(2SO(4))-GalNAc(6SO(4)), is present at the nonreducing terminal of chondroitin sulfate (CS), and this structure was synthesized from a unique sequence, GalNAc(4SO(4))-GlcA(2SO(4))-GalNAc(6SO(4)), by sulfation with N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase [3].
• N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of N-acetylgalactosamine 4-sulfate (GalNAc(4SO4)) [4].
• Oligo I was much better acceptor for GalNAc4S-6ST than GalNAc(4SO4)-GlcAGalNAc(6SO4) [4].
• When CS-A was incubated with [35S]PAPS and GalNAc4S-6ST and the 35S-labeled product was digested with chondroitinase ACII, a 35S-labeled trisaccharide (Oligo III) containing [35S]GalNAc(4,6-SO4) residue at the nonreducing end was obtained [4].
• Collectively, these results are consistent with a function for hBRAG as a B cell surface signaling receptor molecule [5].

Biological context of GALNAC4S-6ST

• Additionally, their use in cell surface biotinylation and flow cytometry reveals subcellular hBRAG pools both at cell surface and intracellular locations [5].
• Consistent with its cell surface expression and possible link to BCR signaling, experiments in which alpha-hBRAG antibodies were used to generate early activation signals suggest a modest but specific element of tyrosine phosphorylation occurring through a putative hBRAG receptor [5].
• The hBRAG gene was localized to the long arm of chromosome 10 (10q26) [6].
• Subsequent screenings of a pre-B cDNA library with 3G1 led to the identification of a complete cDNA we have termed hBRAG (human B-cell RAG-Associated Gene) [6].
• Transfection of the full-length hBRAG cDNA increased levels of human RAG1 transcripts in the B cell line OCI LY8-C3P, but not in the non-lymphoid line K562, suggesting a B cell-specific role for the hBRAG product in regulating RAG expression [6].

Anatomical context of GALNAC4S-6ST

• In human tissues, hBRAG is expressed at highest levels in B cell-enriched tissues, but is not expressed in fetal or adult thymus [6].
• Northern blot analysis indicated a close association of the 5.0-kb hBRAG mRNA transcript with RAG1 in numerous human pro-B, pre-B and mature B cell lines assessed, but not in human T cell lines [6].
• The results show that GalNAc4S-6ST is differentially expressed in the anterior visceral ectoderm at stage E5.5 and later becomes restricted to the embryonic endoderm, especially in the prospective midgut region [2].

Associations of GALNAC4S-6ST with chemical compounds

• We previously identified human GalNAc4S-6ST cDNA and showed that the recombinant GalNAc4S-6ST could transfer sulfate efficiently to the nonreducing terminal GalNAc(4SO4) residues [4].
• A unique nonreducing terminal modification of chondroitin sulfate by N-acetylgalactosamine 4-sulfate 6-o-sulfotransferase [4].
• Characterization of the human B cell RAG-associated gene, hBRAG, as a B cell receptor signal-enhancing glycoprotein dimer that associates with phosphorylated proteins in resting B cells [5].
• We found that phenyl beta-GalNAc(4SO(4)) inhibits GalNAc4S-6ST competitively and also serves as an acceptor [7].
• We have previously cloned N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), which transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the C-6 hydroxyl group of the GalNAc 4-sulfate residue of chondroitin sulfate A and forms chondroitin sulfate E containing GlcA-GalNAc(4,6-SO(4)) repeating units [7].

Other interactions of GALNAC4S-6ST

• Comparison between the human serum enzyme and the N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (formerly designated "E6-sulfotransferase") from squid cartilage indicated that the latter is distinct from the former in introducing sulfate predominantly into the interior portion of chondroitin sulfate [8].
• Co-immunoprecipitation experiments with hBRAG antisera detected the association of hBRAG with phosphorylated proteins in resting B cells, including the protein tyrosine kinase Hck, which is subsequently dephosphorylated upon B cell receptor (BCR) ligation [5].

Analytical, diagnostic and therapeutic context of GALNAC4S-6ST

• We have analyzed the expression pattern of the GalNAc4S-6ST gene during early mouse embryonic development by whole mount in situ hybridization [2].

References