Disease relevance of CHST3

• Dot blot analysis has shown that human C4ST is strongly expressed in colorectal adenocarcinoma and peripheral blood leukocytes, whereas strong expression of human chondroitin 6-sulfotransferase (C6ST) is observed in aorta and testis [1].

High impact information on CHST3

• Our results indicate that the mutation in CHST3 described here causes a specific but generalized defect of CS chain sulfation resulting in chondrodysplasia with major involvement of the spine [2].
• C6ST-1 catalyzes the modifying step of chondroitin sulfate (CS) synthesis by transferring sulfate to the C-6 position of the N-acetylgalactosamine of chondroitin [2].
• We used recombinant C6ST-1 to show that the identified missense mutation completely abolishes C6ST-1 activity [2].
• The polypeptide, which we term NSIST (nervous system involved sulfotransferase), shows extensive, although not complete, homology to a chondroitin-6-sulfotransferase and limited homology to other sulfotransferases [3].
• Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates [4].

Biological context of CHST3

• In the present study, we screened DNA from 48 healthy Japanese volunteers for SNPs at the CHST1 and CHST3 gene loci, by means of direct sequencing combined with a polymerase chain reaction method for amplifying genomic DNA, and characterized 77 SNPs and four insertion-deletion polymorphisms [5].
• The amino acid sequence displayed 24% identity to the human C6ST-1, and the highest sequence identity was found in the COOH-terminal catalytic domain [6].
• In situ hybridization assessed ECM gene expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase [7].

Associations of CHST3 with chemical compounds

• We sequenced candidate genes from the region and identified a missense mutation in the chondroitin 6-O-sulfotransferase (C6ST-1) gene (CHST3) changing an arginine into a glutamine (R304Q) in the well conserved 3'-phosphoadenosine 5'-phosphosulfate binding site [2].
• Enzymatic sulfation of galactose residue of keratan sulfate by chondroitin 6-sulfotransferase [8].
• All the enzymes were strongly inhibited by heparin and dextran sulfate, whereas only the chondroitin 6-O-sulfotransferase was inhibited by sulfated galactosaminoglycans [9].

Other interactions of CHST3

• The identification of the reaction product indicated that the enzyme is a novel chondroitin 6-O-sulfotransferase (C6ST-2) that mainly transfers sulfate to N-acetylgalactosamine [6].
• Rounded cells grown in collagen gel showed expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase; expression of these genes was absent in spindle shaped cells [10].

Analytical, diagnostic and therapeutic context of CHST3

• Molecular cloning, expression, and chromosomal mapping of human chondroitin 4-sulfotransferase, whose expression pattern in human tissues is different from that of chondroitin 6-sulfotransferase [1].

References