Beta-1,4-galactosyltransferase 7 also known as galactosyltransferase I is an enzyme that in humans is encoded by the B4GALT7 gene. Galactosyltransferase I catalyzes the synthesis of the glycosaminoglycan-protein linkage in proteoglycans. Proteoglycans in turn are structural components of the extracellular matrix that is found between cells in connective tissues.
Galactosyltransferase I is one of seven ò-1,4-galactosyltransferase (ò4GalT) enzymes. These enzymes are type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a ò-1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: ò4GalT1 and ò4GalT2, ò4GalT3 and ò4GalT4, ò4GalT5 and ò4GalT6, and ò4GalT7. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein (GlcA-ò-1,3-Gal-ò-1,3-Gal-ò-1,4-Xyl-beta1-O-Ser) linkage found in proteoglycans. Manganese is required as a cofactor. This enzyme differs from the other six beta4GalTs because it lacks the conserved ò4GalT1-ò4GalT6 Cys residues and it is located in cis-Golgi instead of trans-Golgi.
Mutations in the B4GALT7 gene that result in a defective galactosyltransferase I enzyme with reduced or absent activity are associated with Spondylodysplastic, formerly progeroid type EhlersâÂÂDanlos syndrome. The reduced activity of B4GALT7 is associated with a reduced substitution of the proteoglycans decorin and biglycan with glycosaminoglycan carbohydrate chains, and with alterations in heparan sulfate biosynthesis, resulting in delayed wound repair, altered migration, adhesion and contractility of patient fibroblasts. Since mutations in B4GALT7 impair a glycosylation pathway, the resulting subtype of EhlersâÂÂDanlos syndrome may be considered a congenital disorder of glycosylation (CDG), according to the new CDG nomenclature.
Mutations in B4GALT7 cause Larsen syndrome.