Beta-1,4-galactosyltransferase 7 also known as galactosyltransferase I is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''B4GALT7''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Galactosyltransferase I

catalyzes Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

the synthesis of the

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...

-protein linkage in

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to w ...

s. Proteoglycans in turn are structural components of the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

that is found between cells in

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

Function

Galactosyltransferase I is one of seven β-1,4-

galactosyltransferase Galactosyltransferase is a type of glycosyltransferase which catalyzes the transfer of galactose Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about ...

(β4GalT) enzymes. These enzymes are type II membrane-bound

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

s that appear to have exclusive specificity for the donor substrate

UDP-galactose Uridine diphosphate galactose (Uridine diphosphate, UDP-galactose) is an intermediate in the production of polysaccharides. It is important in nucleotide sugars metabolism, and is the substrate for the transferase B4GALT5. Sugar metabolism Urid ...

; all transfer galactose in a β-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 In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

signal sequence that directs the protein to the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: β4GalT1 and β4GalT2, β4GalT3 and β4GalT4, β4GalT5 and β4GalT6, and β4GalT7. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein (GlcA-β-1,3-Gal-β-1,3-Gal-β-1,4-Xyl-beta1-O-Ser) linkage found in

proteoglycans Proteoglycans are proteins that are heavily glycosylation, glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalent bond, covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a ...

Manganese Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

is required as a cofactor. This enzyme differs from the other six beta4GalTs because it lacks the conserved β4GalT1-β4GalT6 Cys residues and it is located in cis-Golgi instead of trans-Golgi.

Clinical significance

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 Ehlers-Danlos syndrome. The reduced activity of B4GALT7 is associated with a reduced substitution of the

decorin Decorin is a protein that in humans is encoded by the ''DCN'' gene. Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a ...

and

biglycan Biglycan is a small leucine-rich repeat proteoglycan (SLRP) which is found in a variety of extracellular matrix tissues, including bone, cartilage and tendon. In humans, biglycan is encoded by the ''BGN'' gene which is located on the X chromosome ...

with

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

chains, and with alterations in

heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs in a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...

biosynthesis, resulting in delayed

wound repair Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective tissue, connective layer) form a protect ...

, altered migration, adhesion and contractility of patient

fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

. Since mutations in B4GALT7 impair a glycosylation pathway, the resulting subtype of Ehlers-Danlos syndrome may be considered a

congenital disorder of glycosylation A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defect ...

(CDG), according to the new CDG nomenclature. Mutations in B4GALT7 cause

Larsen syndrome Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients.Mitra, N., Kannan, N., Kumar, V.S., Kavita, G. "Larsen Syndrom ...

References

External links

*
PDBe-KB
provides an overview of all the structure information available in the PDB for Human Beta-1,4-galactosyltransferase 7

Function

Clinical significance

References

External links

Further reading