GAL3ST4

GAL3ST4
Identifiers
Aliases	GAL3ST4 , GAL3ST-4, galactose-3-O-sulfotransferase 4
External IDs	OMIM: 608235 MGI: 1916254 HomoloGene: 11633 GeneCards: GAL3ST4
Gene location (Human)
Chr.	Chromosome 7 (human)
End	100,168,617 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	138,271,102 bp
RNA expression pattern
	Top expressed in
	parotid gland; ; skin of abdomen; ; vulva; ; thymus; ; nipple; ; ganglionic eminence; ; synovial membrane; ; endothelial cell; ; hair follicle; ; inferior ganglion of vagus nerve;
	Top expressed in
	lip; ; esophagus; ; zone of skin; ; hippocampus proper; ; urinary bladder; ; quadriceps femoris muscle; ; hypothalamus; ; superior frontal gyrus; ; ileum; ; neural tube;
	More reference expression data
	n/a
Gene ontology
Molecular function	galactose 3-O-sulfotransferase activity ; transferase activity ; galactosylceramide sulfotransferase activity ; proteoglycan sulfotransferase activity ; 3'-phosphoadenosine 5'-phosphosulfate binding ;
Cellular component	integral component of membrane ; Golgi cisterna membrane ; Golgi apparatus ; extracellular exosome ; membrane ;
Biological process	glycolipid biosynthetic process ; sulfur compound metabolic process ; cell-cell signaling ; glycoprotein metabolic process ; oligosaccharide metabolic process ; proteoglycan biosynthetic process ;
	Sources:Amigo / QuickGO
Orthologs
	79690
	330217
	ENSG00000197093
	ENSMUSG00000075593
	Q96RP7
	n/a
	NM_024637
	NM_001033416 ; NM_001347507 ; NM_001361283
	NP_078913
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated March 04, 2023

Galactose-3-O-sulfotransferase 4 is an enzyme that in humans is encoded by the GAL3ST4 gene.^[5]^[6]

This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate to the C-3' position of galactose residues in O-linked glycoproteins. This enzyme is highly specific for core 1 structures, with asialofetuin, Gal-beta-1,3-GalNAc and Gal-beta-1,3 (GlcNAc-beta-1,6)GalNAc being good substrates.^[6]

Mutations

Pectus Excavatum, the most common deformity of the chest wall, is believed to have a genetic component. The condition is believed to be passed either dominantly or recessively by a gene of unknown identity. A study performed in 2012 by Wu et al.^[7] states that pectus excavatum displays dominant inheritance via a mutation in GAL3ST4. The study proposes mutation g.chr7: 99764688G>A affects the first exon of GAL3ST4 resulting in tryptophan replacing arginine at residue 11 of the encoded protein. This mutation is highly likely to disrupt the normal function of the encoded protein. GAL3ST4 is typically responsible for catalyzing “the C-3 sulfation of galactoses in O-linked glycoproteins”.^[8] Mutation of this gene results in alterations of the typical sulfation pattern of glycan chains, which will alter the physiologic functions of various glycoproteins. For normal development of cartilage and bone to occur, sulfation of proteoglycans must occur. Mutations of proteins responsible for other aspects of sulfation and sulfatases have been linked to several mutations affecting the skeleton. Through the evaluation of several participants with pectus excavatum, Wu et al. determined mutation of GAL3ST4 is most likely responsible for the dominant inheritance pattern of pectus excavatum through alterations of the encoded proteins.

Related Research Articles

Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units. The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case of the sulfated glycosaminoglycan keratan, where, in place of the uronic sugar there is a galactose unit. GAGs are found in vertebrates, invertebrates and bacteria. Because GAGs are highly polar molecules and attract water; the body uses them as lubricants or shock absorbers.

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB, and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.

Carbohydrate sulfotransferase 6 is an enzyme that in humans is encoded by the CHST6 gene.

UDP-N-acetylglucosamine—dolichyl-phosphate N-acetylglucosaminephosphotransferase is an enzyme that in humans is encoded by the DPAGT1 gene.

Carbohydrate sulfotransferase 2 is an enzyme that in humans is encoded by the CHST2 gene.

Carbohydrate sulfotransferase 4 is an enzyme that in humans is encoded by the CHST4 gene.

ST3 beta-galactoside alpha-2,3-sialyltransferase 3, also known as ST3GAL3, is a protein which in humans is encoded by the ST3GAL3 gene.

Carbohydrate sulfotransferase 1 is an enzyme that in humans is encoded by the CHST1 gene.

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.

Galactose-3-O-sulfotransferase 2 is an enzyme that in humans is encoded by the GAL3ST2 gene.

Beta-1,4-galactosyltransferase 2 is an enzyme that in humans is encoded by the B4GALT2 gene.

Beta-1,4-galactosyltransferase 5 is an enzyme that in humans is encoded by the B4GALT5 gene.

Beta-1,3-galactosyltransferase 5 is an enzyme that in humans is encoded by the B3GALT5 gene.

Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 is an enzyme that in humans is encoded by the B3GAT2 gene.

Beta-1,4-galactosyltransferase 4 is an enzyme that in humans is encoded by the B4GALT4 gene.

Beta-1,4-galactosyltransferase 3 is an enzyme that in humans is encoded by the B4GALT3 gene.

Galactose-3-O-sulfotransferase 3 is an enzyme that in humans is encoded by the GAL3ST3 gene.

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3 is an enzyme that in humans is encoded by the NDST3 gene. It catalyses the reaction:

3'-phosphoadenylyl sulfate + α-D-glucosaminyl-[heparan sulfate]_(n) = adenosine 3',5'-bisphosphate + 2 H⁺ + N-sulfo-α-D-glucosaminyl-[heparan sulfate]_(n)

<span class="mw-page-title-main">Carbohydrate sulfotransferase</span>

Carbohydrate sulfotransferases are sulfotransferase enzymes that transfer sulfate to carbohydrate groups in glycoproteins and glycolipids. Carbohydrates are used by cells for a wide range of functions from structural purposes to extracellular communication. Carbohydrates are suitable for such a wide variety of functions due to the diversity in structure generated from monosaccharide composition, glycosidic linkage positions, chain branching, and covalent modification. Possible covalent modifications include acetylation, methylation, phosphorylation, and sulfation. Sulfation, performed by carbohydrate sulfotransferases, generates carbohydrate sulfate esters. These sulfate esters are only located extracellularly, whether through excretion into the extracellular matrix (ECM) or by presentation on the cell surface. As extracellular compounds, sulfated carbohydrates are mediators of intercellular communication, cellular adhesion, and ECM maintenance.

O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000197093 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000075593 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Seko A, Hara-Kuge S, Yamashita K (Jul 2001). "Molecular cloning and characterization of a novel human galactose 3-O-sulfotransferase that transfers sulfate to gal beta 1-->3galNAc residue in O-glycans". J Biol Chem. 276 (28): 25697–704. doi: 10.1074/jbc.M101558200 . PMID 11333265.
1 2 "Entrez Gene: GAL3ST4 galactose-3-O-sulfotransferase 4".
↑ Wu, S., Sun, X., Zhu, W., Huang, Y., Mou, L., Liu, M., ... & Wang, Z. (2012). Evidence for GAL3ST4 mutation as the potential cause of pectus excavatum. Cell research, 22(12), 1712-1715.
↑ Seko A, Hara-Kuge S, Yamashita K. Molecular cloning and characterization of a novel human galactose 3-O-sulfotransferase that transfers sulfate to Galβ1→3GalNAc residue in O-glycans. J Biol Chem. 2001;276:25697–25704.

GAL3ST4

Contents

Mutations

Related Research Articles

References

Further reading