Termination of O-glycan biosynthesis O-linked glycosylation of mucins Authored: Jassal, B, 2010-07-19 Edited: Jassal, B, 2010-07-19 GENE ONTOLOGYGO:0016266 Mucins are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most metazoa. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. To date, there are approximately 20 genes that express mucins. Mature mucins are composed of two distinct regions:<br>(1) The amino- and carboxy-terminal regions are very lightly glycosylated, but rich in cysteines. The cysteine residues participate in establishing disulfide linkages within and among mucin monomers.<br>(2) A large central region rich in serine, threonine and proline residues called the variable number of tandem repeat (VNTR) region which can become heavily O-glycosylated with hundreds of O-GalNAc glycans.<br> N-acetyl-galactosamine (GalNAc) is the first glycan to be attached, forming the simplest mucin O-glycan. After this, several different pathways are possible generating "core" structures. Four core structures are commonly formed, several others are possible but infrequent. O-linked glycans are often capped by the addition of a sialic acid residue, terminating the addition of any more O-glycans (Brockhausen et al, 2009; Tarp and Clausen, 2008). Pubmed17988798 Pubmed20301232 Reactome Database ID Release 43913709 Reactome, http://www.reactome.org ReactomeREACT_115606 Reviewed: Ferrer, A, 2011-11-04 PathwayStep3190 PathwayStep3196 PathwayStep3182 PathwayStep3181 PathwayStep3186 PathwayStep3185 PathwayStep3184 PathwayStep3183 PathwayStep3189 PathwayStep3188 PathwayStep3187 Addition of GlcNAc to Core 3 forms a Core 4 glycoprotein Addition of GlcNAc to the Tn antigen via an alpha-1,3 linkage forms a Core 5 glycoprotein Addition of GlcNAc to the T antigen forms a Core 2 glycoprotein Addition of GlcNAc to the Tn antigen forms a Core 3 glycoprotein Addition of GalNAc to the Tn antigen via an alpha-1,6 linkage forms a Core 7 glycoprotein Addition of galactose to the Tn antigen via an alpha-1,3 linkage forms a Core 8 glycoprotein Addition of GlcNAc to the Tn antigen via a beta-1,6 linkage forms a Core 6 glycoprotein Addition of galactose to Core 6 glycoprotein C1GALT1 transfers galactose to the Tn antigen forming Core 1 glycoproteins (T antigens) Addition of GalNAc to mucins to form the Tn antigen