O-glycosylation of TSR domain-containing proteins

Stable Identifier
Homo sapiens
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The O-fucosylation of proteins containing thrombospondin type 1 repeat (TSR) domains is an important PTM, regulating many biological processes such as Notch signalling, inflammation, wound healing, angiogenesis amd neoplasia (Adams & Tucker 2000, Moremen et al. 2012). Fucose addition is carried out by two protein fucosyltransferases, POFUT1 and 2. Only POFUT2 recognises the consensus sequence CSXS/TCG found in TSR1 domains and the fucosyl residue is attached to the hydroxyl group of conserved serine (S) or threonine (T) residues within the consensus sequence. The modification was first demonstrated on thrombospondin 1, found in platelets and the ECM (Hofsteenge et al. 2001, Luo et al. 2006). The resulting O-fucosyl-protein is subsequently a substrate for beta-1,3-glucosyltransferase-like protein (B3GALTL), which adds a glucosyl moiety to form the rare disaccharide modification Glc-beta-1,3-Fuc. More than 60 human proteins contain TSR1 domains, The disaccharide modification has been demonstrated on a small number of these TSR1 domain-containing proteins such as thrombospondin 1 (Hofsteenge et al. 2001, Luo et al. 2006), properdin (Gonzalez de Peredo et al. 2002) and F-spondin (Gonzalez de Peredo et al. 2002). The ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin type-1 repeats) superfamily consists of 19 secreted metalloproteases (ADAMTS proteases) and at lease five ADAMTS-like proteins in humans. Five members of the ADAMTS superfamily have also had experimental confirmation of the disaccharide modification. Examples are ADAMTS13 (Ricketts et al. 2007) and ADAMTSL1 (Wang et al. 2007). In the two reactions described here, the TSR1 domain-containing proteins with similarity to the experimentally confirmed ones are included as putative substrates.

Literature References
PubMed ID Title Journal Year
17395589 O-fucosylation is required for ADAMTS13 secretion

Haltiwanger, RS, Dlugosz, M, Luther, KB, Majerus, EM, Ricketts, LM

J. Biol. Chem. 2007
10842357 The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development

Adams, JC, Tucker, RP

Dev. Dyn. 2000
16464858 Two distinct pathways for O-fucosylation of epidermal growth factor-like or thrombospondin type 1 repeats

Haltiwanger, RS, Nita-Lazar, A, Luo, Y

J. Biol. Chem. 2006
11067851 C-mannosylation and O-fucosylation of the thrombospondin type 1 module

Huwiler, KG, Mosher, DF, Hofsteenge, J, Lawler, J, Hess, D, Macek, B, Peter-Katalinic, J

J. Biol. Chem. 2001
12096136 C-mannosylation and o-fucosylation of thrombospondin type 1 repeats

Hofsteenge, J, Hess, D, Klein, D, Gonzalez de Peredo, A, Peter-Katalinic, J, Macek, B

Mol. Cell Proteomics 2002
22722607 Vertebrate protein glycosylation: diversity, synthesis and function

Tiemeyer, M, Moremen, KW, Nairn, AV

Nat. Rev. Mol. Cell Biol. 2012
17395588 O-fucosylation of thrombospondin type 1 repeats in ADAMTS-like-1/punctin-1 regulates secretion: implications for the ADAMTS superfamily

Apte, SS, Haltiwanger, RS, Dlugosz, M, Raed, M, Somerville, RP, Wang, LW

J. Biol. Chem. 2007
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