CHSY1 transfers GlcA to chondroitin

Stable Identifier
Reaction [transition]
Homo sapiens
A glucuronate moiety is added to chondroitin
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A glucuronate (GlcA) moiety is added to the chondroitin chain by dual-activity enzymes, the chondroitin sulfate synthases 1-3 (CHSY1, CHPF and CHSY3) (Kitagawa et al. 2001, Yada et al. 2003, Yada et al. 2003b). They possess both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. These three enzymes require divalent metals as cofactors, manganese producing the highest activities. Another candidate enzyme, chondroitin sulfate glucuronyltransferase (CHPF2) possess only beta-1,3-glucuronic acid transferase activity (Izumikawa et al. 2008, Gotoh et al. 2002). Defects in CHSY1 cause Temtamy preaxial brachydactyly syndrome (TPBS) (MIM:605282) (Tian et al. 2010, Li et al. 2010).

Literature References
PubMed ID Title Journal Year
21129728 Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling

Yigit, G, Aglan, M, Laue, K, Baessmann, I, Wakeling, EL, Topaloglu, AK, Temtamy, S, Hammerschmidt, M, Kotan, LD, Amr, K, Nürnberg, G, Pawlik, B, Hegele, RA, Wollnik, B, Canan, H, Lanktree, MB, Li, Y, Nürnberg, P, Quarrell, OW, May, KW, Yilmaz, M

Am J Hum Genet 2010
11514575 Molecular cloning and expression of a human chondroitin synthase

Uyama, T, Kitagawa, H, Sugahara, K

J Biol Chem 2001
12761225 Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities

Yada, T, Kwon, YD, Kudo, T, Iwasaki, H, Gotoh, M, Watanabe, H, Go, M, Togayachi, A, Kimata, K, Sato, T, Kaseyama, H, Shionyu, M, Narimatsu, H, Kikuchi, N

J Biol Chem 2003
12145278 Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase that transfers glucuronic acid to N-acetylgalactosamine

Inaba, N, Yada, T, Sato, T, Kudo, T, Iwasaki, H, Gotoh, M, Mochizuki, H, Watanabe, H, Narimatsu, H, Togayachi, A, Akashima, T, Kimata, K

J Biol Chem 2002
21129727 Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling

Ling, L, Lee, H, Al-Hadidy, A, Ababneh, OH, Hamamy, H, O'Connor, B, Merriman, B, Tian, J, Shboul, M, Masri, A, Nelson, SF, Reversade, B, Cool, S

Am J Hum Genet 2010
12907687 Chondroitin sulfate synthase-3. Molecular cloning and characterization

Yada, T, Kwon, YD, Sato, T, Kudo, T, Iwasaki, H, Gotoh, M, Watanabe, H, Kaseyama, H, Narimatsu, H, Togayachi, A, Kikuchi, N, Kimata, K

J Biol Chem 2003
18316376 Identification of chondroitin sulfate glucuronyltransferase as chondroitin synthase-3 involved in chondroitin polymerization: chondroitin polymerization is achieved by multiple enzyme complexes consisting of chondroitin synthase family members

Tamura, J, Shiozawa, S, Kitagawa, H, Sugahara, K, Izumikawa, T, Koike, T

J Biol Chem 2008
Catalyst Activity

N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity of CHSY1 [Golgi membrane]

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