Reactome | HAS1,2,3 mediate the polymerization and export of HA

HAS1,2,3 mediate the polymerization and export of HA

Stable Identifier

R-HSA-2160851

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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HAS1,2,3 mediate the polymerization and export of HA

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The integral membrane dual-action glycosyltransferase proteins hyaluronan synthases 1-3 (HAS1-3) (Shyjan et al. 1996, Watanabe & Yamaguchi 1996, Spicer et al. 1997 respectively) catalyze the synthesis of hyaluron (hyaluronic acid, hyaluronate, HA) by polymerization of glucuronic acid (GlcA) with N-acetylglucosamine (GlcNAc) using UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylglucosamine (UDP-GlcNAc). The resulting polymer can be as large as 10 miilion Da. As HA is synthesised it is extruded from the cell by HAS1-3. Structural analyses of a virus HAS and a bacterial HAS of the same type as vertebrate HAS revealed that the enzyme creates a continuous transmembrane channel upon priming with a GlcNAc monosaccharide (Hubbard et al., 2012; Maloney et al. 2022; reviewed in DeAngelis & Zimmer, 2023). HAS2 is stimulated by UTP and UDP-glucose (Jokela et al., 2017; 2014).

Literature References

PubMed ID	Title	Journal	Year
28188289	Human Keratinocytes Respond to Extracellular UTP by Induction of Hyaluronan Synthase 2 Expression and Increased Hyaluronan Synthesis Jokela, T, Kärnä, R, Rauhala, L, Bart, G, Pasonen-Seppänen, S, Oikari, S, Tammi, MI, Tammi, RH	J Biol Chem	2017
8798477	Molecular identification of a putative human hyaluronan synthase Watanabe, K, Yamaguchi, Y	J Biol Chem	1996
8798544	Functional cloning of the cDNA for a human hyaluronan synthase Shyjan, AM, Heldin, P, Butcher, EC, Yoshino, T, Briskin, MJ	J Biol Chem	1996
22343360	The hyaluronan synthase catalyzes the synthesis and membrane translocation of hyaluronan Hubbard, C, McNamara, JT, Azumaya, C, Patel, MS, Zimmer, J	J Mol Biol	2012
9083017	Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase Spicer, AP, Olson, JS, McDonald, JA	J Biol Chem	1997
35355017	Structure, substrate recognition and initiation of hyaluronan synthase Maloney, FP, Kuklewicz, J, Corey, RA, Bi, Y, Ho, R, Mateusiak, L, Pardon, E, Steyaert, J, Stansfeld, PJ, Zimmer, J	Nature	2022
24847057	Extracellular UDP-glucose activates P2Y14 Receptor and Induces Signal Transducer and Activator of Transcription 3 (STAT3) Tyr705 phosphorylation and binding to hyaluronan synthase 2 (HAS2) promoter, stimulating hyaluronan synthesis of keratinocytes Jokela, TA, Kärnä, R, Makkonen, KM, Laitinen, JT, Tammi, RH, Tammi, MI	J Biol Chem	2014
37769351	Hyaluronan synthases; mechanisms, myths, & mysteries of three types of unique bifunctional glycosyltransferases DeAngelis, PL, Zimmer, J	Glycobiology	2023