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Hyaluronan synthases (HAS) are membrane-bound enzymes that use UDP-α-N-acetyl-D-glucosamine and UDP-α-D-glucuronate as substrates to produce the glycosaminoglycan hyaluronan at the cell surface and extrude it through the membrane into the extracellular space.
Hyaluronan synthase 2 is an enzyme that in humans is encoded by the HAS2 gene. [5] [6]Hyaluronan or hyaluronic acid is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix.
Hyaluronic acid (/ ˌ h aɪ. ə l j ʊəˈr ɒ n ɪ k /; [1] [2] abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues.
HAS1 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase (DG42) from Xenopus laevis, and a recently described murine hyaluronan synthase. [6]
Hyaluronan synthase, that is a membrane-binding enzyme, is one of the factors that reduces the production of HA. Hyaluronan synthase limits hyaluronic acid production by affecting cell morphology. Hyaluronan synthase limits hyaluronic acid production by affecting cell morphology.
Hyaluronan synthase 3 is an enzyme that in humans is encoded by the HAS3 gene. [5] [6] [7]The protein encoded by this gene is involved in the synthesis of the unbranched glycosaminoglycan hyaluronan, or hyaluronic acid, which is a major constituent of the extracellular matrix.
The reason for this apparent contradiction is that both the accumulation of hyaluronic acid (due to increased hyaluronan synthase levels and decreased HYAL levels) and the degradation of hyaluronic acid into hyaluronic acid oligosaccharides by high HYAL levels result in increased tumor malignancy. [5]
Cell surface interactions involving hyaluronan are its well-known coupling with CD44, which may be related to tumor progression, and also with RHAMM (Hyaluronan-mediated motility receptor), which has been implicated in developmental processes, tumor metastasis, and pathological reparative processes.