HAS1

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	Wikidata
View/Edit Human

Hyaluronan synthase 1 is an enzyme that in humans is encoded by the HAS1 gene.^[1]^[2]

Structure

Hyaluronan or hyaluronic acid (HA) 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. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded via ABC-transporter into the extracellular space.^[3]

Function

It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. 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.^[2]

References

↑ Spicer AP, Seldin MF, Olsen AS, Brown N, Wells DE, Doggett NA, Itano N, Kimata K, Inazawa J, McDonald JA (Jul 1997). "Chromosomal localization of the human and mouse hyaluronan synthase genes". Genomics. 41 (3): 493–7. doi:10.1006/geno.1997.4696. PMID 9169154.
↑ ^2.0 ^2.1 "Entrez Gene: HAS1 hyaluronan synthase 1".
↑ Schulz T, Schumacher U, Prehm P (July 2007). "Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP". J. Biol. Chem. 282 (29): 20999–1004. doi:10.1074/jbc.M700915200. PMID 17540771.

Spicer AP, Nguyen TK (1999). "Mammalian hyaluronan synthases: investigation of functional relationships in vivo". Biochem. Soc. Trans. 27 (2): 109–15. PMID 10093717.
Mian N (1987). "Analysis of cell-growth-phase-related variations in hyaluronate synthase activity of isolated plasma-membrane fractions of cultured human skin fibroblasts". Biochem. J. 237 (2): 333–42. PMC 1146992. PMID 3099751.
Itano N, Kimata K (1996). "Molecular cloning of human hyaluronan synthase". Biochem. Biophys. Res. Commun. 222 (3): 816–20. doi:10.1006/bbrc.1996.0827. PMID 8651928.
Shyjan AM, Heldin P, Butcher EC, et al. (1996). "Functional cloning of the cDNA for a human hyaluronan synthase". J. Biol. Chem. 271 (38): 23395–9. doi:10.1074/jbc.271.38.23395. PMID 8798544.
Simpson MA, Wilson CM, Furcht LT, et al. (2002). "Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells". J. Biol. Chem. 277 (12): 10050–7. doi:10.1074/jbc.M110069200. PMID 11790779.
Calabro A, Oken MM, Hascall VC, Masellis AM (2002). "Characterization of hyaluronan synthase expression and hyaluronan synthesis in bone marrow mesenchymal progenitor cells: predominant expression of HAS1 mRNA and up-regulated hyaluronan synthesis in bone marrow cells derived from multiple myeloma patients". Blood. 100 (7): 2578–85. doi:10.1182/blood-2002-01-0030. PMID 12239172.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Adamia S, Crainie M, Kriangkum J, et al. (2003). "Abnormal expression of hyaluronan synthases in patients with Waldenstrom's macroglobulimenia". Semin. Oncol. 30 (2): 165–8. doi:10.1053/sonc.2003.50042. PMID 12720129.
Suzuki K, Yamamoto T, Usui T, et al. (2004). "Expression of hyaluronan synthase in intraocular proliferative diseases: regulation of expression in human vascular endothelial cells by transforming growth factor-beta". Jpn. J. Ophthalmol. 47 (6): 557–64. doi:10.1016/j.jjo.2003.09.001. PMID 14636845.
Adamia S, Reiman T, Crainie M, et al. (2005). "Intronic splicing of hyaluronan synthase 1 (HAS1): a biologically relevant indicator of poor outcome in multiple myeloma". Blood. 105 (12): 4836–44. doi:10.1182/blood-2004-10-3825. PMC 1894997. PMID 15731173.
Yabushita H, Kishida T, Fusano K, et al. (2005). "Role of hyaluronan and hyaluronan synthase in endometrial cancer". Oncol. Rep. 13 (6): 1101–5. doi:10.3892/or.13.6.1101. PMID 15870928.
Stuhlmeier KM, Pollaschek C (2006). "Adenovirus-mediated gene transfer of mutated IkappaB kinase and IkappaBalpha reveal NF-kappaB-dependent as well as NF-kappaB-independent pathways of HAS1 activation". J. Biol. Chem. 280 (52): 42766–73. doi:10.1074/jbc.M503374200. PMID 16258173.
Grskovic B, Pollaschek C, Mueller MM, Stuhlmeier KM (2006). "Expression of hyaluronan synthase genes in umbilical cord blood stem/progenitor cells". Biochim. Biophys. Acta. 1760 (6): 890–5. doi:10.1016/j.bbagen.2006.02.002. PMID 16564133.
Kao JJ (2007). "The NF-kappaB inhibitor pyrrolidine dithiocarbamate blocks IL-1beta induced hyaluronan synthase 1 (HAS1) mRNA transcription, pointing at NF-kappaB dependence of the gene HAS1". Exp. Gerontol. 41 (6): 641–7. doi:10.1016/j.exger.2006.04.003. PMID 16723203.
Campo GM, Avenoso A, Campo S, et al. (2007). "TNF-alpha, IFN-gamma, and IL-1beta modulate hyaluronan synthase expression in human skin fibroblasts: synergistic effect by concomital treatment with FeSO4 plus ascorbate". Mol. Cell. Biochem. 292 (1–2): 169–78. doi:10.1007/s11010-006-9230-7. PMID 16786194.
Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
Meran S, Thomas D, Stephens P, et al. (2007). "Involvement of hyaluronan in regulation of fibroblast phenotype". J. Biol. Chem. 282 (35): 25687–97. doi:10.1074/jbc.M700773200. PMID 17611197.
Kyossev Z, Weigel PH (2007). "An enzyme capture assay for analysis of active hyaluronan synthases". Anal. Biochem. 371 (1): 62–70. doi:10.1016/j.ab.2007.08.025. PMID 17904513.

[pmid9169154-1] Spicer AP, Seldin MF, Olsen AS, Brown N, Wells DE, Doggett NA, Itano N, Kimata K, Inazawa J, McDonald JA (Jul 1997). "Chromosomal localization of the human and mouse hyaluronan synthase genes". Genomics. 41 (3): 493–7. doi:10.1006/geno.1997.4696. PMID 9169154.

[entrez-2] 2.0 ^2.1 "Entrez Gene: HAS1 hyaluronan synthase 1".

[pmid17540771-3] Schulz T, Schumacher U, Prehm P (July 2007). "Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP". J. Biol. Chem. 282 (29): 20999–1004. doi:10.1074/jbc.M700915200. PMID 17540771.

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[2]

[3]

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

HAS1

Contents

Structure

Function

References

Further reading

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