Hyaluronan synthase 2 is an enzyme that in humans is encoded by the HAS2gene.[1][2]
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. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. Hyaluronic acid is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded via ABC-Transporter[3] into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. Hyaluronic acid is produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of hyaluronic acid are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of hyaluronic acid with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of hyaluronic acid receptors has been correlated with tumor metastasis. HAS2 is a member of the vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to glycosaminoglycan synthetase (DG42) from Xenopus laevis, and human and murine hyaluronan synthase 1.[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. PMID9169154.
↑Schulz,T.; Schumacher,U.; Prehm,P. Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. J.Biol.Chem.282,20999-21004
Watanabe K, Yamaguchi Y (1996). "Molecular identification of a putative human hyaluronan synthase". J. Biol. Chem. 271 (38): 22945–8. doi:10.1074/jbc.271.38.22945. PMID8798477.
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. PMID11790779.
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. PMID14636845.
Sussmann M, Sarbia M, Meyer-Kirchrath J, et al. (2004). "Induction of hyaluronic acid synthase 2 (HAS2) in human vascular smooth muscle cells by vasodilatory prostaglandins". Circ. Res. 94 (5): 592–600. doi:10.1161/01.RES.0000119169.87429.A0. PMID14752026.
Monslow J, Williams JD, Guy CA, et al. (2004). "Identification and analysis of the promoter region of the human hyaluronan synthase 2 gene". J. Biol. Chem. 279 (20): 20576–81. doi:10.1074/jbc.M312666200. PMID14988410.
Morerio C, Rapella A, Rosanda C, et al. (2005). "PLAG1-HAS2 fusion in lipoblastoma with masked 8q intrachromosomal rearrangement". Cancer Genet. Cytogenet. 156 (2): 183–4. doi:10.1016/j.cancergencyto.2004.04.017. PMID15642402.
Ducale AE, Ward SI, Dechert T, Yager DR (2005). "Regulation of hyaluronan synthase-2 expression in human intestinal mesenchymal cells: mechanisms of interleukin-1beta-mediated induction". Am. J. Physiol. Gastrointest. Liver Physiol. 289 (3): G462–70. doi:10.1152/ajpgi.00494.2004. PMID15677552.
Saavalainen K, Pasonen-Seppänen S, Dunlop TW, et al. (2005). "The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal growth factor responding gene". J. Biol. Chem. 280 (15): 14636–44. doi:10.1074/jbc.M500206200. PMID15722343.
Chao H, Spicer AP (2005). "Natural antisense mRNAs to hyaluronan synthase 2 inhibit hyaluronan biosynthesis and cell proliferation". J. Biol. Chem. 280 (30): 27513–22. doi:10.1074/jbc.M411544200. PMID15843373.
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. PMID16564133.
Monslow J, Williams JD, Fraser DJ, et al. (2006). "Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene". J. Biol. Chem. 281 (26): 18043–50. doi:10.1074/jbc.M510467200. PMID16603733.
Selbi W, Day AJ, Rugg MS, et al. (2007). "Overexpression of hyaluronan synthase 2 alters hyaluronan distribution and function in proximal tubular epithelial cells". J. Am. Soc. Nephrol. 17 (6): 1553–67. doi:10.1681/ASN.2005080879. PMID16687630.
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. PMID16786194.
Cook AC, Chambers AF, Turley EA, Tuck AB (2006). "Osteopontin induction of hyaluronan synthase 2 expression promotes breast cancer malignancy". J. Biol. Chem. 281 (34): 24381–9. doi:10.1074/jbc.M602694200. PMID16807238.
Klewer SE, Yatskievych T, Pogreba K, Stevens MV, Antin PB, Camenisch TD (2006). "Has2 expression in heart forming regions is independent of BMP signaling". Gene Expr Patterns. 6 (5): 462–70. doi:10.1016/j.modgep.2005.11.005. PMID16458617.
Camenisch TD, Schroeder JA, Bradley J, Klewer SE, McDonald JA (2002). "Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors". Nat. Med. 8 (8): 850–5. doi:10.1038/nm742. PMID12134143.
