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HAS2
Introduction
Hyaluronan synthase 2 is an enzyme that in humans is encoded by the HAS2 gene.[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
References
- β 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): 493β7. doi:10.1006/geno.1997.4696. PMIDΒ 9169154.
- β 2.0 2.1 “Entrez Gene: HAS2 hyaluronan synthase 2”.
- β 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
Further reading
Further reading
- Spicer AP, Nguyen TK (1999). “Mammalian hyaluronan synthases: investigation of functional relationships in vivo”. Biochem. Soc. Trans. 27 (2): 109β15. PMIDΒ 10093717.
- Watanabe K, Yamaguchi Y (1996). “Molecular identification of a putative human hyaluronan synthase”. J. Biol. Chem. 271 (38): 22945β8. doi:10.1074/jbc.271.38.22945. PMIDΒ 8798477.
- 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): 10050β7. doi:10.1074/jbc.M110069200. PMIDΒ 11790779.
- 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): 16899β903. doi:10.1073/pnas.242603899. PMCΒ 139241. PMIDΒ 12477932.
- 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): 557β64. doi:10.1016/j.jjo.2003.09.001. PMIDΒ 14636845.
- 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): 592β600. doi:10.1161/01.RES.0000119169.87429.A0. PMIDΒ 14752026.
- 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): 20576β81. doi:10.1074/jbc.M312666200. PMIDΒ 14988410.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). “The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)”. Genome Res. 14 (10B): 2121β7. doi:10.1101/gr.2596504. PMCΒ 528928. PMIDΒ 15489334.
- Morerio C, Rapella A, Rosanda C, et al. (2005). “PLAG1-HAS2 fusion in lipoblastoma with masked 8q intrachromosomal rearrangement”. Cancer Genet. Cytogenet. 156 (2): 183β4. doi:10.1016/j.cancergencyto.2004.04.017. PMIDΒ 15642402.
- 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): G462β70. doi:10.1152/ajpgi.00494.2004. PMIDΒ 15677552.
- Saavalainen K, Pasonen-SeppΓ€nen 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): 14636β44. doi:10.1074/jbc.M500206200. PMIDΒ 15722343.
- Chao H, Spicer AP (2005). “Natural antisense mRNAs to hyaluronan synthase 2 inhibit hyaluronan biosynthesis and cell proliferation”. J. Biol. Chem. 280 (30): 27513β22. doi:10.1074/jbc.M411544200. PMIDΒ 15843373.
- Nishida Y, Knudson W, Knudson CB, Ishiguro N (2005). “Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity”. Exp. Cell Res. 307 (1): 194β203. doi:10.1016/j.yexcr.2005.03.026. PMCΒ 3182490. PMIDΒ 15922739.
- 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): 890β5. doi:10.1016/j.bbagen.2006.02.002. PMIDΒ 16564133.
- 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): 18043β50. doi:10.1074/jbc.M510467200. PMIDΒ 16603733.
- 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): 1553β67. doi:10.1681/ASN.2005080879. PMIDΒ 16687630.
- 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 (1β2): 169β78. doi:10.1007/s11010-006-9230-7. PMIDΒ 16786194.
- 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): 24381β9. doi:10.1074/jbc.M602694200. PMIDΒ 16807238.
- 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): 462β70. doi:10.1016/j.modgep.2005.11.005. PMIDΒ 16458617.
- 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): 850β5. doi:10.1038/nm742. PMIDΒ 12134143.
- Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro A Jr, Kubalak S, Klewer SE, McDonald JA (2000). “Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme”. J Clin Invest. 106 (3): 349β60. doi:10.1172/JCI10272. PMCΒ 314332. PMIDΒ 10930438.
