HAS2
Hyaluronan synthase 2 is an enzyme that in humans is encoded by the HAS2 gene.[1][2]
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[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. 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. HAS2 is a member of the newly identified 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. PMID 9169154.
- ↑ 2.0 2.1 "Entrez Gene: HAS2 hyaluronan synthase 2".
- ↑ 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
- Spicer AP, Nguyen TK (1999). "Mammalian hyaluronan synthases: investigation of functional relationships in vivo". Biochem. Soc. Trans. 27 (2): 109–15. PMID 10093717.
- 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. PMID 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): 10050–7. doi:10.1074/jbc.M110069200. PMID 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): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 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): 557–64. doi:10.1016/j.jjo.2003.09.001. PMID 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): 592–600. doi:10.1161/01.RES.0000119169.87429.A0. PMID 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): 20576–81. doi:10.1074/jbc.M312666200. PMID 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): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 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): 183–4. doi:10.1016/j.cancergencyto.2004.04.017. PMID 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): G462–70. doi:10.1152/ajpgi.00494.2004. PMID 15677552.
- 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. PMID 15722343.
- 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. PMID 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): 194–203. doi:10.1016/j.yexcr.2005.03.026. PMC 3182490. PMID 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): 890–5. doi:10.1016/j.bbagen.2006.02.002. PMID 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): 18043–50. doi:10.1074/jbc.M510467200. PMID 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): 1553–67. doi:10.1681/ASN.2005080879. PMID 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 (1–2): 169–78. doi:10.1007/s11010-006-9230-7. PMID 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): 24381–9. doi:10.1074/jbc.M602694200. PMID 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): 462–70. doi:10.1016/j.modgep.2005.11.005. PMID 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): 850–5. doi:10.1038/nm742. PMID 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): 349–60. doi:10.1172/JCI10272. PMC 314332. PMID 10930438.
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