HAS1

Hyaluronan synthase 1 is an enzyme that in humans is encoded by the HAS1 gene.

HAS1
Identifiers
Aliases	HAS1, HAS, hyaluronan synthase 1
External IDs	OMIM: 601463; MGI: 106590; HomoloGene: 1165; GeneCards: HAS1; OMA:HAS1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.41 Start 51,713,112 bp End 51,723,991 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 A3.2|17 10.53 cM Start 18,063,585 bp End 18,075,467 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle parietal pleura vena cava germinal epithelium right ovary synovial joint left ovary synovial membrane pericardium middle temporal gyrus Top expressed in ankle joint ankle genital tubercle tail of embryo embryo facial motor nucleus trachea aortic valve submandibular gland ascending aorta More reference expression data BioGPS More reference expression data
Gene ontology Molecular function glycosyltransferase activity transferase activity hyaluronan synthase activity protein binding identical protein binding Cellular component cytoplasm integral component of membrane plasma membrane integral component of plasma membrane membrane Biological process cell adhesion negative regulation of fibroblast migration hyaluronan biosynthetic process cellular response to platelet-derived growth factor stimulus extracellular matrix assembly glycosaminoglycan biosynthetic process extracellular polysaccharide biosynthetic process estrous cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3036 15116 Ensembl ENSG00000105509 ENSMUSG00000003665 UniProt Q92839 Q61647 RefSeq (mRNA) NM_001297436 NM_001523 NM_008215 RefSeq (protein) NP_001284365 NP_001514 NP_032241 Location (UCSC) Chr 19: 51.71 – 51.72 Mb Chr 17: 18.06 – 18.08 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

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.

Further reading

• Spicer AP, Nguyen TK (1999). "Mammalian hyaluronan synthases: investigation of functional relationships in vivo". Biochem. Soc. Trans. 27 (2): 109–15. doi:10.1042/bst0270109. 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. doi:10.1042/bj2370333. 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. Bibcode:2002PNAS...9916899M. 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. S2CID 54406345.
• 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. S2CID 37598580.
• 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.