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Gene Review

Has1  -  hyaluronan synthase1

Mus musculus

Synonyms: HA synthase 1, Has, Hyaluronan synthase 1, Hyaluronate synthase 1, Hyaluronic acid synthase 1
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Disease relevance of Has1

  • The structure and organization of mouse hyaluronan synthase 1 gene, HAS1 were determined by direct sequencing of lambda phage clones carrying the entire gene and by application of the long and accurate (LA)-PCR method to amplify regions encompassing the exon-intron boundaries and all of the exons [1].
  • The deduced protein sequence of Xenopus DG42 shows similarity to Rhizobium Nod C, Streptococcus Has A, and fungal chitin synthases [2].
  • Lung metastasis after i.v. injection of HAS1 transfectants was also recovered significantly [3].
  • Subcutaneous injection of SCID mice with hyaluronan synthase (HAS) antisense-transfected cells produced tumors threefold to fourfold smaller than control transfectants [4].
  • No contribution of the Has system to heme utilization was observed in either E. coli or Y. pestis under the conditions we tested [5].

High impact information on Has1

  • Other experiments demonstrate that expression of DG42 under plasmid control in mouse 3T3 cells gives rise to chitooligosaccharide synthase activity without an increase in HA synthase level [2].
  • In vertebrates, hyaluronan biosynthesis is regulated by three transmembrane catalytic enzymes denoted Has1, Has2 and Has3 [6].
  • Expression of mouse hyaluronan synthase 1 (HAS1) by transfection into HAS- cells defective in hyaluronan synthase activity rescued hyaluronan matrix formation as well as hyaluronan production [3].
  • CD8{alpha}beta Has Two Distinct Binding Modes of Interaction with Peptide-Major Histocompatibility Complex Class I [7].
  • CD43 Deficiency Has No Impact in Competitive In Vivo Assays of Neutrophil or Activated T Cell Recruitment Efficiency [8].

Chemical compound and disease context of Has1


Biological context of Has1


Anatomical context of Has1

  • After E8.5, Has1 expression disappears, but Has2 continues to be strongly, albeit transiently, expressed in numerous tissues, including the branchial arches and craniofacial structures such as the palatal shelves and lens pit [14].
  • The maximal amount of the upregulated Has1 mRNA in keratinocytes at 2 h after stimulation decreased time-dependently to the nonstimulated level at 18 h, although the stimulation for 18 h of fibroblasts was effective on the expression of both Has mRNA [15].
  • Therefore, HAS cDNA is responsible for the activity of the hyaluronan synthase, a key enzyme of hyaluronan synthesis in eukaryotic cells [11].
  • HAS-, a mouse mammary carcinoma mutant cell line, which is defective in hyaluronan synthase activity, was first established and used as a recipient for the expression cloning [11].
  • Expression regulation of hyaluronan synthase in corneal endothelial cells [16].

Associations of Has1 with chemical compounds


Other interactions of Has1

  • Our results indicate that, whereas Has2 is exclusively expressed in some tissues, its expression pattern overlaps and/or complements that of Has1 and Has3 in others [14].
  • The 52 kDa protein cross-reacted with poly- and monoclonal antibodies raised against the streptococcal hyaluronate synthase and the 60 kDa protein was recognized by monoclonal antibodies raised against a hyaluronate receptor [17].
  • We examined the expression pattern of hyaluronan synthase (HAS) mRNAs in the uterine cervix of pregnant mice [18].

Analytical, diagnostic and therapeutic context of Has1


  1. The gene structure and promoter sequence of mouse hyaluronan synthase 1. Yamada, Y., Itano, N., Zako, M., Yoshida, M., Lenas, P., Niimi, A., Ueda, M., Kimata, K. Biochem. J. (1998) [Pubmed]
  2. Homologs of the Xenopus developmental gene DG42 are present in zebrafish and mouse and are involved in the synthesis of Nod-like chitin oligosaccharides during early embryogenesis. Semino, C.E., Specht, C.A., Raimondi, A., Robbins, P.W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Relationship between hyaluronan production and metastatic potential of mouse mammary carcinoma cells. Itano, N., Sawai, T., Miyaishi, O., Kimata, K. Cancer Res. (1999) [Pubmed]
  4. Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised mice. Simpson, M.A., Wilson, C.M., McCarthy, J.B. Am. J. Pathol. (2002) [Pubmed]
  5. Identification and characterization of the hemophore-dependent heme acquisition system of Yersinia pestis. Rossi, M.S., Fetherston, J.D., Létoffé, S., Carniel, E., Perry, R.D., Ghigo, J.M. Infect. Immun. (2001) [Pubmed]
  6. XHas2 activity is required during somitogenesis and precursor cell migration in Xenopus development. Ori, M., Nardini, M., Casini, P., Perris, R., Nardi, I. Development (2006) [Pubmed]
  7. CD8{alpha}beta Has Two Distinct Binding Modes of Interaction with Peptide-Major Histocompatibility Complex Class I. Chang, H.C., Tan, K., Hsu, Y.M. J. Biol. Chem. (2006) [Pubmed]
  8. CD43 Deficiency Has No Impact in Competitive In Vivo Assays of Neutrophil or Activated T Cell Recruitment Efficiency. Carlow, D.A., Ziltener, H.J. J. Immunol. (2006) [Pubmed]
  9. A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells. Yoshihara, S., Kon, A., Kudo, D., Nakazawa, H., Kakizaki, I., Sasaki, M., Endo, M., Takagaki, K. FEBS Lett. (2005) [Pubmed]
  10. The W-Beijing Lineage of Mycobacterium tuberculosis Overproduces Triglycerides and Has the DosR Dormancy Regulon Constitutively Upregulated. Reed, M.B., Gagneux, S., Deriemer, K., Small, P.M., Barry, C.E. J. Bacteriol. (2007) [Pubmed]
  11. Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase. Itano, N., Kimata, K. J. Biol. Chem. (1996) [Pubmed]
  12. Gene expression, synthesis and degradation of hyaluronan during differentiation of 3T3-L1 adipocytes. Allingham, P.G., Brownlee, G.R., Harper, G.S., Pho, M., Nilsson, S.K., Brown, T.J. Arch. Biochem. Biophys. (2006) [Pubmed]
  13. Intracellular signal transduction for serum activation of the hyaluronan synthase in eukaryotic cell lines. Klewes, L., Prehm, P. J. Cell. Physiol. (1994) [Pubmed]
  14. Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns. Tien, J.Y., Spicer, A.P. Dev. Dyn. (2005) [Pubmed]
  15. Putative hyaluronan synthase mRNA are expressed in mouse skin and TGF-beta upregulates their expression in cultured human skin cells. Sugiyama, Y., Shimada, A., Sayo, T., Sakai, S., Inoue, S. J. Invest. Dermatol. (1998) [Pubmed]
  16. Expression regulation of hyaluronan synthase in corneal endothelial cells. Usui, T., Amano, S., Oshika, T., Suzuki, K., Miyata, K., Araie, M., Heldin, P., Yamashita, H. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  17. The hyaluronate synthase from a eukaryotic cell line. Klewes, L., Turley, E.A., Prehm, P. Biochem. J. (1993) [Pubmed]
  18. Regulation of hyaluronan synthases in mouse uterine cervix. Uchiyama, T., Sakuta, T., Kanayama, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  19. Molecular cloning and characterization of a putative mouse hyaluronan synthase. Spicer, A.P., Augustine, M.L., McDonald, J.A. J. Biol. Chem. (1996) [Pubmed]
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