HGNC Approved Gene Symbol: HAS3
Cytogenetic location: 16q22.1 Genomic coordinates (GRCh38): 16:69,083,484-69,118,719 (from NCBI)
For background information on hyaluronan (HA) and HA synthases, such as HAS3, see HAS1 (601463).
By degenerate PCR, Spicer et al. (1997) isolated a genomic fragment of human HAS3 and genomic and cDNA clones of mouse Has3. The amino acid sequences encoded by the partial human HAS3 fragment and the corresponding region of mouse Has3 are 99% conserved. The authors noted that the high degree of sequence conservation between specific human and mouse HASs contrasts with the lower level of identity between HASs within a species, suggesting an evolutionary conservation of functionally important residues and differences in the mode of action of the various HASs. The predicted 554-amino acid mouse Has3 protein has several consensus HA-binding motifs and multiple transmembrane domains, with 2 at the N terminus and a cluster at the C terminus. Northern blot analysis of the mouse embryo showed that Has3 is predominantly expressed at late gestation as a major, approximately 6.0- to 6.5-kb transcript and a minor, approximately 4.0-kb transcript.
Monslow et al. (2003) identified a splice variant of human HAS3.
Spicer et al. (1997) found that expression of mouse Has3 in COS-1 cells led to high levels of HA biosynthesis.
Monslow et al. (2003) determined that the HAS3 gene has 4 exons and spans about 12.5 kb. Exons 1 and 4 are subject to alternative splicing. HAS3 has 2 promoter regions, and the 500-bp region upstream of each transcription start site contains either 46 or 56 transcription factor-binding sites. Upstream of exon 1 is a (GT)n repeat sequence.
By PCR screening somatic cell hybrid DNAs and a YAC contig, Spicer et al. (1997) localized the human HAS3 gene to chromosome 16q22.1. By interspecific backcross analysis, they mapped the mouse Has3 gene to chromosome 8. Since HAS1 (601463), HAS2 (601636), and HAS3 are located on different autosomes, Spicer et al. (1997) suggested that the HAS gene family arose comparatively early in vertebrate evolution by sequential duplication of an ancestral HAS gene.
Monslow, J., Williams, J. D., Norton, N., Guy, C. A., Price, I. K., Coleman, S. L., Williams, N. M., Buckland, P. R., Spicer, A. P., Topley, N., Davies, M., Bowen, T. The human hyaluronan synthase genes: genomic structures, proximal promoters and polymorphic microsatellite markers. Int. J. Biochem. Cell Biol. 35: 1272-1283, 2003. [PubMed: 12757764] [Full Text: https://doi.org/10.1016/s1357-2725(03)00048-7]
Spicer, A. P., Olson, J. S., McDonald, J. A. Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase. J. Biol. Chem. 272: 8957-8961, 1997. [PubMed: 9083017] [Full Text: https://doi.org/10.1074/jbc.272.14.8957]
Spicer, A. P., Seldin, M. F., Olsen, A. S., Brown, N., Wells, D. E., Doggett, N. A., Itano, N., Kimata, K., Inazawa, J., McDonald, J. A. Chromosomal localization of the human and mouse hyaluronan synthase genes. Genomics 41: 493-497, 1997. [PubMed: 9169154] [Full Text: https://doi.org/10.1006/geno.1997.4696]