Three independently expressed hyaluronan synthase genes have been identified in the human genome. HAS2 is present in chromosome 8q24.12, while HAS1 and HAS3 have been identified to loci 19q13.4 and 16q22.1 respectively.

The HAS2 gene encodes for a 552 amino acid product comprised of 4 exons. Translation starts at the first nucleotide of exon 2 while a discrete 5-untranslated region (UTR) is formed in exon 1.

Hyaluronan is catalyzed by three membrane-embedded HA synthases, although HAS2 is the only essential gene. The isozymes are coded by 3 separate genes that, although related, are unlinked in the chromosome. Regulation occurs at transcription, post-translational levels, as well as, by alternative splicing, differential sub-cellular localization and epigenetic processes. Hyaluronan deposits in the extracellular matrix have been associated with a variety of cellular processes such as motility, adhesion, division, morphogenesis, wound healing and vascular development. HAS2 overexpression, as well as, amplification of locus 8q24.12, has been implicated in tumor proliferation and metastasis in genitourinary tumors. Recently, the degree to which HA synthases can overexpressed has suggested the likelihood the gene may play contradicting roles as tumor suppressor and oncogene.

HAS2, a member of the glycosyl transferase family 2 proteins, is a multipass transmembrane protein that catalyses the polymerization of the integral extrecellular matrix component Hyaluronic acid from intracellular UDP-esterified precursor, resulting in glucuronic acid and N-acetylglucosamine dissacharide motifs.

HAS2 is one of the three characterized HA synthases responsible for the polymerization of Hyaluronic Acid in the extracellular matrix and is the only essential gene of the family. Although all three isozymes are equally capable of synthesizing HA polymers, it has been shown that HAS2 is the main HA synthase polymerizing long hyaluronan chains of MW ~2x10⁶ Daltons.

The extent of HAS2 expression and catalytic activity has been linked to specific interactions between the extracellular hyaluronan and the HA receptors, CD44 and RHAMM, distributed in the plasma membrane. The underlying signaling pathways regulating HAS2 expression have not been fully characterized. A number of distinctively regulated factors have been associated with HA deposition and HAS2 expression such as IL-1beta, NF-kappaB, all-trans-Retinoic Acid, SP1, Ras, TGF-beta1 among many others.

HAS2 is localized in the plasma membrane as a multipass transmembrane protein. Although it has been suggested the human HAS2 may share the same proposed topological domains as its bacterial counterpart, the extent to which this statement trully represents its actual architecture has not yet been shown.

Hyaluronan synthase 2 is responsible for the synthesis and deposition of hyaluronan in the extracellular matrix. HAS2 is a member of the glycosyl transferase 2 protein family and catalyses the addition of UDP-esterified residues, to form glucuronic acid and N-acetylglucosamine dissacharide motifs present in HA molecules. Interactions between plasma membrane embedded HA receptors with hyaluronan in the cellular matrix have been suggested to either induce or repress HAS2s catalytic activity. The presence of hyaluronan in the extracellular matrix has been linked to a great number of vital cellular processes such cell division, motility and morphogenesis, among many others. HAS2 is either an oncogene or a tumor suppressor depending on the concentration and length of HA products deposited in the extracellular matrix. Long HA chains of high molecular weight in high concentrations have been linked with supressing angiogenesis and tumor proliferation, whereas 2-3 fold HAS2 overexpression has been implicated in the proliferation and metastasis in various genitourinary tumor types.

A total of 3 mammalian HAS genes have been isolated and identified (HAS1, HAS2, HAS3). Although they share similar amino acid sequences and structural conformations, each isozyme present different spacial and temporal expression patterns, molecular stability, kinetic properties and ability of yielding hyaluronan chains different in length and concentration.

Developmental studies have described mutations disrupting HAS2 synthesis as embryonic lethal. Such mutations prevent cardiac endothelial to mesenchymal transition, resulting in failed heart morphogenesis.