4.D.1.1.18
Hyaluronan synthase 2, HAS2, of 552 aas and 7 or 8 TMSs with 2 or 3 TMSs at the N-terminus and 5 TMSs at the C-terminus. It is 50% identical to HAS1 (TC# 4.D.1.1.10). It catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer and is essential to hyaluronan synthesis, a major component of most extracellular matrices. It plays a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. Autophagic degradation of HAS2 in endothelial cells provides a mechanism for the regulation of angiogenesis (Chen et al. 2020).  This is one of three isoenzymes responsible for cellular hyaluronan synthesis, and it is responsible for the synthesis of high molecular mass hyaluronan. It is produced in increased amounts in the mole rat where it extends life span and decreases the incidence of cancer. "Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and possibly to the longevity of the longest-lived rodent-the naked mole-rat (Zhang et al. 2023).