Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction and it is particularly responsible for the synthesis of high molecular mass hyaluronan (PubMed:10455188). Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development (PubMed:10930438). May also play a role in vasculogenesis. High molecular mass hyaluronan also play a role in early contact inhibition a process which stops cell growth when cells come into contact with each other or the extracellular matrix. Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation (By similarity). This is one of three isoenzymes responsible for cellular hyaluronan synthesis and it is particularly responsible for the synthesis of high molecular mass hyaluronan (PubMed:10455188). [hyaluronan](n) + UDP-N-acetyl-alpha-D-glucosamine = H(+) + N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP N-acetyl-beta-D-glucosaminyl-(1->4)-[hyaluronan](n) + UDP-alpha-D-glucuronate = [hyaluronan](n+1) + H(+) + UDP Glycan biosynthesis; hyaluronan biosynthesis. Homodimer; dimerization promotes enzymatic activity. Forms heterodimer with HAS3. Forms heterodimer with HAS1. Travels from endoplasmic reticulum (ER), Golgi to plasma membrane and either back to endosomes and lysosomes, or out into extracellular vesicles. Post-translational modifications control HAS2 trafficking. Expressed in heart, brain, spleen, lung and skeletal muscle. Detected from 7.5 dpc through birth. At 8.5 dpc, predominantly expressed in the epithelium of the foregut diverticulum, the cephalic mesenchyme, the allantois, and in the myocardium and endocardium of the heart. At 9.5 dpc, prominent expression is detected in cephalic, foregut and periaortic mesenchymes, the septum transversum and the cardiovascular system. Also present in the atrial and ventricular endothelium and the myocardium of the atrioventricular canal region. By 10.5 dpc, highly expressed in endothelial cells in the atrioventricular canal and outflow tract that transform into mesenchymal cells and invade the underlying matrix. Later, expressed by mesenchymal cells during elevation of the secondary palate and by hypertrophic chondrocytes within epiphysial growth plates. Phosphorylation at Thr-328 is essential for hyaluronan synthase activity. O-GlcNAcylation at Ser-221 increases the stability of HAS2 and plasma membrane localization. Ubiquitination at Lys-190; this ubiquitination is essential for hyaluronan synthase activity and homo- or hetero-oligomerization. Can also be poly-ubiquitinated. Deubiquitinated by USP17L22/USP17 and USP4. USP17L22/USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked polyubiquitin chains, whereas USP4 preferentially removes monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked polyubiquitin chain. Embryonic lethal. At day 9.5 dpc, the distribution of homozygous embryos approaches Mendelian frequency while only occasional viable embryos were found at 10.5 dpc. Embryos exhibited growth retardation, scant numbers of red blood cells, and lacked vitelline vessels in the yolk sac. The visceral endoderm and mesoderm forming the yolk sac was not fused except at discrete foci. The heart was thinwalled and relatively bloodless, and often exhibited marked pericardial swelling. The heart lacks cardiac jelly, endocardial cushions and trabeculae. A marked reduction in vessels in homozygous embryos is also observed. Somites were present but distorted. Some of the 9.5 dpc embryos had failed to turn, and exhibited posterior defects as well as cephalic mesenchyme abnormalities. Belongs to the NodC/HAS family. an unexpected turn of events - Issue 155 of December 2013