Hyaluronan synthase 2
Function
Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer (Probable) (PubMed:20507985, PubMed:21228273, PubMed:23303191, PubMed:32993960). 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 (PubMed:20507985, PubMed:21228273, PubMed:8798477). This is one of three isoenzymes responsible for cellular hyaluronan synthesis and it is particularly responsible for the synthesis of high molecular mass hyaluronan (By similarity).
Involvement in disease
A chromosomal aberration involving HAS2 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1 intrachromosomal rearrangement with PLAG1.
Pathway
Glycan biosynthesis; hyaluronan biosynthesis.
Post-translational modifications
Phosphorylation at Thr-328 is essential for hyaluronan synthase activity (PubMed:32993960). Phosphorylation at Thr-110 is required for transport from ER to Golgi (PubMed:30394292).
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 (PubMed:20507985). Deubiquitinated by USP17 and USP4. 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 (PubMed:28604766).
Sequence Similarities
Belongs to the NodC/HAS family.
Tissue Specificity
Expressed in fibroblasts.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Vesicle
- Golgi apparatus membrane
- Multi-pass membrane protein
- Lysosome
- Travels from endoplasmic reticulum (ER), Golgi to plasma membrane and either back to endosomes and lysosomes, or out into extracellular vesicles (PubMed:30394292). Post-translational modifications control HAS2 trafficking (PubMed:30394292).
Alternative names
Hyaluronan synthase 2, Hyaluronate synthase 2, Hyaluronic acid synthase 2, HA synthase 2, HAS2