HAS2

Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS2 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to glycosaminoglycan synthetase (DG42) from Xenopus laevis, and human and murine hyaluronan synthase 1.

Full Name

Hyaluronan Synthase 2

Function

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. Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development. 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 (By similarity).

Biological Process

Atrioventricular canal development Source: UniProtKB
Bone morphogenesis Source: Ensembl
Cellular response to fluid shear stress Source: BHF-UCL
Cellular response to interleukin-1 Source: BHF-UCL
Cellular response to platelet-derived growth factor stimulus Source: UniProtKB
Cellular response to tumor necrosis factor Source: BHF-UCL
Endocardial cushion to mesenchymal transition Source: UniProtKB
Estrous cycle Source: Ensembl
Extracellular matrix assembly Source: UniProtKB
Extracellular polysaccharide biosynthetic process Source: UniProtKB
Hyaluronan biosynthetic process Source: UniProtKB
Kidney development Source: UniProtKB
Positive regulation of cell migration Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of hyaluronan biosynthetic process Source: Ensembl
Positive regulation of keratinocyte migration Source: Ensembl
Positive regulation of keratinocyte proliferation Source: Ensembl
Positive regulation of monocyte aggregation Source: BHF-UCL
Positive regulation of smooth muscle cell migration Source: Ensembl
Positive regulation of substrate adhesion-dependent cell spreading Source: Ensembl
Positive regulation of urine volume Source: UniProtKB
Regulation of extracellular matrix assembly Source: Ensembl
Renal water absorption Source: UniProtKB
Vasculogenesis Source: UniProtKB

Cellular Location

Membrane

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.

Topology

Cytoplasmic: 1-11
Helical: 12-32
Extracellular: 33-45
Helical: 46-66
Cytoplasmic: 67-374
Helical: 375-395
Extracellular: 396-402
Helical: 403-423
Cytoplasmic: 424-429
Helical: 430-450
Extracellular: 451-475
Helical: 476-496
Cytoplasmic: 497-510
Helical: 511-531
Extracellular: 532-552