Hyaluronidase-2 (HYAL2)

Hyaluronidase-2 (HYAL2) is a weak acid-active, glycosylphosphatidylinositol-anchored cell surface enzyme that catalyzes the initial step in hyaluronan degradation, breaking down this major extracellular matrix glycosaminoglycan into smaller fragments for subsequent lysosomal degradation by other enzymes[1][3]. While HYAL2 has limited intrinsic hyaluronidase activity, it also has non-enzymatic functions such as modulating the cellular pericellular coat (glycocalyx) and influencing cell motility through interaction with the principal hyaluronan receptor CD44 and associated cytoskeletal proteins (ERM family)[2]. HYAL2 serves as a cell surface receptor for the oncogenic Jaagsiekte sheep retrovirus and is considered a putative tumor suppressor gene, with its loss or reduction implicated in cancer pathogenesis[1]. Mutations in HYAL2 are also linked to Hyal2 deficiency syndromes. The gene resides in a chromosome region associated with tumor suppression and is structurally related to other hyaluronidases[1][3].

Other names

LUCA2Hyal-2Hyaluronoglucosaminidase-2Lung carcinoma protein 2Lysosomal hyaluronidasePH-20 homologMCCS

Enzymatic degradation of hyaluronan (limited, primarily at acidic pH); Modulation of CD44-mediated signaling and cytoskeletal interactions, impacting cell motility.