Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.
Subcellular locations: Nucleus, Cytoplasm, Endoplasmic reticulum, Cell membrane, Membrane, Clathrin-coated pit, Secreted
Retained in the endoplasmic reticulum (ER) in a HSPA5/BIP-dependent manner. Colocalized with clathrin heavy chain/CLTC in clathrin-coated vesicles. Strongly detected in the cytoplasm of breast carcinoma cells, whereas poorly detected in adjacent normal epithelial cells, stromal cells, or benign breast tissues. Localized in the nucleus and cytoplasm of colon adenocarcinomas.
Expressed in dermal and in synovial fibroblasts. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in both ductal carcinoma and invasive breast cancer cells compared with benign epithelial cells (at protein level). Strongly expressed in brain, placenta, prostate, breast, lung and testis. Expressed in fibroblasts, epithelial cells and cancer cells. In ear, it is specifically expressed in inner ear. Expressed in cochlea and vestibule tissues. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in colon adenocarcinomas compared with normal colonic mucosas. Strongly expressed in breast cancer as compared to normal breast tissue.