Function: Receptor for hyaluronic acid (HA). Mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands such as osteopontin, collagens, and matrix metalloproteinases (MMPs). Adhesion with HA plays an important role in cell migration, tumor growth and progression. In cancer cells, may play an important role in invadopodia formation. Also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events. Ref.31
Subunit structure: Interacts with PKN2
By similarity. Interacts with HA, as well as other glycosaminoglycans, collagen, laminin, and fibronectin via its N-terminal segment. Interacts with ANK, the ERM proteins (VIL2, RDX and MSN), and NF2 via its C-terminal segment. Ref.41
Subcellular location: Membrane; Single-pass type I membrane protein. Note: Colocalizes with actin in membrane protrusions at wounding edges
By similarity.
Tissue specificity: Isoform 10 (epithelial isoform) is expressed by cells of epithelium and highly expressed by carcinomas. Expression is repressed in neuroblastoma cells.
Domain: The lectin-like LINK domain is responsible for hyaluronan binding
By similarity.
Post-translational modification: Proteolytically cleaved in the extracellular matrix by specific proteinases (possibly MMPs) in several cell lines and tumors. Ref.28N- and O-glycosylated. O-glycosylation contains more-or-less-sulfated chondroitin sulfate glycans, whose number may affect the accessibility of specific proteinases to their cleavage site(s). It is uncertain if O-glycosylation occurs on Thr-637 or Thr-638. Ref.28 Ref.39Phosphorylated; activation of PKC results in the dephosphorylation of Ser-706 (constitutive phosphorylation site), and the phosphorylation of Ser-672. Ref.26 Ref.27
Polymorphism: CD44 is responsible for the Indian blood group system. The molecular basis of the In(A)=In1/In(B)=In2 blood group antigens is a single variation in position 46; In(B), the most frequent allele, has Arg-46.
Sequence similarities: Contains 1 Link domain.
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