CD44

CD44 is a type I transmembrane protein and a member of the cartilage link protein family. It is involved in cell-cell and cell-matrix interactions and signal transduction. Several CD44 ligands have been identified. The most extensively characterized ligand for CD44 is hyaluronan, a component of the extracellular matrix. CD44 protein is expressed on the majority of immune cells. The binding of CD44 to hyaluronan is induced on T lymphocytes after activation by antigen and on monocytes after stimulation by inflammatory agents. Under inflammatory conditions, CD44 on endothelial cells presents hyaluronan to CD44 on activated T lymphocytes and mediates a rolling interaction under flow conditions. Perturbations of the hyaluronan-CD44 interaction at the plasma membrane by various antagonists result in attenuation of receptor tyrosine kinase and transporter activities and inhibition of tumor progression in vivo.

CD44 Related Areas

Immunology>>Cluster of Differentiation>>CD44

CD44 Alternative Names

CD44, AL133330.1, CDW44, CSPG8, ECMR-III, HCELL, HUTCH-I, IN, LHR, MC56, MDU2, MDU3, MGC10468, MIC4, Pgp1 [Homo sapiens]

Cd44, RP23-203N8.3, AU023126, AW121933, AW146109, HERMES, Ly-24, Pgp-1 [Mus musculus]

Summaries for CD44

Entrez Gene summary for CD44:

The CD44 protein encoded by CD44 gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This CD44 protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this CD44 gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]

OMIM - description for CD44:

CD44 is an integral cell membrane glycoprotein with a postulated role in matrix adhesion lymphocyte activation and lymph node homing (Aruffo et al., 1990).

Wikipedia summary for CD44:

The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 gene.

Human CD44 Protein General Information

 

• Protein names: CD_antigen, Short Name=CD40
• Sequence length: 742 AA.
• Domain: The lectin-like LINK domain is responsible for hyaluronan binding
• Sequence similarities: Contains 1 Link domain.
• Post-translational modification: CD44 is proteolytically cleaved in the extracellular matrix by specific proteinases (possibly MMPs) in several cell lines and tumors.N-glycosylated.O-glycosylated; CD44 contains more-or-less-sulfated chondroitin sulfate glycans, whose number may affect the accessibility of specific proteinases to their cleavage site(s).Phosphorylated; activation of PKC results in the dephosphorylation of Ser-706 (constitutive phosphorylation site), and the phosphorylation of Ser-672.
• Subunit structure: CD44 interacts with PKN2. 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.
• Subcellular location: Membrane; Single-pass type I membrane protein. Note: Colocalizes with actin in membrane protrusions at wounding edges
• Tissue specificity: Isoform 10 (epithelial isoform) is expressed by cells of epithelium and highly expressed by carcinomas. Expression is repressed in neuroblastoma cells.
• 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.

General information above from UniProt

Function for CD44 Protein

UniProtKB:

Receptor for hyaluronic acid (HA). CD44 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 CD44 plays an important role in cell migration, tumor growth and progression. Also it is 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.

Genatlas:

• CD44 participates in lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis
• lymphocyte homing receptor, CD44 is involved in extracellular matrix adhesion, in myeloid differentiation, lymphocyte activation and lymph node homing
• CD44 is main cell surface receptor for hyaluronate adhesion to mucosal high endothelial venule and to type1 and 6 collagen
• CD44 plays a role in resolving lung inflammation (Pubmed 11935029)
• CD44 mediates macrophage recruitment and protective immunity against tuberculosis (Pubmed 12618522)
• CD44 plays a role in anchorage of the actin cytoskeleton to the plasma membrane, which is important for cell motility
• CD44 is a critical inhibitor of TNF-driven joint destruction and inflammatory bone loss (Pubmed 15781582)
• primary cell surface receptor for hyaluronan, CD44 binds ligand via a lectin-like fold (Pubmed 17293874)
• CD44 is integral hyaluronan receptor that can promote or inhibit motogenic signaling in tumor cells (Pubmed 17392272)
• CD44 may mediate binding of calcium oxalate crystals to tubular epithelia via the ligands osteopontin (OPN) and hyaluronan (Pubmed 18787423)
• CD44 plays a role in early human nephron formation and branching morphogenesis (Pubmed 18787423)
• CD44 has a significant role in the development of choroidal neovascularization (Pubmed 19339747)
• role for CD44 in the pathogenesis of systemic lupus erythematosus and other inflammatory diseases (Pubmed 21194677)
• transmembrane glycoprotein that serves as the principal cell surface receptor for hyaluronan (HA) and can affect numerous cellular processes, including cell adhesion, proliferation, and migration (Pubmed 20663864)
• imported from the cytoplasm to the nucleus by transportin 1 (TNPO1)where it induces gene transcription (Pubmed 20663864)
• CD44 is early cell surface marker of the Müller glia lineage, and Notch signalling was involved in commitment of retinal progenitor cells to CD44 positive Müller glial precursor cells (Pubmed 20969572)
• expanded role for CD44 receptor/ligand interactions in directing cell trafficking via a step 2–bypass pathway of integrin activation (Pubmed 21257905)
• presence of Hyaluronan is required for CD44/EGFR coupling following TGFB1 stimulation, in oral fibroblasts (Pubmed 21454519)

Homology for human CD44

• ortholog to Cd44, Mus musculus
• ortholog to LOC100330801, Danio rerio
• ortholog to Cd44, Rattus norvegicus
• ortholog to CD44, Pan troglodytes

Phenotype Information for CD44

• Gene/Locus: CD44, MDU2, MDU3, MIC4
• Phenotype: [Blood group, Indian system]

Phenotype Information for CD44 from OMIM (Online Mendelian Inheritance in Man)