1. Gene Aliases

CD44, HUTCH-I, HCELL, CSPG8, MC56, Pgp1, MDU2, MDU3, MIC4, IN, Hematopoietic Cell E- And L-Selectin Ligand, GP90 Lymphocyte Homing/Adhesion Receptor, Chondroitin Sulfate Proteoglycan 8, Extracellular Matrix Receptor III, Homing Cell Adhesion Molecule, Heparan Sulfate Proteoglycan, Phagocytic Glycoprotein 1, Phagocyte Glycoprotein 1, Hyaluronate Receptor, In(Lu) Related-P80, Hermes Antigen, CD44 Antigen, Hermes-1, ECMR-III, HUTCH-1, ECM-III, Epican, PGP-1, CD44R, CDw44, H-CAM, LHR, CD44 Antigen (Homing Function And Indian Blood Group System), Homing Function And Indian Blood Group System, Extracellular Matrix Receptor-III, Cell Surface Glycoprotein CD44, Indian Blood Group Antigen, Phagocytic Glycoprotein I, Soluble CD44, CDW44, PGP-I

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD44&keywords=cd44].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

T cell activation [The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific. GO:0042110]

Wnt signaling pathway [The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state. GO:0016055]

blood vessel maturation [A developmental process, independent of morphogenetic (shape) change, that is required for a blood vessel to attain its fully functional state. GO:0001955]

branching involved in prostate gland morphogenesis [The process in which the branching structure of the prostate gland is generated and organized. A branch is a division or offshoot from a main stem. GO:0060442]

branching involved in ureteric bud morphogenesis [The process in which the branching structure of the ureteric bud is generated and organized. The ureteric bud is an epithelial tube that grows out from the metanephric duct. The bud elongates and branches to give rise to the ureter and kidney collecting tubules. GO:0001658]

cartilage development [The process whose specific outcome is the progression of a cartilage element over time, from its formation to the mature structure. Cartilage elements are skeletal elements that consist of connective tissue dominated by extracellular matrix containing collagen type II and large amounts of proteoglycan, particularly chondroitin sulfate. GO:0051216]

cell adhesion [The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules. GO:0007155]

cell migration [The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. GO:0016477]

cellular response to fibroblast growth factor stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an fibroblast growth factor stimulus. GO:0044344]

cytokine-mediated signaling pathway [The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. GO:0019221]

hyaluronan catabolic process [The chemical reactions and pathways resulting in the breakdown of hyaluronan, the naturally occurring anionic form of hyaluronic acid, any member of a group of glycosaminoglycans, the repeat units of which consist of beta-1,4 linked D-glucuronyl-beta-(1,3)-N-acetyl-D-glucosamine. GO:0030214]

inflammatory response [The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. GO:0006954]

macrophage fusion [The binding and fusion of a macrophage to one or more other cells to form a multinucleated cell. GO:0034238]

monocyte aggregation [The adhesion of one monocyte to one or more other monocytes via adhesion molecules. GO:0070487]

negative regulation of CD4-positive, alpha-beta T cell proliferation [Any process that stops, prevents or reduces the frequency, rate or extent of CD4-positive, alpha-beta T cell proliferation. GO:2000562]

negative regulation of DNA damage response, signal transduction by p53 class mediator [Any process that stops, prevents, or reduces the frequency, rate or extent of the cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage. GO:0043518]

negative regulation of apoptotic process [Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.|This term should only be used when it is not possible to determine which phase or subtype of the apoptotic process is negatively regulated by a gene product. Whenever detailed information is available, the more granular children terms should be used. GO:0043066]

negative regulation of inflammatory response [Any process that stops, prevents, or reduces the frequency, rate or extent of the inflammatory response. GO:0050728]

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator. GO:1902166]

negative regulation of mature B cell apoptotic process [Any process that stops, prevents, or reduces the frequency, rate, or extent of mature B cell apoptotic process. GO:0002906]

negative regulation of regulatory T cell differentiation [Any process that stops, prevents, or reduces the rate of differentiation of regulatory T cells.|Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'. GO:0045590]

neuron projection development [The process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). GO:0031175]

positive regulation of ERK1 and ERK2 cascade [Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. GO:0070374]

positive regulation of gene expression [Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). GO:0010628]

positive regulation of heterotypic cell-cell adhesion [Any process that activates or increases the frequency, rate, or extent of heterotypic cell-cell adhesion. GO:0034116]

positive regulation of monocyte aggregation [Any process that activates or increases the frequency, rate or extent of monocyte aggregation. GO:1900625]

positive regulation of neutrophil apoptotic process [Any process that activates or increases the frequency, rate, or extent of neutrophil apoptotic process. GO:0033031]

positive regulation of peptidyl-serine phosphorylation [Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine. GO:0033138]

positive regulation of peptidyl-tyrosine phosphorylation [Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine. GO:0050731]

receptor-mediated endocytosis [An endocytosis process in which cell surface receptors ensure specificity of transport. A specific receptor on the cell surface binds tightly to the extracellular macromolecule (the ligand) that it recognizes; the plasma-membrane region containing the receptor-ligand complex then undergoes endocytosis, forming a transport vesicle containing the receptor-ligand complex and excluding most other plasma-membrane proteins. Receptor-mediated endocytosis generally occurs via clathrin-coated pits and vesicles. GO:0006898]

regulation of cell growth [Any process that modulates the frequency, rate, extent or direction of cell growth. GO:0001558]

regulation of lamellipodium morphogenesis [Any process that modulates the frequency, rate or extent of lamellipodium morphogenesis. GO:2000392]

response to nutrient levels [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus reflecting the presence, absence, or concentration of nutrients. GO:0031667]

response to organic cyclic compound [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. GO:0014070]

response to vitamin A [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin A stimulus. GO:0033189]

wound healing involved in inflammatory response [The series of events that restore integrity to damaged tissue that contribute to an inflammatory response. GO:0002246]

wound healing, spreading of cells [The migration of a cell along or through a wound gap that contributes to the reestablishment of a continuous surface. GO:0044319]

MSigDB Signatures:

REACTOME_GLYCOSAMINOGLYCAN_METABOLISM: Glycosaminoglycan metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_GLYCOSAMINOGLYCAN_METABOLISM.html]

REACTOME_HEMOSTASIS: Hemostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HEMOSTASIS.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

REACTOME_NEUTROPHIL_DEGRANULATION: Neutrophil degranulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NEUTROPHIL_DEGRANULATION.html]

WP_PLEURAL_MESOTHELIOMA: Pleural mesothelioma [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PLEURAL_MESOTHELIOMA.html]

BIOCARTA_NEUTROPHIL_PATHWAY: Neutrophil and Its Surface Molecules [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_NEUTROPHIL_PATHWAY.html]

REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION: Extracellular matrix organization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION.html]

BIOCARTA_MONOCYTE_PATHWAY: Monocyte and its Surface Molecules [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_MONOCYTE_PATHWAY.html]

KEGG_ECM_RECEPTOR_INTERACTION: ECM-receptor interaction [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_ECM_RECEPTOR_INTERACTION.html]

REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX: Degradation of the extracellular matrix [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX.html]

REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL: Cell surface interactions at the vascular wall [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL.html]

REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM: Cytokine Signaling in Immune system [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM.html]

REACTOME_HYALURONAN_METABOLISM: Hyaluronan metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HYALURONAN_METABOLISM.html]

WP_CKAP4_SIGNALING_PATHWAY_MAP: CKAP4 signaling pathway map [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CKAP4_SIGNALING_PATHWAY_MAP.html]

REACTOME_HYALURONAN_UPTAKE_AND_DEGRADATION: Hyaluronan uptake and degradation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HYALURONAN_UPTAKE_AND_DEGRADATION.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this 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 protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this 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]

GeneCards Summary: CD44 (CD44 Molecule (Indian Blood Group)) is a Protein Coding gene. Diseases associated with CD44 include Lichen Sclerosus and Pleural Mesothelioma. Among its related pathways are Glycosaminoglycan metabolism and Innate Immune System. Gene Ontology (GO) annotations related to this gene include transmembrane signaling receptor activity and cytokine receptor activity. An important paralog of this gene is LYVE1.

UniProtKB/Swiss-Prot Summary: Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment [PMID: 16541107, PMID: 19703720, PMID: 22726066]. Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection [PMID: 7528188]. Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases [PMID: 18757307, PMID: 23589287]. Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion [PMID: 15123640].

8. Cellular Location of Gene Product

Cytoplasmic and membranous expression in most epithelial and lymphoid tissues. Mainly localized to the plasma membrane. In addition localized to the Golgi apparatus. Predicted location: Secreted, Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000026508/subcellular]

9. Mechanistic Information

Summary

The upregulation of CD44 in response to kidney injury, such as ischemia-reperfusion injury (IRI), enhances the cell's ability to bind hyaluronic acid (HA), a major component of the extracellular matrix [CS: 8]. This binding is central to several repair and adaptive processes [CS: 7]. In kidney repair, such as in IRI, the increased expression of CD44 facilitates the attachment of HA to the damaged proximal tubules [CS: 8]. This interaction plays a key role in tissue regeneration, as it helps in organizing the extracellular matrix, which is crucial for the repair and recovery of the injured tissue [CS: 9]. Moreover, this binding modulates signaling pathways, aiding cellular response and recovery in damaged kidneys [CS: 8].

In the context of RCC (Renal Cell Carcinoma), the increased expression of CD44 and its interaction with HA take on a different role, contributing to the malignancy's progression [CS: 7]. The CD44-HA binding on cancer cells heightens their motility and invasiveness, facilitating the spread to surrounding tissues and distant metastasis [CS: 8]. This process is further compounded by CD44's involvement in activating signaling pathways that promote cancer cell survival and proliferation, such as the PI3K/AKT pathway [CS: 8]. Thus, while CD44's upregulation in diseases like RCC can be detrimental by aiding cancer progression [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: salivary gland (tissue enhanced) [https://www.proteinatlas.org/ENSG00000026508/tissue]

Cell type enchanced: ductal cells, exocrine glandular cells, granulocytes, langerhans cells, monocytes (cell type enhanced) [https://www.proteinatlas.org/ENSG00000026508/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest