• ECMR III
• H-CAM
• HUTCH-1
• Hermes
• Lu, In-related
• Pgp-1
• gp85

MAJOR LINKS FOR CD44  

• NCBI LocusLink Record: 960
• Mendelian Inheritance in Man (OMIM): 107269
• SwissProt annotated protein record: P16070

• CD44 serves as a recyclable receptor for hyaluronan, which is internalized by endocytosis and catabolized
• CD44 may also anchor epithelial cells to hyaluronan in basement membranes and to maintain polar orientation

CELLULAR FUNCTION OF CD44  

• CD44 is involved in leukocyte attachment to and rolling on endothelial cells, homing to peripheral lymphoid organs and to sites of inflammation, and leukocyte aggregation
• Signaling through CD44 induces cytokine release and T cell activation
• The ability of CD44 to bind its ligands and growth factors changes with pattern of glycosylation

DISEASE RELEVANCE OF CD44 AND FUNCTION OF CD44 IN INTACT ANIMAL  

• CD44 mAbs inhibit inflammation in mouse models of arthritis
• CD44/HA interactions also have a possible role in tumor metastasis

MOLECULAR STRUCTURE OF CD44  

• The sequence of cDNA encoding the standard form of CD44 predicts a transmembrane protein of 37kD with 341 amino acids
• Extracellular domain of 248 amino acids,
• A transmembrane domain of 21 amino acids
• A cytoplasmic domain of 72 amino acids
• The amino-terminal 120 amino acids of CD44S have homology to cartilage link and proteoglycan core proteins known to interact with hyaluronan

MOLECULAR MASS OF CD44  

POST-TRANSCRIPTIONAL MODIFICATION OF CD44  

• The standard form of CD44 is generated by exons 1-5, 15-17 and 19 due to alternate splicing of a single gene containing 19 exons in humans (20 in mice) spanning approximately 50 kb of DNA

POST-TRANSLATIONAL MODIFICATION OF CD44  

• The extracellular domain of the mature protein, resulting from the cleavage of a putative 20-amino acid signal peptide of CD44, contains six cysteine residues that potentially forms a single globular domain
• There are multiple potential sites for N- and O-linked glycosylation, and several sites for chrondroitin sulfate modification
• Four of six serine residues in the cytoplasmic domain, S271, S303, S305 and S317 are potential sites for phosphorylation

SUBSTRATES FOR CD44   - No information

ENZYMES WHICH MODIFY CD44  

LIGANDS FOR CD44 AND MOLECULES ASSOCIATED WITH CD44  

• The standard form of CD44, the most predominant isoform among the many identified isoforms, is widely expressed on the surface of most cell types
• Very few types of tissue or cells lack CD44
• Cells and tissues that lack CD44 include platelets, hepatocytes, certain lymphoid cell lines, cardiac muscle, kidney tubular epithelium, testis and portions of the skin

• A structure for hyaladherins is now available, with the interesting similarity to C type lectins (Cell 86:767-775,1996.)

SELECTION OF OTHER CD44-SPECIFIC REFERENCE MAB  

REVIEWS

1. Haynes BF,Liao HX,Patton KL The transmembrane hyaluronate receptor (CD44): multiple functions, multiple forms. Cancer Cells 1991 3:347 PubMed

2. Lesley J,Hyman R,Kincade PW CD44 and its interaction with extracellular matrix. Adv Immunol 1993 54:271 PubMed

PRIMARY CITATIONS

3. Aruffo A,Stamenkovic I,Melnick M,Underhill CB,Seed B CD44 is the principal cell surface receptor for hyaluronate. Cell 1990 61:1303 PubMed

4. Bartolazzi A,Nocks A,Aruffo A,Spring F,Stamenkovic I Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. J Cell Biol 1996 132:1199 PubMed

5. Goldstein LA,Zhou DF,Picker LJ,Minty CN,Bargatze RF,Ding JF,Butcher EC A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell 1989 56:1063 PubMed

6. Kalomiris EL,Bourguignon LY Lymphoma protein kinase C is associated with the transmembrane glycoprotein, GP85, and may function in GP85-ankyrin binding. J Biol Chem 1989 264:8113 PubMed

7. Katoh S,Zheng Z,Oritani K,Shimozato T,Kincade PW Glycosylation of CD44 negatively regulates its recognition of hyaluronan. J Exp Med 1995 182:419 ** PubMed

8. Kohda D,Morton CJ,Parkar AA,Hatanaka H,Inagaki FM,Campbell ID,Day AJ Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration. Cell 1996 86:767 PubMed

9. Mikecz K,Brennan FR,Kim JH,Glant TT Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine arthritis. Nat Med 1995 1:558 PubMed

10. Miyake K,Underhill CB,Lesley J,Kincade PW Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med 1990 172:69 ** PubMed

11. Screaton GR,Bell MV,Jackson DG,Cornelis FB,Gerth U,Bell JI Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A 1992 89:12160 PubMed

12. Stamenkovic I,Amiot M,Pesando JM,Seed B A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell 1989 56:1057 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov