• LIMP
• MLA1
• PTLGP40
• gp55
• granulophysin
• lysosomal-membrane-associated glycoprotein 3, LAMP-3
• melanoma-associated antigen, ME491
• neuroglandular antigen, NGA

MAJOR LINKS FOR CD63  

• NCBI LocusLink Record: 967
• Mendelian Inheritance in Man (OMIM): 155740
• SwissProt annotated protein record: P08962

CELLULAR FUNCTION OF CD63  

• CD63 transfection reduced melanoma cell motility on fibronectin, collagen and laminin, and reduced the growth and metastasis of melanoma cells in nude mice (Radford et al. 1995,1997)**
• CD63 has been used as a marker for late endosomes**

DISEASE RELEVANCE OF CD63 AND FUNCTION OF CD63 IN INTACT ANIMAL  

• CD63 in intracellular granules is exported to the cell surface upon activation of platelets, endothelial cells, and granulocytes. Thus, it can be used to identify platelet activation in vivo**
• CD63 can also be used as a marker for primary melanomas
• CD63 shows increased expression in atherosclerotic plaques in Watanabe rabbits
• CD63 is deficient in dense granules of platelets from patients with Hermansky-Pudlak syndrome, but is unlikely to be the primary defect**

• Families in which CD63 is a member
  • CD63-->lamp
  • CD63-->TM4SF subfamily 1-->TM4SF

MOLECULAR STRUCTURE OF CD63  

• CD63 contains four hydrophobic transmembrane domains with a major extracellular region of 95 amino acids between transmembrane segments 3 and 4
• CD63 has three putative N-glycosylation sites and shows a cell-type specific glycosylation
• The COOH-terminal sequence SGYEVM functions as a lysosomal targeting sequence

MOLECULAR MASS OF CD63  

POST-TRANSCRIPTIONAL MODIFICATION OF CD63   - Unknown**

POST-TRANSLATIONAL MODIFICATION OF CD63  

• CD63 is heavily glycosylated with 30-70% of its size attributed to N-glycosylation
• The three N-glycans of CD63 resemble poly-N-acetyllactosamines structures characteristic of lysosomal membrane proteins

• The expression of CD63 is regulated
• Potential SP1, AP-1, AP-2 an ETF sites are present in the 5[prime]-flanking region (-381 to -6) (Hotta et al. 1992)
• A cryptic promoter that contains positive and negative regulatory elements is found in the first intron (Takahashi et al. 1991)

SUBSTRATES FOR CD63   - No information**

ENZYMES WHICH MODIFY CD63   - No information**

LIGANDS FOR CD63 AND MOLECULES ASSOCIATED WITH CD63  

• Intracellular lysosomal/endosomal/granule protein, in Weibel-Palade bodies of vascular endothelium**
• Translocated to the surface of activated platelets, endothelium**
• Degranulated neutrophils, monocytes, macrophages, and endothelium
• Immunohistochemistry showed staining of fibroblasts, osteoclasts, smooth muscle, neural tissue (brain white matter and peripheral nerves) and synovial lining cells

• CD63, like other TM4SF proteins, may be localized into molecular complexes**
• While exact functions remain unknown, CD63 may function as a transmembrane adapter protein, linking other transmembrane proteins and signaling proteins**

SELECTION OF OTHER CD63-SPECIFIC REFERENCE MAB  

REVIEWS

PRIMARY CITATIONS

1. Berditchevski F, Bazzoni G and Hemler ME. Specific association of CD63 with the VLA-3 and VLA-6 integrins. J. Biol. Chem. 1995 270:17784 PubMed

2. Berditchevski F, Tolias KF, Wong K, Carpenter CL and Hemler ME. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J. Biol. Chem. 1997 272:2595 ** PubMed

3. Berditchevski F, Zutter MM and Hemler ME. Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). Mol. Biol. Cell 1996 7:193 PubMed

4. Hotta H, Miyamoto H, Hara I, Takahashi N and Homma M. Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences. Biochem. Biophys. Res. Commun. 1992 185:436 PubMed

5. Kitani S, Berenstein E, Mergenhagen S, Tempst P and Siraganian RP. A cell surface glycoprotein of rat basophilic leukemia cells close to the high affinity IgE receptor (Fc epsilon RI). Similarity to human melanoma differentiation antigen ME491. J. Biol. Chem. 1991 266:1903 ** PubMed

6. Metzelaar MJ, Wijngaard PL, Peters PJ, Sixma JJ, Nieuwenhuis HK and Clevers HC. CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells. J. Biol. Chem. 1991 266:3239 ** PubMed

7. Nieuwenhuis HK, van Oosterhout JJ, Rozemuller E, van Iwaarden F and Sixma JJ. Studies with a monoclonal antibody against activated platelets: evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation. Blood 1987 70:838, Stars PubMed

8. Nishikata H, Oliver C, Mergenhagen SE and Siraganian RP. The rat mast cell antigen AD1 (homologue to human CD63 or melanoma antigen ME491) is expressed in other cells in culture. J. Immunol. 1992 149:862 ** PubMed

9. Radford KJ, Mallesch J and Hersey P. Suppression of human melanoma cell growth and metastasis by the melanoma-associated antigen CD63 (ME491). Int. J. Cancer 1995 62:631 ** PubMed

10. Radford KJ, Thorne RF and Hersey P. CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma. Biochem. Biophys. Res. Commun. 1996 222:13 ** PubMed

11. Radford KJ, Thorne RF and Hersey P. Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line. J. Immunol. 1997 158:3353 ** PubMed

12. Sikora LK, Pinto A, Demetrick DJ, Dixon WT, Urbanski SJ, Temple W and Jerry LM. Characterization of a novel neuroglandular antigen (NGA) expressed on abnormal human melanocytes. Int. J. Cancer 1987 39:138 ** PubMed

13. Takahashi N, Hotta H and Homma M. Activation and suppression of a cryptic promoter in the intron of the human melanoma-associated ME491 antigen gene. Jpn. J. Cancer Res. 1991 82:1239 PubMed

14. Vischer UM and Wagner DD. CD63 is a component of Weibel-Palade bodies of human endothelial cells. Blood 1993 82:1184 ** 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