CD63 ME491, PTLGP40, LIMP, gp55, granulophysin, LAMP-3 (lysosomal-membrane-associated glycoprotein)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 4 span
Nerve
Brain
Monocyte
Macrophage
Platelet
Granulocyte
Lymphocyte
Endothelium
Neutrophil
Fibroblast
T Cell
Muscle, Smooth
Osteoclast
B Cell
40 / 40
60 / 60

Expression
CD63 is expressed on intracellular lysosomal/endosomal/granule protein in Weibel Palade bodies of vascular endothelium.  CD63 expression in lysosomes moves to the cell membrane upon activation, suggesting it is involved in the degradation process.  The presence of CD63 on syncytiotrophoblasts probably relates to the transport of nutrients from maternal to fetal blood.  CD63 is translocated to the surface of activated platelets and endothelium and is expressed on degranulated neutrophils, monocytes, macrophages and endothelium.  Immunohistochemistry showed staining of fibroblasts, osteoclasts, smooth muscle, neural tissue including brain white matter and peripheral nerve and synovial lining cells.


Structure
MOLECULAR FAMILY NAME:  Belongs to the tetraspanin family.

CD63 is a multi-pass type-3, 4 span glycoprotein.  It contains 4 hydrophobic  transmembrane domains with a large 95 aa heavily glycosylated extracellular domain between the transmembrane segments 3 and 4 and a smaller extracellular domain between the transmembrane dominas 1 and 2.  CD63 has 3 putative N-glycosylation sites and shows a cell-type specific glycosylation and N-glycans are characteristic of those found on lysosomal membrane proteins.  The COOH-terminal sequence SGYEVM functions as a lysosomal targeting sequence.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
All 40-60 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD63 is heavily glycosylated with 30%-70% of its size attributed to N-glycosylation.  The 3 N-glycans of CD63 resemble poly-N-acetyllactosamines structures characteristic of lysosomal membrane proteins.

Ligands
CD63 associates non-covalently with the TM4SF molecules CD9 and CD81, and with the integrins CD29/CD49c (VLA-3), CD29/CD49d (VLA-4) and CD29/CD49f (VLA-6).  In human neutrophils, CD63 associates with the integrin CD11/CD18 and the Src family protein tyrosine kinases Lyn and Hck. In rat lymph node cells, CD63 is associated with a protein tyrosine phosphatase.  No extracellular ligand has been identified for CD63.

LIGANDS AND MOLECULES ASSOCIATED WITH CD63
Molecule Comment
VLA-3 (CD29/CD49c) CD63 has been shown to associate with VLA-3 (CD29/CD49c) by co-precipitation
VLA-6 (CD29/CD49f) CD63 has been shown to associate with VLA-3 (CD29/CD49c) by co-precipitation
CD9 Formation of complexes involving CD63 and the TM4SF protein CD9 have also been identified by co-precipitation
CD81 Formation of complexes involving CD63 and the TM4SF protein CD81 have also been identified by co-precipitation
PI 4-kinase CD63 is also associated with PI 4-kinase




Function
CD63 mediates signal transduction events that play a role in the regulation of cell development, activation, growth and motility.  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 is detected in exosomes secreted by a variety of cells, which appear to be capable of delivering antigens and other molecules to target cells.  CD63 may function as an adhesion molecule in this system.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD63 IN INTACT ANIMAL

CD63 may play a role as a tumor suppressor gene since expression of CD63 in human melanoma cells reduces tumor spread and metastasis.  CD63 transfection reduced melanoma cell motility on fibronectin, collagen and laminin and reduced the growth and metastasis of melanoma cells in nude mice.  CD63 is thought to be associated with the early stages of melanoma cell motility and adhesion to ligands of β1 integrins in extracellular matrix.  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.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD63

The expression of CD63 is regulated. Potential SP1, AP-1, AP-2 and ETF sites are present in the 5 prime-flanking region (-381 to -6).  A cryptic promoter that contains positive and negative regulatory elements is found in the 1st intron.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD63: No information.

ADDITIONAL INSIGHTS

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.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 967P08962
MouseP41731D16432
RatS16776P28648X61654
Antibodies
CC25   View Reactivity
H5C6   View Reactivity

Revised June 25, 2008


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