|CD222||IGF2R (insulin-like growth factor 2 receptor), M6P-R (mannose-6-phosphate receptor)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|250 / 250|
300 / 300
|CD222 is expressed on many cell types such as fibroblasts, granulocytes, lymphocytes and myocytes. A truncated form of the receptor of 220 kDa is present in human and bovine serum. Receptor expression is highest at 16-20 days of embryonal development, mainly in the heart, and declines during the postnatal period in rat and mouse tissues. The majority of CD222 is in the late endosomal/prelysosomal compartment, only about 5%-10% is in the plasma membrane.|
|MOLECULAR FAMILY NAME: Belongs to the insulin-like growth receptor family.|
CD222 is a single-pass type-1 250 kDa glycoprotein. It contains a 40 aa signal sequence, an 134 aa - 167 aa extracellular domain which consists of 15 homologous domains with the 13th domain having a 43 aa insert that is a fibronectin-like collagen-binding domain and 19 N-linked glycosylation sites but not all are used, a 23 aa long transmembrane domain and an 164 aa long carboxyl-terminal cytoplasmic domain whic contains an internalization signal. CD222 was originally identified as a receptor for insulin-like growth factor 2 (IGF2) and mannose-6 phosphate (M6P)-containing proteins such as lysosomal hydrolases. Lysosomal enzymes are sorted to lysosomes by CD222 either from the Golgi, where the enzymes acquire M6P, or from the extracellular space. The majority of the molecules are approximately 90%-95% and are located intracellularly, only 5%-10% is present on the cell membrane. The internalization rate seems to be enhanced by ligand induced dimerization of CD222 as well as by phosphorylation of its cytoplasmic serine.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
CD222 has 19 potential N-glycosylation sites some of which utilize palmitoylation and cytoplasmic serine phosphorylation. Cleavage of the extracellular portion releases a 220 kDa soluble form into the serum and an incomplete glycosylated form of 230 kDa occurs in monocytes. The position of the cleavage site is unknown.
| LIGANDS AND MOLECULES ASSOCIATED WITH CD222|
|CD222 binds and internalizes a variety of extracellular ligands and directs them to lysosomes and sorts newly synthesized M6P-containing lysosomal enzymes and transports newly synthesized acid hydrolases to lysosomes. CD222 binds and internalizes IGF2 independently of M6P. CD222 is a receptor which participates in the activation of latent TGFb as a receptor for M6P containing latency association peptide (LAP) and CD222 complexes with CD87 and plasminogen for activation of LTGFb. The main functions of CD222 include internalization of IGF2, internalization of sorting of lysosomal enzymes and other M6P-containing proteins such as latent TGFb as well as regulation of TGFb activity. |
There is controversial evidence for CD222 mediated signal transduction via heteromeric G proteins. CD222 is used as an anchor by acid lysosomal hydrolases during degradation of pericellular and extracellular proteoglycans.
The biochemical activity of CD222 is the internalization of IGF2 and lysosomal enzymes and the binding and activation of latent TGFb.
DISEASE RELEVANCE AND FUNCTION OF CD222 IN INTACT ANIMAL
CD222 has been reported to be involved in cell adhesion and growth regulation of myeloma cells. CD222 is associated with hepatocellular carcinoma. CD222 -/- null mice exhibit organ and skeletal abnormalities and die at birth. The main cause of their death is probably the loss of the CD222 internalization machinery, because CD222 -/- mice in IGF2 -/- or IGF2R -/- background survive. CD222 is often mutated in several forms of cancer and its is suggested to be a tumor suppressor oncogene. Proliferin-induced angiogenesis is mediated by CD222. Chlamydia pneumoniae uses CD222 as a receptor and as a means of infecting endothelial cells. Activation of CD222 by IGF-II stimulates increased insulin secretion by pancreatic β cells. Signaling by CD222 promotes exocytosis in insulin-secreting cells.
|CD222 is involved in lysosomal sorting and internalization.|
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD222: No information.
The enzymatic activity is not known.
ENZYMES WHICH MODIFY CD222
Database accession numbers
Revised June 25, 2008