CD73 ECTO-5'-nucleotidase
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
T Cell
B Cell
Peripheral blood
Endothelial Cell
Epithelial Cell
Dendritic Cell
Follicular Cell
Lymphocyte
69 / 69
72 / 72

Expression
Among T and B lymphocytes, expression is restricted to subpopulations.  Approximately 25% of CD3+, 10% of CD4+ and 50% of CD8+ peripheral blood T cells express CD73. The expression is confined to the CD28+ subset.  Approximately 75% of adult peripheral blood B cells express CD73.  CD73 expression increases during the development of both T and B lymphocytes.  Expression is also found on follicular dendritic cells, epithelial, various lymphomas and leukemias and endothelial cells.


Structure
MOLECULAR FAMILY NAME:  Belongs to the 5'-nucleotidase family.

CD73 is a single-pass GPI-anchored 548 aa glycoprotein.  It contains a potential 26 aa extracellular domain which contains a N-terminal signal sequence and a C-terminus that contains a stretch of uncharged and hydrophobic aa residues which are exchanged for a GPI-anchor bound to Ser-523 and a cytoplasmic domain. 
 
MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Myeloma cell line U266 69 kDa
Freshly isolated peripheral blood lymphocytes 70 kDa
Cultured endothelial cells 70 kDa
Human placenta 72 kDa

There are no differences in size under reduced vs. unreduced conditions in different cell types.

POST-TRANSCRIPTIONAL MODIFICATION: No information

POST-TRANSLATIONAL MODIFICATION

CD73 is N-glycosylated and is sialylated but not O-glycosylation.  There appears to be tissue and species-specific variation in terms of the type and degree of N-linked glycosylation but the placental molecule probably contains 4 N-linked carbohydrate side chains, of which 3 are of the complex type and 1 of the high mannose type.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD73: No information.



Function
A possible function for CD73 is to regulate the availability of adenosine for interaction with the cell surface adenosine receptor by converting AMP to adenosine.  In common with other GPI-anchored surface proteins, CD73 can mediate co-stimulatory signals in T cell activation.  It has been shown, however, that in order to transmit co-stimulatory signals CD73 does not require either the GPI-anchor or its 5'-NT activity.  It has been reported that CD73 has a function in mediating lymphocyte adhesion to endothelium.  The most recent data propose a role for CD73 in controlling the B cell-follicular dendritic cell (FDC) interactions, with the CD73 expressed on FDC acting together with an unknown ligand expressed on the B-cell surface.  CD73 expression on lymphocyte and endothelial cell surfaces seems to be very differently controlled, as mAb triggering of CD73 on lymphocytes causes rapid shedding of the molecule but has no effect on the endothelial cell molecule.  Moreover, mAb triggering of lymphocyte CD73, but not of the endothelial cell, causes phosphorylation of certain proteins.

BIOCHEMICAL ACTIVITY

CD73 possess the enzymatic activity of a 5'-nucleotidase and catalyses the dephosphorylation of purine and pyrimidine ribo- and deoxyribonucleoside monophosphates to their corresponding nucleosides.  Triggering of lymphocyte CD73 with mAb causes phosphorylation and dephosphorylation of certain, yet unknown protein substrates.

DISEASE RELEVANCE AND FUNCTION OF CD73 IN INTACT ANIMAL

During the development of both T and B lymphocytes, CD73 expression is increased and has been described as a lymphocyte maturation marker.  Abnormally low ecto-5'-NT activity has been found on lymphocytes of patients suffering with a variety of immunodeficiency diseases including severe combined immunodeficiency, X-linked agammaglobulinemia, common variable immunodeficiency, selective IgA deficiency, Wiskott-Aldrich syndrome and AIDS characterized by a block in lymphocyte maturation.  CD73 is expressed on a variety of lymphomas and leukemias including acute T-cell leukemia, chronic lymphocyte leukemia and acute lymphoblastic leukemia where high CD73 expression is a poor prognostic indicator.



Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD73: No information.

SUBSTRATES
Molecular Comment
AMP CD73 (ecto-5'-nucleotidase) hydrolyses extracellular adenosine monophosphate (AMP) into adenosine

ENZYMES WHICH MODIFY CD73: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4907P21589
MouseL12059
Antibodies
AD2   View Reactivity

Revised June 25, 2008


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