• Ecto-5'-nucleotidase

MAJOR LINKS FOR CD73  

• NCBI LocusLink Record: 4907
• Mendelian Inheritance in Man (OMIM): 129190
• SwissProt annotated protein record: P21589

• CD73 possesses 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. (Airas et al. 1997)**

CELLULAR FUNCTION OF CD73  

• A possible function for CD73 is to regulate the availability of adenosine for interaction with cell surface adenosine receptor by converting AMP to adenosine
• In common with other GPI anchored surface proteins CD73 can mediate costimulatory signals in T cell activation. (Thompson et al. 1989)*
• It has been shown, however, that in order to transmit costimulatory 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 (Airas et al. 1995)*
• The most recent data proposes a role for CD73 in controlling 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 (Airas et al. 1996)*
• 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 such effect on the endothelial cell molecule. Moreover, mAb triggering of lymphocyte CD73 but not of endothelial cell CD73 causes phosphorylation of certain proteins (Airas et al. 1997)**

DISEASE RELEVANCE OF CD73 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 (Thompson et al. 1986)*
• Abnormally low ecto-5'-NT activity has been found on lymphocytes of patients suffering with a variety of immunodeficiency diseases characterized by a block in lymphocyte maturation (Salazar-Gonzales et al. 1985)*
• CD73 is expressed on a variety of lymphomas and leukemias including acute T-cell leukemia, chronic lymphocytic leukemia and acute lymphoblastic leukemia where high CD73 expression is a poor prognostic indicator (Gutensohn et al. 1990)*

• Families in which CD73 is a member
  • CD73-->ectoenzyme
  • CD73-->5'-nucleotidase
  • CD73-->Glycosyl phosphatidyl inositol anchored

MOLECULAR STRUCTURE OF CD73  

• The primary cDNA structure of CD73 has been determined for three different human tissues, i.e. placenta, peripheral blood lymphocytes and endothelial cells. All these sequences are practically identical to each other.
• (Zimmerman 1992 and Airas et al. 1997)**
• The sequenced cDNA's all encode protein with a potential N-terminal signal sequence consisting of 26 predominantly hydrophobic amino acids and the mature protein is expected to consist of 548 amino acids which corresponds to a molecular mass of about 63 kDa (Zimmerman 1992 and Airas et al. 1997)**
• The C-terminus contains a stretch of uncharged and hydrophobic amino acid residues which are exchanged for a glycosylphosphatidylinositol (GPI) anchor bound to Ser-523 (Zimmerman 1992 and Airas et al. 1997)**

MOLECULAR MASS OF CD73  

• There are no differences in size under reduced vs. unreduced conditions in different cell types (Airas et al. 1993)**

POST-TRANSCRIPTIONAL MODIFICATION OF CD73   - No information

POST-TRANSLATIONAL MODIFICATION OF CD73  

• CD73 is N-glycosylated (Zimmerman 1992)**
• CD73 is sialylated (Zimmerman 1992)**
• No O-linked carbohydrates have been detected (Zimmerman 1992)**
• 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 four N-linked carbohydrate side chains, of which three are of the complex type and one of the high mannose type (Zimmerman 1992)**

SUBSTRATES FOR CD73  

ENZYMES WHICH MODIFY CD73   - No information

LIGANDS FOR CD73 AND MOLECULES ASSOCIATED WITH CD73   - No information

• Among T and B lymphocytes, expression restricted to subpopulations. (Thompson et al. 1990)*
• Approximately 25% of CD3+, 10% of CD4+ and 50% of CD8+ peripheral blood T cells express CD73, and expression is confined to the CD28+ subset. (Thompson et al. 1990)*
• Approximately 75% of adult peripheral blood B cells express CD73. (Thompson et al. 1990)*
• CD73 expression increases during the development of both T and B lymphocytes. (Thompson et al. 1990)*
• Also found on follicular dendritic cells, epithelial cells and endothelial cells (Thompson et al. 1990)*

• The human CD73 gene has been mapped to region q14-q21 of chromosome 6.

SELECTION OF OTHER CD73-SPECIFIC REFERENCE MAB  

REVIEWS

Zimmermann H 5'-Nucleotidase: molecular structure and functional aspects. Biochem J 1992 285:345 ** PubMed

PRIMARY CITATIONS

1. Thomson LF,Ruedi JM,Glass A,Moldenhauer G,Moller P,Low MG,Klemens MR,Massaia M,Lucas AH Production and characterization of monoclonal antibodies to the glycosyl phosphatidylinositol-anchored lymphocyte differentiation antigen ecto-5'-nucleotidase (CD73). Tissue Antigens 1990 35:9 PubMed

2. Airas L,Salmi M,Jalkanen S Lymphocyte-vascular adhesion protein-2 is a novel 70-kDa molecule involved in lymphocyte adhesion to vascular endothelium. J Immunol 1993 151:4228 PubMed

3. Thompson LF,Ruedi JM,O'Connor RD,Bastian JF Ecto-5'-nucleotidase expression during human B cell development. An explanation for the heterogeneity in B lymphocyte ecto-5'-nucleotidase activity in patients with hypogammaglobulinemia. J Immunol 1986 137:2496 * PubMed

4. Salazar-Gonzalez JF,Moody DJ,Giorgi JV,Martinez-Maza O,Mitsuyasu RT,Fahey JL Reduced ecto-5'-nucleotidase activity and enhanced OKT10 and HLA-DR expression on CD8 (T suppressor/cytotoxic) lymphocytes in the acquired immune deficiency syndrome: evidence of CD8 cell immaturity. J Immunol 1985 135:1778 PubMed

5. Barcos, M., Pollard, C., Thompson, L. F., Stoll, H., and Evans, R. L. Leukemia and Lymphoma 6, 503-512(1992).

6. Thompson LF Ecto-5'-nucleotidase can provide the total purine requirements of mitogen-stimulated human T cells and rapidly dividing human B lymphoblastoid cells. J Immunol 1985 134:3794 PubMed

7. Thompson LF,Ruedi JM,Glass A,Low MG,Lucas AH Antibodies to 5'-nucleotidase (CD73), a glycosyl-phosphatidylinositol- anchored protein, cause human peripheral blood T cells to proliferate. J Immunol 1989 143:1815 PubMed

8. Gutensohn W,Resta R,Misumi Y,Ikehara Y,Thompson LF Ecto-5'-nucleotidase activity is not required for T cell activation through CD73. Cell Immunol 1995 161:213 PubMed

9. Airas L,Hellman J,Salmi M,Bono P,Puurunen T,Smith DJ,Jalkanen S CD73 is involved in lymphocyte binding to the endothelium: characterization of lymphocyte-vascular adhesion protein 2 identifies it as CD73. J Exp Med 1995 182:1603 PubMed

10. Airas L,Jalkanen S CD73 mediates adhesion of B cells to follicular dendritic cells. Blood 1996 88:1755 PubMed

11. Airas L,Niemela J,Salmi M,Puurunen T,Smith DJ,Jalkanen S Differential regulation and function of CD73, a glycosyl- phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells. J Cell Biol 1997 136:421 ** PubMed

WWW RESOURCES

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Modified 10/14/99   mpr@mail.nih.gov