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Literature summary for 3.1.3.5 extracted from
- 5'-Nucleotidases and their new roles in NAD+ and phosphate metabolism (2010), New J. Chem., 34, 845-853.
No PubMed abstract available
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 2,3-bisphosphoglycerate | activates cytosolic 5'-nucleotidase II | Homo sapiens |  |
| ATP | activates cytosolic 5'-nucleotidase II | Homo sapiens | |
| dATP | activates cytosolic 5'-nucleotidase II | Homo sapiens | |
| Diadenosine tetraphosphate | activates cytosolic 5'-nucleotidase II by increase binding and dimer formation, interface binding structure modeling | Homo sapiens | |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene NT5E at 6q14-q21 encodes CD73 | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| alpha/beta-methylene-ADP | a specific CD73 inhibitor | Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | complex allosteric regulation of cytosolic 5'-nucleotidase II | Homo sapiens | |
| 1.2 | - |
5'-UMP | 5'-nucleotidase Sdt1, pH not specified in the publication, temperature not specified in the publication | Saccharomyces cerevisiae | |
| 2.3 | - |
5'-CMP | 5'-nucleotidase Sdt1, pH not specified in the publication, temperature not specified in the publication | Saccharomyces cerevisiae | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cell surface | CD73 | Homo sapiens | 9986 | - |
| cytosol | - |
Homo sapiens | 5829 | - |
| extracellular | - |
Corynebacterium glutamicum | - |
- |
| extracellular | cell surface | Homo sapiens | - |
- |
| intracellular | - |
Homo sapiens | 5622 | - |
| membrane | membrane-bound 5'-nucleotidases are ectoenzymes | Homo sapiens | 16020 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 71000 | - |
homodimeric CD73 | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5'-AMP + H2O | Homo sapiens | - |
adenosine + phosphate | - |
? | |
| 5'-CMP + H2O | Homo sapiens | - |
cytidine + phosphate | - |
? | |
| 5'-CMP + H2O | Saccharomyces cerevisiae | Sdt1 | cytidine + phosphate | - |
? | |
| 5'-dCMP + H2O | Homo sapiens | - |
2'-deoxycytidine + phosphate | - |
? | |
| 5'-dGMP + H2O | Homo sapiens | - |
deoxyguanosine + phosphate | - |
? | |
| 5'-dIMP + H2O | Homo sapiens | - |
deoxyinosine + phosphate | - |
? | |
| 5'-dTMP + H2O | Homo sapiens | - |
deoxythymidine + phosphate | - |
? | |
| 5'-dUMP + H2O | Homo sapiens | - |
deoxyuridine + phosphate | - |
? | |
| 5'-GMP + H2O | Homo sapiens | - |
guanosine + phosphate | - |
? | |
| 5'-IMP + H2O | Homo sapiens | - |
inosine + phosphate | - |
? | |
| 5'-IMP + H2O | Saccharomyces cerevisiae | Isn1 | inosine + phosphate | - |
? | |
| 5'-UMP + H2O | Homo sapiens | - |
uridine + phosphate | - |
? | |
| 5'-UMP + H2O | Saccharomyces cerevisiae | Sdt1 | uridine + phosphate | - |
? | |
| 5'-XMP + H2O | Homo sapiens | - |
xanthosine + phosphate | - |
? | |
| additional information | Saccharomyces cerevisiae | Sdt1 is highly specific for 5'-UMP and 5'-CMP, and shows negligible activity on purine nucleoside monophosphates, 3'-monophosphates or nucleoside triphosphates | ? | - |
? | |
| additional information | Homo sapiens | Usha, Pho5, Sdt1 and Phm8 are phosphate starvation-induced 5'-nucleotidases with diverse substrate specificities that liberate phosphate under phosphate starvation conditions | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Corynebacterium glutamicum | - |
- |
- |
| Homo sapiens | - |
gene NT5E at 6q14-q21 encodes CD73 | - |
| Saccharomyces cerevisiae | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| B-lymphocyte | CD73 is a lymphocyte surface antigen | Homo sapiens | - |
| dendritic cell | CD73 | Homo sapiens | - |
| forestomach | CD73 | Homo sapiens | - |
| kidney | CD73 | Homo sapiens | - |
| additional information | the enzyme is ubiquitously expressed among cell types. Quantitative real time-PCR for determination of CD73 distribution. CD73 is widely expressed in vertebrate tissues and is prominently expressed on B and T cells and certain types of dendritic cells. It shows variable expression among cell types within other tissues including skeletal muscle, thymus, spleen, kidney and forestomach | Homo sapiens | - |
| skeletal muscle | CD73 | Homo sapiens | - |
| spleen | CD73 | Homo sapiens | - |
| T-lymphocyte | CD73 is a lymphocyte surface antigen | Homo sapiens | - |
| thymus | CD73 | Homo sapiens | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 16600 | - |
substrate IMP, 5'-nucleotidase Isn1, pH not specified in the publication, temperature not specified in the publication | Saccharomyces cerevisiae |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2'-chloro-2'-deoxyAMP + H2O | cNII | Homo sapiens | 2'-chloro-2'-deoxyadenosine + phosphate | - |
? | |
| 3'-azido-3'deoxy-dTMP + H2O | cNII | Homo sapiens | 3'-azido-3'-deoxythymidine + phosphate | - |
? | |
| 5'-AMP + H2O | - |
Homo sapiens | adenosine + phosphate | - |
? | |
| 5'-AMP + H2O | CD73 | Homo sapiens | adenosine + phosphate | - |
? | |
| 5'-CMP + H2O | - |
Homo sapiens | cytidine + phosphate | - |
? | |
| 5'-CMP + H2O | Sdt1 | Saccharomyces cerevisiae | cytidine + phosphate | - |
? | |
| 5'-CMP + H2O | CD73 | Homo sapiens | cytidine + phosphate | - |
? | |
| 5'-dCMP + H2O | - |
Homo sapiens | 2'-deoxycytidine + phosphate | - |
? | |
| 5'-dCMP + H2O | CD73 | Homo sapiens | 2'-deoxycytidine + phosphate | - |
? | |
| 5'-dGMP + H2O | - |
Homo sapiens | deoxyguanosine + phosphate | - |
? | |
| 5'-dGMP + H2O | cNII | Homo sapiens | deoxyguanosine + phosphate | - |
? | |
| 5'-dIMP + H2O | - |
Homo sapiens | deoxyinosine + phosphate | - |
? | |
| 5'-dIMP + H2O | cNII | Homo sapiens | deoxyinosine + phosphate | - |
? | |
| 5'-dTMP + H2O | - |
Homo sapiens | deoxythymidine + phosphate | - |
? | |
| 5'-dTMP + H2O | CD73 | Homo sapiens | deoxythymidine + phosphate | - |
? | |
| 5'-dUMP + H2O | - |
Homo sapiens | deoxyuridine + phosphate | - |
? | |
| 5'-dUMP + H2O | CD73 | Homo sapiens | deoxyuridine + phosphate | - |
? | |
| 5'-GMP + H2O | - |
Homo sapiens | guanosine + phosphate | - |
? | |
| 5'-GMP + H2O | cNII, CD73 | Homo sapiens | guanosine + phosphate | - |
? | |
| 5'-IMP + H2O | - |
Homo sapiens | inosine + phosphate | - |
? | |
| 5'-IMP + H2O | Isn1 | Saccharomyces cerevisiae | inosine + phosphate | - |
? | |
| 5'-IMP + H2O | cNII, CD73 | Homo sapiens | inosine + phosphate | - |
? | |
| 5'-UMP + H2O | - |
Homo sapiens | uridine + phosphate | - |
? | |
| 5'-UMP + H2O | Sdt1 | Saccharomyces cerevisiae | uridine + phosphate | - |
? | |
| 5'-UMP + H2O | CD73 | Homo sapiens | uridine + phosphate | - |
? | |
| 5'-XMP + H2O | - |
Homo sapiens | xanthosine + phosphate | - |
? | |
| 5'-XMP + H2O | cNII, CD73 | Homo sapiens | xanthosine + phosphate | - |
? | |
| 5-fluoro-dUMP + H2O | cNII | Homo sapiens | 5-fluoro-uridine + phosphate | - |
? | |
| additional information | Sdt1 is highly specific for 5'-UMP and 5'-CMP, and shows negligible activity on purine nucleoside monophosphates, 3'-monophosphates or nucleoside triphosphates | Saccharomyces cerevisiae | ? | - |
? | |
| additional information | Usha, Pho5, Sdt1 and Phm8 are phosphate starvation-induced 5'-nucleotidases with diverse substrate specificities that liberate phosphate under phosphate starvation conditions | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homodimer | CD73 | Homo sapiens |
| tetramer | cytosolic 5'-nucleotidase II, cNII, is a tetramer, formed from two homodimers | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 5'-nucleotidase | - |
Corynebacterium glutamicum |
| CD73 | - |
Homo sapiens |
| cNII | - |
Homo sapiens |
| cytosolic 5'-nucleotidase | - |
Homo sapiens |
| cytosolic 5'-nucleotidase II | - |
Homo sapiens |
| Isn1 | - |
Saccharomyces cerevisiae |
| membrane-bound 5'-nucleotidase | - |
Homo sapiens |
| More | cytosolic 5'-nucleotidases are members of the haloacid dehalogenase superfamily. CD73 belongs to a conserved superfamily of metallophosphodiesterases | Homo sapiens |
| More | the Isn1 polypeptide is a member of the HAD superfamily | Saccharomyces cerevisiae |
| NMN 5'-nucleotidase | - |
Saccharomyces cerevisiae |
| Phm8 | - |
Homo sapiens |
| Phm8 | - |
Saccharomyces cerevisiae |
| Pho5 | - |
Homo sapiens |
| Sdt1 | - |
Homo sapiens |
| Sdt1 | - |
Saccharomyces cerevisiae |
| UshA | - |
Homo sapiens |
| UshA | - |
Corynebacterium glutamicum |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Corynebacterium glutamicum | 5'-nucleotidase UshA is induced when phosphate is limiting | up |
| Saccharomyces cerevisiae | 5'-nucleotidases Sdt1 and Phm8 are induced at the transcript level by phosphate starvation | up |
| Homo sapiens | CD73 is highly induced by ischemia and hypoxia, and increased expression in cardiac ischemia is mediated by a positive feedback loop involving adenosine. Though CD73 is mainly regulated transcriptionally, cross linking of CD38, a cell surface glycoprotein with cyclic ADP-ribose hydrolase activity, causes upregulation of CD73 via export of protein to the cell surface that is independent of new transcription | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | cytosolic 5'-nucleotidase cN-II is implicated in drug resistance in patients and dephosphorylates 5-fluoro-dUMP, 3'-azido-3-dTMP, 2'-chloro-2'-deoxyAMP, and related compounds, which represent the monophosphorylated forms of nucleoside prodrugs | Homo sapiens |
| metabolism | 5'-nucleotidases are involved in the purine and pyrimidine nucleotide metabolic pathways, overview. CD73 enzymatic activity is implicated in two major extracellular metabolic pathways with distinct physiological roles, extracellular adenosine nucleotide and NAD+ metabolism | Homo sapiens |
| additional information | CD73 is highly induced by ischemia and hypoxia, and increased expression in cardiac ischemia is mediated by a positive feedback loop involving adenosine | Homo sapiens |
| physiological function | 5'-nucleotidase activities regulate the quantity of nucleotides generated from both de novo and salvage pathways, overview. 5'-Nucleotidase designates a set of enzymes, which catalyze the hydrolysis of ribonucleoside and deoxyribonucleoside monophosphates into the corresponding nucleosides plus phosphate. 5'-Nucleotidases are classified according to subcellular localization, nucleobase specificity and their ability to hydrolyze deoxynucleoside monophosphate substrates. Membrane-bound 5'-nucleotidases are ectoenzymes principally involved in salvage of extracellular nucleosides, and often display a preference toward adenosine monophosphate, thereby modulating signal transduction cascades involving purinergic receptors. Cytosolic 5'-nucleotidases are members of the haloacid dehalogenase superfamily of enzymes, which are two-domain proteins containing a modified Rossman fold as the core and a variable cap structure. Extracellular and intracellular 5'-nucleotidase activities participate in purine and pyrimidine salvage to support balanced synthesis of nucleotides, which is critical for maintaining high fidelity DNA replication. The major physiological roles for CD73 in extracellular adenosine metabolism are severalfold, overview. cNII is subject to complex allosteric regulation | Homo sapiens |
| physiological function | 5'-nucleotidase UshA is required for growth when nucleotides are provided as the sole source of phosphate, a condition that is likely relevant to bacterial growth in the wild | Corynebacterium glutamicum |
| physiological function | ISN1 is responsible for virtually all IMP 5'-nucleotidase activity in budding yeast cells and is required for cells to release inosine into the culture medium | Saccharomyces cerevisiae |
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