Activating Compound | Comment | Organism | Structure |
---|---|---|---|
phosphatidylinositol 4,5-biphosphate | Enhances PTEN phosphatase activity by inducing conformational change by binding to the PTEN N-terminal domain. Binding constants are in accord with enzyme kinetic measurements showing that phosphatidylinositol 4,5-bisphosphate enhances phosphatidylinositol 3,4,5-triphosphate hydrolysis more effectively than phosphatidylserine, and the binding constant of phosphatidylinositol 4,5-biphosphate of 8.14 microM is in general agreement with the phosphatidylinositol 4,5-bisphosphate concentration requires to activate the PTEN phosphatase. The magnitude of this binding constant indicates that PTEN-phosphatidylinositol 4,5-bisphosphate interactions are physiologically relevant since the effective cellular concentration of phosphatidylinositol 4,5-bisphosphate is thought to be 10 microM, and local phosphatidylinositol 4,5-bisphosphate concentrations are likely to reach even higher levels. Increasing the phosphatidylserine concentration to 25 mol results in stronger binding, but even for these higher surface charge densities, binding constant is still lower than the corresponding values for the phosphatidylcholine/phosphatidylinositol 4,5-bisphosphate vesicle system. | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
The cDNA encoding full-length 1-403 PTEN is cloned into the NdeI and XhoI sites of the pET30b vector, thereby introducing a poly-His tag at the C-terminus. Point mutations are introduced with the Quick-Change site-directed mutagenesis kit. Deletion mutant 16-403 is prepared by PCR with the Phusion DNA polymerase. PTEN proteins are expressed in Escherichia coli BL21 (DE3) cells. | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
DELTA1-15 | phosphatidylinositol 4,5-biphosphate has no effect on binding of PTEN16-403 | Homo sapiens |
K13E | the binding of the PTEN mutant K13E, which is a tumor-derived mutation that renders PTEN inactive, is not affected by phosphatidylinositol 4,5-biphosphate | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | N-terminal domain of PTEN binds anionic lipids via nonspecific electrostatic interactions | ? | - |
? | |
additional information | Homo sapiens | PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that is mutated or deleted in a variety of human tumors, and even loss of only one PTEN gene profoundly affects carcinogenesis | ? | - |
? | |
additional information | Homo sapiens | PTEN binds synergistically phosphatidylinositol 4,5-biphosphate and phosphatidylserine | ? | - |
? | |
additional information | Homo sapiens | PTEN encodes a phosphatidylinositol phosphate phosphatase specific for the 3-position of the inositol ring, it influences many biological processes in both developing and adult organisms | ? | - |
? | |
phosphatidylinositol 3,4,5-triphosphate + H2O | Homo sapiens | - |
phosphatidylinositol 4,5-bisphosphate + phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
Poly-His tag proteins are purified with a HisTrap HP kit using buffers with 10 mM mercaptoethanol, enzymes are further purified with a gel filtration column in 100 mM NaCl, 10 mM Tris, pH 7.4, and 1 mM dithiothreitol. Final purification is done with a anion exchange column in 10 mM Tris, pH 7.4 with a linear gradient from 50-600 mM NaCl. | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | N-terminal domain of PTEN binds anionic lipids via nonspecific electrostatic interactions | Homo sapiens | ? | - |
? | |
additional information | PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that is mutated or deleted in a variety of human tumors, and even loss of only one PTEN gene profoundly affects carcinogenesis | Homo sapiens | ? | - |
? | |
additional information | PTEN binds synergistically phosphatidylinositol 4,5-biphosphate and phosphatidylserine | Homo sapiens | ? | - |
? | |
additional information | PTEN encodes a phosphatidylinositol phosphate phosphatase specific for the 3-position of the inositol ring, it influences many biological processes in both developing and adult organisms | Homo sapiens | ? | - |
? | |
phosphatidylinositol 3,4,5-triphosphate + H2O | - |
Homo sapiens | phosphatidylinositol 4,5-bisphosphate + phosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
PTEN | - |
Homo sapiens |
PTEN phosphatase | - |
Homo sapiens |