Literature summary for 3.1.3.67 extracted from

Leslie, N.R.; Batty, I.H.; Maccario, H.; Davidson, L.; Downes, C.P.
Understanding PTEN regulation: PIP2, polarity and protein stability (2008), Oncogene, 27, 5464-5476.

Activating Compound

Activating Compound	Comment	Organism	Structure
acidic lipids	acidic lipids, and phosphatidylinositol 4,5-bisphosphate in particular, cause a conformational change within the enzyme and allosteric activation	Homo sapiens
additional information	treatment of many cell types with proteasome inhibitors enhances the levels of PTEN protein	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
S380A	greater catalytic activity than an unphosphorylated, bacterially expressed wild type enzyme	Homo sapiens
T382A	greater catalytic activity than an unphosphorylated, bacterially expressed wild type enzyme	Homo sapiens
T383A	greater catalytic activity than an unphosphorylated, bacterially expressed wild type enzyme	Homo sapiens

General Stability

General Stability	Organism
the PDZ-binding domain binds to several proteins, including MAGI-2 and MAST205, these interactions appear to enhance the stability of PTEN, as interference with either these binding partners or the ability of PTEN to bind them greatly reduces stability. A protein named PICT-1 (protein interacting with the C-tail-1) interacts with the C-terminus of PTEN, promoting both phosphorylation and stability of PTEN	Homo sapiens

Organism

the PDZ-binding domain binds to several proteins, including MAGI-2 and MAST205, these interactions appear to enhance the stability of PTEN, as interference with either these binding partners or the ability of PTEN to bind them greatly reduces stability. A protein named PICT-1 (protein interacting with the C-tail-1) interacts with the C-terminus of PTEN, promoting both phosphorylation and stability of PTEN

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
additional information	PTEN function is very frequently lost during the development of epithelial-derived tumors, and many such tumors are believed to undergo a form of epithelial to mesenchymal transition before these metastasize	Homo sapiens
reactive oxygen species	oxidation of the active site cysteine by reactive oxygen species inhibits PTEN	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-
nucleus	-	Homo sapiens	5634	-
plasma membrane	stably, but transiently bound	Homo sapiens	5886	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O	Homo sapiens	dual-specific phosphatase	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + phosphate	-	?
additional information	Homo sapiens	PTEN acts to suppress cell growth, proliferation and survival, and in a more cell-specific manner, PTEN plays a role in the establishment of polarity and inhibits the migration of several mammalian cell types	?	-	?
additional information	Homo sapiens	PTEN exists in a high activity state when it binds transiently at membrane surfaces containing its substrate and other lipids, such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine	?	-	?
additional information	Homo sapiens	the PTEN tumor suppressor is a lipid and protein phosphatase that inhibits phosphoinositide 3-kinase-dependent signalling by dephosphorylating phosphatidylinositol 3,4,5-trisphosphate	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
acetylation	inhibiton of PTEN	Homo sapiens
phosphoprotein	phosphorylation of several serine and threonine residues in the C-terminus of the protein inhibits PTEN, e.g., suppressing of membrane association, nuclear localization, PDZ-binding, ubiquitination, degradation and phosphatase activity. The phosphorylation sites form 2 separable groups comprising a close cluster of 4 residues, Ser380, Thr382, Thr383 and Ser385, and a pair of residues slightly more N-terminal, Thr366 and Ser370. The 380-385 cluster sites all appear to be phosphorylated by protein kinase CK2.	Homo sapiens
phosphoprotein	tyrosine residues, present in most examples of a rare subset of lung tumours, but not detected in the great majority. PTEN tyrosine phosphorylation may occur only in certain cell types and circumstances, or that only an extremely small proportion of the cellular PTEN becomes tyrosine phosphorylated	Homo sapiens
ubiquitination	regulation of activity, mono- and polyubiquitinated, PTEN has 2 canonical PEST motifs, a signature in many short-lived proteins degraded by ubiquitin-proteasome pathway, controlling of nuclear localization and PTEN stability	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
B-lymphocyte	-	Homo sapiens	-
cardiac muscle	-	Homo sapiens	-
epithelial cell	-	Homo sapiens	-
fibroblast	-	Homo sapiens	-
HEK-293 cell	-	Homo sapiens	-
HeLa cell	-	Homo sapiens	-
lung	-	Homo sapiens	-
skeletal muscle	-	Homo sapiens	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
additional information	-	PTEN is an interfacially activated enzyme. PTEN can exist in 2 active states, one favouring metabolism of soluble substrates and the interfacially activity state is necessary for efficient metabolism of phosphatidylinositol 3,4,5-trisphosphate.	Homo sapiens
additional information	-	regulation of PTEN activity and expression serves not only to modulate the temporal and spatial distribution of phosphatidylinositol 3,4,5-trisphosphate but also its availability for an alternative route of metabolism to phosphatidylinositol 4,5-bisphosphate by 5-phosphatases	Homo sapiens
additional information	-	the scale of the interfacial activation when PTEN associates with a membrane or vesicular substrate depends largely on the composition of the membrane and particularly its surface characteristics, these includes the overall surface charge, largely determined both by its phosphatidylserine content and on the presence of phosphatidylinositol 4,5-bisphosphate	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + H2O	dual-specific phosphatase	Homo sapiens	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + phosphate	-	?
additional information	PTEN acts to suppress cell growth, proliferation and survival, and in a more cell-specific manner, PTEN plays a role in the establishment of polarity and inhibits the migration of several mammalian cell types	Homo sapiens	?	-	?
additional information	PTEN exists in a high activity state when it binds transiently at membrane surfaces containing its substrate and other lipids, such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine	Homo sapiens	?	-	?
additional information	the PTEN tumor suppressor is a lipid and protein phosphatase that inhibits phosphoinositide 3-kinase-dependent signalling by dephosphorylating phosphatidylinositol 3,4,5-trisphosphate	Homo sapiens	?	-	?
additional information	oxidation of PTEN by H2O2 oxidative stress in vitro leads to the formation of a disulfide bond between the active site Cys124 and another very closely Cys71, activates the phosphoinositide 3-kinase-dependent pathway	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
PTEN	-	Homo sapiens