Difference between revisions of "Phosphatase Subfamily PTEN"
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PTEN is found in almost all eukaryotes. | PTEN is found in almost all eukaryotes. | ||
| − | ===Domain | + | ===Domain=== |
| − | PTENs typically have a phosphatase domain followed by a C2 domain. | + | PTENs typically have a phosphatase domain followed by a C2 domain. C2 domain tethers PTEN to vesicles by specifically binding to phosphatidylinositol 3-phosphate (PI(3)P) (the signature lipid of endosomes) through the CBR3 loop (see [http://www.cell.com/molecular-cell/abstract/S1097-2765(15)00176-8?rss=yes here]). |
| − | + | The N-terminus of human PTEN contains a nuclear localization signal (NLS) (7-31), an overlapping PIP2-binding motif (PBM) (6-15) and cytoplasmic localization signal (CLS) (19-25) (positions are numbered by human PTEN) <cite>Gil15</cite>. | |
| − | + | ===== Fungi lost C2 domain ===== | |
| + | Some homologs have PH (phospholipid-binding) or LIM domains. Yeast PTEN TEP1 lacks the C2 domain, but its functions as PTEN <cite>Heymont00</cite>. The C2 domain is actually absent from all fungi, but present in amoeba and basal eukaryotes (see technical notes). | ||
===Functions=== | ===Functions=== | ||
Revision as of 15:59, 29 June 2015
Phosphatase Classification: Superfamily CC1: Family PTEN: Subfamily PTEN
PTEN subfamily is named after its single member in human, PTEN, which dephosphorylates phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)P3 or PIP3). PTEN is one of the most commonly lost tumor suppressors in human cancer.
Evolution
PTEN is found in almost all eukaryotes.
Domain
PTENs typically have a phosphatase domain followed by a C2 domain. C2 domain tethers PTEN to vesicles by specifically binding to phosphatidylinositol 3-phosphate (PI(3)P) (the signature lipid of endosomes) through the CBR3 loop (see here).
The N-terminus of human PTEN contains a nuclear localization signal (NLS) (7-31), an overlapping PIP2-binding motif (PBM) (6-15) and cytoplasmic localization signal (CLS) (19-25) (positions are numbered by human PTEN) [1].
Fungi lost C2 domain
Some homologs have PH (phospholipid-binding) or LIM domains. Yeast PTEN TEP1 lacks the C2 domain, but its functions as PTEN [2]. The C2 domain is actually absent from all fungi, but present in amoeba and basal eukaryotes (see technical notes).
Functions
PTEN is a critical negative regulator of PI3K signaling. PI3K produce the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PI (3,4,5)) trisphosphate (PI(3,4,5)P3/PIP3) in response to activation of receptor tyrosine kinases (RTKs), G-protein-coupled receptors, or membrane-bound oncogenes [3, 4]. It dephosphorylates the lipid second messenger, PI (3,4,5) [5]. It is tumor suppressor among the most frequently altered genes in cancer [6, 7].
References
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- Error fetching PMID 11070083:
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- Error fetching PMID 9593664:
- Error fetching PMID 9072974:
- Error fetching PMID 9090379:
