Difference between revisions of "Phosphatase Subfamily PTEN"
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Revision as of 21:15, 1 July 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 [1].
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) [2].
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 [3]. 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 [4, 5]. It dephosphorylates the lipid second messenger, PI (3,4,5) [6]. It is mostly found in the cell cytoplasm, tethered to endosome vesicles. This localization regulates the enzyme’s activity towards specific lipids and influences its control of cell growth [7]. PTEN is tumor suppressor among the most frequently altered genes in cancer [8, 9].
Technical notes
Fungi lost C2 domain
We observed the absence of C2 domain in budding yeast and its presence in Dictystelium. We then asked i) whether C2 domain is generally absent from all fungi, ii) whether C2 domain is generally present in amoeba and/or basal eukaryotes, which means the presence of C2 domain before fungi diverged from other eukaryotes and lost C2 domain. To answer the questions, we BLASTed the sequence of the C2 domain of human PTEN (188-379) against NR dataset limiting the organisms to non-metazoa eukaryotes using NCBI BLAST server. We then manually looked through the domain combination of the hits of amoebazoa and basal eukaryotes through the link to sequence page, which has the link of conserved domain. In brief, we found, i) no hit from fungi, ii) the hits from amoebazoa and basal eukaryotes usually have the C2 domain.
References
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- Error fetching PMID 25875300:
- Error fetching PMID 11070083:
- Error fetching PMID 16847462:
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- Error fetching PMID 9593664:
- Error fetching PMID 26017306:
- Error fetching PMID 9072974:
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