Phosphatase Subfamily PTEN - Revision history

Gerard at 15:11, 22 March 2017

2017-03-22T15:11:19Z

Gerard at 13:23, 9 September 2016

2016-09-09T13:23:23Z

Mark: /* References */

2016-04-27T20:45:30Z

‎References

Mark: /* Functions */

2016-04-27T20:44:58Z

‎Functions

Gerard at 00:47, 2 April 2016

2016-04-02T00:47:56Z

Mark: /* References */

2015-07-01T21:15:15Z

‎References

Mark: /* Functions */

2015-07-01T21:14:54Z

‎Functions

Mark at 20:53, 1 July 2015

2015-07-01T20:53:08Z

Mark: /* Fungi lost C2 domain */

2015-06-29T16:09:14Z

‎Fungi lost C2 domain

Mark at 16:07, 29 June 2015

2015-06-29T16:07:41Z

@@ Line 25: / Line 25: @@
 === Technical notes ===
 ===== Fungal loss of the 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.
+We observed the absence of C2 domain in budding yeast and its presence in Dictyostelium. 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===

@@ Line 14: / Line 14: @@
 ===== Fungal loss of C2 domain =====
 The C2 domain is lost from all fungi, including S. cerevisiae TEP1, though it still functions as a PTEN <cite>Heymont00</cite>. The C2 domain is present in animals, Dictyostelium, and other basal eukaryotes  (see technical notes). Some fungal homologs have PH (phospholipid-binding) or LIM domains.
 ===Functions===
@@ Line 36: / Line 39: @@
 #Steck97 pmid=9090379
 #Vanhaesebroeck12 pmid=22358332
 </biblio>

@@ Line 32: / Line 32: @@
 #Maehama98 pmid=9593664
 #Naguib15 pmid=25866245
 #Stambolic15 pmid=26017306
 #Steck97 pmid=9090379
 #Vanhaesebroeck12 pmid=22358332
 </biblio>

@@ Line 16: / Line 16: @@
 ===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  <cite>Engelman06, Vanhaesebroeck12</cite>. It dephosphorylates the lipid second messenger, PI (3,4,5) <cite>Maehama98</cite>. 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 <cite> Stambolic15</cite>. PTEN is a tumor suppressor and among the most frequently altered genes in cancer <cite>Li97, Steck97</cite>.
+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  <cite>Engelman06, Vanhaesebroeck12</cite>. It dephosphorylates the lipid second messenger, PI (3,4,5) <cite>Maehama98</cite>. 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 <cite> Stambolic15</cite>.
 === Technical notes ===

@@ Line 1: / Line 1: @@
 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_PTEN|Family PTEN]]: [[Phosphatase_Subfamily_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.
+PTEN 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===
@@ Line 9: / Line 10: @@
 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 <cite>Naguib15</cite>.
-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>.
+The N-terminus of human PTEN contains a nuclear localization signal (NLS) (7-31), an overlapping PIP2-binding motif (PBM) (6-15) and a cytoplasmic localization signal (CLS) (19-25) (positions are numbered by human PTEN) <cite>Gil15</cite>.
-===== Fungi lost C2 domain =====
+===== Fungal loss of 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).
+The C2 domain is lost from all fungi, including S. cerevisiae TEP1, though it still functions as a PTEN <cite>Heymont00</cite>. The C2 domain is present in animals, Dictyostelium, and other basal eukaryotes  (see technical notes). Some fungal homologs have PH (phospholipid-binding) or LIM domains.
 ===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  <cite>Engelman06, Vanhaesebroeck12</cite>. It dephosphorylates the lipid second messenger, PI (3,4,5) <cite>Maehama98</cite>. 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 <cite> Stambolic15</cite>. PTEN is tumor suppressor among the most frequently altered genes in cancer <cite>Li97, Steck97</cite>.
+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  <cite>Engelman06, Vanhaesebroeck12</cite>. It dephosphorylates the lipid second messenger, PI (3,4,5) <cite>Maehama98</cite>. 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 <cite> Stambolic15</cite>. PTEN is a tumor suppressor and among the most frequently altered genes in cancer <cite>Li97, Steck97</cite>.
 === Technical notes ===
-===== Fungi lost C2 domain =====
+===== Fungal loss of the 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.