Phosphatase Subamily Paladin - Revision history

Gerard: /* Domain */

2016-12-21T23:05:51Z

‎Domain

Gerard: /* Function */

2016-09-10T17:31:23Z

‎Function

Gerard: /* Function */

2016-09-10T17:30:56Z

‎Function

Gerard: /* Evolution */

2016-03-17T02:46:46Z

‎Evolution

Gerard at 03:42, 1 February 2016

2016-02-01T03:42:00Z

Gerard: /* Function */

2016-02-01T03:18:07Z

‎Function

Gerard: /* Function */

2016-02-01T01:43:44Z

‎Function

Gerard: /* Domain */

2016-01-31T23:52:00Z

‎Domain

Gerard: /* Domain */

2016-01-31T23:48:43Z

‎Domain

Gerard: /* Domain */

2016-01-31T23:48:09Z

‎Domain

@@ Line 6: / Line 6: @@
 === Domain ===
-Paladins have two CC1 phosphatase domains similar to each other in sequence. They are similar to bacterial cysteine [https://en.wikipedia.org/wiki/Phytase phytases] whose crystal structures have a CC1 fold (so called "PTP-like") <cite>Chu04, Gruninger12, Gruninger14, Weber14</cite>. It is not known whether paladin acts as a protein or non-protein phosphatases. Most Paladins have two active domains, as seen by retention of the Cx5R catalytic motif, but some have a single inactive domain, and rarely, both domains are inactive.
+Paladins have two CC1 phosphatase domains similar to each other in sequence. They are similar to bacterial cysteine [https://en.wikipedia.org/wiki/Phytase phytases] whose crystal structures have a CC1 fold (so called "PTP-like") <cite>Chu04, Gruninger12, Gruninger14, Weber14</cite>. It is not known whether paladin acts as a protein or non-protein phosphatases. Most Paladins have two active domains, as seen by retention of the Cx5R catalytic motif, but some have a single inactive domain, and rarely (e.g. in sea urchin), both domains are inactive.
 Notes:

@@ Line 13: / Line 13: @@
 === Function ===
-Paladin has been very little studied. Human Paladin (PALD, PALD1) was shown to inhibit insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not shown if paladin is an Akt phosphatase <cite>Huang</cite>. In a related [http://www.google.com.na/patents/WO2006052510A2?cl=en patent filing] it was claimed that mutation of the catalytic cysteine in the first domain abolished this activity, but mutation of the second domain did not, and that paladin physically associates with the insulin receptor. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>. Paladin has been claimed to be an 'antiphosphatase' <cite></cite> because it's neural crest phenotype is independent of one of the catalytic cysteines, but that does not exclude a catalytic role in other functions.
+Paladin has been very little studied. Human Paladin (PALD, PALD1) was shown to inhibit insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not shown if paladin is an Akt phosphatase <cite>Huang</cite>. In a related [http://www.google.com.na/patents/WO2006052510A2?cl=en patent filing] it was claimed that mutation of the catalytic cysteine in the first domain abolished this activity, but mutation of the second domain did not, and that paladin physically associates with the insulin receptor. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>. Paladin has been claimed to be an 'antiphosphatase' <cite>Roffers-Agarwal12</cite> because its neural crest phenotype is independent of one of the catalytic cysteines, but that does not exclude a catalytic role in other functions.
 === References ===

@@ Line 13: / Line 13: @@
 === Function ===
-Paladin has been very little studied. Human Paladin (PALD, PALD1) was shown to inhibit of insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not determined if paladin is an Akt phosphatase <cite>Huang</cite>. In a related [http://www.google.com.na/patents/WO2006052510A2?cl=en patent filing] it was claimed that mutation of the catalytic cysteine in the first domain abolished this activity, but mutation of the second domain did not, and that paladin physically associates with the insulin receptor. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>.
+Paladin has been very little studied. Human Paladin (PALD, PALD1) was shown to inhibit insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not shown if paladin is an Akt phosphatase <cite>Huang</cite>. In a related [http://www.google.com.na/patents/WO2006052510A2?cl=en patent filing] it was claimed that mutation of the catalytic cysteine in the first domain abolished this activity, but mutation of the second domain did not, and that paladin physically associates with the insulin receptor. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>. Paladin has been claimed to be an 'antiphosphatase' <cite></cite> because it's neural crest phenotype is independent of one of the catalytic cysteines, but that does not exclude a catalytic role in other functions.
 === References ===

@@ Line 3: / Line 3: @@
 === Evolution ===
-Paladins are found in vertebrates and early metazoa such as sponge, trichoplax and nematostella but absent from arthropoda and nematoda. Paladins are also found in most plants and a small number of fungi (see internal database [http://resdev.gene.com/gOrtholog/view/cluster/MC0005718/overview gOrtholog]).
+Paladins are found in vertebrates and early metazoa such as sponge, trichoplax and nematostella but absent from arthropods and nematodes. Paladins are also found in most plants and a small number of fungi (see internal database [http://resdev.gene.com/gOrtholog/view/cluster/MC0005718/overview gOrtholog]).
 === Domain ===

@@ Line 13: / Line 13: @@
 === Function ===
-Paladin has been very little studied. Human Paladin (PALD, PALD1) was shown to inhibit of insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not determined if paladin is an Akt phosphatase. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>.
+Paladin has been very little studied. Human Paladin (PALD, PALD1) was shown to inhibit of insulin signaling by decreasing phosphorylation of Akt, both by knockdown and overexpression, though it was not determined if paladin is an Akt phosphatase <cite>Huang</cite>. In a related [http://www.google.com.na/patents/WO2006052510A2?cl=en patent filing] it was claimed that mutation of the catalytic cysteine in the first domain abolished this activity, but mutation of the second domain did not, and that paladin physically associates with the insulin receptor. Similar over- and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function. Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>.
 === References ===

@@ Line 15: / Line 15: @@
 Paladin has been very little studied. Human Paladin (PALD, PALD1) was found as an inhibitor of insulin signaling by knockdown and overexpression. Similar over and under-expression showed a role in neural crest cell formation and migration in chicken <cite>Roffers-Agarwal12</cite> and mutation of the two Cx5R cysteines did not affect this function.
-Paladin's physiological substrate(s) is unclear. But, the bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>.
+Paladin's physiological substrate(s) is unclear. Bacterial cysteine phytases dephosphorylate myo-inositol 1,2,3,4,5,6-hexakisphosphate, but not pTyr <cite>Chu04</cite>.
 === References ===

@@ Line 6: / Line 6: @@
 === Domain ===
-The Paladin subfamily has two phosphatase domains close to each in sequence. Both domains are homologous to cysteine phytases in bacteria whose crystal structures have a CC1 fold (so called "PTP-like") <cite>Chu04, Gruninger12, Gruninger14, Weber14</cite>. Similar to protein phosphatases of CC1 fold such as PTPs and DSPs, these phytases are cysteine-based and have CX<sub>5</sub>R motif. Both of phosphatase domains of paladin contain CX<sub>5</sub>R motif. Based upon our current understanding of CC1 fold phosphatases, we predict paladin to be catalytically active.
+Paladins have two CC1 phosphatase domains similar to each other in sequence. They are similar to bacterial cysteine phytases whose crystal structures have a CC1 fold (so called "PTP-like") <cite>Chu04, Gruninger12, Gruninger14, Weber14</cite>. Similar to protein phosphatases of CC1 fold such as PTPs and DSPs, these phytases are cysteine-based and have CX<sub>5</sub>R motif. Both of phosphatase domains of paladin contain CX<sub>5</sub>R motif. Based upon our current understanding of CC1 fold phosphatases, we predict paladin to be catalytically active.
 Notes:
 * The cysteine phytases is a class of phytases. The phytases remove phosphate from myo-inositol 1,2,3,4,5,6-hexakisphosphate. They have four distinct folds, including purple acid phosphatase in human.
 * The homology between paladin and cysteine phytases were detected by HHpred and BLASTing against PDB database. The top hits of HHpred are cysteine phytases with identity around 20% followed by DSPs with slightly higher identity but lower coverage.
 === Function ===