Phosphatase Family PHP - Revision history

Gerard: /* Functions */

2016-05-14T22:38:21Z

‎Functions

2016-05-14T22:37:51Z

‎Evolution

2016-05-14T22:37:31Z

‎Evolution

2015-06-02T17:18:33Z

‎Evolution

2015-06-02T17:16:55Z

2015-06-02T01:44:38Z

2015-06-02T01:44:20Z

‎Evolution

2015-06-02T01:43:06Z

‎Evolution

2015-06-02T01:35:42Z

‎Domain

2015-06-01T23:38:11Z

@@ Line 17: / Line 17: @@
 === Functions ===
-Several substrates have been reported, including ''beta'' subunit of heterotrimeric G proteins <cite>Maurer04</cite>, the metabolic enzyme adenosine 5’-triphosphate-citrate lyase (ACL) <cite>Klumpp03</cite>, and the Ca2+-activated K+ channel KCa3.1 <cite>Skolnik08</cite>. These are known or suspected substrates of the nucleoside diphosphate kinases ([http://kinase.com/wiki/index.php/Kinase_Group_NDK NDK]).
+Several substrates have been reported, including beta subunit of heterotrimeric G proteins <cite>Maurer04</cite>, the metabolic enzyme adenosine 5’-triphosphate-citrate lyase (ACL) <cite>Klumpp03</cite>, and the Ca2+-activated K+ channel KCa3.1 <cite>Skolnik08</cite>. These are known or suspected substrates of the nucleoside diphosphate kinases ([http://kinase.com/wiki/index.php/Kinase_Group_NDK NDK]).
 Its role in neuronal cells is particularly interesting. Human PHP (PHPT1) is widely expressed across different tissues, most abundantly in cerebellum and pituitary, according to RNA-seq data from [http://www.gtexportal.org/home/gene/PHPT1 GTEx]. In ''C. elegans'', PHP is expressed exclusively in neurons <cite>Klumpp02</cite>. In human cells, the overexpression of PHPT1 decreases the activity of adenosine 5’-triphosphate-citrate lyase (ACL) and reduces the viability of neuronal cells <cite>Klumpp09</cite>.

@@ Line 11: / Line 11: @@
 * Motif 4: 75 GGGx[RK]IxH 81
 * Motif 5: 92 GxSxxxGxAxH 102
-Note: His-53 and Lys-21 are critical to its catalytic activity (see below).
+His-53 and Lys-21 are required for catalytic activity (see below).
 === Domain ===

@@ Line 5: / Line 5: @@
 === Evolution ===
-PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in ''Drosophila melanogaster''. Three of them (janA, janB, con) arranged as tandem duplications which are conserved other flies of melanogaster group. The janA is canonical PHP, but the other three have substitution at conserved positions  of canonical PHPs (memo: carry out positive selection analysis to infer whether they evolved different functions). The most conserved positions include:
+PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in ''Drosophila melanogaster''. Three of them (janA, janB, con) arranged as tandem duplications which are conserved other flies of melanogaster group. The janA is canonical PHP, but the other three have substitution at conserved positions  of canonical PHPs. The most conserved positions include:
 * Motif 1: 18 GxFKY 22
 * Motif 2: 45 RG 46

@@ Line 5: / Line 5: @@
 === Evolution ===
-PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in ''Drosophila melanogaster''. Three of them (janA, janB, con) arranged as tandem duplications which are conserved other flies of melanogaster group. The janA is canonical PHP, but the other three have substitution at conserved positions  of canonical PHPs (memo: carry out positive selection analysis to infer whether they evolved different functions). They The most conserved positions include:
+PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in ''Drosophila melanogaster''. Three of them (janA, janB, con) arranged as tandem duplications which are conserved other flies of melanogaster group. The janA is canonical PHP, but the other three have substitution at conserved positions  of canonical PHPs (memo: carry out positive selection analysis to infer whether they evolved different functions). The most conserved positions include:
 * Motif 1: 18 GxFKY 22
 * Motif 2: 45 RG 46

@@ Line 5: / Line 5: @@
 === Evolution ===
-PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in fruit fly. The most conserved positions include:
+PHP is found throughout eukaryotes, though lost from fungi. It is usually single copy per genome, but four are found in ''Drosophila melanogaster''. Three of them (janA, janB, con) arranged as tandem duplications which are conserved other flies of melanogaster group. The janA is canonical PHP, but the other three have substitution at conserved positions  of canonical PHPs (memo: carry out positive selection analysis to infer whether they evolved different functions). They The most conserved positions include:
 * Motif 1: 18 GxFKY 22
 * Motif 2: 45 RG 46

@@ Line 8: / Line 8: @@
 === Domain ===
-PHP has a single domain: catalytic domain. The structure of the domain has been solved and a potential enzymatic mechanism proposed <cite>Gong</cite>.
+PHP has a single domain: catalytic domain. The structure of the domain has been solved and a potential enzymatic mechanism proposed (see figure 4 in <cite>Gong</cite>): (i) the substrate binds to the protein by forming four H-bonds; (ii) His-53 acts as a general base to activate a water molecule, which in turn functions as a nucleophile to attack the phosphate substrate; and (iii) the positively charged amine group of Lys-21 helps in stabilizing the transition state during catalysis.
 === Functions ===

@@ Line 13: / Line 13: @@
 Several substrates have been reported, including ''beta'' subunit of heterotrimeric G proteins <cite>Maurer04</cite>, the metabolic enzyme adenosine 5’-triphosphate-citrate lyase (ACL) <cite>Klumpp03</cite>, and the Ca2+-activated K+ channel KCa3.1 <cite>Skolnik08</cite>. These are known or suspected substrates of the nucleoside diphosphate kinases ([http://kinase.com/wiki/index.php/Kinase_Group_NDK NDK]).
-Its role in neuronal cells is particularly interesting. In ''C. elegans'', PHP is expressed exclusively in neurons <cite>Klumpp02</cite>. In human cells, the overexpression of PHPT1 decreases the activity of adenosine 5’-triphosphate-citrate lyase (ACL) and reduces the viability of neuronal cells <cite>Klumpp09</cite>.
+Its role in neuronal cells is particularly interesting. Human PHP (PHPT1) is widely expressed across different tissues, most abundantly in cerebellum and pituitary, according to RNA-seq data from [http://www.gtexportal.org/home/gene/PHPT1 GTEx]. In ''C. elegans'', PHP is expressed exclusively in neurons <cite>Klumpp02</cite>. In human cells, the overexpression of PHPT1 decreases the activity of adenosine 5’-triphosphate-citrate lyase (ACL) and reduces the viability of neuronal cells <cite>Klumpp09</cite>.
 === References ===