Phosphatase Subfamily PGAM5 - Revision history

Gerard at 22:51, 25 October 2016

2016-10-25T22:51:23Z

Mark at 18:16, 23 September 2015

2015-09-23T18:16:07Z

Mark: /* References */

2015-09-23T18:14:28Z

‎References

Mark: /* Functions */

2015-09-23T18:14:12Z

‎Functions

Mark at 20:19, 2 June 2015

2015-06-02T20:19:33Z

Mark: /* Functions */

2015-06-02T20:19:08Z

‎Functions

Mark: /* Domain */

2015-06-02T20:11:31Z

‎Domain

Mark: /* Domain Structure */

2015-06-02T20:10:09Z

‎Domain Structure

Mark at 20:09, 2 June 2015

2015-06-02T20:09:57Z

Mark: /* Functions */

2015-06-02T19:45:31Z

‎Functions

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 __NOTOC__
-[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PGAM5|Subfamily PGAM5]]
+[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]]:  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PGAM5|Subfamily PGAM5]]
 PGAM5 is a mitochondrial protein serine phosphatase with multiple distinct substrates.

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 #chen14 pmid=24746696
 #Kang15 pmid=26381214
 </biblio>

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 #PGAM5_2 pmid=22265414
 #chen14 pmid=24746696
 </biblio>

← Older revision		Revision as of 18:14, 23 September 2015
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	* FUNDC1. Human PGAM5 also dephosphorylates FUNDC1 at Ser-13 and thereby activates mitophagy <cite>chen14</cite>.		* FUNDC1. Human PGAM5 also dephosphorylates FUNDC1 at Ser-13 and thereby activates mitophagy <cite>chen14</cite>.
		+
		+	PGAM5 is activated by RIPK3 in the immune responses to tumours and liver inflammation mediated by natural killer T-cells <cite>Kang15</cite>.

	PGAM5 is specifically expressed in testis, according to [http://www.gtexportal.org/home/gene/PGAM5 GTEx]. Its known substrates do not have similar tissue-specific expression pattern according to GTEx data: [http://www.gtexportal.org/home/gene/MAP3K5 ASK1 (MAP3K5)] is widely expressed, most abundant in adrenal gland and ovary; [http://www.gtexportal.org/home/gene/DNM1L Drp1 (DNM1L)] is widely expressed, most abundant in brain; [http://www.gtexportal.org/home/gene/FUNDC1 FUNDC1] is also widely expressed in different tissues.		PGAM5 is specifically expressed in testis, according to [http://www.gtexportal.org/home/gene/PGAM5 GTEx]. Its known substrates do not have similar tissue-specific expression pattern according to GTEx data: [http://www.gtexportal.org/home/gene/MAP3K5 ASK1 (MAP3K5)] is widely expressed, most abundant in adrenal gland and ovary; [http://www.gtexportal.org/home/gene/DNM1L Drp1 (DNM1L)] is widely expressed, most abundant in brain; [http://www.gtexportal.org/home/gene/FUNDC1 FUNDC1] is also widely expressed in different tissues.

@@ Line 2: / Line 2: @@
 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_HP|Fold HP]]: [[Phosphatase_Superfamily_HP|Superfamily HP]] (histidine phosphatase):  [[Phosphatase_Family_HP1|HP, branch1 family]]: [[Phosphatase_Subfamily_PGAM5|Subfamily PGAM5]]
-PGAM5 is a mitochondrial protein phosphatase with multiple distinct substrates.
+PGAM5 is a mitochondrial protein serine phosphatase with multiple distinct substrates.
 === Evolution ===

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 === Functions ===
-PGAM5 dephosphorylates and activates MAP kinase kinase kinase ASK1 (MAP3K5). PGAM5 is anchored in the mitochondrial membrane and it lacks mutase activity, but instead it associates with ASK1 and activates ASK1 by dephosphorylation of inhibitory sites. Mutation of an active site His-105 in PGAM5 abolished phosphatase activity with ASK1 and pThr peptides as substrates <cite>PGAM5_1</cite>. The Drosophila and ''Caenorhabditis elegans'' orthologs of PGAM5 also exhibit specific Ser/Thr phosphatase activity and activate the corresponding Drosophila and ''C. elegans'' ASK1 kinases <cite>PGAM5_1</cite>.
+PGAM5 is anchored in the mitochondrial membrane <cite>Sekine12, PGAM5_1</cite>. It functions as phosphatase rather than mutase. Its substrates include:
-PGAM5 also dephosphorylates the Ser-637 site of the GTPase Drp1 (DNM1L, dynamin 1-like) as a member of a RIP1- and RIP3-containing protein complex in response to necrosis induction. The dephosphorylation activates the GTPase activity of Drp1 and causes mitochondrial fragmentation, an early and obligatory step for necrosis <cite>PGAM5_2</cite>.
+* ASK1 (MAP3K5). PGAM5 dephosphorylates and activates MAP kinase kinase kinase ASK1 (MAP3K5). Mutation of an active site His-105 in PGAM5 abolished phosphatase activity with ASK1 and pThr peptides as substrates <cite>PGAM5_1</cite>. The Drosophila and ''Caenorhabditis elegans'' orthologs of PGAM5 also exhibit specific Ser/Thr phosphatase activity and activate the corresponding Drosophila and ''C. elegans'' ASK1 kinases <cite>PGAM5_1</cite>. The authors of <cite>PGAM5_1</cite> have tried but failed to find out the substrate residues of ASK1. They ruled out the possibility of Ser-83, Ser-966, and Ser-1033, though.
-Human PGAM5 also dephosphorylates FUNDC1 at Ser-13 and thereby activates mitophagy <cite>chen14</cite>.
+* Drp1 (DNM1L). PGAM5 also dephosphorylates the Ser-637 site of the GTPase Drp1 (DNM1L, dynamin 1-like) as a member of a RIP1- and RIP3-containing protein complex in response to necrosis induction. The dephosphorylation activates the GTPase activity of Drp1 and causes mitochondrial fragmentation, an early and obligatory step for necrosis <cite>PGAM5_2</cite>.
 PGAM5 is specifically expressed in testis, according to [http://www.gtexportal.org/home/gene/PGAM5 GTEx]. Its known substrates do not have similar tissue-specific expression pattern according to GTEx data: [http://www.gtexportal.org/home/gene/MAP3K5 ASK1 (MAP3K5)] is widely expressed, most abundant in adrenal gland and ovary;  [http://www.gtexportal.org/home/gene/DNM1L Drp1 (DNM1L)] is widely expressed, most abundant in brain; [http://www.gtexportal.org/home/gene/FUNDC1 FUNDC1] is also widely expressed in different tissues.

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 === Domain===
-Metazoan PGAM5 has a N-terminal transmembrane region and a HP1 phosphatase domain.
+Metazoan PGAM5 has a N-terminal mitochondria targeting sequence localizes PGAM5 to inner mitochondria membrane <cite>Sekine12</cite> and a HP1 phosphatase domain.
 === Functions ===

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 PGAM5 is found in metazoa and many protists but is absent from fungi, plants, and amoebozoa.
-=== Domain Structure===
+=== Domain===
 Metazoan PGAM5 has a N-terminal transmembrane region and a HP1 phosphatase domain.

← Older revision		Revision as of 20:09, 2 June 2015
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		+	__NOTOC__
	[[Phosphatase classification\|Phosphatase Classification]]: [[Phosphatase_Fold_HP\|Fold HP]]: [[Phosphatase_Superfamily_HP\|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP1\|HP, branch1 family]]: [[Phosphatase_Subfamily_PGAM5\|Subfamily PGAM5]]		[[Phosphatase classification\|Phosphatase Classification]]: [[Phosphatase_Fold_HP\|Fold HP]]: [[Phosphatase_Superfamily_HP\|Superfamily HP]] (histidine phosphatase): [[Phosphatase_Family_HP1\|HP, branch1 family]]: [[Phosphatase_Subfamily_PGAM5\|Subfamily PGAM5]]