Difference between revisions of "Phosphatase Subfamily PGAM5"
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| − | + | PGAM5 is anchored in the mitochondrial membrane <cite>Sekine12, PGAM5_1</cite>. It functions as phosphatase rather than mutase. Its substrates include: | |
| − | PGAM5 | + | * 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>. |
| + | |||
| + | * FUNDC1. Human PGAM5 also dephosphorylates FUNDC1 at Ser-13 and thereby activates mitophagy <cite>chen14</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. | ||
Revision as of 20:19, 2 June 2015
Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): HP, branch1 family: Subfamily PGAM5
PGAM5 is a mitochondrial protein phosphatase with multiple distinct substrates.
Evolution
PGAM5 is found in metazoa and many protists but is absent from fungi, plants, and amoebozoa.
Domain
Metazoan PGAM5 has a N-terminal mitochondria targeting sequence localizes PGAM5 to inner mitochondria membrane [1] and a HP1 phosphatase domain.
Functions
PGAM5 is anchored in the mitochondrial membrane [1, 2]. It functions as phosphatase rather than mutase. Its substrates include:
- 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 [2]. 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 [2]. The authors of [2] 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.
- 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 [3].
- FUNDC1. Human PGAM5 also dephosphorylates FUNDC1 at Ser-13 and thereby activates mitophagy [4].
PGAM5 is specifically expressed in testis, according to GTEx. Its known substrates do not have similar tissue-specific expression pattern according to GTEx data: ASK1 (MAP3K5) is widely expressed, most abundant in adrenal gland and ovary; Drp1 (DNM1L) is widely expressed, most abundant in brain; FUNDC1 is also widely expressed in different tissues.
References
Error fetching PMID 19590015:
Error fetching PMID 22265414:
Error fetching PMID 24746696:
Error fetching PMID 22265414:
Error fetching PMID 24746696:
- Error fetching PMID 19590015:
- Error fetching PMID 22265414:
- Error fetching PMID 24746696:
