Phosphatase Family PPM - Revision history

Gerard: /* PPM1D (WIP1): oncogene in different cancer types */

2017-07-24T16:53:52Z

‎PPM1D (WIP1): oncogene in different cancer types

Gerard: /* PPM1G (PP2Cγ): mRNA splicing and histone regulation */

2017-07-24T16:51:50Z

‎PPM1G (PP2Cγ): mRNA splicing and histone regulation

Gerard at 16:51, 24 July 2017

2017-07-24T16:51:09Z

Gerard at 15:07, 24 March 2017

2017-03-24T15:07:18Z

Gerard: /* Unclassified phosphatases */

2017-03-24T15:06:27Z

‎Unclassified phosphatases

Gerard: /* PP2D1 */

2017-03-04T21:33:51Z

‎PP2D1

Gerard: /* LRR-PPM */

2017-03-04T21:31:39Z

‎LRR-PPM

Gerard: /* KAPP-like */

2017-03-04T21:30:33Z

‎KAPP-like

Gerard at 01:08, 4 March 2017

2017-03-04T01:08:39Z

Gerard: /* PPM1E (POXP): the phosphatases of CAMKs and PAK */

2017-03-04T00:46:54Z

‎PPM1E (POXP): the phosphatases of CAMKs and PAK

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 ===== [[Phosphatase_Subfamily_PPM1D|PPM1D]] (WIP1): oncogene in different cancer types =====
-The PPM1D subfamily is an oncogene conserved from Monosiga to human. It regulates cell homeostasis in response to DNA damage. It dephosphorylates p53 and its various target kinases, such as ATM, Chk1 and Chk2. It also dephosphorylates p38/MAPK, tumor suppressors INK4A and ARF, RelA subunit of NF-kappaB, gamma-H2AX and etc. (PS: ATM and PPM1D have a significant overlap of their substrate proteins, -the same residues on a set of proteins, including p53, Mdm2, Chk2 and gamma-H2AX at least.)
+The PPM1D subfamily is an oncogene conserved from Monosiga to human. It regulates cell homeostasis in response to DNA damage. It dephosphorylates the DNA damage response kinases ATM and ATR as well as their phosphorylation targets, p53, Mdm2, Chk2 and gH2AX. It also dephosphorylates p38/MAPK, the tumor suppressors INK4A and ARF, and the RelA subunit of NF-kappaB.
 ===== [[Phosphatase_Subfamily_PPM1E|PPM1E]] (POXP): the phosphatases of CAMKs and PAK =====

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 ===== [[Phosphatase_Subfamily_PPM1G|PPM1G]] (PP2Cγ): mRNA splicing and histone regulation =====
-The PPM1G subfamily is found across [[Phosphatase_Glossary#Metazoa|metazoa]]. PPM1G has a predicted N-terminal myristoylation site, C-terminal nuclear localization signaling, and a characteristic phosphatase domain inserted by an acidic domain. It is involved in pre-mRNA splicing, histone regulation, and cell cycle.
+PPM1G is found across [[Phosphatase_Glossary#Metazoa|metazoa]]. PPM1G has a predicted N-terminal myristoylation site, C-terminal nuclear localization signaling, and a characteristic phosphatase domain inserted by an acidic domain. It is involved in pre-mRNA splicing, histone regulation, and cell cycle.
 ===== [[Phosphatase_Subfamily_PPM1D|PPM1D]] (WIP1): oncogene in different cancer types =====

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 PPM (a.k.a. PP2C) is serine/threonine phosphatase found in all eukaryotes, and related to bacterial sporulation protein SpoIIE.
-Human PPMs exclusively dephoshorylate pSer/pThr. All PPMs are active, except that TAB1 has been reported as pseudophosphatase ([http://www.ncbi.nlm.nih.gov/pubmed/16879102 Conner et al. 2006]). In contrast with PPP, the other major Ser/Thr phosphatase family, PPP does not generally rely on targeting subunits.
+Human PPMs exclusively dephoshorylate pSer/pThr. All PPMs are active, except that TAB1 has been reported as pseudophosphatase ([http://www.ncbi.nlm.nih.gov/pubmed/16879102 Conner et al. 2006]). Unlike the other major Ser/Thr phosphatase family, PPP, PPM does not generally rely on targeting subunits.
-Many if not most PPMs requires two even three metal ions, either Mg<sup>2+</sup> or Mn<sup>2+</sup> to activate its phosphatase activity <cite>Tanoue13</cite>.
+Most PPM require two even three metal ions, either Mg<sup>2+</sup> or Mn<sup>2+</sup> to activate its phosphatase activity <cite>Tanoue13</cite>.
-The PPM subfamilies have different insertions to the core of phosphatase domain, including those are conserved and pretty long, suggesting their importance to the specific functions of individual subfamilies. For instance, the PPM1G subfamily has an inserted acidic region of 54 aa long; PPM1H has an inserted region of ~60 aa; PPM1A has a ~80 aa residues to the C-terminal, which consists of three antiparallel alpha helices and form a cleft between it and the catalytic domain.
+The PPM subfamilies have different insertions to the core of phosphatase domain, some quite conserved and long, suggesting their importance to the specific functions of individual subfamilies. For instance, the PPM1G subfamily has an inserted acidic region of 54 aa long; PPM1H has an inserted region of ~60 aa; PPM1A has a ~80 aa residues insert to the C-terminal, which consists of three antiparallel alpha helices and form a cleft between it and the catalytic domain.
 === Subfamilies ===

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 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_PPM|Fold PPM]]: [[Phosphatase_Superfamily_PPM|Superfamily PPM]]: [[Phosphatase_Family_PPM|Family PPM]]
-PPM (a.k.a. PP2C) is serine/threonine phosphatase found in all the eukaryotes, and related to bacterial sporulation protein SpoIIE.
+PPM (a.k.a. PP2C) is serine/threonine phosphatase found in all eukaryotes, and related to bacterial sporulation protein SpoIIE.
 Human PPMs exclusively dephoshorylate pSer/pThr. All PPMs are active, except that TAB1 has been reported as pseudophosphatase ([http://www.ncbi.nlm.nih.gov/pubmed/16879102 Conner et al. 2006]). In contrast with PPP, the other major Ser/Thr phosphatase family, PPP does not generally rely on targeting subunits.

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 * Budding yeast [[Phosphatase_Gene_PTC1|PTC1]]. Its functions have been reviewed in <cite> Arino11,  Sharmin14 </cite>. PTC1 is found in most fungi (see our [http://resdev.gene.com/gOrtholog/view/cluster/MC0007538/overview internal data]).
-* Budding yeast [[Phosphatase_Gene_PTC6|PTC6]] is found in a broad of fungi except Encephalitozoon of Microsporida. In budding yeast, Ptp6p locates both in the intermembrane and mitochondria. The same as Ptc5p, it regulates the phosphorylation state of Pda1p, the E1alpha subunit of the pyruvate dehydrogenase (PDH). Though PTC6 and PTC5 (of [[Phosphatase_Subfamily_PDPc|PDPc subfamily]] share a large overlap of phenotypes, but they may have distinct molecular functions <cite> Arino11 </cite>.
+* Budding yeast [[Phosphatase_Gene_PTC6|PTC6]] is found in a broad of fungi. In budding yeast, Ptp6p locates both in the intermembrane and mitochondria. Along with Ptc5p, it regulates the phosphorylation state of Pda1p, the E1alpha subunit of the pyruvate dehydrogenase (PDH). PTC6 and PTC5 (of [[Phosphatase_Subfamily_PDPc|PDPc subfamily]] share a large overlap of phenotypes, but they may have distinct molecular functions <cite> Arino11 </cite>.
 * Budding yeast [[Phosphatase_Gene_CYR1|CYR1]] encodes adenylate cyclase in budding yeast. The protein has a domain combination of 1) Adenylate cyclase G-alpha binding domain, 2) Ubiquitin domain CYR1 adenylate cyclase, 3) Leucine repeats, 4) PPM phosphatase domain, and 5) cyclase homology domain. CYR1 is found in most fungi including both Ascomycota and Basidiomycota (also by BLAST NR database and [http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Search&term=18511290 Newton's review]). CYR1 is close to PHLPP in phosphatase domain sequence, but they have distinct domain structure and molecular function.
-* Dictyostelium [[Phosphatase_Gene_spnA|spnA]] has two domains, Galpha subunit family of GTP binding proteins at N-terminal, and PPM phosphatase domain at C-terminal. It functions in cell autonomous for prestalk differentiation, and cell non-autonomous for pre spore differentiation (see summary from [http://dictybase.org/gene/DDB_G0276155 DictyBase]).
+* Dictyostelium [[Phosphatase_Gene_spnA|spnA]] has two domains, Galpha subunit family of GTP binding proteins at N-terminal, and PPM phosphatase domain at C-terminal. It functions cell autonomously for prestalk differentiation, and cell non-autonomously for prespore differentiation (see summary from [http://dictybase.org/gene/DDB_G0276155 DictyBase]).
 === Phosphatase domain structure ===

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 ===== [[Phosphatase_Subfamily_PP2D1|PP2D1]] =====
-The function of the PP2D1 subfamily is unknown. It is found in frog, birds, platypus and mammals. It is also found sparsely from Trichoplax to fish, including Nematostella, Saccoglossus, Ciona, lancelets, and Tetraodon (but not zebrafish). It has a predicted nuclear localization signaling (NLS) at the N-terminal.
+The function of the PP2D1 subfamily is unknown. It is found across the eumetazoa, but frequently lost, including from C. elegans, Drosophila and zebrafish. It has an N-terminal predicted nuclear localization signaling (NLS).
 ===== [[Phosphatase_Subfamily_CG9801|CG9801]] =====

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 ===== [[Phosphatase_Subfamily_LRR-PPM|LRR-PPM]] =====
-The LRR-PPM subfamily has a unique domain combination of leucine riches repeats (LRRs) and PPM phosphatase domain. It is mainly found in Dictyostelid.
+The LRR-PPM subfamily has a combination of leucine riches repeats (LRRs) and PPM phosphatase domain. It is found in Amoebozoa. It does not have any clear orthology to the other LRR-PPM family,  [[Phosphatase_Subfamily_PHLPP|PHLPP]]
 ===== [[Phosphatase_Subfamily_KAPP-like|KAPP-like]] =====

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 ===== [[Phosphatase_Subfamily_KAPP-like|KAPP-like]] =====
-The subfamily is mainly found in close to plant PPM phosphatase KAPP (see [http://www.ncbi.nlm.nih.gov/gene/832048]), a regulator of the receptor-like kinase (RLK) signaling pathway. Plant RLKs are counterpart of animal receptor kinases. But, the subfamily is mainly found in Dictyostelid . It may not function in the same way as plant KAPPs, since it does not the FHA domain common in plant KAPPs.
+The subfamily is similar to the plant PPM phosphatase KAPP (see [http://www.ncbi.nlm.nih.gov/gene/832048]), a regulator of the receptor-like kinase (RLK) signaling pathway. Plant RLKs are counterpart of animal receptor kinases. This subfamily is found in Dictyostelids and lacks the FHA domain found in plant KAPPs.
 === Unclassified phosphatases ===

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 ===== [[Phosphatase_Subfamily_PPM1E|PPM1E]] (POXP): the phosphatases of CAMKs and PAK =====
-The PPM1E subfamily is named after two human PPMs, [[Phosphatase_Gene_PPM1E|PPM1E]] (also known as [http://www.ncbi.nlm.nih.gov/gene/22843 POXP1, PP2CH, caMKN, CaMKP-N]) and [[Phosphatase_Gene_PPM1F|PPM1F]] (also known as [http://www.ncbi.nlm.nih.gov/gene/9647 POXP2, CAMKP, FEM-2, hFEM-2, CaMKPase]). The subfamily has a single copy in most non-vertebrates from Monosiga to ciona, and duplicated when vertebrates emerged. Both PPM1E and PPM1F dephosphorylate kinases CaMK2g and PAK, and PPM1E can also dephosphorylate CaMK4 (of different families from CaMK2g).
+The PPM1E subfamily contains the human genes  [[Phosphatase_Gene_PPM1E|PPM1E]] and [[Phosphatase_Gene_PPM1F|PPM1F]], and a single gene in most invertebrates. Both PPM1E and PPM1F dephosphorylate kinases CaMK2g and PAK, and PPM1E can also dephosphorylate CaMK4.
 ===== [[Phosphatase_Subfamily_PPM1H|PPM1H]] =====