Difference between revisions of "Phosphatase Subfamily PPM1E"
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_PPM|Superfamily PPM (PP2C)]]: [[Phosphatase_Family_PPM|Family PPM (PP2C)]]: [[Phosphatase_Subfamily_PPM1E|Subfamily PPM1E]] (POXP, FEM-2) | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_PPM|Superfamily PPM (PP2C)]]: [[Phosphatase_Family_PPM|Family PPM (PP2C)]]: [[Phosphatase_Subfamily_PPM1E|Subfamily PPM1E]] (POXP, FEM-2) | ||
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=== Evolution === | === Evolution === | ||
Revision as of 16:46, 10 June 2015
Phosphatase Classification: Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1E (POXP, FEM-2)
Contents
Evolution
CAMK2
Domain
Functions
Human PPM1E and PPM1F
Human has two members: PPM1E (POPX1, PP2CH, caMKN, CaMKP-N) and PPM1F (POPX2, CAMKP, CaMKPase, FEM-2, hFEM-2).
Human PPM1EHuman PPM1F is widely expressed in different tissues, as shown by Western blotting analysis [1, 2].
PPM1E and PPM1F have different sub-cellular localizations. Human PPM1E is localized to nculear [3]; PPM1F is localized to cytosol [1, 2]. Human PPM1E has two C-terminal nuclear localization signals (NLSs), at 668-702 and 706-742, respectively [4]. The two NLSs can not be computational identified by NLS prediction tools NLS mapper and NLStradamus.
Both PPM1E and PPM1F dephosphorylate and deactivates kinases of CAMK (Ca2+/calmodulin-dependent protein kinase) group as evidenced by extensive studies. CAMK2 is regulated by autophosphorylation at multiple sites, including Thr-286 activates CAMK2. PPM1F dephosphorylate Thr-286 on CAMK2 in fibroblasts [5]. Human PPM1E dephosphorylates CAMK4 and nuclear CAMK2, while PPM1F dephosphorylates CAMK1 and cytosolic CAMK2 [2, 3]. Rat PPM1F extracted from brain also dephosphorylates CAMK2, but not phosphorylase kinase, histones, MBP, α-casein, andd phosphorylase α [6]. In addition, human PPM1F regulates the phosphorylation level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in by dephosphorylating and deactivating CAMKs that are responsible for the phosphorylation of GAPDH.
Both PPM1E and PPM1F can dephosphorylate and inactivate p21 (Cdc42/Rac)-activated kinase (PAK), which is potently activated by autophosphorylation at multiple sites [7]. PPM1E can bind to PAK interacting guanine nucleotide exchange factor PIX [7]. The association between PPM1E/PPM1F with PAX complex may allow PAK to cycle rapidly between active and inactive states [7].
Other substrates and interacting partners:
- Human PPM1F dephoshorylates serine-690 of KIF3A, which is phosphorylated by CAMK2. KIF3A is a motor subunit which forms a heterotrimeric complex with KIF3B, another motor subunit, and KAP3, the non-motor subunit [8].
- Human PPM1E dephosphorylates 5'-AMP-activated protein kinase (AMPK) [9].
- Human PPM1F can dephosphorylate C. elegans fem-3 [2], but fem-3 is only found in Caenorhabditis according to OrthoDB.
- By proteomic approach, it was found that human PPM1F regulates the activity of glycogen synthase kinase-3 (GSK3) [10] and MAPK1/3 [11], therefore regulating cancer cell motility [12]. GSK3 is not the subtratre of PPM1F, and it is unclear whether PPM1F directly dephosphorylate MAPK1/3.
- Human PPM1F interacts with the formin protein mDia1 (DIAPH1) and decreases the ability of mDia1 to activate the transcription of serum response element (SRE) [13].
PPM1E is proposed to be regulated by oxidation/reduction at Cys-359 [14].
C. elegans fem-2
Fem-2 is C. elegans PPM1E, which, together with fem-1 and fem-3, is required by male sexual development in C. elegans [15]. Crystal structure of C. elegans Fem-2 shows two structural domains: N-terminal domain from 13-160 and C-terminal phosphatase domain from 161-436 [16]. Fem-2 associates with fem-1 and fem-3 via its N-terminal domain [16]. However, the N-terminal domain is only found in several nematodes, by BLASTing the region against NR database. Meanwhile, fem-3 is only present in Caenorhabditis by BLASTing the protein sequence of longest isoform against NR database; Fem-1 is found throughout metazoa (see internal data).
Fem-2 exhibits magnesium-dependent casein phosphatase activity in vitro [15].
References
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