Difference between revisions of "Phosphatase Subfamily MTMR1"

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__NOTOC__
 
__NOTOC__
  
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|FoldCC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]:  [[Phosphatase_Family_Myotubularin|Family Myotubularin]]
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]:  [[Phosphatase_Family_Myotubularin|Family Myotubularin]]: [[Phosphatase_Subfamily_MTMR1|Subfamily MTMR1]]
  
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MTMR1 is a lipid phosphatase that dephosphorylates the second messenger phosphatidylinositol 3-monophosphate [PI(3)P].
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CTDSPL2 (CTD small phosphatase like 2) is a poorly-studied RNA polymerase CTD phosphatase which is found in most eukaryotes.
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===Evolution===
 
===Evolution===
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CTDSPL2 is found as a single copy gene in most eukaryotes. It is absent from all but a few basal fungi, and is also lost in Drosophilids. The human gene is called CTSDPL2, HSPC058, HSPC129, or SCP4
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MTMR1 is found throughout holozoa <cite>Chen</cite>. It consists of three members in human, MTM1, MTMR1 and MTMR2. In fruit fly and C elegans, a single copy is found. In most vertebrates from fish to human, MTM1 and MTMR1 are adjacent on the X chromosome (see [http://www.genomicus.biologie.ens.fr/genomicus-78.01/cgi-bin/phyloview.pl?root=2198950&amp;id=2199015&amp;xhide=108:107:105:110:69:96:97:63:111:-2198950:94:92:82:115:76:46:48:57:56:67:112:78:61:3:99:52:24:81:58:10:55:83&amp;xcollapse=-2198950&amp; Genomicus]).
  
 
===Domain Structure===
 
===Domain Structure===
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Usually a C-terminal phosphatase domain with a relatively poorly conserved N-terminal extension
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MTMR1 has a [http://pfam.xfam.org/family/PF02893.15 GRAM] domain, phosphatase domain and coiled-coil region. The GRAM domain is similar to the PH domain in structure and is found in membrane-associated proteins. As shown in [[Phosphatase_Subfamily_MTMR3|MTMR3 subfamily]], the GRAM domain can bind to phosphoinositide lipids. The coiled-coil domain has been shown to mediate the interaction between [[Phosphatase_Gene_MTMR2|MTMR2]] and the [[Phosphatase_Subfamily_MTMR5|MTMR5 subfamily]] members MTMR13 and MTMR5 in human <cite>kim03, robinson05</cite>.
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===Catalytic activity===
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Human CTDSPL2 has experimentally-shown activity <cite>qian</cite> and orthologs are also predicted to be active.
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===Functions===
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===Catalytic activity and functions===
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Human CTDSPL2 binds and dephosphorylates Smad1/5/8, and attenuates signaling through the BMP pathway <cite>Zhao</cite>
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Human MTM1 has phosphatase activity towards the second messenger phosphatidylinositol 3-monophosphate [PI(3)P] in vitro and in human <cite>taylor00, blondeau00</cite>.
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Human MTMR1 and MTMR2 have been shown to dephosphorylate PI(3)P (<cite>bujbello02</cite> and <cite>kim01</cite>, respectively). Although the enzymatic properties of the three human phosphatases are indistinguishable, their functions are not totally redundant. MTM1 and MTMR2 are differentially regulated in the aspects of developmental expression and subcellular localization, resulting in their use of specific cellular pools of PI(3)P <cite>kim01</cite>.
  
 
===Related Kinases===
 
===Related Kinases===
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See [[CTD_Phosphorylation|Phosphorylation of RNA polymerase II C-terminal domain]].
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See [http://en.wikipedia.org/wiki/Phosphoinositide_3-kinase PI3K].
  
 
===References===
 
===References===
 
<biblio>
 
<biblio>
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#qian pmid=17487459
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#Chen pmid=28400531
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#Zhao pmid=25100727
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#kim03 pmid=12668758
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#robinson05 pmid=15998640
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#blondeau00 pmid=11001925
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#taylor00 pmid=10900271
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#bujbell02 pmid=12217958
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#kim01 pmid=11733541
 
</biblio>
 
</biblio>

Latest revision as of 23:54, 13 April 2017


Phosphatase Classification: Fold CC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR1

MTMR1 is a lipid phosphatase that dephosphorylates the second messenger phosphatidylinositol 3-monophosphate [PI(3)P].

Evolution

MTMR1 is found throughout holozoa [1]. It consists of three members in human, MTM1, MTMR1 and MTMR2. In fruit fly and C elegans, a single copy is found. In most vertebrates from fish to human, MTM1 and MTMR1 are adjacent on the X chromosome (see Genomicus).

Domain Structure

MTMR1 has a GRAM domain, phosphatase domain and coiled-coil region. The GRAM domain is similar to the PH domain in structure and is found in membrane-associated proteins. As shown in MTMR3 subfamily, the GRAM domain can bind to phosphoinositide lipids. The coiled-coil domain has been shown to mediate the interaction between MTMR2 and the MTMR5 subfamily members MTMR13 and MTMR5 in human [2, 3].

Catalytic activity and functions

Human MTM1 has phosphatase activity towards the second messenger phosphatidylinositol 3-monophosphate [PI(3)P] in vitro and in human [4, 5]. Human MTMR1 and MTMR2 have been shown to dephosphorylate PI(3)P ([6] and [7], respectively). Although the enzymatic properties of the three human phosphatases are indistinguishable, their functions are not totally redundant. MTM1 and MTMR2 are differentially regulated in the aspects of developmental expression and subcellular localization, resulting in their use of specific cellular pools of PI(3)P [7].

Related Kinases

See PI3K.

References

  1. Chen MJ, Dixon JE, and Manning G. Genomics and evolution of protein phosphatases. Sci Signal. 2017 Apr 11;10(474). DOI:10.1126/scisignal.aag1796 | PubMed ID:28400531 | HubMed [Chen]
  2. Kim SA, Vacratsis PO, Firestein R, Cleary ML, and Dixon JE. Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4492-7. DOI:10.1073/pnas.0431052100 | PubMed ID:12668758 | HubMed [kim03]
  3. Robinson FL and Dixon JE. The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a membrane-associated pseudophosphatase also mutated in type 4B Charcot-Marie-Tooth disease. J Biol Chem. 2005 Sep 9;280(36):31699-707. DOI:10.1074/jbc.M505159200 | PubMed ID:15998640 | HubMed [robinson05]
  4. Taylor GS, Maehama T, and Dixon JE. Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy, dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate. Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8910-5. DOI:10.1073/pnas.160255697 | PubMed ID:10900271 | HubMed [taylor00]
  5. Blondeau F, Laporte J, Bodin S, Superti-Furga G, Payrastre B, and Mandel JL. Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. Hum Mol Genet. 2000 Sep 22;9(15):2223-9. DOI:10.1093/oxfordjournals.hmg.a018913 | PubMed ID:11001925 | HubMed [blondeau00]
  6. Kim SA, Taylor GS, Torgersen KM, and Dixon JE. Myotubularin and MTMR2, phosphatidylinositol 3-phosphatases mutated in myotubular myopathy and type 4B Charcot-Marie-Tooth disease. J Biol Chem. 2002 Feb 8;277(6):4526-31. DOI:10.1074/jbc.M111087200 | PubMed ID:11733541 | HubMed [kim01]
  7. Buj-Bello A, Furling D, Tronchère H, Laporte J, Lerouge T, Butler-Browne GS, and Mandel JL. Muscle-specific alternative splicing of myotubularin-related 1 gene is impaired in DM1 muscle cells. Hum Mol Genet. 2002 Sep 15;11(19):2297-307. DOI:10.1093/hmg/11.19.2297 | PubMed ID:12217958 | HubMed [bujbell02]
All Medline abstracts: PubMed | HubMed
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