Phosphatase Family Myotubularin - Revision history

Gerard at 13:54, 9 September 2016

2016-09-09T13:54:02Z

Gerard at 13:53, 9 September 2016

2016-09-09T13:53:42Z

Gerard at 05:45, 9 March 2016

2016-03-09T05:45:23Z

Mark: /* References */

2015-10-28T18:21:20Z

‎References

Mark: /* Myotubularin phosphatase domain */

2015-10-28T18:20:35Z

‎Myotubularin phosphatase domain

Mark at 17:48, 28 October 2015

2015-10-28T17:48:52Z

Mark: /* Subfamilies in other clades */

2015-06-29T20:38:17Z

‎Subfamilies in other clades

Mark: /* Subfamilies present in human */

2015-06-27T19:13:29Z

‎Subfamilies present in human

Mark: /* Reference */

2015-06-26T00:35:18Z

‎Reference

Mark: /* Subfamilies */

2015-06-26T00:35:07Z

‎Subfamilies

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 Myotubularins are lipid phosphatases that dephosphorylate various phosphatidylinositol phosphates.
-===Protein Phosphatase Activity?====
+===Protein Phosphatase Activity?===
 Myotubularins may have protein substrates. Two reports on MTMR4, from the [[Phosphatase_Subfamily_MTMR3|MTMR3]] subfamily show dephosphorylation of R-SMADs and biological effects in human and fly, and an insect member of the [[Phosphatase_Subfamily_MTMR14|MTMR14]] subfamily also showed tyrosine phosphatase activity.

← Older revision		Revision as of 13:53, 9 September 2016
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	Myotubularins are lipid phosphatases that dephosphorylate various phosphatidylinositol phosphates.		Myotubularins are lipid phosphatases that dephosphorylate various phosphatidylinositol phosphates.
		+
		+	===Protein Phosphatase Activity?====
		+	Myotubularins may have protein substrates. Two reports on MTMR4, from the [[Phosphatase_Subfamily_MTMR3\|MTMR3]] subfamily show dephosphorylation of R-SMADs and biological effects in human and fly, and an insect member of the [[Phosphatase_Subfamily_MTMR14\|MTMR14]] subfamily also showed tyrosine phosphatase activity.

	=== Myotubularin phosphatase domain ===		=== Myotubularin phosphatase domain ===

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 [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]: [[Phosphatase_Superfamily_CC1|Superfamily CC1]]:  [[Phosphatase_Family_Myotubularin|Family Myotubularin]]
 === Myotubularin phosphatase domain ===
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 ===== [[Phosphatase_Subfamily_Ank-MTM|Ank-MTM]]  =====
-The subfamily has Ank repeats at N-terminal. It is found not only in ''Dictyostelium discoideum'' but also other Dictyosteliida.
+The subfamily has Ank repeats at N-terminal. It is found in ''Dictyostelium discoideum'' and other Dictyosteliida.
 ===== [[Phosphatase_Subfamily_pats1|Pats1]] =====
-The subfamily named after one of the two ''Dictyostelium discoideum'' myotubularins, pats1 and roco9. The subfamily is found in amoebazoa. The phosphatase domain is quite diverged from other myotubularins. It has a protein kinase domain.  It is classified as [http://kinase.com/web/current/kinbase/genes/Family/LRRK/ TKL group, LRRK family in kinase.com].
+The subfamily named after one of the two ''Dictyostelium discoideum'' myotubularins, pats1 and roco9. The subfamily is found in amoebozoa. The phosphatase domain is quite diverged from other myotubularins, and is linked to a protein kinase domain from the [http://kinase.com/web/current/kinbase/genes/Family/LRRK/ LRRK family].
 === Accessory domains: GRAM, FYVE, C1, coiled coils ===

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 === References ===
 <biblio>
 #Robinson06 pmid=16828287
 #taylor00 pmid=10900271
 </biblio>

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 The myotubularin phosphatase domains (PD) can be grouped into two types: i) typical and ii) atypical, i.e. MTMR14. The typical PD usually has a length of ~380 aa, except MTMR5 subfamily which has ~520 aa; MTMR14 has a length of ~160 aa (see [[HMM_PD00142|here]]). It is worthy pointing out that MTMR14 is catalytically active, while MTMR5, MTMR9, MTMR10 are inactive, although they have typical PDs.
+We define myotubularin PD according to the crystal structures of human MTMR2 <cite>Begley03</cite>, MTMR6 and MTMR8 <cite>Yoo15</cite>. They have typical PDs of ~380 aa. The PDs are ~45 aa longer than those defined by Pfam profile [http://pfam.xfam.org/family/PF06602.10 Myotub-related (PF06602)]. The region is part of the structure and important to myotubularin's functions. The region together with another helix and loop mediates the dimer formation of MTMR8 <cite>Yoo15</cite>. It contains a helix (helix 15) and loop in MTMR2 structure, and two helices (helix 15 and 16) and the loop between them in MTMR8 structure. The region is conserved in sequence, particularly at the positions W541 (460), N553 (472), and W576 (496). The missense mutations of W541 and N553 are disease-associated <cite>Begley03</cite>.  The positions are numbered by MTMR2 (MTMR8 in parenthesis).
 === Subfamilies present in human ===

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 === Subfamilies in other clades ===
-* [[Phosphatase_Subfamily_YMR1|YMR1]] is named after the only myotubularin in budding yeast, YMR1. It encodes PI(3)P phosphatase <cite>taylor00</cite>.
+===== [[Phosphatase_Subfamily_YMR1|YMR1]] =====
-* [[Phosphatase_Subfamily_Ank-MTM|Ank-MTM]]  is specific in ''Dictyostelium discoideum'', which has two myotubularins containing tandem Ank domains.
+===== [[Phosphatase_Subfamily_Ank-MTM|Ank-MTM]]  =====
-* [[Phosphatase_Subfamily_pats1|Pats1]] is named after one of the two ''Dictyostelium discoideum'' myotubularins, pats1 and roco9, diverged from other myotubularins. Both of them have protein kinase domain. They are classified as [http://kinase.com/web/current/kinbase/genes/Family/LRRK/ TKL group, LRRK family in kinase.com].
+===== [[Phosphatase_Subfamily_pats1|Pats1]] =====
 === Domains ===

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 Another feature of myotubularins is a significant number of pseudophosphatases within the family. 6 out of 15 human myotubularins are catalytically inactive. Their major functions are regulating the enzymatic activity of active myotubularins, e.g. the pairs between [[Phosphatase_Subfamily_MTMR1|MTMR1]]:[[Phosphatase_Subfamily_MTMR5|MTMR5]], [[Phosphatase_Subfamily_MTMR6|MTMR6]]:[[Phosphatase_Subfamily_MTMR9|MTMR9]]. All the interactions are mediated via coiled coils. One explanation is that MTMR1 and MTMR6 have the same ancestor, MTMR5 and MTMR9 have the same ancestor, their ancestors interacted via coiled coils. Alternatively, the coiled-coil interactions mediated MTMR1:MTMR5 and MTMR6:MTMR9 evolved, independently.
-* [[Phosphatase_Subfamily_MTMR1|MTMR1]] dephosphorylates the second messenger phosphatidylinositol 3-monophosphate [PI(3)P]. It is conserved across holozoa. The pseudophosphatase [[Phosphatase_Subfamily_MTMR5|MTMR5]] can regulate its enzymatic activity.
+===== [[Phosphatase_Subfamily_MTMR1|MTMR1]] =====
-* [[Phosphatase_Subfamily_MTMR5|MTMR5]] (SBF) is a subfamily of '''pseudophosphatase''' conserved in metazoa. It regulates the active [[Phosphatase_Subfamily_MTMR1|MTMR1]] subfamily by protein interactions.
+===== [[Phosphatase_Subfamily_MTMR3|MTMR3]] =====
-* [[Phosphatase_Subfamily_MTMR6|MTMR6]] is a phosphoinositide phosphatase found in holozoa. Its enzymatic activity is regulated by [[Phosphatase_Subfamily_MTMR9|MTMR9]].
+===== [[Phosphatase_Subfamily_MTMR5|MTMR5]] (SBF): catalytically inactive =====
-* [[Phosphatase_Subfamily_MTMR9|MTMR9]] is a conserved '''pseudophosphatase''' across holozoa. It regulates active phosphatases of subfamily [[Phosphatase_Subfamily_MTMR6|MTMR6]].
+===== [[Phosphatase_Subfamily_MTMR6|MTMR6]] =====
-* [[Phosphatase_Subfamily_MTMR3|MTMR3]] is an inositol lipid 3-phosphatase. It is probably a protein phosphatase of receptor-regulated SMAD. It is found throughout metazoa, with a signature FYVE domain.
+===== [[Phosphatase_Subfamily_MTMR9|MTMR9]]: catalytically inactive =====
-* [[Phosphatase_Subfamily_MTMR14|MTMR14]] is an active phosphatase found in most holozoa and slime molds. Its putative substrates are phosphatidylinositol bisphophosphates PtdIns(3,5)P2 and PtdIns (3,4)P2.
+===== [[Phosphatase_Subfamily_MTMR10|MTMR10]]: catalytically inactive =====
-* [[Phosphatase_Subfamily_MTMR10|MTMR10]] is a conserved '''pseudophosphatase''' in metazoa. Its molecular function is unclear.
+===== [[Phosphatase_Subfamily_MTMR14|MTMR14]]  =====
 === Subfamilies in other clades ===