Difference between revisions of "Phosphatase Subfamily MTMR5"
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===Domain Structure=== | ===Domain Structure=== | ||
MTMR5 subfamily has a [http://www.jbc.org/content/286/16/13791.short DENN domain], [http://pfam.xfam.org/family/PF02893.15 PH/GRAM] domain, phosphatase domain, coiled-coil domain and PH domain. The GRAM domain is similar to PH domain in structure and is found in membrane-associated proteins. | MTMR5 subfamily has a [http://www.jbc.org/content/286/16/13791.short DENN domain], [http://pfam.xfam.org/family/PF02893.15 PH/GRAM] domain, phosphatase domain, coiled-coil domain and PH domain. The GRAM domain is similar to PH domain in structure and is found in membrane-associated proteins. | ||
| + | |||
| + | DENN domains interact directly with members of the Rab family of small GTPases and that DENN domains function enzymatically as Rab-specific guanine nucleotide exchange factors. MTMR5 and MTMR13 have GEF activity toward Rab28, a poorly characterized and distant member of the Rab superfamily<cite>yashimura10</cite>. | ||
| + | |||
| + | Coiled-coil domain mediates the interactions of MTMR5 and MTMR13 with MTMR2, which results in the increase of enzymatic activity of MTMR2<cite>kim03</cite>. | ||
===Catalytic activity and functions=== | ===Catalytic activity and functions=== | ||
| Line 17: | Line 21: | ||
===Disease=== | ===Disease=== | ||
| − | Mice deficient for MTMR5 | + | Mice deficient for MTMR5 exhibit male infertility characterized by azoospermia <cite>firestein02</cite>. |
| + | |||
| + | loss of Mtmr13 in mice leads to a peripheral neuropathy with many of the key features of Charcot–Marie–Tooth disease type 4B (CMT4B), which is a severe, demyelinating peripheral neuropathy characterized by slowed nerve conduction velocity, axon loss, and distinctive myelin outfolding and infolding <cite>robinson08</cite>. | ||
===References=== | ===References=== | ||
<biblio> | <biblio> | ||
| + | #yashimura10 pmid=20937701 | ||
#kim03 pmid=12668758 | #kim03 pmid=12668758 | ||
| + | #robinson08 pmid=18349142 | ||
#firestein pmid=11994405 | #firestein pmid=11994405 | ||
</biblio> | </biblio> | ||
Revision as of 01:05, 31 December 2014
Phosphatase Classification: FoldCC1: Superfamily CC1: Family Myotubularin: Subfamily MTMR5 (SBF)
[a punch line at here]
Evolution
MTMR5 subfamily is found throughout metazoan. It consists of two members in human, MTMR5 and MTMR13, also called SBF1 and SBF2, respectively. In fruit fly and C elegans, a single copy is found.
Domain Structure
MTMR5 subfamily has a DENN domain, PH/GRAM domain, phosphatase domain, coiled-coil domain and PH domain. The GRAM domain is similar to PH domain in structure and is found in membrane-associated proteins.
DENN domains interact directly with members of the Rab family of small GTPases and that DENN domains function enzymatically as Rab-specific guanine nucleotide exchange factors. MTMR5 and MTMR13 have GEF activity toward Rab28, a poorly characterized and distant member of the Rab superfamily[1].
Coiled-coil domain mediates the interactions of MTMR5 and MTMR13 with MTMR2, which results in the increase of enzymatic activity of MTMR2[2].
Catalytic activity and functions
MTMR5 subfamily is conservatively inactive in metazoan.
Human MTMR5 interact with MTMR2 (see MTMR1 subfamily) via its coiled-coil domain and mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization [2]. This is a good example of inactive phosphatase functions as regulator of active phosphatase.
Disease
Mice deficient for MTMR5 exhibit male infertility characterized by azoospermia [3].
loss of Mtmr13 in mice leads to a peripheral neuropathy with many of the key features of Charcot–Marie–Tooth disease type 4B (CMT4B), which is a severe, demyelinating peripheral neuropathy characterized by slowed nerve conduction velocity, axon loss, and distinctive myelin outfolding and infolding [4].
References
- Yoshimura S, Gerondopoulos A, Linford A, Rigden DJ, and Barr FA. Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. J Cell Biol. 2010 Oct 18;191(2):367-81. DOI:10.1083/jcb.201008051 |
- 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 |
- Robinson FL, Niesman IR, Beiswenger KK, and Dixon JE. Loss of the inactive myotubularin-related phosphatase Mtmr13 leads to a Charcot-Marie-Tooth 4B2-like peripheral neuropathy in mice. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4916-21. DOI:10.1073/pnas.0800742105 |
- Firestein R, Nagy PL, Daly M, Huie P, Conti M, and Cleary ML. Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1. J Clin Invest. 2002 May;109(9):1165-72. DOI:10.1172/JCI12589 |
