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6  structures 529  species 2  interactions 3107  sequences 124  architectures

Family: Myotub-related (PF06602)

Summary: Myotubularin-like phosphatase domain

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This is the Wikipedia entry entitled "Myotubularin". More...

Myotubularin Edit Wikipedia article

Myotubularin-related
PDB 1m7r EBI.jpg
Structure of a phosphoinositide phosphatase.[1]
Identifiers
Symbol Myotub-related
Pfam PF06602
InterPro IPR010569
SCOP 1m7r
SUPERFAMILY 1m7r
OPM protein 1zvr

Myotubularin domain represents a region within eukaryotic myotubularin-related proteins that is sometimes found with the GRAM domain IPR004182. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate.[2] Mutations in gene encoding myotubularin-related proteins have been associated with disease.[3]

Human proteins containing this domain

MTM1; MTMR1; MTMR10; MTMR11; MTMR12; MTMR2; MTMR3; MTMR4; MTMR6; MTMR7; MTMR8; MTMR9; SBF1; SBF2;

References

  1. ^ Begley MJ, Taylor GS, Kim SA, Veine DM, Dixon JE, Stuckey JA (December 2003). "Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome". Mol. Cell 12 (6): 1391–402. doi:10.1016/S1097-2765(03)00486-6. PMID 14690594. 
  2. ^ Majerus PW, Nandurkar HH, Layton M, Laporte J, Selan C, Corcoran L, Caldwell KK, Mochizuki Y, Mitchell CA (2003). "Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP". Proc. Natl. Acad. Sci. U.S.A. 100 (15): 8660–8665. doi:10.1073/pnas.1033097100. PMC 166368. PMID 12847286. 
  3. ^ Suter U, Berger P, Bonneick S, Willi S, Wymann M (2002). "Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1". Hum. Mol. Genet. 11 (13): 1569–1579. doi:10.1093/hmg/11.13.1569. PMID 12045210. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR010569

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Myotubularin-like phosphatase domain Provide feedback

This family represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate [1]. Mutations in gene encoding myotubularin-related proteins have been associated with disease [2].

Literature references

  1. Nandurkar HH, Layton M, Laporte J, Selan C, Corcoran L, Caldwell KK, Mochizuki Y, Majerus PW, Mitchell CA; , Proc Natl Acad Sci U S A 2003;100:8660-8665.: Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP. PUBMED:12847286 EPMC:12847286

  2. Berger P, Bonneick S, Willi S, Wymann M, Suter U; , Hum Mol Genet 2002;11:1569-1579.: Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1. PUBMED:12045210 EPMC:12045210


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR010569

This entry represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate [PUBMED:12847286]. Mutations in gene encoding myotubularin-related proteins have been associated with disease [PUBMED:12045210].

Myotubularin phosphatases are members of the protein tyrosine phosphatase (PTP) superfamily. The PTP domain is found in a diverse group of enzymes that catalyse phosphoester hydrolysis using a cysteine nucleophile and an arginine residue that binds to oxygen atoms of the phosphate. These two catalytically essential residues are found in a Cys-x(5)-Arg motif, which is a hallmark of PTP domains. The PTP superfamily of enzymes includes tyrosine-specific, dual specificity, low molecular weight, and Cdc25 phosphatases. All of these enzymes utilise phosphoproteins as substrates. Unlike these members of PTPs, enzymes that contain the tensin and myotubularin PTP domain utilise the phosphoinositide as its physiologic substrate. Myotubularins are 3-phosphatases specific for membrane-embedded PtdIns3P and PtdIns(3,5)P2, two PIs that function within the endosomal-lysosomal pathway [PUBMED:9818190, PUBMED:16828287].

The myotubularin phosphatase domain consists of a central seven stranded beta sheet flanked by thirteen alpha helices [PUBMED:14690594]. Although its core structure is similar to that of other PTP superfamily members, the myotubularin phosphatase domain is much larger. It contains an extra C-terminal region, which could be implicated in protein-protein interactions. The active site motif forms a P-loop at the base of a substrate binding pocket that is characteristic of PTP domains. This pocket is significantly deeper than that of other PTP pockets, which could explain the difference in substrate specificity.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Phosphatase (CL0031), which has the following description:

This family includes tyrosine and dual specificity phosphatase enzymes.

The clan contains the following 10 members:

CDKN3 DSPc DSPn DUF442 Init_tRNA_PT Myotub-related PTPlike_phytase Y_phosphatase Y_phosphatase2 Y_phosphatase3

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(235)
Full
(3107)
Representative proteomes NCBI
(5034)
Meta
(25)
RP15
(471)
RP35
(833)
RP55
(1294)
RP75
(1724)
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  Seed
(235)
Full
(3107)
Representative proteomes NCBI
(5034)
Meta
(25)
RP15
(471)
RP35
(833)
RP55
(1294)
RP75
(1724)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(235)
Full
(3107)
Representative proteomes NCBI
(5034)
Meta
(25)
RP15
(471)
RP35
(833)
RP55
(1294)
RP75
(1724)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_795 (release 10.0)
Previous IDs: none
Type: Domain
Author: Vella Briffa B, Bateman A
Number in seed: 235
Number in full: 3107
Average length of the domain: 301.20 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 39.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.4 21.4
Trusted cut-off 21.4 21.4
Noise cut-off 21.3 21.3
Model length: 346
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Interactions

There are 2 interactions for this family. More...

GRAM Myotub-related

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Myotub-related domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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