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14  structures 1356  species 0  interactions 10172  sequences 240  architectures

Family: Myotub-related (PF06602)

Summary: Myotubularin-like phosphatase domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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
SymbolMyotub-related
PfamPF06602
InterProIPR010569
SCOPe1m7r / SUPFAM
OPM superfamily130
OPM protein1zvr

Myotubularin domain represents a region within eukaryotic myotubularin-related proteins that is sometimes found with the GRAM domain InterProIPR004182. 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


Internal database links

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.

The myotubularin family includes catalytically inactive members, or pseudophosphatases, which contain inactivating substitutions in the phosphatase domain [ PUBMED:16787938 ].

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 16 members:

CDKN3 DSPc DSPn DUF442 Init_tRNA_PT LMWPc Myotub-related NleF_casp_inhib PTPlike_phytase PTS_IIB Rhodanese Ssu72 Syja_N 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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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
(203)
Full
(10172)
Representative proteomes UniProt
(17929)
RP15
(1611)
RP35
(4022)
RP55
(8731)
RP75
(11420)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(203)
Full
(10172)
Representative proteomes UniProt
(17929)
RP15
(1611)
RP35
(4022)
RP55
(8731)
RP75
(11420)
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
(203)
Full
(10172)
Representative proteomes UniProt
(17929)
RP15
(1611)
RP35
(4022)
RP55
(8731)
RP75
(11420)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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.

Note: You can also download the data file for the tree.

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
Sequence Ontology: SO:0000417
Author: Vella Briffa B , Bateman A
Number in seed: 203
Number in full: 10172
Average length of the domain: 309.80 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 39.20 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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: 356
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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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 14 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2JUZ0 View 3D Structure Click here
A0A0G2JXT6 View 3D Structure Click here
A0A0G2K1P1 View 3D Structure Click here
A0A0P0XIA6 View 3D Structure Click here
A0A0R4IDR8 View 3D Structure Click here
A0A0R4IFR5 View 3D Structure Click here
A0A0R4II68 View 3D Structure Click here
A0A1D6GIU5 View 3D Structure Click here
A0A1D6KMT0 View 3D Structure Click here
A0A1D8PEF4 View 3D Structure Click here
A0A2R8PWA9 View 3D Structure Click here
A0A2R8QR85 View 3D Structure Click here
A0JMF6 View 3D Structure Click here
A0JMF6 View 3D Structure Click here
A0JMK5 View 3D Structure Click here
A1ZAS8 View 3D Structure Click here
A2BGG1 View 3D Structure Click here
A4FU01 View 3D Structure Click here
A4FU01 View 3D Structure Click here
A4HYZ1 View 3D Structure Click here
B5DEJ9 View 3D Structure Click here
D3ZA31 View 3D Structure Click here
D3ZQH5 View 3D Structure Click here
D3ZQH5 View 3D Structure Click here
D3ZW40 View 3D Structure Click here
E7F4G2 View 3D Structure Click here
E7F7E6 View 3D Structure Click here
E7F7E6 View 3D Structure Click here
E9PXF8 View 3D Structure Click here
F1QFI4 View 3D Structure Click here
F1QTP6 View 3D Structure Click here
F4J3T8 View 3D Structure Click here
F4JWB3 View 3D Structure Click here
F8W5H1 View 3D Structure Click here
G3V810 View 3D Structure Click here
G3V810 View 3D Structure Click here
G5ED68 View 3D Structure Click here
K7LKG8 View 3D Structure Click here
K7N4D7 View 3D Structure Click here
M0RAP5 View 3D Structure Click here
O13819 View 3D Structure Click here
O95248 View 3D Structure Click here
P47147 View 3D Structure Click here
Q13496 View 3D Structure Click here
Q13613 View 3D Structure Click here
Q13614 View 3D Structure Click here
Q13615 View 3D Structure Click here
Q1ZXD2 View 3D Structure Click here
Q22712 View 3D Structure Click here
Q3V1L6 View 3D Structure Click here
Q3V1L6 View 3D Structure Click here
Q4CXS8 View 3D Structure Click here
Q4D1E4 View 3D Structure Click here
Q4D1E4 View 3D Structure Click here
Q4D1P6 View 3D Structure Click here
Q4D230 View 3D Structure Click here
Q4DUM8 View 3D Structure Click here
Q4DUM8 View 3D Structure Click here
Q54C52 View 3D Structure Click here
Q54GQ1 View 3D Structure Click here
Q54PL3 View 3D Structure Click here
Q54TD5 View 3D Structure Click here
Q54YC2 View 3D Structure Click here
Q55AZ2 View 3D Structure Click here
Q55E04 View 3D Structure Click here
Q55EE1 View 3D Structure Click here
Q58EE0 View 3D Structure Click here
Q5FVM6 View 3D Structure Click here
Q5PQT2 View 3D Structure Click here
Q5RHK5 View 3D Structure Click here
Q5XIN4 View 3D Structure Click here
Q6AXQ4 View 3D Structure Click here
Q6TEL0 View 3D Structure Click here
Q6ZPE2 View 3D Structure Click here
Q7TPM9 View 3D Structure Click here
Q7TPM9 View 3D Structure Click here
Q7YU03 View 3D Structure Click here
Q80TA6 View 3D Structure Click here
Q86WG5 View 3D Structure Click here
Q8K296 View 3D Structure Click here
Q8MLR7 View 3D Structure Click here
Q8SZY7 View 3D Structure Click here
Q8VE11 View 3D Structure Click here
Q91XS1 View 3D Structure Click here
Q965W9 View 3D Structure Click here
Q96EF0 View 3D Structure Click here
Q96QG7 View 3D Structure Click here
Q9C0I1 View 3D Structure Click here
Q9N589 View 3D Structure Click here
Q9NXD2 View 3D Structure Click here
Q9NXD2 View 3D Structure Click here
Q9NYA4 View 3D Structure Click here
Q9TXP3 View 3D Structure Click here
Q9VGH9 View 3D Structure Click here
Q9VMI9 View 3D Structure Click here
Q9VY15 View 3D Structure Click here
Q9Y216 View 3D Structure Click here
Q9Y217 View 3D Structure Click here
Q9Z2C4 View 3D Structure Click here
Q9Z2C5 View 3D Structure Click here
Q9Z2C9 View 3D Structure Click here
Q9Z2D0 View 3D Structure Click here
Q9Z2D1 View 3D Structure Click here
V6CJW9 View 3D Structure Click here