Mtmr2 myotubularin related protein 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mtmr2provided by MGI
Official Full Name: myotubularin related protein 2provided by MGI
Primary source: MGI:MGI:1924366
See related: Ensembl:ENSMUSG00000031918 AllianceGenome:MGI:1924366
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: 6030445P13Rik
Summary: Enables identical protein binding activity; phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity; and phosphatidylinositol-3-phosphate phosphatase activity. Acts upstream of or within negative regulation of myelination; nervous system development; and phosphatidylinositol dephosphorylation. Located in vacuolar membrane. Is expressed in several structures, including eye; genitourinary system; gut; immune system; and nervous system. Used to study Charcot-Marie-Tooth disease type 4B1. Human ortholog(s) of this gene implicated in Charcot-Marie-Tooth disease type 4B1. Orthologous to human MTMR2 (myotubularin related protein 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in adrenal adult (RPKM 8.9), cerebellum adult (RPKM 7.0) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 A1; 9 3.44 cM

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (13660397..13720192)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (13747260..13808896)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

we identified a PI(3,5)P2 binding region in Piezo2, but not Piezo1, that confers sensitivity to Mtmr2 as indicated by functional analysis of a domain-swapped Piezo2 mutant. Altogether, our results propose local PI(3,5)P2 modulation via Mtmr2 in the vicinity of Piezo2 as a novel mechanism to dynamically control Piezo2-dependent mechanotransduction in peripheral sensory neurons.
Title: Myotubularin related protein-2 and its phospholipid substrate PIP(2) control Piezo2-mediated mechanotransduction in peripheral sensory neurons.
analysis of epistasis between Mtm1 and Dnm2 reveal possibilities for DNM2 knockdown as a therapeutic approach for X-linked centronuclear myopathy (XLCNM), or myotubular myopathy
Title: Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice.
Expression of several MTMR2 isoforms ameliorates the myopathic phenotype owing to MTM1 loss, with increased muscle force, reduced myofiber atrophy, and reduction of the intracellular disorganization hallmarks associated with myotubular myopathy.
Title: Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy.
Mtmr2 and Mtmr13 depend upon each other to achieve wild-type levels of protein expression. Mtmr2 stabilizes Mtmr13 on membranes, indicating that the Mtmr13 pseudophosphatase is regulated by its catalytically active binding partner.
Title: The CMT4B disease-causing phosphatases Mtmr2 and Mtmr13 localize to the Schwann cell cytoplasm and endomembrane compartments, where they depend upon each other to achieve wild-type levels of protein expression.
data indicate that Mtmr2 and Mtmr13/Sbf2 play critical roles in the sorting and modulation of cellular signalling which are likely to be disturbed in Charcot-Marie-Tooth disease type 4B
Title: The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling.
Here we provide strong evidence that Mtmr2 and Fig4 functionally interact in both Schwann cells and neurons, and we reveal for the first time a role of Mtmr2 in neurons in vivo
Title: Genetic interaction between MTMR2 and FIG4 phospholipid phosphatases involved in Charcot-Marie-Tooth neuropathies.
Interaction of Discs large 1 (Dlg1) with the Sec8 exocyst component promotes membrane addition, whereas with Mtmr2, negatively regulates membrane formation.
Title: Dlg1, Sec8, and Mtmr2 regulate membrane homeostasis in Schwann cell myelination.
Schwann cell-autonomous loss of Mtmr2-Dlg1 interaction dysregulates membrane homeostasis in the paranodal region, thereby producing outfolding and recurrent loops of myelin.
Title: Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis.
Mtmr2 forms a dimer and the C-terminal coiled-coil is responsible for homodimerization, in addition to membrane association
Title: Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module.
Loss of Mtmr2 in Schwann cells, but not in motor neurons, is both sufficient and necessary to cause Charcot-Marie-Tooth type neuropaathy.
Title: Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-Tooth type 4B1 neuropathy with myelin outfoldings.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:236056

Mtmr2 (e-PCR), detects polymorphism
- UniSTS:496011

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphatidylinositol phosphate phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity	ISS Inferred from Sequence or Structural Similarity more info
enables phosphatidylinositol-3-phosphate phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol-3-phosphate phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3-phosphate phosphatase activity	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-3-phosphate phosphatase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in dendritic spine maintenance	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within myelin assembly	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within myelin assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of myelination	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of endocytosis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of excitatory postsynaptic potential	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of myelination	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of myelination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of receptor catabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of receptor internalization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuron development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in phosphatidylinositol dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within phosphatidylinositol dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol dephosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within phosphatidylinositol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of early endosome to late endosome transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of phosphatidylinositol dephosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of phosphatidylinositol dephosphorylation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
located_in axon	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dendritic spine	ISO Inferred from Sequence Orthology more info
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density	ISO Inferred from Sequence Orthology more info
located_in synaptic membrane	ISO Inferred from Sequence Orthology more info
located_in synaptic vesicle	ISO Inferred from Sequence Orthology more info
located_in vacuolar membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2; myotubularin-related protein 2

Names: phosphatidylinositol-3,5-bisphosphate 3-phosphatase; phosphatidylinositol-3-phosphate phosphatase

NP_001359502.1

EC 3.1.3.95

NP_001360802.1

EC 3.1.3.95

NP_001360803.1

EC 3.1.3.95

NP_001360804.1

EC 3.1.3.95

NP_001360805.1

EC 3.1.3.95

NP_001360806.1

EC 3.1.3.95

NP_001360807.1

EC 3.1.3.95

NP_076347.3

EC 3.1.3.95

XP_036011299.1

EC 3.1.3.95

XP_036011300.1

EC 3.1.3.95

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001372573.1 → NP_001359502.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 2

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030, Q6P572

Conserved Domains (2) summary

pfam06602
Location:120 → 456

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain
NM_001373873.1 → NP_001360802.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 3

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030

Conserved Domains (2) summary

pfam06602
Location:192 → 494

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:73 → 187

PH-like; Pleckstrin homology-like domain
NM_001373874.1 → NP_001360803.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 4

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030

Conserved Domains (2) summary

pfam06602
Location:130 → 463

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain
NM_001373875.1 → NP_001360804.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 2

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030, Q6P572

Related

ENSMUSP00000115906.2, ENSMUST00000155679.8

Conserved Domains (2) summary

pfam06602
Location:120 → 456

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain
NM_001373876.1 → NP_001360805.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 2

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030, Q6P572

Conserved Domains (2) summary

pfam06602
Location:120 → 456

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain
NM_001373877.1 → NP_001360806.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 2

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030, Q6P572

Conserved Domains (2) summary

pfam06602
Location:120 → 456

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain
NM_001373878.1 → NP_001360807.1 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 2

Status: VALIDATED

Source sequence(s)

CT010488

UniProtKB/TrEMBL

Q3V030, Q6P572

Conserved Domains (2) summary

pfam06602
Location:120 → 456

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain
NM_023858.4 → NP_076347.3 phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 isoform 1

See identical proteins and their annotated locations for NP_076347.3

Status: VALIDATED

Source sequence(s)

CT010488

Consensus CDS

CCDS22818.3

UniProtKB/Swiss-Prot

B8JJF4, Q8VHA7, Q9Z2D1

UniProtKB/TrEMBL

Q3V030

Related

ENSMUSP00000034396.8, ENSMUST00000034396.14

Conserved Domains (2) summary

pfam06602
Location:192 → 528

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:73 → 187

PH-like; Pleckstrin homology-like domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

13660397..13720192

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036155406.1 → XP_036011299.1 myotubularin-related protein 2 isoform X1

Conserved Domains (2) summary

pfam06602
Location:270 → 603

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:141 → 255

PH-like; Pleckstrin homology-like domain
XM_036155407.1 → XP_036011300.1 myotubularin-related protein 2 isoform X2

UniProtKB/TrEMBL

Q3V030

Conserved Domains (2) summary

pfam06602
Location:130 → 463

Myotub-related; Myotubularin-like phosphatase domain

cl17171
Location:1 → 115

PH-like; Pleckstrin homology-like domain