UniProt functional annotation for Q13614



	UniProt functional annotation for Q13614

UniProt code: Q13614.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3- phosphate and phosphatidylinositol 3,5-bisphosphate (PubMed:11733541, PubMed:12668758, PubMed:21372139, PubMed:14690594). Binds phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4,5- trisphosphate (By similarity). Stabilizes SBF2/MTMR13 at the membranes (By similarity). Specifically in peripheral nerves, stabilizes SBF2/MTMR13 protein (By similarity). {ECO:0000250|UniProtKB:Q9Z2D1, ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139}.

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3- phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol) + phosphate; Xref=Rhea:RHEA:12316, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088; EC=3.1.3.64; Evidence={ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139};

Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5- bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:39019, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57795, ChEBI:CHEBI:57923; EC=3.1.3.95; Evidence={ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:14690594, ECO:0000269|PubMed:21372139};

Catalytic activity: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1-D-myo-inositol-3- phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol) + phosphate; Xref=Rhea:RHEA:42328, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:65221, ChEBI:CHEBI:78934; Evidence={ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:21372139};

Catalytic activity: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5- bisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:45632, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:78911, ChEBI:CHEBI:85342; Evidence={ECO:0000269|PubMed:21372139};

Activity regulation: Interaction with SBF1/MTMR5 increases phosphatase activity. {ECO:0000269|PubMed:12668758}.

Subunit: Homodimer (via coiled-coil domain) (PubMed:12668758, PubMed:15998640). Heterotetramer consisting of one MTMR2 dimer and one SBF2/MTMR13 dimer (PubMed:15998640). Heterodimer with SBF1/MTMR5 (PubMed:12668758, PubMed:21372139). Heterodimer with MTMR12 (PubMed:12847286). {ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:12847286, ECO:0000269|PubMed:15998640, ECO:0000269|PubMed:21372139}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:11733541, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:15998640}. Early endosome membrane {ECO:0000269|PubMed:15998640, ECO:0000269|PubMed:21372139}; Peripheral membrane protein {ECO:0000269|PubMed:15998640, ECO:0000269|PubMed:21372139}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:12668758}. Cell projection, axon {ECO:0000250|UniProtKB:Q9Z2D1}. Endosome membrane {ECO:0000250|UniProtKB:Q9Z2D1}; Peripheral membrane protein {ECO:0000305}. Note=Partly associated with membranes (PubMed:12668758, PubMed:15998640, PubMed:21372139). Localizes to vacuoles in hypo- osmotic conditions (By similarity). {ECO:0000250|UniProtKB:Q9Z2D1, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:15998640, ECO:0000269|PubMed:21372139}.

Domain: The coiled-coil domain mediates homodimerization (PubMed:12668758, PubMed:15998640). Also mediates interaction with SBF1/MTMR5 (PubMed:12668758). By mediating MTMR2 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By similarity). {ECO:0000250|UniProtKB:Q9Z2D1, ECO:0000269|PubMed:12668758, ECO:0000269|PubMed:15998640}.

Domain: The GRAM domain mediates binding to phosphatidylinositol 4- phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5- bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. {ECO:0000250|UniProtKB:Q9Z2D1}.

Ptm: Phosphorylation at Ser-58 decreases MTMR2 localization to endocytic vesicular structures. {ECO:0000269|PubMed:21372139}.

Disease: Charcot-Marie-Tooth disease 4B1 (CMT4B1) [MIM:601382]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie- Tooth disease are designated CMT4. {ECO:0000269|PubMed:10802647, ECO:0000269|PubMed:12398840}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the protein-tyrosine phosphatase family. Non- receptor class myotubularin subfamily. {ECO:0000305}.

Sequence caution: Sequence=BAA83025.2; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3- phosphate and phosphatidylinositol 3,5-bisphosphate (PubMed:11733541, PubMed:12668758, PubMed:21372139, PubMed:14690594). Binds phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4,5- trisphosphate (By similarity). Stabilizes SBF2/MTMR13 at the membranes (By similarity). Specifically in peripheral nerves, stabilizes SBF2/MTMR13 protein (By similarity). {ECO:0000250\|UniProtKB:Q9Z2D1, ECO:0000269\|PubMed:11733541, ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:14690594, ECO:0000269\|PubMed:21372139}.


Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3- phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol) + phosphate; Xref=Rhea:RHEA:12316, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088; EC=3.1.3.64; Evidence={ECO:0000269\|PubMed:11733541, ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:14690594, ECO:0000269\|PubMed:21372139};
Catalytic activity:		Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5- bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:39019, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57795, ChEBI:CHEBI:57923; EC=3.1.3.95; Evidence={ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:14690594, ECO:0000269\|PubMed:21372139};
Catalytic activity:		Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1-D-myo-inositol-3- phosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol) + phosphate; Xref=Rhea:RHEA:42328, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:65221, ChEBI:CHEBI:78934; Evidence={ECO:0000269\|PubMed:11733541, ECO:0000269\|PubMed:21372139};
Catalytic activity:		Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5- bisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo- inositol-5-phosphate) + phosphate; Xref=Rhea:RHEA:45632, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:78911, ChEBI:CHEBI:85342; Evidence={ECO:0000269\|PubMed:21372139};
Activity regulation:		Interaction with SBF1/MTMR5 increases phosphatase activity. {ECO:0000269\|PubMed:12668758}.
Subunit:		Homodimer (via coiled-coil domain) (PubMed:12668758, PubMed:15998640). Heterotetramer consisting of one MTMR2 dimer and one SBF2/MTMR13 dimer (PubMed:15998640). Heterodimer with SBF1/MTMR5 (PubMed:12668758, PubMed:21372139). Heterodimer with MTMR12 (PubMed:12847286). {ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:12847286, ECO:0000269\|PubMed:15998640, ECO:0000269\|PubMed:21372139}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:11733541, ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:15998640}. Early endosome membrane {ECO:0000269\|PubMed:15998640, ECO:0000269\|PubMed:21372139}; Peripheral membrane protein {ECO:0000269\|PubMed:15998640, ECO:0000269\|PubMed:21372139}. Cytoplasm, perinuclear region {ECO:0000269\|PubMed:12668758}. Cell projection, axon {ECO:0000250\|UniProtKB:Q9Z2D1}. Endosome membrane {ECO:0000250\|UniProtKB:Q9Z2D1}; Peripheral membrane protein {ECO:0000305}. Note=Partly associated with membranes (PubMed:12668758, PubMed:15998640, PubMed:21372139). Localizes to vacuoles in hypo- osmotic conditions (By similarity). {ECO:0000250\|UniProtKB:Q9Z2D1, ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:15998640, ECO:0000269\|PubMed:21372139}.
Domain:		The coiled-coil domain mediates homodimerization (PubMed:12668758, PubMed:15998640). Also mediates interaction with SBF1/MTMR5 (PubMed:12668758). By mediating MTMR2 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By similarity). {ECO:0000250\|UniProtKB:Q9Z2D1, ECO:0000269\|PubMed:12668758, ECO:0000269\|PubMed:15998640}.
Domain:		The GRAM domain mediates binding to phosphatidylinositol 4- phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5- bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. {ECO:0000250\|UniProtKB:Q9Z2D1}.
Ptm:		Phosphorylation at Ser-58 decreases MTMR2 localization to endocytic vesicular structures. {ECO:0000269\|PubMed:21372139}.
Disease:		Charcot-Marie-Tooth disease 4B1 (CMT4B1) [MIM:601382]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie- Tooth disease are designated CMT4. {ECO:0000269\|PubMed:10802647, ECO:0000269\|PubMed:12398840}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the protein-tyrosine phosphatase family. Non- receptor class myotubularin subfamily. {ECO:0000305}.
Sequence caution:		Sequence=BAA83025.2; Type=Erroneous initiation; Evidence={ECO:0000305};