SBF2
Domain
The C-terminal domain mediates homodimerization (By similarity). By mediating SBF2/MTMR13 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By similarity).
The GRAM domain mediates binding to phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3,4,5-trisphosphate.
The PH domain binds preferentially phosphatidylinositol 3,4,5-trisphosphate (By similarity). Appears to be dispensable for localization to membranes (By similarity).
Function
Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28 (PubMed:20937701, PubMed:25648148). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (PubMed:20937701, PubMed:25648148). In response to starvation-induced autophagy, activates RAB21 which in turn binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (PubMed:25648148). Acts as an adapter for the phosphatase MTMR2 (By similarity). Increases MTMR2 catalytic activity towards phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards phosphatidylinositol 3-phosphate (By similarity).
Involvement in disease
Charcot-Marie-Tooth disease 4B2
CMT4B2
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.
Tissue Specificity
Widely expressed. Expressed in spinal cord.
Cellular localization
- Cytoplasm
- Cytoplasm
- Perinuclear region
- Membrane
- Peripheral membrane protein
- Endosome membrane
- Peripheral membrane protein
- Cell projection
- Axon
- Associated with membranes (PubMed:15998640). Localizes to vacuoles in hypo-osmotic conditions (By similarity). Membrane localization is likely to be mediated via its interaction with MTMR2 (By similarity).
Alternative names
CMT4B2, KIAA1766, MTMR13, SBF2, Myotubularin-related protein 13, Inactive phosphatidylinositol 3-phosphatase 13, SET-binding factor 2