DNM2
Function
Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton (PubMed:15731758, PubMed:19605363, PubMed:19623537, PubMed:33713620, PubMed:34744632). Plays an important role in vesicular trafficking processes, namely clathrin-mediated endocytosis (CME), exocytic and clathrin-coated vesicle from the trans-Golgi network, and PDGF stimulated macropinocytosis (PubMed:15731758, PubMed:19623537, PubMed:33713620). During vesicular trafficking process, associates to the membrane, through lipid binding, and self-assembles into ring-like structure through oligomerization to form a helical polymer around the vesicle membrane and leading to vesicle scission (PubMed:17636067, PubMed:34744632, PubMed:36445308). Plays a role in organization of the actin cytoskeleton by mediating arrangement of stress fibers and actin bundles in podocytes (By similarity). During organization of the actin cytoskeleton, self-assembles into ring-like structure that directly bundles actin filaments to form typical membrane tubules decorated with dynamin spiral polymers (By similarity). Self-assembly increases GTPase activity and the GTP hydrolysis causes the rapid depolymerization of dynamin spiral polymers, and results in dispersion of actin bundles (By similarity). Remodels, through its interaction with CTTN, bundled actin filaments in a GTPase-dependent manner and plays a role in orchestrating the global actomyosin cytoskeleton (PubMed:19605363). The interaction with CTTN stabilizes the interaction of DNM2 and actin filaments and stimulates the intrinsic GTPase activity that results in actin filament-barbed ends and increases the sensitivity of filaments in bundles to the actin depolymerizing factor, CFL1 (By similarity). Plays a role in the autophagy process, by participating in the formation of ATG9A vesicles destined for the autophagosomes through its interaction with SNX18 (PubMed:29437695), by mediating recycling endosome scission leading to autophagosome release through MAP1LC3B interaction (PubMed:29437695, PubMed:32315611). Also regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity). Also plays a role in cytokinesis (By similarity). May participate in centrosome cohesion through its interaction with TUBG1 (By similarity). Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Involved in membrane tubulation (PubMed:24135484).
Involvement in disease
Myopathy, centronuclear, 1
CNM1
A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
None
The disease is caused by variants affecting the gene represented in this entry.
Lethal congenital contracture syndrome 5
LCCS5
A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth.
None
The disease is caused by variants affecting the gene represented in this entry.
Charcot-Marie-Tooth disease, dominant intermediate B
CMTDIB
A 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. The dominant intermediate type B is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
None
The disease is caused by variants affecting the gene represented in this entry.
Charcot-Marie-Tooth disease, axonal, 2M
CMT2M
An axonal 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). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Ser-848 by GSK3-alpha relieves the inhibition of BIN1 and promotes endocytosis (PubMed:36445308). Phosphorylation at Ser-764 by CDK1 is greatly increased upon mitotic entry (PubMed:20496096). It regulates cytokinesis downstream of calcineurin, and does not affect clathrin-mediated endocytosis (By similarity). Dephosphorylated by calcineurin/PP2 during cytokinesis in a Ca(2+)- and calmodulin-dependent manner (PubMed:20496096). Phosphorylated on tyrosine residues by EGFR and after activation of SRC (By similarity).
Sequence Similarities
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Tissue Specificity
Widely expressed (PubMed:7590285). Expressed in skeletal muscle and the peripheral nerve (PubMed:19623537).
Cellular localization
- Cytoplasm
- Cytoskeleton
- Cytoplasmic vesicle
- Clathrin-coated vesicle
- Cell projection
- Uropodium
- Endosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Centriole
- Recycling endosome
- Cell projection
- Phagocytic cup
- Cytoplasmic vesicle
- Phagosome membrane
- Peripheral membrane protein
- Cell projection
- Podosome
- Cytoplasm
- Cell junction
- Postsynaptic density
- Synapse
- Synaptosome
- Midbody
- Membrane
- Clathrin-coated pit
- Localized in recycling endosomes fragment to release nascent autophagosomes (PubMed:32315611). Co-localizes with PIK3C3 and RAB5A to the nascent phagosome. Localized at focal ahesion site upon induction of focal adhesions and stress-fiber formation, when interacts with SDC4 (By similarity). Exists as a dynamic component of the centrosome. Associates with clathrin-coated vesicles at both the plasma membrane and the trans-Golgi network (TGN) (By similarity).
Alternative names
DYN2, DNM2, Dynamin-2, Dynamin 2, Dynamin II