| Comment type | Description |
|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=6; Name=1; IsoId=O35303-1; Sequence=Displayed; Name=2; IsoId=O35303-2; Sequence=VSP_013697, VSP_013701; Name=3; Synonyms=DLP1-37; IsoId=O35303-3; Sequence=VSP_013698, VSP_013699; Name=4; IsoId=O35303-4; Sequence=VSP_013696; Note=No experimental confirmation available.; Name=5; Synonyms=DLP1-11; IsoId=O35303-5; Sequence=VSP_013702; Name=6; IsoId=O35303-6; Sequence=VSP_013700; Note=No experimental confirmation available.; |
| Catalytic Activity | GTP + H(2)O = GDP + phosphate. |
| Domain | The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization |
| Function | Functions in mitochondrial and peroxisomal division. Mediates membrane fission through oligomerization into membrane- associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism. Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage. Required for normal brain development, including that of cerebellum. Facilitates developmentally regulated apoptosis during neural tube formation. Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues. Also required for mitochondrial fission during mitosis. Required for formation of endocytic vesicles. Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles. Required for programmed necrosis execution. {ECO:0000269|PubMed:11553726, ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:12861026, ECO:0000269|PubMed:17301055, ECO:0000269|PubMed:18250306, ECO:0000269|PubMed:23792689}. |
| Induction | By bezafibrate |
| Interaction | P53563-1:Bcl2l1; NbExp=2; IntAct=EBI-1767447, EBI-287204; |
| Ptm | O-GlcNAcylation augments the level of the GTP-bound active form of DRP1 and induces translocation from the cytoplasm to mitochondria in cardiomyocytes. It also decreases phosphorylation at Ser-656 |
| Ptm | Phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission. Phosphorylation on Ser-656 inhibits mitochondrial fission probably through preventing intramolecular interaction. Dephosphorylated on this site by PPP3CA which promotes mitochondrial fission. Phosphorylation on Ser-635 also promotes mitochondrial fission (By similarity) |
| Ptm | S-nitrosylation increases DNM1L dimerization, mitochondrial fission and causes neuronal damage |
| Ptm | Sumoylated on various lysine residues within the B domain, probably by MUL1. Sumoylation positively regulates mitochondrial fission. Desumoylated by SENP5 during G2/M transition of mitosis. Appears to be linked to its catalytic activity (By similarity) |
| Ptm | Ubiquitinated by MARCH5 |
| Similarity | Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family |
| Similarity | Contains 1 dynamin-type G (guanine nucleotide-binding) domain |
| Similarity | Contains 1 GED domain. {ECO:0000255|PROSITE- ProRule:PRU00720}. |
| Subcellular Location | Cytoplasm, cytosol . Golgi apparatus . Endomembrane system; Peripheral membrane protein. Mitochondrion outer membrane; Peripheral membrane protein. Peroxisome . Membrane, clathrin-coated pit. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane. Note=Mainly cytosolic. Translocated to the mitochondrial membrane through O-GlcNAcylation and interaction with FIS1. Colocalized with MARCH5 at mitochondrial membrane. Localizes to mitochondria at sites of division. Localizes to mitochondria following necrosis induction. Associated with peroxisomal membranes, partly recruited there by PEX11B. May also be associated with endoplasmic reticulum tubules and cytoplasmic vesicles and found to be perinuclear. In some cell types, localizes to the Golgi complex. Binds to phospholipid membranes (By similarity) |
| Subunit | Homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule. Oligomerizes in a GTP-dependent manner to form membrane- associated tubules with a spiral pattern. Can also oligomerize to form multimeric ring-like structures. Interacts with GSK3B and MARCH5. Interacts (via the GTPase and B domains) with UBE2I; the interaction promotes sumoylation of DNM1L, mainly in its B domain. Interacts with PPP3CA; the interaction dephosphorylates DNM1L and regulates its transition to mitochondria. Interacts with BCL2L1 isoform BCL-X(L) and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF. Interacts with FIS1. Interacts with MIEF2 and MIEF1; this regulates GTP hydrolysis and DNM1L oligomerization. Interacts with PGAM5; this interaction leads to dephosphorylation at Ser-656 and activation of GTPase activity and eventually to mitochondria fragmentation. {ECO:0000269|PubMed:10679301, ECO:0000269|PubMed:12861026, ECO:0000269|PubMed:18250306, ECO:0000269|PubMed:23792689}. |
| Tissue Specificity | Expressed in all tissues tested (at protein level). Longer isoforms are preferentially expressed in brain |