UniProtKB - O00429 (DNM1L_HUMAN)
Protein
Dynamin-1-like protein
Gene
DNM1L
Organism
Homo sapiens (Human)
Status
Functioni
Functions in mitochondrial and peroxisomal division (PubMed:9570752, PubMed:9786947, PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17553808, PubMed:17460227, PubMed:18695047, PubMed:18838687, PubMed:19638400, PubMed:19411255, PubMed:19342591, PubMed:23921378, PubMed:23283981, PubMed:23530241, PubMed:29478834, PubMed:32484300, PubMed:27145208, PubMed:26992161, PubMed:27301544, PubMed:27328748). 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 (PubMed:23530241, PubMed:23584531). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23921378, PubMed:23283981, PubMed:29899447). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:29899447). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity). Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:27145208, PubMed:26992161, PubMed:27301544, PubMed:27328748). Facilitates developmentally regulated apoptosis during neural tube formation (By similarity). 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 (By similarity). Required for formation of endocytic vesicles (PubMed:9570752, PubMed:20688057, PubMed:23792689). 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 (PubMed:17015472, PubMed:23792689). Required for programmed necrosis execution (PubMed:22265414). Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834).By similarity27 Publications
Inhibits peroxisomal division when overexpressed.1 Publication
Inhibits peroxisomal division when overexpressed.1 Publication
Catalytic activityi
- EC:3.6.5.52 Publications
Activity regulationi
GTPase activity is increased by binding to phospholipid membranes.1 Publication
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 32 – 40 | GTP1 Publication | 9 | |
| Nucleotide bindingi | 215 – 221 | GTP1 Publication | 7 | |
| Nucleotide bindingi | 246 – 249 | GTP1 Publication | 4 |
GO - Molecular functioni
- BH2 domain binding Source: Ensembl
- clathrin binding Source: Ensembl
- GTPase activator activity Source: ParkinsonsUK-UCL
- GTPase activity Source: UniProtKB
- GTP binding Source: UniProtKB-KW
- GTP-dependent protein binding Source: ParkinsonsUK-UCL
- identical protein binding Source: IntAct
- lipid binding Source: UniProtKB-KW
- microtubule binding Source: GO_Central
- protein-containing complex binding Source: Ensembl
- protein homodimerization activity Source: UniProtKB
- small GTPase binding Source: ParkinsonsUK-UCL
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- calcium ion transport Source: Ensembl
- cellular response to oxygen-glucose deprivation Source: Ensembl
- cellular response to thapsigargin Source: Ensembl
- dynamin family protein polymerization involved in mitochondrial fission Source: UniProtKB
- execution phase of apoptosis Source: Reactome
- heart contraction Source: Ensembl
- intracellular distribution of mitochondria Source: ParkinsonsUK-UCL
- membrane fusion Source: UniProtKB
- mitochondrial fission Source: UniProtKB
- mitochondrial fragmentation involved in apoptotic process Source: UniProtKB
- mitochondrial membrane fission Source: UniProtKB
- mitochondrion morphogenesis Source: MGI
- mitochondrion organization Source: ParkinsonsUK-UCL
- necroptotic process Source: UniProtKB
- negative regulation of mitochondrial fusion Source: Ensembl
- peroxisome fission Source: UniProtKB
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of dendritic spine morphogenesis Source: Ensembl
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of mitochondrial fission Source: ParkinsonsUK-UCL
- positive regulation of neutrophil chemotaxis Source: CACAO
- positive regulation of protein secretion Source: UniProtKB
- positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
- positive regulation of synaptic vesicle endocytosis Source: Ensembl
- positive regulation of synaptic vesicle exocytosis Source: Ensembl
- protein complex oligomerization Source: UniProtKB
- protein-containing complex assembly Source: UniProtKB
- protein localization to mitochondrion Source: Ensembl
- regulation of ATP metabolic process Source: Ensembl
- regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
- regulation of gene expression Source: Ensembl
- regulation of mitochondrion organization Source: UniProtKB
- regulation of peroxisome organization Source: UniProtKB
- regulation of ubiquitin protein ligase activity Source: Ensembl
- release of cytochrome c from mitochondria Source: UniProtKB
- response to flavonoid Source: Ensembl
- response to hypobaric hypoxia Source: Ensembl
- rhythmic process Source: UniProtKB-KW
- synaptic vesicle endocytosis Source: Ensembl
- synaptic vesicle recycling via endosome Source: Ensembl
Keywordsi
| Molecular function | Hydrolase |
| Biological process | Biological rhythms, Endocytosis, Necrosis |
| Ligand | GTP-binding, Lipid-binding, Nucleotide-binding |
Enzyme and pathway databases
| PathwayCommonsi | O00429 |
| Reactomei | R-HSA-75153, Apoptotic execution phase |
| SIGNORi | O00429 |
Protein family/group databases
| TCDBi | 1.N.6.1.2, the mitochondrial inner/outer membrane fusion (mmf) family |
Names & Taxonomyi
| Protein namesi | Recommended name: Dynamin-1-like protein (EC:3.6.5.5)Alternative name(s): Dnm1p/Vps1p-like protein Short name: DVLP Dynamin family member proline-rich carboxyl-terminal domain less Short name: Dymple Dynamin-like protein Dynamin-like protein 4 Dynamin-like protein IV Short name: HdynIV Dynamin-related protein 1 |
| Gene namesi | Name:DNM1L Synonyms:DLP1, DRP1 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:2973, DNM1L |
| MIMi | 603850, gene |
| neXtProti | NX_O00429 |
| VEuPathDBi | HostDB:ENSG00000087470.17 |
Subcellular locationi
Peroxisome
Mitochondrion
- Mitochondrion outer membrane 3 Publications; Peripheral membrane protein
Golgi apparatus
Cytoplasm and Cytosol
Other locations
- Endomembrane system ; Peripheral membrane protein
- clathrin-coated pit By similarity
- synaptic vesicle membrane By similarity
Note: Mainly cytosolic. Translocated to the mitochondrial membrane through O-GlcNAcylation and interaction with FIS1. Colocalized with MARCHF5 at mitochondrial membrane. Localizes to mitochondria at sites of division. Localizes to mitochondria following necrosis induction. Recruited to the mitochondrial outer membrane by interaction with MIEF1. Mitochondrial recruitment is inhbited by C11orf65/MFI (By similarity). 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 (By similarity). Binds to phospholipid membranes (By similarity).By similarity
Cytoskeleton
- microtubule Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum Source: ParkinsonsUK-UCL
- endoplasmic reticulum membrane Source: ParkinsonsUK-UCL
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- Golgi membrane Source: Ensembl
Mitochondrion
- mitochondrial membrane Source: GO_Central
- mitochondrial outer membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Peroxisome
- peroxisome Source: UniProtKB
Plasma Membrane
- clathrin-coated pit Source: UniProtKB-SubCell
- presynaptic endocytic zone membrane Source: Ensembl
Other locations
- brush border Source: Ensembl
- cytoplasm Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
- membrane Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
- protein-containing complex Source: UniProtKB
- synaptic vesicle membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell junction, Coated pit, Cytoplasm, Cytoplasmic vesicle, Golgi apparatus, Membrane, Mitochondrion, Mitochondrion outer membrane, Peroxisome, SynapsePathology & Biotechi
Involvement in diseasei
May be associated with Alzheimer disease through amyloid-beta-induced increased S-nitrosylation of DNM1L, which triggers, directly or indirectly, excessive mitochondrial fission, synaptic loss and neuronal damage.1 Publication
Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy. After birth, infants present in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. Other features include mildly elevated plasma concentration of very-long-chain fatty acids, lactic acidosis, microcephaly, deep-set eyes, optic atrophy and hypoplasia, and an abnormal gyral pattern in both frontal lobes associated with dysmyelination.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_080870 | 36 | S → G in EMPF1; autosomal recessive; impaired mitochondrial membrane fission; hypomorphic mutation retaining partial activity in mitochondrial membrane fission. 1 PublicationCorresponds to variant dbSNP:rs879255688EnsemblClinVar. | 1 | |
| Natural variantiVAR_076316 | 362 | G → D in EMPF1; unknown pathological significance; unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site; presence of concentric cristae and/or increased dense granules in some mitochondria. 2 PublicationsCorresponds to variant dbSNP:rs879255685EnsemblClinVar. | 1 | |
| Natural variantiVAR_076317 | 362 | G → S in EMPF1; the mutation acts in a dominant-negative manner; defects observed in mitochondrial fission; significant decrease in mitochondrial respiratory chain complex IV activity. 1 PublicationCorresponds to variant dbSNP:rs886037861EnsemblClinVar. | 1 | |
| Natural variantiVAR_063704 | 395 | A → D in EMPF1; the mutation acts in a dominant-negative manner; defects observed in both mitochondrial and peroxisomal fission; reduced oligomerization, decreased mitochondrial recruitment. 2 PublicationsCorresponds to variant dbSNP:rs121908531EnsemblClinVar. | 1 | |
| Natural variantiVAR_076318 | 403 | R → C in EMPF1; the mutation acts in a dominant-negative manner; reduced oligomerization; decreased mitochondrial recruitment; defects observed in mitochondrial fission. 1 PublicationCorresponds to variant dbSNP:rs863223953EnsemblClinVar. | 1 | |
| Natural variantiVAR_080872 | 406 | L → S in EMPF1; impaired mitochondrial and peroxisomal membrane fission. 1 Publication | 1 |
Optic atrophy 5 (OPA5)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of optic atrophy, a disease characterized by progressive visual loss in association with a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA5 is an autosomal dominant non-syndromic form that manifests as slowly progressive visual loss with variable onset from the first to third decades. Additional ocular abnormalities may include central scotoma and dyschromatopsia.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_080869 | 2 | E → A in OPA5; changed localization to mitochondrion; impaired mitochondrial membrane fission. 1 PublicationCorresponds to variant dbSNP:rs1555229948EnsemblClinVar. | 1 | |
| Natural variantiVAR_080871 | 192 | A → E in OPA5; changed localization to mitochondrion; impaired mitochondrial membrane fission. 1 PublicationCorresponds to variant dbSNP:rs1555119216EnsemblClinVar. | 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 34 | Q → A: Abolishes GTP hydrolysis. 1 Publication | 1 | |
| Mutagenesisi | 38 | K → A: Loss of GTPase activity. Impairs mitochondrial division and induces changes in peroxisome morphology. No effect on oligomerization. Increase in sumoylation by SUMO3. 6 Publications | 1 | |
| Mutagenesisi | 38 | K → E: Overexpression delays protein secretion. Rescues fragmented or truncated mitochondria in PRKN- or PINK1-depleted cells. 6 Publications | 1 | |
| Mutagenesisi | 39 | S → A: Abolishes GTP hydrolysis. 3 Publications | 1 | |
| Mutagenesisi | 39 | S → I: Decreased localization to the perinuclear region. 3 Publications | 1 | |
| Mutagenesisi | 39 | S → N: Reduces peroxisomal abundance. 3 Publications | 1 | |
| Mutagenesisi | 41 | V → F: Temperature-sensitive. Impairs mitochondrial division. 1 Publication | 1 | |
| Mutagenesisi | 59 | T → A: Abolishes GTP hydrolysis. Impairs mitochondrial division. Reduces peroxisomal abundance. 3 Publications | 1 | |
| Mutagenesisi | 146 | D → A: Abolishes GTP hydrolysis. 1 Publication | 1 | |
| Mutagenesisi | 149 | G → A: Abolishes GTP hydrolysis. 1 Publication | 1 | |
| Mutagenesisi | 190 | D → A: Unable to homooligomerize. Unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site. 1 Publication | 1 | |
| Mutagenesisi | 216 | K → A: Abolishes GTP hydrolysis. 1 Publication | 1 | |
| Mutagenesisi | 218 | D → A: Abolishes GTP hydrolysis. 1 Publication | 1 | |
| Mutagenesisi | 221 | D → A: Unable to homooligomerize. Unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site. 1 Publication | 1 | |
| Mutagenesisi | 281 | G → D: Temperature-sensitive. Impairs mitochondrial division. 1 Publication | 1 | |
| Mutagenesisi | 300 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 345 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 361 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 367 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 401 – 404 | GPRP → AAAA: Impairs formation of higher order oligomers, but not homodimerization. 1 Publication | 4 | |
| Mutagenesisi | 431 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 446 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 470 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 490 | E → A: Does not impair homodimerization and formation of higher order oligomers. 1 Publication | 1 | |
| Mutagenesisi | 490 | E → R: Impairs homodimerization and formation of higher order oligomers. 1 Publication | 1 | |
| Mutagenesisi | 505 | C → A: No effect on S-nitrosylation. 1 Publication | 1 | |
| Mutagenesisi | 532 | K → R: Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-535; R-558 and R-568. 1 Publication | 1 | |
| Mutagenesisi | 535 | K → R: Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-532; R-558 and R-568. 1 Publication | 1 | |
| Mutagenesisi | 558 | K → R: Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-532; R-535 and R-568. 1 Publication | 1 | |
| Mutagenesisi | 568 | K → R: Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-532; R-535 and R-558. 1 Publication | 1 | |
| Mutagenesisi | 594 | K → R: Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-597; R-606 and R-608. 1 Publication | 1 | |
| Mutagenesisi | 597 | K → R: Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-594; R-606 and R-608. 1 Publication | 1 | |
| Mutagenesisi | 606 | K → R: Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-594; R-597 and R-608. 1 Publication | 1 | |
| Mutagenesisi | 608 | K → R: Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-594; R-597 and R-606. 1 Publication | 1 | |
| Mutagenesisi | 616 | S → A: Loss of activity. Little effect on mitochondrial morphology. Translocated to mitochondria. 2 Publications | 1 | |
| Mutagenesisi | 637 | S → A: Abolishes phosphorylation. Reduces interaction with MIEF1 and MIEF2. Promotes mitochondrial fission and cell vulnerability to apoptotic insults. Mostly mitochondrial. Disrupts, in vitro, binding to FIS1. 4 Publications | 1 | |
| Mutagenesisi | 637 | S → D: Impairs intramolecular interactions but not homooligomerization. Does not reduce interaction with MIEF1 and MIEF2. Impairs formation of higher order oligomers but not homodimerization. Unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site. Slight reduction in GTPase activity. Inhibits mitochondrial fission. Retained in the cytoplasm. 5 Publications | 1 | |
| Mutagenesisi | 644 | C → A: Abolishes S-nitrosylation. Reduced dimerization and no enhancement of GTPase activity. 1 Publication | 1 | |
| Mutagenesisi | 668 | K → E: Abolishes homodimerization and formation of higher order oligomers. 1 Publication | 1 | |
| Mutagenesisi | 679 | K → A: Diminishes intramolecular interaction between GTP-middle domain and GED domain but no effect on homooligomerization. Marked reduction in GTPase activity, in vitro. Decreased mitochondrial division. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
| DisGeNETi | 10059 |
| MalaCardsi | DNM1L |
| MIMi | 610708, phenotype 614388, phenotype |
| NIAGADSi | ENSG00000087470 |
| OpenTargetsi | ENSG00000087470 |
| Orphaneti | 98673, Autosomal dominant optic atrophy, classic form 330050, DNM1L-related encephalopathy due to mitochondrial and peroxisomal fission defect |
| PharmGKBi | PA27441 |
Miscellaneous databases
| Pharosi | O00429, Tbio |
Genetic variation databases
| BioMutai | DNM1L |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000206566 | 1 – 736 | Dynamin-1-like proteinAdd BLAST | 736 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
| Modified residuei | 529 | PhosphoserineCombined sources | 1 | |
| Cross-linki | 532 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Cross-linki | 535 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Modified residuei | 548 | PhosphoserineCombined sources | 1 | |
| Cross-linki | 558 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Cross-linki | 568 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Glycosylationi | 585 | O-linked (GlcNAc) threonineBy similarity | 1 | |
| Glycosylationi | 586 | O-linked (GlcNAc) threonineBy similarity | 1 | |
| Cross-linki | 594 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Modified residuei | 597 | N6-acetyllysine; alternateBy similarity | 1 | |
| Cross-linki | 597 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||
| Cross-linki | 606 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Modified residuei | 607 | PhosphoserineCombined sources | 1 | |
| Cross-linki | 608 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
| Modified residuei | 616 | Phosphoserine; by CDK1 and PINK1Combined sources3 Publications | 1 | |
| Modified residuei | 637 | Phosphoserine; by CAMK1 and PKA5 Publications | 1 | |
| Modified residuei | 644 | S-nitrosocysteine1 Publication | 1 |
Post-translational modificationi
Phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission (PubMed:17301055, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:23283981, PubMed:29478834). Phosphorylation on Ser-637 by CAMK1 and PKA inhibits the GTPase activity, leading to a defect in mitochondrial fission promoting mitochondrial elongation (PubMed:17553808, PubMed:18695047, PubMed:23283981, PubMed:29478834). Dephosphorylated on this site by PPP3CA which promotes mitochondrial fission (PubMed:18838687). Phosphorylation on Ser-616 by CDK1 and PINK1 activates the GTPase activity and promotes mitochondrial fission (PubMed:18838687, PubMed:32484300). Phosphorylated in a circadian manner at Ser-637 (PubMed:29478834).7 Publications
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.3 Publications
S-nitrosylation increases DNM1L dimerization, mitochondrial fission and causes neuronal damage.1 Publication
Ubiquitination by MARCHF5 affects mitochondrial morphology.2 Publications
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-637 (By similarity).By similarity
Keywords - PTMi
Acetylation, Glycoprotein, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugationProteomic databases
| CPTACi | CPTAC-57 |
| EPDi | O00429 |
| jPOSTi | O00429 |
| MassIVEi | O00429 |
| MaxQBi | O00429 |
| PaxDbi | O00429 |
| PeptideAtlasi | O00429 |
| PRIDEi | O00429 |
| ProteomicsDBi | 34194 4122 47884 [O00429-1] 47885 [O00429-2] 47886 [O00429-3] 47887 [O00429-4] 47888 [O00429-5] 47889 [O00429-6] |
PTM databases
| GlyGeni | O00429, 2 sites |
| iPTMneti | O00429 |
| MetOSitei | O00429 |
| PhosphoSitePlusi | O00429 |
| SwissPalmi | O00429 |
Expressioni
Tissue specificityi
Ubiquitously expressed with highest levels found in skeletal muscles, heart, kidney and brain. Isoform 1 is brain-specific. Isoform 2 and isoform 3 are predominantly expressed in testis and skeletal muscles respectively. Isoform 4 is weakly expressed in brain, heart and kidney. Isoform 5 is dominantly expressed in liver, heart and kidney. Isoform 6 is expressed in neurons.5 Publications
Gene expression databases
| Bgeei | ENSG00000087470, Expressed in intestine and 246 other tissues |
| ExpressionAtlasi | O00429, baseline and differential |
| Genevisiblei | O00429, HS |
Organism-specific databases
| HPAi | ENSG00000087470, Low tissue specificity |
Interactioni
Subunit structurei
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.
Interacts with GSK3B and MARCHF5.
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 MFF; the interaction is inhinited by C11orf65/MFI.
Interacts with FIS1.
Interacts with MIEF2 and MIEF1; GTP-dependent, 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.
By similarity17 PublicationsBinary interactionsi
Hide detailsO00429
DNM1L - isoform 2 [O00429-3]
DNM1L - isoform 3 [O00429-4]
| With | #Exp. | IntAct |
|---|---|---|
| itself | 2 | EBI-4420450,EBI-4420450 |
GO - Molecular functioni
- BH2 domain binding Source: Ensembl
- clathrin binding Source: Ensembl
- GTP-dependent protein binding Source: ParkinsonsUK-UCL
- identical protein binding Source: IntAct
- microtubule binding Source: GO_Central
- protein homodimerization activity Source: UniProtKB
- small GTPase binding Source: ParkinsonsUK-UCL
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
| BioGRIDi | 115370, 252 interactors |
| CORUMi | O00429 |
| DIPi | DIP-42704N |
| IntActi | O00429, 222 interactors |
| MINTi | O00429 |
| STRINGi | 9606.ENSP00000449089 |
Miscellaneous databases
| RNActi | O00429, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SMRi | O00429 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 22 – 302 | Dynamin-type GPROSITE-ProRule annotationAdd BLAST | 281 | |
| Domaini | 644 – 735 | GEDPROSITE-ProRule annotationAdd BLAST | 92 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 32 – 39 | G1 motifPROSITE-ProRule annotation | 8 | |
| Regioni | 58 – 60 | G2 motifPROSITE-ProRule annotation | 3 | |
| Regioni | 146 – 149 | G3 motifPROSITE-ProRule annotation | 4 | |
| Regioni | 215 – 218 | G4 motifPROSITE-ProRule annotation | 4 | |
| Regioni | 245 – 248 | G5 motifPROSITE-ProRule annotation | 4 | |
| Regioni | 344 – 489 | Middle domain1 PublicationAdd BLAST | 146 | |
| Regioni | 448 – 685 | Interaction with GSK3B1 PublicationAdd BLAST | 238 | |
| Regioni | 502 – 569 | B domain1 PublicationAdd BLAST | 68 | |
| Regioni | 654 – 668 | Important for homodimerization1 PublicationAdd BLAST | 15 |
Domaini
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.1 Publication
Sequence similaritiesi
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.PROSITE-ProRule annotation
Phylogenomic databases
| eggNOGi | KOG0446, Eukaryota |
| GeneTreei | ENSGT00940000155504 |
| HOGENOMi | CLU_008964_5_4_1 |
| InParanoidi | O00429 |
| OMAi | KTRVNIM |
| PhylomeDBi | O00429 |
| TreeFami | TF352031 |
Family and domain databases
| CDDi | cd08771, DLP_1, 1 hit |
| DisProti | DP01537 [O00429-3] DP01540 |
| Gene3Di | 2.30.29.30, 1 hit |
| InterProi | View protein in InterPro IPR030556, DNM1L IPR001401, Dynamin_GTPase IPR019762, Dynamin_GTPase_CS IPR022812, Dynamin_SF IPR000375, Dynamin_stalk IPR030381, G_DYNAMIN_dom IPR003130, GED IPR020850, GED_dom IPR027417, P-loop_NTPase IPR011993, PH-like_dom_sf |
| PANTHERi | PTHR11566, PTHR11566, 1 hit PTHR11566:SF39, PTHR11566:SF39, 1 hit |
| Pfami | View protein in Pfam PF01031, Dynamin_M, 1 hit PF00350, Dynamin_N, 1 hit PF02212, GED, 1 hit |
| PRINTSi | PR00195, DYNAMIN |
| SMARTi | View protein in SMART SM00053, DYNc, 1 hit SM00302, GED, 1 hit |
| SUPFAMi | SSF52540, SSF52540, 1 hit |
| PROSITEi | View protein in PROSITE PS00410, G_DYNAMIN_1, 1 hit PS51718, G_DYNAMIN_2, 1 hit PS51388, GED, 1 hit |
Sequences (9+)i
Sequence statusi: Complete.
This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basketThis entry has 9 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: O00429-1) [UniParc]FASTAAdd to basket
Also known as: HdynIV-WT, DLP1F
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL
60 70 80 90 100
LPRGTGIVTR RPLILQLVHV SQEDKRKTTG EENGVEAEEW GKFLHTKNKL
110 120 130 140 150
YTDFDEIRQE IENETERISG NNKGVSPEPI HLKIFSPNVV NLTLVDLPGM
160 170 180 190 200
TKVPVGDQPK DIELQIRELI LRFISNPNSI ILAVTAANTD MATSEALKIS
210 220 230 240 250
REVDPDGRRT LAVITKLDLM DAGTDAMDVL MGRVIPVKLG IIGVVNRSQL
260 270 280 290 300
DINNKKSVTD SIRDEYAFLQ KKYPSLANRN GTKYLARTLN RLLMHHIRDC
310 320 330 340 350
LPELKTRINV LAAQYQSLLN SYGEPVDDKS ATLLQLITKF ATEYCNTIEG
360 370 380 390 400
TAKYIETSEL CGGARICYIF HETFGRTLES VDPLGGLNTI DILTAIRNAT
410 420 430 440 450
GPRPALFVPE VSFELLVKRQ IKRLEEPSLR CVELVHEEMQ RIIQHCSNYS
460 470 480 490 500
TQELLRFPKL HDAIVEVVTC LLRKRLPVTN EMVHNLVAIE LAYINTKHPD
510 520 530 540 550
FADACGLMNN NIEEQRRNRL ARELPSAVSR DKSSKVPSAL APASQEPSPA
560 570 580 590 600
ASAEADGKLI QDSRRETKNV ASGGGGVGDG VQEPTTGNWR GMLKTSKAEE
610 620 630 640 650
LLAEEKSKPI PIMPASPQKG HAVNLLDVPV PVARKLSARE QRDCEVIERL
660 670 680 690 700
IKSYFLIVRK NIQDSVPKAV MHFLVNHVKD TLQSELVGQL YKSSLLDDLL
710 720 730
TESEDMAQRR KEAADMLKAL QGASQIIAEI RETHLW
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| F8VZ52 | F8VZ52_HUMAN | Dynamin-1-like protein | DNM1L | 261 | Annotation score: | ||
| B4DDQ3 | B4DDQ3_HUMAN | Dynamin-1-like protein | DNM1L | 180 | Annotation score: | ||
| B4DPZ9 | B4DPZ9_HUMAN | Dynamin-1-like protein | DNM1L | 156 | Annotation score: | ||
| F8VYL3 | F8VYL3_HUMAN | Dynamin-1-like protein | DNM1L | 117 | Annotation score: | ||
| F8VUJ9 | F8VUJ9_HUMAN | Dynamin-1-like protein | DNM1L | 172 | Annotation score: | ||
| F8W1W3 | F8W1W3_HUMAN | Dynamin-1-like protein | DNM1L | 168 | Annotation score: | ||
| F8VR28 | F8VR28_HUMAN | Dynamin-1-like protein | DNM1L | 97 | Annotation score: | ||
| H0YHY4 | H0YHY4_HUMAN | Dynamin-1-like protein | DNM1L | 54 | Annotation score: | ||
| H0YI79 | H0YI79_HUMAN | Dynamin-1-like protein | DNM1L | 48 | Annotation score: |
Sequence cautioni
The sequence BAD92307 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 208 | R → C in AAC35283 (PubMed:9731200).Curated | 1 | |
| Sequence conflicti | 208 | R → C in AAD39541 (PubMed:10749171).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_080869 | 2 | E → A in OPA5; changed localization to mitochondrion; impaired mitochondrial membrane fission. 1 PublicationCorresponds to variant dbSNP:rs1555229948EnsemblClinVar. | 1 | |
| Natural variantiVAR_080870 | 36 | S → G in EMPF1; autosomal recessive; impaired mitochondrial membrane fission; hypomorphic mutation retaining partial activity in mitochondrial membrane fission. 1 PublicationCorresponds to variant dbSNP:rs879255688EnsemblClinVar. | 1 | |
| Natural variantiVAR_022446 | 71 | S → T3 PublicationsCorresponds to variant dbSNP:rs1064610Ensembl. | 1 | |
| Natural variantiVAR_080871 | 192 | A → E in OPA5; changed localization to mitochondrion; impaired mitochondrial membrane fission. 1 PublicationCorresponds to variant dbSNP:rs1555119216EnsemblClinVar. | 1 | |
| Natural variantiVAR_076316 | 362 | G → D in EMPF1; unknown pathological significance; unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site; presence of concentric cristae and/or increased dense granules in some mitochondria. 2 PublicationsCorresponds to variant dbSNP:rs879255685EnsemblClinVar. | 1 | |
| Natural variantiVAR_076317 | 362 | G → S in EMPF1; the mutation acts in a dominant-negative manner; defects observed in mitochondrial fission; significant decrease in mitochondrial respiratory chain complex IV activity. 1 PublicationCorresponds to variant dbSNP:rs886037861EnsemblClinVar. | 1 | |
| Natural variantiVAR_063704 | 395 | A → D in EMPF1; the mutation acts in a dominant-negative manner; defects observed in both mitochondrial and peroxisomal fission; reduced oligomerization, decreased mitochondrial recruitment. 2 PublicationsCorresponds to variant dbSNP:rs121908531EnsemblClinVar. | 1 | |
| Natural variantiVAR_076318 | 403 | R → C in EMPF1; the mutation acts in a dominant-negative manner; reduced oligomerization; decreased mitochondrial recruitment; defects observed in mitochondrial fission. 1 PublicationCorresponds to variant dbSNP:rs863223953EnsemblClinVar. | 1 | |
| Natural variantiVAR_080872 | 406 | L → S in EMPF1; impaired mitochondrial and peroxisomal membrane fission. 1 Publication | 1 | |
| Natural variantiVAR_030489 | 426 | E → D. Corresponds to variant dbSNP:rs2389105Ensembl. | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_054544 | 1 – 43 | MEALI…SSVLE → MFHKKINGKQQEKKMTLLHG KTQDTFLKGWKQKNGVNFFT PKI in isoform 7. 1 PublicationAdd BLAST | 43 | |
| Alternative sequenceiVSP_054545 | 44 – 246 | Missing in isoform 7. 1 PublicationAdd BLAST | 203 | |
| Alternative sequenceiVSP_039097 | 83 | N → NDPATWKNSRHLSK in isoform 6, isoform 8 and isoform 9. 2 Publications | 1 | |
| Alternative sequenceiVSP_013685 | 533 – 569 | Missing in isoform 3 and isoform 9. 3 PublicationsAdd BLAST | 37 | |
| Alternative sequenceiVSP_013686 | 533 – 558 | Missing in isoform 2. 1 PublicationAdd BLAST | 26 | |
| Alternative sequenceiVSP_013687 | 544 – 569 | Missing in isoform 5. 1 PublicationAdd BLAST | 26 | |
| Alternative sequenceiVSP_013688 | 559 – 569 | Missing in isoform 4 and isoform 8. 2 PublicationsAdd BLAST | 11 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 3W6N | X-ray | 2.00 | A/B | 1-329 | [»] | |
| A/B | 709-736 | [»] | ||||
| 3W6O | X-ray | 1.90 | A/B | 1-329 | [»] | |
| A/B | 709-736 | [»] | ||||
| 3W6P | X-ray | 1.70 | A/B | 1-329 | [»] | |
| A/B | 709-736 | [»] | ||||
| 4BEJ | X-ray | 3.48 | A/B/C/D | 1-736 | [»] | |
| 4H1U | X-ray | 2.30 | A | 1-327 | [»] | |
| A | 711-736 | [»] | ||||
| 4H1V | X-ray | 2.30 | A | 1-327 | [»] | |
| A | 711-736 | [»] | ||||
| 5WP9 | electron microscopy | 4.22 | A/C/E/G/I/K/M/O | 1-736 | [»] | |
| SMRi | O00429 | |||||
| ModBasei | Search... | |||||
| PDBe-KBi | Search... | |||||
Protein-protein interaction databases
| BioGRIDi | 115370, 252 interactors |
| CORUMi | O00429 |
| DIPi | DIP-42704N |
| IntActi | O00429, 222 interactors |
| MINTi | O00429 |
| STRINGi | 9606.ENSP00000449089 |
Protein family/group databases
| TCDBi | 1.N.6.1.2, the mitochondrial inner/outer membrane fusion (mmf) family |
PTM databases
| GlyGeni | O00429, 2 sites |
| iPTMneti | O00429 |
| MetOSitei | O00429 |
| PhosphoSitePlusi | O00429 |
| SwissPalmi | O00429 |
Genetic variation databases
| BioMutai | DNM1L |
Proteomic databases
| CPTACi | CPTAC-57 |
| EPDi | O00429 |
| jPOSTi | O00429 |
| MassIVEi | O00429 |
| MaxQBi | O00429 |
| PaxDbi | O00429 |
| PeptideAtlasi | O00429 |
| PRIDEi | O00429 |
| ProteomicsDBi | 34194 4122 47884 [O00429-1] 47885 [O00429-2] 47886 [O00429-3] 47887 [O00429-4] 47888 [O00429-5] 47889 [O00429-6] |
Protocols and materials databases
| Antibodypediai | 4096, 677 antibodies |
| DNASUi | 10059 |
Genome annotation databases
Organism-specific databases
| CTDi | 10059 |
| DisGeNETi | 10059 |
| GeneCardsi | DNM1L |
| HGNCi | HGNC:2973, DNM1L |
| HPAi | ENSG00000087470, Low tissue specificity |
| MalaCardsi | DNM1L |
| MIMi | 603850, gene 610708, phenotype 614388, phenotype |
| neXtProti | NX_O00429 |
| NIAGADSi | ENSG00000087470 |
| OpenTargetsi | ENSG00000087470 |
| Orphaneti | 98673, Autosomal dominant optic atrophy, classic form 330050, DNM1L-related encephalopathy due to mitochondrial and peroxisomal fission defect |
| PharmGKBi | PA27441 |
| VEuPathDBi | HostDB:ENSG00000087470.17 |
| GenAtlasi | Search... |
Phylogenomic databases
| eggNOGi | KOG0446, Eukaryota |
| GeneTreei | ENSGT00940000155504 |
| HOGENOMi | CLU_008964_5_4_1 |
| InParanoidi | O00429 |
| OMAi | KTRVNIM |
| PhylomeDBi | O00429 |
| TreeFami | TF352031 |
Enzyme and pathway databases
| PathwayCommonsi | O00429 |
| Reactomei | R-HSA-75153, Apoptotic execution phase |
| SIGNORi | O00429 |
Miscellaneous databases
| BioGRID-ORCSi | 10059, 477 hits in 1003 CRISPR screens |
| ChiTaRSi | DNM1L, human |
| GeneWikii | DNM1L |
| GenomeRNAii | 10059 |
| Pharosi | O00429, Tbio |
| PROi | PR:O00429 |
| RNActi | O00429, protein |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSG00000087470, Expressed in intestine and 246 other tissues |
| ExpressionAtlasi | O00429, baseline and differential |
| Genevisiblei | O00429, HS |
Family and domain databases
| CDDi |