Tchem DNM1L Dynamin-1-like protein

Protein Summary

Description

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. The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (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). 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. Plays an important role in mitochondrial fission during mitosis (PubMed:26992161, PubMed:27301544, PubMed:27328748). 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. Isoform 1: Inhibits peroxisomal division when overexpressed. Isoform 4: Inhibits peroxisomal division when overexpressed. This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

Uniprot Accession IDs

• O00429
• A8K4X9
• B4DGC9
• B4DSU8
• J3KPI2
• O14541
• O60709
• Q59GN9
• Q7L6B3
• Q8TBT7
• Q9BWM1
• Q9Y5J2

Gene Name

• DNM1L

Ensembl ID

• ENST00000266481
• ENSP00000266481
• ENSG00000087470
• ENST00000381000
• ENSP00000370388
• ENST00000414834
• ENSP00000404160
• ENST00000452533
• ENSP00000415131
• ENST00000547312
• ENSP00000448610
• ENST00000549701
• ENSP00000450399
• ENST00000553257
• ENSP00000449089

Symbol

• DLP1
• DRP1
• DLP1
• DRP1
• DVLP
• EMPF
• OPA5
• EMPF1
• DYMPLE
• HDYNIV

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	1
molecular function	0.98
protein domain	0.97
transcription factor perturbation	0.97
disease perturbation	0.9

Protein Classes

PANTHER Classes

Protein / Hydrolase / Dynamin-1-like Protein

Protein / Enzyme Modulator / G-protein / Small Gtpase / Dynamin-1-like Protein

Protein / Cytoskeletal Protein / Microtubule Family Cytoskeletal Protein / Dynamin-1-like Protein

DTO Classes

Protein / Enzyme Modulator / G-protein / Small Gtpase / Dynamin-1-like Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 964.46   (req: < 5)

Gene RIFs: 285   (req: <= 3)

Antibodies: 580   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 964.46   (req: >= 5)

Gene RIFs: 285   (req: > 3)

Antibodies: 580   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 50

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0