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: 841.12   (req: < 5)

Gene RIFs: 162   (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: 841.12   (req: >= 5)

Gene RIFs: 162   (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

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (2)

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1 – 2 of 2

CHEMBL4471636

DNM1LTchem

pIC50 : 6.14

CHEMBL4467972

DNM1LTchem

pIC50 : 6.04

Protein-Protein Interactions (214)

Explore Interacting Targets

1 – 10 of 214

• See Interactions on String-DB

DPPA5

Tbio

Novelty:  0.09402178

p_int:  0.999999953

p_ni:  4.6e-8

p_wrong:  2e-9

Data Source:  BioPlex

CPNE2

Tdark

Novelty:  0.24188419

p_int:  0.999997296

p_ni:  0.000002704

Score:  0.159

Data Source:  BioPlex,STRINGDB

NUFIP1

Tbio

Novelty:  0.11726869

p_int:  0.99981869

p_ni:  0.000181244

p_wrong:  6.7e-8

Data Source:  BioPlex

JTB

Tbio

Novelty:  0.06646216

p_int:  0.997861319

p_ni:  0.00213787

p_wrong:  8.12e-7

Data Source:  BioPlex

CA14

Tclin

Family:  Enzyme

Novelty:  0.00864764

p_int:  0.996576656

p_ni:  0.003226159

p_wrong:  0.000197185

Data Source:  BioPlex

DNAAF2

Tbio

Novelty:  0.01254416

p_int:  0.995801917

p_ni:  0.004198082

p_wrong:  1e-9

Data Source:  BioPlex

FGL1

Tbio

Novelty:  0.02650803

p_int:  0.99537157

p_ni:  0.004628384

p_wrong:  4.6e-8

Data Source:  BioPlex

DGUOK

Tbio

Family:  Kinase

Novelty:  0.00897987

p_int:  0.985328318

p_ni:  0.014522653

p_wrong:  0.000149029

Score:  0.194

Data Source:  BioPlex,STRINGDB

HAX1

Tbio

Novelty:  0.00749205

p_int:  0.979649932

p_ni:  0.020349974

p_wrong:  9.4e-8

Score:  0.215

Data Source:  BioPlex,STRINGDB

CYB5B

Tbio

Novelty:  0.09395308

p_int:  0.965333197

p_ni:  0.034666655

p_wrong:  1.48e-7

Score:  0.303

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (1)

Explore Nearest Tclin Targets

Upstream (1)

1 – 1 of 1

TNF

Tclin

Family:  Other

KEGG Distance:  8

Common Pathways:  3

1: TNF signaling pathway

2: Necroptosis

3: NOD-like receptor signaling pathway

Pathways (7)

Reactome (3)

KEGG (3)

WikiPathways (1)

Apoptosis (R-HSA-109581)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Apoptotic execution phase	52 targets	R-HSA-75153
Reactome	Programmed Cell Death	180 targets	R-HSA-5357801

Name	Explore in Pharos	Explore in Source
Apoptosis	177 targets	R-HSA-109581
Apoptotic execution phase	52 targets	R-HSA-75153
Programmed Cell Death	180 targets	R-HSA-5357801

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (71)

Functions (13)

Components (21)

Processes (37)

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1 – 10 of 13

GO Term	Evidence	Assigned by
GTP-dependent protein binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
GTPase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
Rab GTPase binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
microtubule binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
GTPase activator activity	Inferred by Curator (IC)	ParkinsonsUK-UCL
BH2 domain binding	Inferred from Electronic Annotation (IEA)	Ensembl
clathrin binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (3)

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1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	3	3	3		94.8
atrial fibrillation	EFO_0000275	3	2	0	1.1	78.2
platelet count	EFO_0004309	1	1	1		31.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	3		94.8
atrial fibrillation	EFO_0000275	0	1.1	78.2
platelet count	EFO_0004309	1		31.4

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Cell junction
Coated pit
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Disease mutation
Endocytosis

GWAS Trait Find Similar Targets

No Header	No Header
atrial fibrillation
mean platelet volume
platelet count

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	dynamin 1 like	VGNC:13030	465266
Macaque	dynamin 1 like		695388
Mouse	dynamin 1-like	MGI:1921256	74006
Rat	dynamin 1-like	RGD:620416	114114
Dog	dynamin 1 like	VGNC:40032	477649

Species	Name	OMA	EggNOG	Inparanoid
Chimp	dynamin 1 like
Macaque	dynamin 1 like
Mouse	dynamin 1-like
Rat	dynamin 1-like
Dog	dynamin 1 like

Publication Statistics

PubMed Score 841.12

PubMed score by year

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PubTator Score 320.88

PubTator score by year

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Related Publications

Text Mined References (207)

GeneRif Annotations (162)

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PMID	Year	Title