Contents

Search

dynamin-1-like protein; Dnm1p/Vps1p-like protein; DVLP; dynamin family member proline-rich carboxyl-terminal domain less; Dymple; dynamin-like protein; dynamin-like protein 4; dynamin-like protein IV; HdynIV; dynamin-related protein 1 (DNM1L, DLP1, DRP1)

Function: - functions in mitochondrial & peroxisomal division - mediates membrane fission through oligomerization into ring-like structures which wrap around the scission site to constict & sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism - required for normal brain development - facilitates developmentally-regulated apoptosis during neural tube development - required for a normal rate of cytochrome c release & caspase activation during apoptosis - also required for mitochondrial fission during mitosis - may be involved in vesicle transport - isoform 1 & isoform 4 inhibit peroxisomal division when overexpressed - phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission - phosphorylation on Ser-637 inhibits mitochondrial fission probably through preventing intramolecular interaction - dephosphorylated on Ser-637 by PPP3CA which promotes mitochondrial fission - phosphorylation on Ser-616 also promotes mitochondrial fission - 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 - S-nitrosylation increases DNM1L dimerization, mitochondrial fission & causes neuronal damage - ubiquitination by MARCH5 affects mitochondrial morphology - homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule - can self-assemble in multimeric ring-like structures - interacts with BCL2L1 - interaction stimulates GTPase activity of DMN1L in synapses & increases the number of axonal mitochondria & the size & number of synaptic vesicle clusters - interacts with FIS1 (putative) - interacts with GSK3B & MARCH5 - interacts (via the GTPase & B domains) with UBE2I - interaction promotes sumoylation of DNM1L, mainly in ite B domain - interacts with PPP3CA - interaction dephosphorylates DNM1L & regulates its transition to mitochondria - interacts with MID49 & MID51 Structure: - the GED domain folds back to interact, in cis, with the GTP-binding domain & middle domain, & interacts, in trans, with the GED domains of other DNM1L molecules, & is thus critical for activating GTPase activity & for DNM1L dimerization - belongs to the dynamin family - contains 1 GED domain Compartment: - cytoplasm, Golgi, endomembrane system - mainly cytosolic - translocated to the mitochondrial membrane through interaction with FIS1 - colocalized with MARCH5 at mitochondrial membrane - localizes to mitochondria at sites of division - associated with peroxisomal membranes, partly recruited there by PEX11B - may also be associated with endoplasmic reticulum tubules & cytoplasmic vesicles & found to be perinuclear - in some cell types, localizes to the Golgi complex Alternative splicing: named isoforms=6 Expression: - ubiquitously expressed - highest levels found in skeletal muscles, heart, kidney & brain - isoform 1 is brain-specific - isoform 2 is predominantly expressed in testis - isoform 3 is predominantly expressed in skeletal muscle - isoform 4 is weakly expressed in brain, heart & kidney - isoform 5 is predominantly expressed in liver, heart & kidney - isoform 6 is expressed in neurons Pathology: - may be associated with Alzheimer disease through - beta-amyloid-induced increased S-nitrosylation of DNM1L, which triggers, directly or indirectly, excessive mitochondrial fission, synaptic loss & neuronal damage - defects in DNM1L are the cause EMPF encephalopathy Comparative biology: - hyperactivation in oligodendrocytes may inhibit hexokinase-1 inhibiting glycolysis & triggering NLRP3 inflammasome activation resulting in white matter degeneration in a mouse model for Alzheimer's disease [2]

Related

dynamin 1 (DNM1, DNM)

General

guanosine triphosphatase (GTPase) oligomerizing protein phosphoprotein

Properties

SIZE: entity length = 736 aa MW = 82 kD COMPARTMENT: mitochondria peroxisome cytoplasm cell nucleus golgi endoplasmic reticulum MOTIF: GTPase {1-343} acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl GTP-binding site SITE: 32-39 GTP-binding site SITE: 146-150 GTP-binding site SITE: 215-218 Middle {344-489} GSK3B interaction {448-685} MOTIF: B {502-569} Ser phosphorylation site {S529} Ser phosphorylation site {S548} Ser phosphorylation site {S616} Ser phosphorylation site {S637} GED {644-735}

Database Correlations

OMIM correlations MORBIDMAP 603850 UniProt O00429 PFAM correlations Entrez Gene 10059 Kegg hsa:10059 ENZYME 3.6.5.5

References

  1. UniProt :accession O00429
  2. Zhang X, Wang R, Hu D et al Oligodendroglial glycolytic stress triggers inflammasome activation and neuropathology in Alzheimer's disease. Science Advances 2020. Vol. 6, no. 49, eabb8680. Dec 4 PMID: 33277246 PMCID: PMC7717916 Free PMC article https://advances.sciencemag.org/content/6/49/eabb8680