Mouse anti-Human/Mouse/Rat sapiens (Human) DNM1L Monoclonal Antibody

Function

Inhibits peroxisomal division when overexpressed

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

Disease Association

[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] | Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) : A 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. [The disease is caused by variants affecting the gene represented in this entry] | Optic atrophy 5 (OPA5) : A 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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

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

Subunit

Homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule (PubMed:17553808, PubMed:23530241, PubMed:23584531, PubMed:23977156). Oligomerizes in a GTP-dependent manner to form membrane-associated tubules with a spiral pattern (PubMed:23584531). Interacts with GSK3B and MARCHF5 (PubMed:10749171, PubMed:16874301, PubMed:16936636, PubMed:9731200). Interacts (via the GTPase and B domains) with UBE2I; the interaction promotes sumoylation of DNM1L, mainly in its B domain (PubMed:19638400). Interacts with PPP3CA; the interaction dephosphorylates DNM1L and regulates its transition to mitochondria (PubMed:18838687). 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 (PubMed:23792689). Interacts with MFF; the interaction is inhibited by C11orf65/MFI (By similarity). Interacts with FIS1; may form part of a larger protein complex at the endoplasmic reticulum-mitochondrial interface during mitochondrial fission (PubMed:18695047, PubMed:24196833). Interacts with CANX (PubMed:24196833). Interacts with BCAP31 (PubMed:24196833). Interacts with MIEF2 and MIEF1; GTP-dependent, regulates GTP hydrolysis and DNM1L oligomerization (PubMed:21508961). Interacts with PGAM5; this interaction leads to dephosphorylation at Ser-656 and activation of GTPase activity and eventually to mitochondria fragmentation (PubMed:22265414). Interacts with RALBP1; during mitosis, recruits DNM1L to the mitochondrion and mediates its activation by the mitotic kinase cyclin B-CDK1 (PubMed:21822277). Interacts with FUNDC1; this interaction recruits DNM1L/DRP1 at ER-mitochondria contact sites (PubMed:27145933)

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• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
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• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)