Recombinant Human Dynamin-1-like protein (DNM1L)

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Code CSB-EP007078HU
Size US$306
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP007078HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) DNM1L.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP007078HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) DNM1L.
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Product Details

Purity
Greater than 85% as determined by SDS-PAGE.
Target Names
DNM1L
Uniprot No.
Research Area
Cancer
Alternative Names
DLP1; dnm1l; DNM1L_HUMAN; Dnm1p/Vps1p-like protein; dnml1; DRP1; DVLP; Dymple; Dynamin 1 like; Dynamin family member proline-rich carboxyl-terminal domain less; Dynamin like protein; Dynamin related protein 1; Dynamin-1-like protein; Dynamin-like protein 4; Dynamin-like protein; Dynamin-like protein IV; Dynamin-related protein 1; DYNIV 11; EMPF; EMPF1; FLJ41912; HdynIV; VPS1
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
1-710aa
Target Protein Sequence
MEALIPVINKLQDVFNTVGADIIQLPQIVVVGTQSSGKSSVLESLVGRDLLPRGTGIVTRRPLILQLVHVSQEDKRKTTGEENGVEAEEWGKFLHTKNKLYTDFDEIRQEIENETERISGNNKGVSPEPIHLKIFSPNVVNLTLVDLPGMTKVPVGDQPKDIELQIRELILRFISNPNSIILAVTAANTDMATSEALKISREVDPDGRRTLAVITKLDLMDAGTDAMDVLMGRVIPVKLGIIGVVNRSQLDINNKKSVTDSIRDEYAFLQKKYPSLANRNGTKYLARTLNRLLMHHIRDCLPELKTRINVLAAQYQSLLNSYGEPVDDKSATLLQLITKFATEYCNTIEGTAKYIETSELCGGARICYIFHETFGRTLESVDPLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKRLEEPSLRCVELVHEEMQRIIQHCSNYSTQELLRFPKLHDAIVEVVTCLLRKRLPVTNEMVHNLVAIELAYINTKHPDFADACGLMNNNIEEQRRNRLARELPSAVSRDKLIQDSRRETKNVASGGGGVGDGVQEPTTGNWRGMLKTSKAEELLAEEKSKPIPIMPASPQKGHAVNLLDVPVPVARKLSAREQRDCEVIERLIKSYFLIVRKNIQDSVPKAVMHFLVNHVKDTLQSELVGQLYKSSLLDDLLTESEDMAQRRKEAADMLKALQGASQIIAEIRETHLW
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
84.4 kDa
Protein Length
Full Length of Isoform 2
Tag Info
N-terminal 10xHis-tagged and C-terminal Myc-tagged
Form
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
3-7 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.
Description

The expression region of this recombinant Human DNM1L covers amino acids 1-710. The expected molecular weight for the DNM1L protein is calculated to be 84.4 kDa. This protein is generated in a e.coli-based system. The DNM1L gene fragment has been modified by fusing the N-terminal 10xHis tag and C-terminal Myc tag, providing convenience in detecting and purifying the recombinant DNM1L protein during the following stages.

Human dynamin-1-like protein (DNM1L) is a critical regulator of mitochondrial dynamics. It plays a central role in mitochondrial fission, a process essential for maintaining mitochondrial morphology, distribution, and function. DNM1L facilitates the division of mitochondria into smaller units, allowing for their proper distribution during cell division and ensuring mitochondrial quality control. Dysregulation of mitochondrial dynamics, often associated with abnormal DNM1L activity, is implicated in various diseases, including neurodegenerative disorders and cancer. Understanding the intricate role of DNM1L in mitochondrial dynamics is crucial for unraveling its implications in health and disease and exploring potential therapeutic interventions targeting mitochondrial function.

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Target Background

Function
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. 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. Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner. Plays an important role in mitochondrial fission during mitosis. 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. 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. Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production.; Inhibits peroxisomal division when overexpressed.; Inhibits peroxisomal division when overexpressed.
Gene References into Functions
  1. cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations PMID: 29899447
  2. Data show that increasing dynamin-related protein 1 (Drp1) SUMOylation by knocking down SUMO1-sentrin-SMT3 specific protease 3 (SENP3) reduces both Drp1 binding to mitochondrial fission factor protein (Mff) and stress-induced cytochrome c release. PMID: 28262828
  3. knockdown of LRP6 inhibited the cell viability by activation of Drp1 in glucose deprived-cardiomyocytes. PMID: 29864925
  4. Results suggest that the loss of dynamin-related protein 1 (Drp1) expression could contribute to the development of lung and colon cancers. PMID: 29329364
  5. observations indicate that homozygous p.T115M variant of DNM1L produces a neurological and neurodevelopmental phenotype, consistent with impaired mitochondrial architecture and function, through a diminished ability to oligomerize, which was most prevalent under oxidative stress. PMID: 29110115
  6. Study results reveal a crucial function for Drp1 in regulating tumor growth, mitochondrial morphology, and cell cycle in cutaneous squamous cell carcinoma. PMID: 28818497
  7. Elimination of Drp1 by shRNA or Mdivi-1 (a Drp1-specific inhibitor) suppressed GBP2's regulatory function. Furthermore, GBP2 blocks Drp1 translocation from the cytosol to mitochondria, thereby attenuating Drp1-dependent mitochondrial fission and breast cancer cell invasion. PMID: 29072687
  8. hyperacetylation of microtubules contributes to the recruitment of total Drp1 to mitochondria to enhance fission. PMID: 28757354
  9. Results uncovered a novel mechanism of Drp1-mediated mitochondrial fragmentation in senecionine-induced liver injury. PMID: 28282614
  10. miR-21-5p/203a-3p promote ox-LDL-induced endothelial senescence through down-regulation of Drp1 in a direct or indirect way. PMID: 28347692
  11. this study shows that Drp1 can impact survival of epithelial ovarian cancer patients PMID: 27509055
  12. The structure and function of DNM1L protein in mitochondrial fission is reviewed. PMID: 28132464
  13. Results described a recessive disease caused by DNM1L mutations, with a clinical phenotype resembling mitochondrial disorders but without any typical biochemical features. Two novel DNM1L mutations (one frame-shift mutation and one missense mutation) are identified and was found to be associated with impaired mitochondrial and peroxisomal morphology. PMID: 27328748
  14. Study describes mutations in ZNF143 causing a previously undescribed inherited disorder of vitamin B12 (cobalamin) metabolism. These mutations cause an accumulation of transcobalamin-bound cobalamin within the cells, as well as decreased expression of MMACHC, a cobalamin trafficking protein. PMID: 27349184
  15. The results suggest that endoplasmic reticulum (ER) can function as a platform for Drp1 oligomerization, and that ER-associated Drp1 contributes to mitochondrial division. PMID: 29158231
  16. PRKAA deletion promoted mitochondrial fragmentation in vascular endothelial cells by inhibiting the autophagy-dependent degradation of DNM1L. PMID: 28085543
  17. hepatic stimulator substance could regulate mitochondrial fission and hepatocyte apoptosis during liver ischemia/reperfusion injury by orchestrating the translocation and activation of Drp1 PMID: 28646508
  18. This report describes a patient with a DNM1L mutation and abnormalities in mitochondrial fission and function. The pathogenicity and the dominant nature of the novel p.G362S mutation are demonstrated by overexpression of the mutant gene. PMID: 26992161
  19. In contrast to the initial report of neonatal lethality resulting from DNM1L mutation and DRP1 dysfunction, our results show that milder DRP1 impairment is compatible with normal early development and subsequently results in a distinct set of neurological findings. In addition, we identify a common pathogenic mechanism whereby DNM1L mutations impair mitochondrial fission. PMID: 27145208
  20. These findings provide new insights into MCL-1 ligands, and the interplay between DRP-1 and the anti-apoptotic BCL-2 family members in the regulation of apoptosis PMID: 28079887
  21. High drp1 expression is associated with cisplatin-induced apoptosis of renal tubular epithelial cells. PMID: 28423497
  22. This study demonstrated that Mutations in DNM1L, as in OPA1, result indominant optic atrophy despite opposite effectson mitochondrial fusion and fission. PMID: 28969390
  23. Modulation of mitochondrial fission by increased levels of pDrp1 S616. PMID: 28388446
  24. This is the first study to identify an association between SIRT4 expression and decreased mitochondrial fission, which was driven by Drp1. SIRT4 inhibited Drp1 phosphorylation and weakened Drp1 recruitment to the mitochondrial membrane via an interaction with Fis-1. PMID: 27941873
  25. the mitochondrial morphology of T-cell acute lymphoblastic leukemia cells were altered from elongation to fragmentation because of the extracellular signal-regulated kinase activation-mediated phosphorylation of the pro-fission factor, dynamin-related protein 1 (Drp1), at residue S616. PMID: 27831567
  26. DNM1L was found to be involved in the regulation of collagen secretion and cardiovascular calcification. PMID: 28607103
  27. The authors determine that Dengue virus nonstructural protein (NS)4B, a promising drug target with unknown function, associates with mitochondrial proteins, including Drp1, and alters mitochondria morphology to promote infection. PMID: 27545046
  28. Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP-induced fission. PMID: 27215606
  29. Missense variants in the middle domain of DNM1L is associated with infantile encephalopathy. PMID: 26931468
  30. Genetic silencing of Drp1 increases mitochondrial proton leak in MIN6 cells. Drp1 does not control insulin secretion via its effect on proton leak but instead via modulation of glucose-fueled respiration. PMID: 28174288
  31. DNM1L missense mutation identified in a patient with developmental delay, refractory epilepsy and prolonged survival. Patient fibroblasts showed striking hyperfusion of the mitochondrial network. Bioenergetic studies in patient fibroblasts showed no significant differences versus controls. PMID: 26604000
  32. Disruption of Drp1 and subsequent mitochondrial fragmentation events prevents impaired vascular dilation, restores mitochondrial phenotype, and implicates mitochondrial fission as a primary mediator of endothelial dysfunction PMID: 27923790
  33. MiD49 and MiD51 recruit inactive forms of Drp1 in mitochondrial fission. [review] PMID: 27660309
  34. FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the endoplasmic reticulum-mitochondrial contact site by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells. PMID: 27145933
  35. This study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis. PMID: 27799292
  36. Sustained phosphorylation of Akt by Abeta directly activates Drp1 and inhibits autophagy through the mTOR pathway. Together, these changes elicit abundant mitochondrial fragmentation resulting in ROS-mediated neuronal apoptosis. PMID: 27599716
  37. Drp1 was decreased on mitochondria during Dengue virus infection, as well as Drp1 phosphorylated on serine 616, which is important for mitochondrial fission. PMID: 27816895
  38. These data suggest a model for ARSACS where neurons with reduced levels of sacsin are compromised in their ability to recruit or retain Drp1 at the mitochondrial membrane leading to a decline in mitochondrial health, potentially through impaired mitochondrial quality control. PMID: 27288452
  39. Taken together, our data demonstrate that DRG2 acts as a regulator of mitochondrial fission by controlling the expression of Drp1. PMID: 28363867
  40. results lend further support to the notion that VPS35-DLP1 interaction is key to the retromer-dependent recycling of mitochondrial DLP1 complex during mitochondrial fission and provide a novel therapeutic target to control excessive fission and associated mitochondrial deficits. PMID: 28040727
  41. Mitochondrial morphology and cellular distribution are altered in SPG31 patients and are linked to DRP1 hyperphosphorylation. PMID: 28007911
  42. the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy. PMID: 27903607
  43. Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. PMID: 27495873
  44. that miR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3'untranslated region to regulate Drp-1 promoter hydroxymethylation. PMID: 28294974
  45. Improper transcriptional (in)activation of mitofusin-1 and dynamin-related protein 1 during early in vitro embryo development is associated with a decrease in mitochondrial membrane potential and with embryo fragmentation. PMID: 25033890
  46. this study reveals coordinated increase of mitochondrial biogenesis and mitophagy in which Drp1 plays a central role regulating breast cancer cell metabolism and survival. PMID: 27746856
  47. Dynamin-related protein 1 (Dpr1) activates mitochondrial-dependent apoptosis and indicate that inhibiting Dpr1 function can protect against chlorpyrifos-induced cytotoxicity. PMID: 26598294
  48. Drp1 is in dynamic equilibrium on mitochondria in a fission-independent manner, and that fission factors such as actin filaments target productive oligomerization to fission sites. PMID: 26609810
  49. Dindings demonstrate for the first time, that Drp1 is required for Bax mitochondrial translocation, but Drp1-induced mitochondrial fragmentation alone is not sufficient to induce apoptosis in DLBCL cells. PMID: 26093086
  50. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of heart failure. PMID: 26915633

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Involvement in disease
Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1)
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.
Protein Families
TRAFAC class dynamin-like GTPase superfamily, Dynamin/Fzo/YdjA family
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 b
Database Links

HGNC: 2973

OMIM: 603850

KEGG: hsa:10059

STRING: 9606.ENSP00000450399

UniGene: Hs.556296

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