製品: DRP1 Mouse Monoclonal Antibody
カタログ: BF8306
タンパク質の説明: Mouse monoclonal antibody to DRP1
アプリケーション: WB IHC IF/ICC
反応性: Human
予測: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog, Chicken
分子量: 79kDa; 82kD(Calculated).
ユニプロット: O00429

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製品説明

ソース:
Mouse
アプリケーション:
WB 1:500-1:3000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human
クローナリティ:
Monoclonal [AFfirm8306]
特異性:
DRP1 Mouse Monoclonal Antibody detects endogenous levels of total DRP1
コンジュゲート:
Unconjugated.
精製:
Affinity-chromatography.
保存:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

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;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
発現特異性:
O00429 DNM1L_HUMAN:

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.

タンパク質の説明:
Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6).
タンパク質配列:
MEALIPVINKLQDVFNTVGADIIQLPQIVVVGTQSSGKSSVLESLVGRDLLPRGTGIVTRRPLILQLVHVSQEDKRKTTGEENGVEAEEWGKFLHTKNKLYTDFDEIRQEIENETERISGNNKGVSPEPIHLKIFSPNVVNLTLVDLPGMTKVPVGDQPKDIELQIRELILRFISNPNSIILAVTAANTDMATSEALKISREVDPDGRRTLAVITKLDLMDAGTDAMDVLMGRVIPVKLGIIGVVNRSQLDINNKKSVTDSIRDEYAFLQKKYPSLANRNGTKYLARTLNRLLMHHIRDCLPELKTRINVLAAQYQSLLNSYGEPVDDKSATLLQLITKFATEYCNTIEGTAKYIETSELCGGARICYIFHETFGRTLESVDPLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKRLEEPSLRCVELVHEEMQRIIQHCSNYSTQELLRFPKLHDAIVEVVTCLLRKRLPVTNEMVHNLVAIELAYINTKHPDFADACGLMNNNIEEQRRNRLARELPSAVSRDKSSKVPSALAPASQEPSPAASAEADGKLIQDSRRETKNVASGGGGVGDGVQEPTTGNWRGMLKTSKAEELLAEEKSKPIPIMPASPQKGHAVNLLDVPVPVARKLSAREQRDCEVIERLIKSYFLIVRKNIQDSVPKAVMHFLVNHVKDTLQSELVGQLYKSSLLDDLLTESEDMAQRRKEAADMLKALQGASQIIAEIRETHLW

PTMs - O00429 基板として

Site PTM Type Enzyme
M1 Acetylation
S40 Phosphorylation P49841 (GSK3B)
S44 Phosphorylation P49841 (GSK3B)
T78 Phosphorylation
T79 Phosphorylation
K92 Ubiquitination
K97 Ubiquitination
K99 Ubiquitination
T102 Phosphorylation
R108 Methylation
K123 Ubiquitination
S126 Phosphorylation
K133 Ubiquitination
S136 Phosphorylation
K160 Ubiquitination
S179 Phosphorylation
T193 Phosphorylation
S200 Phosphorylation
K238 Ubiquitination
K255 Ubiquitination
K256 Ubiquitination
Y266 Phosphorylation
K271 Ubiquitination
K272 Ubiquitination
K283 Acetylation
S330 Phosphorylation
C361 S-Nitrosylation
C367 S-Nitrosylation
Y368 Phosphorylation
T394 Phosphorylation
T400 Phosphorylation
S412 Phosphorylation
Y449 Phosphorylation
S529 Phosphorylation
K532 Sumoylation
K535 Sumoylation
K535 Ubiquitination
S544 Phosphorylation
S548 Phosphorylation
S552 Phosphorylation
K558 Sumoylation
K568 Sumoylation
K568 Ubiquitination
S572 Phosphorylation
T586 Phosphorylation
K594 Sumoylation
T595 Phosphorylation
K597 Sumoylation
K597 Ubiquitination
K606 Sumoylation
S607 Phosphorylation
K608 Sumoylation
S616 Phosphorylation P06493 (CDK1) , P28482 (MAPK1) , P27361 (MAPK3) , Q05655 (PRKCD) , Q00535 (CDK5) , P24941 (CDK2)
S637 Phosphorylation P17612 (PRKACA) , Q13464 (ROCK1) , Q13131 (PRKAA1)
C644 S-Nitrosylation
S693 Phosphorylation P49841 (GSK3B)
T701 Phosphorylation
S724 Phosphorylation

研究背景

機能:

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. 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. 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.

PTMs:

Phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission. Phosphorylation on Ser-637 inhibits the GTPase activity, leading to a defect in mitochondrial fission promoting mitochondrial elongation. Dephosphorylated on this site by PPP3CA which promotes mitochondrial fission. Phosphorylation on Ser-616 activates the GTPase activity and promotes mitochondrial fission. Phosphorylated in a circadian manner at Ser-637.

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 and causes neuronal damage.

Ubiquitination by MARCHF5 affects mitochondrial morphology.

O-GlcNAcylation augments the level of the GTP-bound active form of DRP1 and induces translocation from the cytoplasm to mitochondria in cardiomyocytes. It also decreases phosphorylation at Ser-637 (By similarity).

細胞の位置付け:

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.
Note: Mainly cytosolic. Translocated to the mitochondrial membrane through O-GlcNAcylation and interaction with FIS1. Recruited to the mitochondrial outer membrane by interaction with MIEF1. Colocalized with MARCHF5 at mitochondrial membrane. Localizes to mitochondria at sites of division. Localizes to mitochondria following necrosis induction. Associated with peroxisomal membranes, partly recruited there by PEX11B. May also be associated with endoplasmic reticulum tubules and cytoplasmic vesicles and found to be perinuclear. In some cell types, localizes to the Golgi complex. Binds to phospholipid membranes.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

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.

サブユニット構造:

Homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule. Oligomerizes in a GTP-dependent manner to form membrane-associated tubules with a spiral pattern. Interacts with GSK3B and MARCHF5. Interacts (via the GTPase and B domains) with UBE2I; the interaction promotes sumoylation of DNM1L, mainly in its B domain. Interacts with PPP3CA; the interaction dephosphorylates DNM1L and regulates its transition to mitochondria. 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. Interacts with FIS1. Interacts with MIEF2 and MIEF1; GTP-dependent this regulates GTP hydrolysis and DNM1L oligomerization. Interacts with PGAM5; this interaction leads to dephosphorylation at Ser-656 and activation of GTPase activity and eventually to mitochondria fragmentation.

タンパク質ファミリー:

The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization.

Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.

研究領域

· Cellular Processes > Cell growth and death > Necroptosis.   (View pathway)

· Environmental Information Processing > Signal transduction > TNF signaling pathway.   (View pathway)

· Organismal Systems > Immune system > NOD-like receptor signaling pathway.   (View pathway)

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