DNM1L_MOUSE
ID DNM1L_MOUSE Reviewed; 742 AA.
AC Q8K1M6; Q8BNQ5; Q8BQ64; Q8CGD0; Q8K1A1;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Dynamin-1-like protein;
DE EC=3.6.5.5;
DE AltName: Full=Dynamin family member proline-rich carboxyl-terminal domain less;
DE Short=Dymple;
DE AltName: Full=Dynamin-related protein 1;
GN Name=Dnm1l; Synonyms=Drp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Osteoclast;
RX PubMed=14592431; DOI=10.1016/j.bbrc.2003.10.008;
RA Honda S., Hirose S.;
RT "Stage-specific enhanced expression of mitochondrial fusion and fission
RT factors during spermatogenesis in rat testis.";
RL Biochem. Biophys. Res. Commun. 311:424-432(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Brain, Mammary gland, and Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 448-659 (ISOFORM 1).
RX PubMed=11544199; DOI=10.1101/gr.185501;
RA Piao Y., Ko N.T., Lim M.K., Ko M.S.H.;
RT "Construction of long-transcript enriched cDNA libraries from submicrogram
RT amounts of total RNAs by a universal PCR amplification method.";
RL Genome Res. 11:1553-1558(2001).
RN [5]
RP PROTEIN SEQUENCE OF 626-640 AND 725-737, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=9422767; DOI=10.1074/jbc.273.2.1044;
RA Kamimoto T., Nagai Y., Onogi H., Muro Y., Wakabayashi T., Hagiwara M.;
RT "Dymple, a novel dynamin-like high molecular weight GTPase lacking a
RT proline-rich carboxyl-terminal domain in mammalian cells.";
RL J. Biol. Chem. 273:1044-1051(1998).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT IN PURKINJE CELLS.
RX PubMed=19752021; DOI=10.1083/jcb.200903065;
RA Wakabayashi J., Zhang Z., Wakabayashi N., Tamura Y., Fukaya M.,
RA Kensler T.W., Iijima M., Sesaki H.;
RT "The dynamin-related GTPase Drp1 is required for embryonic and brain
RT development in mice.";
RL J. Cell Biol. 186:805-816(2009).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19578372; DOI=10.1038/ncb1907;
RA Ishihara N., Nomura M., Jofuku A., Kato H., Suzuki S.O., Masuda K.,
RA Otera H., Nakanishi Y., Nonaka I., Goto Y., Taguchi N., Morinaga H.,
RA Maeda M., Takayanagi R., Yokota S., Mihara K.;
RT "Mitochondrial fission factor Drp1 is essential for embryonic development
RT and synapse formation in mice.";
RL Nat. Cell Biol. 11:958-966(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-622, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT IN PURKINJE CELLS.
RX PubMed=22564413; DOI=10.1083/jcb.201110034;
RA Kageyama Y., Zhang Z., Roda R., Fukaya M., Wakabayashi J., Wakabayashi N.,
RA Kensler T.W., Reddy P.H., Iijima M., Sesaki H.;
RT "Mitochondrial division ensures the survival of postmitotic neurons by
RT suppressing oxidative damage.";
RL J. Cell Biol. 197:535-551(2012).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23283981; DOI=10.1091/mbc.e12-10-0721;
RA Loson O.C., Song Z., Chen H., Chan D.C.;
RT "Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial
RT fission.";
RL Mol. Biol. Cell 24:659-667(2013).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-603, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-59, CATALYTIC ACTIVITY,
RP AND INTERACTION WITH MIEF1.
RX PubMed=24508339; DOI=10.1016/j.str.2014.01.001;
RA Loson O.C., Liu R., Rome M.E., Meng S., Kaiser J.T., Shan S.O., Chan D.C.;
RT "The mitochondrial fission receptor Mid51 requires ADP as a cofactor.";
RL Structure 22:367-377(2014).
RN [14]
RP FUNCTION.
RX PubMed=29478834; DOI=10.1016/j.cmet.2018.01.011;
RA Schmitt K., Grimm A., Dallmann R., Oettinghaus B., Restelli L.M.,
RA Witzig M., Ishihara N., Mihara K., Ripperger J.A., Albrecht U., Frank S.,
RA Brown S.A., Eckert A.;
RT "Circadian control of DRP1 activity regulates mitochondrial dynamics and
RT bioenergetics.";
RL Cell Metab. 27:657-666(2018).
RN [15]
RP INTERACTION WITH MFF, AND SUBCELLULAR LOCATION.
RX PubMed=30059978; DOI=10.1210/en.2018-00426;
RA Lee J., Pappalardo Z., Chopra D.G., Hennings T.G., Vaughn I., Lan C.,
RA Choe J.J., Ang K., Chen S., Arkin M., McManus M.T., German M.S., Ku G.M.;
RT "A Genetic Interaction Map of Insulin Production Identifies Mfi as an
RT Inhibitor of Mitochondrial Fission.";
RL Endocrinology 159:3321-3330(2018).
RN [16]
RP FUNCTION, PHOSPHORYLATION AT SER-622, AND MUTAGENESIS OF SER-622.
RX PubMed=32484300; DOI=10.15252/embr.201948686;
RA Han H., Tan J., Wang R., Wan H., He Y., Yan X., Guo J., Gao Q., Li J.,
RA Shang S., Chen F., Tian R., Liu W., Liao L., Tang B., Zhang Z.;
RT "PINK1 phosphorylates Drp1S616 to regulate mitophagy-independent
RT mitochondrial dynamics.";
RL EMBO Rep. 21:48686-48686(2020).
CC -!- FUNCTION: Functions in mitochondrial and peroxisomal division
CC (PubMed:19578372, PubMed:19752021, PubMed:22564413, PubMed:23283981,
CC PubMed:24508339, PubMed:29478834, PubMed:32484300). Mediates membrane
CC fission through oligomerization into membrane-associated tubular
CC structures that wrap around the scission site to constrict and sever
CC the mitochondrial membrane through a GTP hydrolysis-dependent mechanism
CC (PubMed:24508339). The specific recruitment at scission sites is
CC mediated by membrane receptors like MFF, MIEF1 and MIEF2 for
CC mitochondrial membranes (PubMed:23283981, PubMed:24508339). While the
CC recruitment by the membrane receptors is GTP-dependent, the following
CC hydrolysis of GTP induces the dissociation from the receptors and
CC allows DNM1L filaments to curl into closed rings that are probably
CC sufficient to sever a double membrane (PubMed:24508339). Acts
CC downstream of PINK1 to promote mitochondrial fission in a PRKN-
CC dependent manner (PubMed:32484300). Plays an important role in
CC mitochondrial fission during mitosis (By similarity). Required for
CC formation of endocytic vesicles (By similarity). Through its function
CC in mitochondrial division, ensures the survival of at least some types
CC of postmitotic neurons, including Purkinje cells, by suppressing
CC oxidative damage (PubMed:19752021, PubMed:22564413). Required for
CC normal brain development, including that of cerebellum
CC (PubMed:19578372, PubMed:22564413). Facilitates developmentally
CC regulated apoptosis during neural tube formation (PubMed:19578372).
CC Required for a normal rate of cytochrome c release and caspase
CC activation during apoptosis; this requirement may depend upon the cell
CC type and the physiological apoptotic cues (PubMed:19578372). Proposed
CC to regulate synaptic vesicle membrane dynamics through association with
CC BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in
CC synaptic vesicles; the function may require its recruitment by MFF to
CC clathrin-containing vesicles (By similarity). Required for programmed
CC necrosis execution (By similarity). Rhythmic control of its activity
CC following phosphorylation at Ser-643 is essential for the circadian
CC control of mitochondrial ATP production (PubMed:29478834).
CC {ECO:0000250|UniProtKB:O00429, ECO:0000269|PubMed:19578372,
CC ECO:0000269|PubMed:19752021, ECO:0000269|PubMed:22564413,
CC ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:24508339,
CC ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:32484300}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.5;
CC Evidence={ECO:0000269|PubMed:24508339};
CC -!- SUBUNIT: Homotetramer; dimerizes through the N-terminal GTP-middle
CC region of one molecule binding to the GED domain of another DNM1L
CC molecule. Oligomerizes in a GTP-dependent manner to form membrane-
CC associated tubules with a spiral pattern. Interacts with GSK3B and
CC MARCHF5. Interacts (via the GTPase and B domains) with UBE2I; the
CC interaction promotes sumoylation of DNM1L, mainly in its B domain.
CC Interacts with PPP3CA; the interaction dephosphorylates DNM1L and
CC regulates its transition to mitochondria. Interacts with BCL2L1 isoform
CC BCL-X(L) and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex
CC in synaptic vesicles that also contains clathrin and MFF. Interacts
CC with MFF; the interaction is inhibited by C11orf65/MFI
CC (PubMed:30059978). Interacts with FIS1. Interacts with MIEF2 and MIEF1;
CC GTP-dependent, regulates GTP hydrolysis and DNM1L oligomerization
CC (PubMed:24508339). Interacts with PGAM5; this interaction leads to
CC dephosphorylation at Ser-656 and activation of GTPase activity and
CC eventually to mitochondria fragmentation. Interacts with RALBP1; during
CC mitosis, recruits DNM1L to the mitochondrion and mediates its
CC activation by the mitotic kinase cyclin B-CDK1 (By similarity).
CC {ECO:0000250|UniProtKB:O00429, ECO:0000269|PubMed:24508339,
CC ECO:0000269|PubMed:30059978}.
CC -!- INTERACTION:
CC Q8K1M6; Q925I1: Atad3; NbExp=13; IntAct=EBI-2365792, EBI-772703;
CC Q8K1M6; Q5S006: Lrrk2; NbExp=5; IntAct=EBI-2365792, EBI-2693710;
CC Q8K1M6; Q6PCP5: Mff; NbExp=2; IntAct=EBI-2365792, EBI-21985996;
CC Q8K1M6; Q8BGV8: Mief1; NbExp=2; IntAct=EBI-2365792, EBI-16092561;
CC Q8K1M6-3; Q8BGV8: Mief1; NbExp=5; IntAct=EBI-16092613, EBI-16092561;
CC Q8K1M6-3; Q5NCS9: Mief2; NbExp=2; IntAct=EBI-16092613, EBI-16092669;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:30059978}.
CC Golgi apparatus {ECO:0000250}. Endomembrane system; Peripheral membrane
CC protein. Mitochondrion outer membrane {ECO:0000269|PubMed:30059978};
CC Peripheral membrane protein. Peroxisome {ECO:0000250}. Membrane,
CC clathrin-coated pit {ECO:0000250}. Cytoplasmic vesicle, secretory
CC vesicle, synaptic vesicle membrane {ECO:0000250}. Note=Mainly
CC cytosolic. Recruited by RALA and RALBP1 to mitochondrion during mitosis
CC (By similarity). Translocated to the mitochondrial membrane through O-
CC GlcNAcylation and interaction with FIS1. Colocalized with MARCHF5 at
CC mitochondrial membrane. Localizes to mitochondria at sites of division.
CC Localizes to mitochondria following necrosis induction. Recruited to
CC the mitochondrial outer membrane by interaction with MIEF1.
CC Mitochondrial recruitment is inhibited by C11orf65/MFI
CC (PubMed:30059978). Associated with peroxisomal membranes, partly
CC recruited there by PEX11B. May also be associated with endoplasmic
CC reticulum tubules and cytoplasmic vesicles and found to be perinuclear.
CC In some cell types, localizes to the Golgi complex (By similarity).
CC Binds to phospholipid membranes. {ECO:0000250,
CC ECO:0000250|UniProtKB:O00429, ECO:0000269|PubMed:30059978}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8K1M6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K1M6-2; Sequence=VSP_013695;
CC Name=3;
CC IsoId=Q8K1M6-3; Sequence=VSP_013690, VSP_013694;
CC Name=4;
CC IsoId=Q8K1M6-4; Sequence=VSP_013689, VSP_013691, VSP_013695;
CC Name=5;
CC IsoId=Q8K1M6-5; Sequence=VSP_013690, VSP_013692, VSP_013693;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum and in several regions
CC of the cerebrum and diencephalon. Strongly expressed in the cerebellar
CC Purkinje cells and in the pontile giant neurons.
CC {ECO:0000269|PubMed:9422767}.
CC -!- DOMAIN: The GED domain folds back to interact, in cis, with the GTP-
CC binding domain and middle domain, and interacts, in trans, with the GED
CC domains of other DNM1L molecules, and is thus critical for activating
CC GTPase activity and for DNM1L dimerization.
CC {ECO:0000250|UniProtKB:O00429}.
CC -!- PTM: Phosphorylation/dephosphorylation events on two sites near the GED
CC domain regulate mitochondrial fission (By similarity). Phosphorylation
CC on Ser-643 inhibits mitochondrial fission probably through preventing
CC intramolecular interaction (By similarity). Dephosphorylated on this
CC site by PPP3CA which promotes mitochondrial fission (By similarity).
CC Phosphorylation on Ser-622 by Pink1 activates the GTPase activity and
CC promotes mitochondrial fission (PubMed:32484300). Phosphorylated in a
CC circadian manner at Ser-643 (By similarity).
CC {ECO:0000250|UniProtKB:O00429, ECO:0000269|PubMed:32484300}.
CC -!- PTM: Sumoylated on various lysine residues within the B domain,
CC probably by MUL1. Sumoylation positively regulates mitochondrial
CC fission. Desumoylated by SENP5 during G2/M transition of mitosis.
CC Appears to be linked to its catalytic activity (By similarity).
CC {ECO:0000250}.
CC -!- PTM: S-nitrosylation increases DNM1L dimerization, mitochondrial
CC fission and causes neuronal damage. {ECO:0000250}.
CC -!- PTM: O-GlcNAcylation augments the level of the GTP-bound active form of
CC DNM1L and induces translocation from the cytoplasm to mitochondria in
CC cardiomyocytes. It also decreases phosphorylation at Ser-643 (By
CC similarity). {ECO:0000250|UniProtKB:O35303}.
CC -!- PTM: Ubiquitination by MARCHF5 affects mitochondrial morphology.
CC {ECO:0000250|UniProtKB:O00429}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show severe developmental
CC abnormalities and die between 10.5 and 12.5 dpc. Compared to wild-type
CC littermates, mutant embryos at 9.5-11.5 dpc have a significantly
CC smaller body size, pulsing, but less developed cardiac structures, a
CC poorly developed liver and a thinner neural tube cell layer. They lack
CC trophoblastic giant cell layer in the placenta. Primary cultures of
CC mutant neuronal cells have severe defects in synapse formation and high
CC sensitivity to Ca(2+)-dependent apoptosis. Within cerebellar neurons,
CC Purkinje cells are particularly sensitive to Dnm1l ablation.
CC Conditional knockout in postmitotic Purkinje cells leads to 40%
CC neuronal degeneration after 3 months and 90% after 6 months.
CC {ECO:0000269|PubMed:19578372, ECO:0000269|PubMed:19752021,
CC ECO:0000269|PubMed:22564413}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE-
CC ProRule:PRU01055}.
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DR EMBL; AB079133; BAC06576.1; -; mRNA.
DR EMBL; AK051443; BAC34640.1; -; mRNA.
DR EMBL; AK080871; BAC38054.1; -; mRNA.
DR EMBL; BC027538; AAH27538.1; -; mRNA.
DR EMBL; BC040777; AAH40777.1; -; mRNA.
DR EMBL; BC079635; AAH79635.1; -; mRNA.
DR EMBL; CF914619; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS27984.1; -. [Q8K1M6-3]
DR CCDS; CCDS70689.1; -. [Q8K1M6-2]
DR CCDS; CCDS88885.1; -. [Q8K1M6-4]
DR RefSeq; NP_001021118.1; NM_001025947.2. [Q8K1M6-3]
DR RefSeq; NP_001263269.1; NM_001276340.1. [Q8K1M6-2]
DR RefSeq; NP_001263270.1; NM_001276341.1. [Q8K1M6-4]
DR RefSeq; NP_690029.2; NM_152816.3.
DR RefSeq; XP_006522694.1; XM_006522631.3. [Q8K1M6-1]
DR AlphaFoldDB; Q8K1M6; -.
DR SMR; Q8K1M6; -.
DR BioGRID; 216417; 25.
DR CORUM; Q8K1M6; -.
DR DIP; DIP-54818N; -.
DR IntAct; Q8K1M6; 34.
DR MINT; Q8K1M6; -.
DR STRING; 10090.ENSMUSP00000111415; -.
DR ChEMBL; CHEMBL2331072; -.
DR GlyGen; Q8K1M6; 2 sites.
DR iPTMnet; Q8K1M6; -.
DR PhosphoSitePlus; Q8K1M6; -.
DR SwissPalm; Q8K1M6; -.
DR EPD; Q8K1M6; -.
DR jPOST; Q8K1M6; -.
DR MaxQB; Q8K1M6; -.
DR PeptideAtlas; Q8K1M6; -.
DR PRIDE; Q8K1M6; -.
DR ProteomicsDB; 277358; -. [Q8K1M6-1]
DR ProteomicsDB; 277359; -. [Q8K1M6-2]
DR ProteomicsDB; 277360; -. [Q8K1M6-3]
DR ProteomicsDB; 277361; -. [Q8K1M6-4]
DR ProteomicsDB; 277362; -. [Q8K1M6-5]
DR Antibodypedia; 4096; 729 antibodies from 38 providers.
DR DNASU; 74006; -.
DR Ensembl; ENSMUST00000023477; ENSMUSP00000023477; ENSMUSG00000022789. [Q8K1M6-3]
DR Ensembl; ENSMUST00000230022; ENSMUSP00000155429; ENSMUSG00000022789. [Q8K1M6-4]
DR Ensembl; ENSMUST00000230038; ENSMUSP00000155605; ENSMUSG00000022789. [Q8K1M6-5]
DR Ensembl; ENSMUST00000230980; ENSMUSP00000155155; ENSMUSG00000022789. [Q8K1M6-2]
DR GeneID; 74006; -.
DR KEGG; mmu:74006; -.
DR UCSC; uc007yij.2; mouse. [Q8K1M6-1]
DR UCSC; uc007yik.2; mouse. [Q8K1M6-4]
DR UCSC; uc007yim.2; mouse. [Q8K1M6-3]
DR UCSC; uc007yin.2; mouse. [Q8K1M6-2]
DR UCSC; uc007yio.2; mouse. [Q8K1M6-5]
DR CTD; 10059; -.
DR MGI; MGI:1921256; Dnm1l.
DR VEuPathDB; HostDB:ENSMUSG00000022789; -.
DR eggNOG; KOG0446; Eukaryota.
DR GeneTree; ENSGT00940000155504; -.
DR HOGENOM; CLU_008964_5_0_1; -.
DR InParanoid; Q8K1M6; -.
DR OrthoDB; 264244at2759; -.
DR PhylomeDB; Q8K1M6; -.
DR TreeFam; TF352031; -.
DR BRENDA; 3.6.5.5; 3474.
DR Reactome; R-MMU-75153; Apoptotic execution phase.
DR BioGRID-ORCS; 74006; 27 hits in 75 CRISPR screens.
DR ChiTaRS; Dnm1l; mouse.
DR PRO; PR:Q8K1M6; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8K1M6; protein.
DR Bgee; ENSMUSG00000022789; Expressed in ventral tegmental area and 254 other tissues.
DR ExpressionAtlas; Q8K1M6; baseline and differential.
DR Genevisible; Q8K1M6; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0099073; C:mitochondrion-derived vesicle; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0098835; C:presynaptic endocytic zone membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0099503; C:secretory vesicle; ISO:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0051433; F:BH2 domain binding; ISO:MGI.
DR GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0030742; F:GTP-dependent protein binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IEA:Ensembl.
DR GO; GO:1904579; P:cellular response to thapsigargin; ISO:MGI.
DR GO; GO:0003374; P:dynamin family protein polymerization involved in mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0060047; P:heart contraction; IMP:ParkinsonsUK-UCL.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; ISO:MGI.
DR GO; GO:0061025; P:membrane fusion; ISO:MGI.
DR GO; GO:0000266; P:mitochondrial fission; IMP:UniProtKB.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; ISO:MGI.
DR GO; GO:0090149; P:mitochondrial membrane fission; ISO:MGI.
DR GO; GO:0070584; P:mitochondrion morphogenesis; ISO:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:0070266; P:necroptotic process; IMP:UniProtKB.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISO:MGI.
DR GO; GO:0016559; P:peroxisome fission; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISO:MGI.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISO:MGI.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:MGI.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; ISO:MGI.
DR GO; GO:2000302; P:positive regulation of synaptic vesicle exocytosis; ISO:MGI.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; IMP:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:1903578; P:regulation of ATP metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1900063; P:regulation of peroxisome organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1904666; P:regulation of ubiquitin protein ligase activity; IMP:MGI.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:1905395; P:response to flavonoid; IEA:Ensembl.
DR GO; GO:1990910; P:response to hypobaric hypoxia; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISO:MGI.
DR GO; GO:0036466; P:synaptic vesicle recycling via endosome; ISO:MGI.
DR CDD; cd08771; DLP_1; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR030556; DNM1L.
DR InterPro; IPR022812; Dynamin.
DR InterPro; IPR001401; Dynamin_GTPase.
DR InterPro; IPR019762; Dynamin_GTPase_CS.
DR InterPro; IPR045063; Dynamin_N.
DR InterPro; IPR000375; Dynamin_stalk.
DR InterPro; IPR030381; G_DYNAMIN_dom.
DR InterPro; IPR003130; GED.
DR InterPro; IPR020850; GED_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11566; PTHR11566; 1.
DR PANTHER; PTHR11566:SF39; PTHR11566:SF39; 1.
DR Pfam; PF01031; Dynamin_M; 1.
DR Pfam; PF00350; Dynamin_N; 1.
DR Pfam; PF02212; GED; 1.
DR PRINTS; PR00195; DYNAMIN.
DR SMART; SM00053; DYNc; 1.
DR SMART; SM00302; GED; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00410; G_DYNAMIN_1; 1.
DR PROSITE; PS51718; G_DYNAMIN_2; 1.
DR PROSITE; PS51388; GED; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Biological rhythms; Coated pit;
KW Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing; Endocytosis;
KW Glycoprotein; Golgi apparatus; GTP-binding; Hydrolase; Isopeptide bond;
KW Lipid-binding; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW Necrosis; Nucleotide-binding; Peroxisome; Phosphoprotein;
KW Reference proteome; S-nitrosylation; Synapse; Ubl conjugation.
FT CHAIN 1..742
FT /note="Dynamin-1-like protein"
FT /id="PRO_0000206567"
FT DOMAIN 22..308
FT /note="Dynamin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT DOMAIN 650..741
FT /note="GED"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00720"
FT REGION 32..39
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 58..60
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 152..155
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 221..224
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 251..254
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 350..495
FT /note="Middle domain"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT REGION 454..691
FT /note="Interaction with GSK3B"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT REGION 508..575
FT /note="B domain"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT REGION 528..560
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..742
FT /note="C-terminal dimerization domain"
FT /evidence="ECO:0000250"
FT REGION 572..594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..674
FT /note="Important for homodimerization"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT BINDING 32..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT BINDING 221..227
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT BINDING 252..255
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 603
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 622
FT /note="Phosphoserine; by PINK1"
FT /evidence="ECO:0000269|PubMed:32484300,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 643
FT /note="Phosphoserine; by CAMK1 and PKA"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 650
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT CARBOHYD 591
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 592
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT CROSSLNK 538
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 541
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 564
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 574
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 600
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 603
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 612
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 614
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..104
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013689"
FT VAR_SEQ 85..90
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_013690"
FT VAR_SEQ 105
FT /note="K -> M (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013691"
FT VAR_SEQ 214..227
FT /note="RRTLAVITKLDLMD -> KGRCLYLMDVDLQW (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_013692"
FT VAR_SEQ 228..742
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_013693"
FT VAR_SEQ 539..575
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_013694"
FT VAR_SEQ 539..564
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14592431,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013695"
FT MUTAGEN 59
FT /note="T->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:24508339"
FT MUTAGEN 622
FT /note="S->A: Loss of activity and phosphorylation. Unable
FT to rescue aberrant mitochondrial fission in PINK1 null
FT mutant neurons."
FT /evidence="ECO:0000269|PubMed:32484300"
FT CONFLICT 165
FT /note="P -> L (in Ref. 1; BAC06576)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="Q -> R (in Ref. 1; BAC06576)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="E -> A (in Ref. 2; BAC34640)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 742 AA; 82658 MW; 5A8679B61A444847 CRC64;
MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL LPRGTGVVTR
RPLILQLVHV SPEDKRKTTG EENGKFQSWR VEAEEWGKFL HTKNKLYTDF DEIRQEIENE
TERISGNNKG VSPEPIHLKV FSPNVVNLTL VDLPGMTKVP VGDQPKDIEL QIRELILRFI
SNPNSIILAV TAANTDMATS EALKISREVD PDGRRTLAVI TKLDLMDAGT DAMDVLMGRV
IPVKLGIIGV VNRSQLDINN KKSVTDSIRD EYAFLQKKYP SLANRNGTKY LARTLNRLLM
HHIRDCLPEL KTRINVLAAQ YQSLLNSYGE PVDDKSATLL QLITKFATEY CNTIEGTAKY
IETSELCGGA RICYIFHETF GRTLESVDPL GGLNTIDILT AIRNATGPRP ALFVPEVSFE
LLVKRQIKRL EEPSLRCVEL VHEEMQRIIQ HCSNYSTQEL LRFPKLHDAI VEVVTCLLRK
RLPVTNEMVH NLVAIELAYI NTKHPDFADA CGLMNNNIEE QRRNRLAREL PSAGSRDKSS
KVPSALAPAS QEPPPAASAE ADGKLIQDNR RETKNVPSAG GGIGDGGQEP TTGNWRGMLK
TSKAEELLAE EKSKPIPIMP ASPQKGHAVN LLDVPVPVAR KLSAREQRDC EVIERLIKSY
FLIVRKNIQD SVPKAVMHFL VNHVKDTLQS ELVGQLYKSS LLDDLLTESE DMAQRRKEAA
DMLKALQGAS QIIAEIRETH LW
