ID DNM1L_MOUSE Reviewed; 736 AA. AC Q8K1M6; E9PUD2; Q8BNQ5; Q8BQ64; Q8CGD0; Q8K1A1; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 27-MAR-2024, sequence version 3. DT 27-MAR-2024, entry version 181. DE RecName: Full=Dynamin-1-like protein {ECO:0000305}; DE EC=3.6.5.5 {ECO:0000269|PubMed:24508339, ECO:0000269|PubMed:29853636}; DE AltName: Full=Dynamin family member proline-rich carboxyl-terminal domain less; DE Short=Dymple {ECO:0000303|PubMed:9422767}; DE AltName: Full=Dynamin-related protein 1; GN Name=Dnm1l {ECO:0000312|MGI:MGI:1921256}; GN Synonyms=Drp1 {ECO:0000303|PubMed:29853636}; 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 [MRNA] (ISOFORMS 3; 6; 7; 8; 9; 10; 11; 12; 13; 14), RP ALTERNATIVE SPLICING, TISSUE SPECIFICITY, FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-38 AND GLY-369 (ISOFORM 14). RX PubMed=29853636; DOI=10.1074/jbc.ra117.001253; RA Itoh K., Adachi Y., Yamada T., Suzuki T.L., Otomo T., McBride H.M., RA Yoshimori T., Iijima M., Sesaki H.; RT "A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, RT and the plasma membrane."; RL J. Biol. Chem. 293:11809-11822(2018). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5). 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 [6] RP PROTEIN SEQUENCE OF 620-634 AND 719-731, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Hippocampus; RA Lubec G., Klug S.; RL Submitted (MAR-2007) to UniProtKB. RN [7] 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 [8] 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 [9] 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, 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 [11] 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 [12] 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 [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-597, 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 [14] 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 [15] 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 [16] 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 [17] RP FUNCTION (ISOFORM 14), TISSUE SPECIFICITY (ISOFORM 14), DISRUPTION RP PHENOTYPE (ISOFORM 14), AND SUBCELLULAR LOCATION (ISOFORM 14). RX PubMed=31603426; DOI=10.7554/elife.44739; RA Itoh K., Murata D., Kato T., Yamada T., Araki Y., Saito A., Adachi Y., RA Igarashi A., Li S., Pletnikov M., Huganir R.L., Watanabe S., Kamiya A., RA Iijima M., Sesaki H.; RT "Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite RT formation independently of mitochondrial division."; RL Elife 8:0-0(2019). RN [18] RP FUNCTION, PHOSPHORYLATION AT SER-616, AND MUTAGENESIS OF SER-616. 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, PubMed:29853636). CC Mediates membrane fission through oligomerization into membrane- CC associated tubular structures that wrap around the scission site to CC constrict and sever the mitochondrial membrane through a GTP CC hydrolysis-dependent mechanism (PubMed:24508339). The specific CC recruitment at scission sites is mediated by membrane receptors like CC MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, CC PubMed:24508339). While the recruitment by the membrane receptors is CC GTP-dependent, the following hydrolysis of GTP induces the dissociation CC from the receptors and allows DNM1L filaments to curl into closed rings CC that are probably sufficient to sever a double membrane CC (PubMed:24508339). Acts downstream of PINK1 to promote mitochondrial CC fission in a PRKN-dependent manner (PubMed:32484300). Plays an CC important role in mitochondrial fission during mitosis (By similarity). CC Required for formation of endocytic vesicles (By similarity). Through CC its function in mitochondrial division, ensures the survival of at CC least some types of postmitotic neurons, including Purkinje cells, by CC suppressing oxidative damage (PubMed:19752021, PubMed:22564413). CC Required for 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-637 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:29853636, CC ECO:0000269|PubMed:32484300}. CC -!- FUNCTION: [Isoform 14]: Regulates postsynaptic clathrin-mediated CC endocytosis by positioning the endocytic zone at the postsynaptic CC density, independently of mitochondrial division. CC {ECO:0000269|PubMed:31603426}. 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, ECO:0000269|PubMed:29853636}; 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 Interacts with FUNDC1; this interaction recruits DNM1L/DRP1 at ER- CC mitochondria contact sites (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|UniProtKB:O00429}. Endomembrane system CC {ECO:0000250|UniProtKB:O00429}. Mitochondrion outer membrane CC {ECO:0000269|PubMed:30059978, ECO:0000305|PubMed:29853636}; Peripheral CC membrane protein. Peroxisome {ECO:0000269|PubMed:29853636}. Membrane, CC clathrin-coated pit {ECO:0000250|UniProtKB:O35303}. Cytoplasmic CC vesicle, secretory vesicle, synaptic vesicle membrane CC {ECO:0000250|UniProtKB:O35303}. Note=Mainly cytosolic. Recruited by CC RALA and RALBP1 to mitochondrion during mitosis (By similarity). CC Translocated to the mitochondrial membrane through O-GlcNAcylation and CC interaction with FIS1. Colocalized with MARCHF5 at mitochondrial CC membrane. Localizes to mitochondria at sites of division. Localizes to CC mitochondria following necrosis induction. Recruited to the CC mitochondrial outer membrane by interaction with MIEF1. Mitochondrial CC recruitment is inhibited by C11orf65/MFI (PubMed:30059978). Associated CC with peroxisomal membranes, partly recruited there by PEX11B. May also CC be associated with endoplasmic reticulum tubules and cytoplasmic CC vesicles and found to be perinuclear. In some cell types, localizes to CC the Golgi complex (By similarity). Binds to phospholipid membranes. CC {ECO:0000250, ECO:0000250|UniProtKB:O00429, CC ECO:0000269|PubMed:30059978}. CC -!- SUBCELLULAR LOCATION: [Isoform 14]: Lysosome CC {ECO:0000269|PubMed:29853636}. Late endosome CC {ECO:0000269|PubMed:29853636}. Cell membrane CC {ECO:0000269|PubMed:29853636}; Peripheral membrane protein. CC Mitochondrion outer membrane {ECO:0000269|PubMed:29853636}; Peripheral CC membrane protein. Postsynaptic density {ECO:0000269|PubMed:31603426}. CC Note=Is recruited to existing interorganelle interfaces between CC mitochondria and lysosomes/ late endosomes (PubMed:29853636). GTP CC hydrolysis and oligomerization are required for its localization to CC lysosomes/late endosomes and the cell membrane (PubMed:29853636). CC {ECO:0000269|PubMed:29853636}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=13; CC Name=12; Synonyms=Drp1-CD {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-12; Sequence=Displayed; CC Name=2; CC IsoId=Q8K1M6-2; Sequence=VSP_062252, VSP_062256; CC Name=3; Synonyms=S-Drp1 {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-3; Sequence=VSP_062255; CC Name=4; CC IsoId=Q8K1M6-4; Sequence=VSP_062249, VSP_062256; CC Name=5; CC IsoId=Q8K1M6-5; Sequence=VSP_062253, VSP_062254; CC Name=6; Synonyms=Drp1-B {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-6; Sequence=VSP_062250, VSP_062255; CC Name=7; Synonyms=Drp1-A {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-7; Sequence=VSP_062252, VSP_062255; CC Name=8; Synonyms=Drp1-C {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-8; Sequence=VSP_062257; CC Name=9; Synonyms=Drp1-D {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-9; Sequence=VSP_062256; CC Name=10; Synonyms=Drp1-BC {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-10; Sequence=VSP_062250, VSP_062257; CC Name=11; Synonyms=Drp1-BD {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-11; Sequence=VSP_062250, VSP_062256; CC Name=13; Synonyms=Drp1-BCD {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-13; Sequence=VSP_062250; CC Name=14; Synonyms=Drp1-ABCD {ECO:0000303|PubMed:29853636}; CC IsoId=Q8K1M6-14; Sequence=VSP_062251; 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 -!- TISSUE SPECIFICITY: [Isoform 3]: Widely expressed. CC {ECO:0000269|PubMed:29853636}. CC -!- TISSUE SPECIFICITY: [Isoform 13]: Brain-specific. CC {ECO:0000269|PubMed:29853636}. CC -!- TISSUE SPECIFICITY: [Isoform 14]: Brain-specific (at protein level) CC (PubMed:29853636, PubMed:31603426). Expressed in most of the subregions CC of the brain, including the cerebellum, midbrain, hippocampus, CC striatum, cerebral cortex, and brain stem. Weakly expressed in the CC olfactory bulb (PubMed:29853636, PubMed:31603426). CC {ECO:0000269|PubMed:29853636, ECO:0000269|PubMed:31603426}. 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-637 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-616 by Pink1 activates the GTPase activity and CC promotes mitochondrial fission (PubMed:32484300). Phosphorylated in a CC circadian manner at Ser-637 (By similarity). Dephosphorylated by PGAM5 CC (By similarity). {ECO:0000250|UniProtKB:O00429, CC 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-637 (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. Homozygous CC mice lacking the DNM1L gene are born at an expected Mendelian ratio CC with normal weights of the body and brain (PubMed:31603426). CC {ECO:0000269|PubMed:19578372, ECO:0000269|PubMed:19752021, CC ECO:0000269|PubMed:22564413, ECO:0000269|PubMed:31603426}. CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase CC superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE- CC ProRule:PRU01055}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR AlphaFoldDB; Q8K1M6; -. DR SMR; Q8K1M6; -. DR BioGRID; 216417; 26. DR CORUM; Q8K1M6; -. DR DIP; DIP-54818N; -. DR IntAct; Q8K1M6; 34. DR MINT; Q8K1M6; -. DR STRING; 10090.ENSMUSP00000155155; -. DR ChEMBL; CHEMBL2331072; -. DR GlyCosmos; Q8K1M6; 2 sites, No reported glycans. DR GlyGen; Q8K1M6; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q8K1M6; -. DR PhosphoSitePlus; Q8K1M6; -. DR SwissPalm; Q8K1M6; -. DR EPD; Q8K1M6; -. DR jPOST; Q8K1M6; -. DR MaxQB; Q8K1M6; -. DR PaxDb; 10090-ENSMUSP00000111415; -. DR PeptideAtlas; Q8K1M6; -. DR ProteomicsDB; 277359; -. [Q8K1M6-2] DR ProteomicsDB; 277360; -. [Q8K1M6-3] DR ProteomicsDB; 277361; -. [Q8K1M6-4] DR ProteomicsDB; 277362; -. [Q8K1M6-5] DR Pumba; Q8K1M6; -. DR Antibodypedia; 4096; 869 antibodies from 38 providers. DR DNASU; 74006; -. DR Ensembl; ENSMUST00000023477.15; ENSMUSP00000023477.8; ENSMUSG00000022789.16. [Q8K1M6-3] DR Ensembl; ENSMUST00000230022.2; ENSMUSP00000155429.2; ENSMUSG00000022789.16. [Q8K1M6-4] DR Ensembl; ENSMUST00000230038.2; ENSMUSP00000155605.2; ENSMUSG00000022789.16. [Q8K1M6-5] DR Ensembl; ENSMUST00000230980.2; ENSMUSP00000155155.2; ENSMUSG00000022789.16. [Q8K1M6-2] DR GeneID; 74006; -. DR KEGG; mmu:74006; -. 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 AGR; MGI:1921256; -. 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 OMA; KICHNCG; -. DR OrthoDB; 1052588at2759; -. 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 80 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 257 other cell types or tissues. DR ExpressionAtlas; Q8K1M6; baseline and differential. DR GO; GO:0005903; C:brush border; IDA:UniProtKB. DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell. 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:0005741; C:mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0099073; C:mitochondrion-derived vesicle; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005777; C:peroxisome; IDA: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:0060090; F:molecular adaptor activity; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; IPI:ParkinsonsUK-UCL. DR GO; GO:0120283; F:protein serine/threonine kinase binding; ISO:MGI. 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:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0071396; P:cellular response to lipid; IEA:Ensembl. DR GO; GO:0060047; P:heart contraction; IMP:ParkinsonsUK-UCL. DR GO; GO:0048312; P:intracellular distribution of mitochondria; ISO:MGI. DR GO; GO:0051179; P:localization; 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:0007005; P:mitochondrion organization; IMP:MGI. DR GO; GO:0160040; P:mitocytosis; 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; IMP: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:1901524; P:regulation of mitophagy; IEA:Ensembl. DR GO; GO:1900063; P:regulation of peroxisome organization; IMP:ParkinsonsUK-UCL. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:MGI. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; 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; 1.20.120.1240; Dynamin, middle domain; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. 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; DYNAMIN; 1. DR PANTHER; PTHR11566:SF39; DYNAMIN-1-LIKE PROTEIN; 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; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00410; G_DYNAMIN_1; 1. DR PROSITE; PS51718; G_DYNAMIN_2; 1. DR PROSITE; PS51388; GED; 1. DR Genevisible; Q8K1M6; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Biological rhythms; Cell membrane; KW Coated pit; Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing; KW Endocytosis; Endosome; Glycoprotein; Golgi apparatus; GTP-binding; KW Hydrolase; Isopeptide bond; Lipid-binding; Lysosome; Membrane; KW Mitochondrion; Mitochondrion outer membrane; Necrosis; Nucleotide-binding; KW Peroxisome; Phosphoprotein; Reference proteome; S-nitrosylation; Synapse; KW Ubl conjugation. FT CHAIN 1..736 FT /note="Dynamin-1-like protein" FT /id="PRO_0000206567" FT DOMAIN 22..302 FT /note="Dynamin-type G" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT DOMAIN 644..735 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 146..149 FT /note="G3 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 215..218 FT /note="G4 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 245..248 FT /note="G5 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 344..489 FT /note="Middle domain" FT /evidence="ECO:0000250|UniProtKB:O00429" FT REGION 448..685 FT /note="Interaction with GSK3B" FT /evidence="ECO:0000250|UniProtKB:O00429" FT REGION 502..569 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 542..736 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 654..668 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 215..221 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:O00429" FT BINDING 246..249 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 529 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00429" FT MOD_RES 597 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 607 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00429" FT MOD_RES 616 FT /note="Phosphoserine; by PINK1" FT /evidence="ECO:0000269|PubMed:32484300, FT ECO:0007744|PubMed:21183079" FT MOD_RES 637 FT /note="Phosphoserine; by CAMK1 and PKA" FT /evidence="ECO:0000250|UniProtKB:O00429" FT MOD_RES 644 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:O00429" FT CARBOHYD 585 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000250" FT CARBOHYD 586 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000250" FT CROSSLNK 532 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 535 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 558 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 568 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 594 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 597 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000250" FT CROSSLNK 606 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 608 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT VAR_SEQ 1..99 FT /note="MEALIPVINKLQDVFNTVGADIIQLPQIVVVGTQSSGKSSVLESLVGRDLLP FT RGTGVVTRRPLILQLVHVSPEDKRKTTGEENGVEAEEWGKFLHTKNK -> M (in FT isoform 4)" FT /id="VSP_062249" FT VAR_SEQ 83 FT /note="N -> NDPATWKNSRHLSK (in isoform 6, isoform 10, FT isoform 11 and isoform 13)" FT /id="VSP_062250" FT VAR_SEQ 84 FT /note="G -> GKFQSWNPATWKNSRHLSKG (in isoform 14)" FT /id="VSP_062251" FT VAR_SEQ 84 FT /note="G -> GKFQSWR (in isoform 2 and isoform 7)" FT /id="VSP_062252" FT VAR_SEQ 208..221 FT /note="RRTLAVITKLDLMD -> KGRCLYLMDVDLQW (in isoform 5)" FT /id="VSP_062253" FT VAR_SEQ 222..736 FT /note="Missing (in isoform 5)" FT /id="VSP_062254" FT VAR_SEQ 533..569 FT /note="Missing (in isoform 3, isoform 7 and isoform 6)" FT /id="VSP_062255" FT VAR_SEQ 533..558 FT /note="Missing (in isoform 2, isoform 4, isoform 9 and FT isoform 11)" FT /id="VSP_062256" FT VAR_SEQ 559..569 FT /note="Missing (in isoform 8 and isoform 10)" FT /id="VSP_062257" FT MUTAGEN 59 FT /note="T->A: Abolishes GTP hydrolysis." FT /evidence="ECO:0000269|PubMed:24508339" FT MUTAGEN 616 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 159 FT /note="P -> L (in Ref. 1; BAC06576)" FT /evidence="ECO:0000305" FT CONFLICT 314 FT /note="Q -> R (in Ref. 1; BAC06576)" FT /evidence="ECO:0000305" FT CONFLICT 513 FT /note="E -> A (in Ref. 3; BAC34640)" FT /evidence="ECO:0000305" FT MUTAGEN Q8K1M6-14:38 FT /note="K->A: Impairs lysosome localization. Impairs late FT endosome localization. Impairs cell membrane localization." FT /evidence="ECO:0000269|PubMed:29853636" FT MUTAGEN Q8K1M6-14:369 FT /note="G->D: Impairs lysosome localization. Impairs late FT endosome localization. Impairs cell membrane localization." FT /evidence="ECO:0000269|PubMed:29853636" SQ SEQUENCE 736 AA; 81825 MW; F9AF7BB2BCB1F469 CRC64; MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL LPRGTGVVTR RPLILQLVHV SPEDKRKTTG EENGVEAEEW GKFLHTKNKL YTDFDEIRQE IENETERISG NNKGVSPEPI HLKVFSPNVV NLTLVDLPGM TKVPVGDQPK DIELQIRELI LRFISNPNSI ILAVTAANTD MATSEALKIS REVDPDGRRT LAVITKLDLM DAGTDAMDVL MGRVIPVKLG IIGVVNRSQL DINNKKSVTD SIRDEYAFLQ KKYPSLANRN GTKYLARTLN RLLMHHIRDC LPELKTRINV LAAQYQSLLN SYGEPVDDKS ATLLQLITKF ATEYCNTIEG TAKYIETSEL CGGARICYIF HETFGRTLES VDPLGGLNTI DILTAIRNAT GPRPALFVPE VSFELLVKRQ IKRLEEPSLR CVELVHEEMQ RIIQHCSNYS TQELLRFPKL HDAIVEVVTC LLRKRLPVTN EMVHNLVAIE LAYINTKHPD FADACGLMNN NIEEQRRNRL ARELPSAGSR DKSSKVPSAL APASQEPPPA ASAEADGKLI QDNRRETKNV PSAGGGIGDG GQEPTTGNWR GMLKTSKAEE LLAEEKSKPI PIMPASPQKG HAVNLLDVPV PVARKLSARE QRDCEVIERL IKSYFLIVRK NIQDSVPKAV MHFLVNHVKD TLQSELVGQL YKSSLLDDLL TESEDMAQRR KEAADMLKAL QGASQIIAEI RETHLW //