ID DNM1L_HUMAN Reviewed; 736 AA. AC O00429; A8K4X9; B4DSU8; O14541; O60709; Q7L6B3; Q8TBT7; Q9BWM1; AC Q9Y5J2; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 2. DT 22-FEB-2012, entry version 99. DE RecName: Full=Dynamin-1-like protein; DE EC=3.6.5.5; DE AltName: Full=Dnm1p/Vps1p-like protein; DE Short=DVLP; DE AltName: Full=Dynamin family member proline-rich carboxyl-terminal domain less; DE Short=Dymple; DE AltName: Full=Dynamin-like protein; DE AltName: Full=Dynamin-like protein 4; DE AltName: Full=Dynamin-like protein IV; DE Short=HdynIV; DE AltName: Full=Dynamin-related protein 1; GN Name=DNM1L; Synonyms=DLP1, DRP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION. RC TISSUE=Hepatoma; RX MEDLINE=98006302; PubMed=9348079; RA Shin H.-W., Shinotsuka C., Torii S., Murakami K., Nakayama K.; RT "Identification and subcellular localization of a novel mammalian RT dynamin-related protein homologous to yeast Vps1p and Dnm1p."; RL J. Biochem. 122:525-530(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT THR-71, TISSUE RP SPECIFICITY, AND INTERACTION WITH GSK3B. RC TISSUE=Liver; RX MEDLINE=98401153; PubMed=9731200; DOI=10.1006/bbrc.1998.9253; RA Hong Y.-R., Chen C.-H., Cheng D.-S., Howng S.-L., Chow C.-C.; RT "Human dynamin-like protein interacts with the glycogen synthase RT kinase 3beta."; RL Biochem. Biophys. Res. Commun. 249:697-703(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-71, TISSUE RP SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-38, AND RP FUNCTION. RC TISSUE=Brain; RX PubMed=9570752; RA Imoto M., Tachibana I., Urrutia R.; RT "Identification and functional characterization of a novel human RT protein highly related to the yeast dynamin-like GTPase Vps1p."; RL J. Cell Sci. 111:1341-1349(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5), VARIANT THR-71, RP TISSUE SPECIFICITY, AND INTERACTION WITH GSK3B. RC TISSUE=Brain; RX MEDLINE=20210729; PubMed=10749171; DOI=10.1089/104454900314573; RA Chen C.-H., Howng S.-L., Hwang S.-L., Chou C.-K., Liao C.-H., RA Hong Y.-R.; RT "Differential expression of four human dynamin-like protein variants RT in brain tumors."; RL DNA Cell Biol. 19:189-194(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 6). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 27-736 (ISOFORM 1). RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP MUTAGENESIS OF SER-39, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND RP SUBCELLULAR LOCATION. RX MEDLINE=98086281; 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 [9] RP SUBCELLULAR LOCATION. RX PubMed=9472031; DOI=10.1083/jcb.140.4.779; RA Yoon Y., Pitts K.R., Dahan S., McNiven M.A.; RT "A novel dynamin-like protein associates with cytoplasmic vesicles and RT tubules of the endoplasmic reticulum in mammalian cells."; RL J. Cell Biol. 140:779-793(1998). RN [10] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION. RX MEDLINE=99003294; PubMed=9786947; DOI=10.1083/jcb.143.2.351; RA Smirnova E., Shurland D.-L., Ryazantsev S.N., van der Bliek A.M.; RT "A human dynamin-related protein controls the distribution of RT mitochondria."; RL J. Cell Biol. 143:351-358(1998). RN [11] RP OLIGOMERIZATION. RX MEDLINE=99115619; PubMed=9915810; DOI=10.1074/jbc.274.5.2780; RA Shin H.-W., Takatsu H., Mukai H., Munekata E., Murakami K., RA Nakayama K.; RT "Intermolecular and interdomain interactions of a dynamin-related GTP- RT binding protein, Dnm1p/Vps1p-like protein."; RL J. Biol. Chem. 274:2780-2785(1999). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-38; VAL-41; THR-59 RP AND GLY-281, AND OLIGOMERIZATION. RX MEDLINE=21405995; PubMed=11514614; RA Smirnova E., Griparic L., Shurland D.-L., van der Bliek A.M.; RT "Dynamin-related protein Drp1 is required for mitochondrial division RT in mammalian cells."; RL Mol. Biol. Cell 12:2245-2256(2001). RN [13] RP MUTAGENESIS OF LYS-38, SUBCELLULAR LOCATION, AND FUNCTION. RX MEDLINE=22499627; PubMed=12499366; DOI=10.1074/jbc.M211761200; RA Koch A., Thiemann M., Grabenbauer M., Yoon Y., McNiven M.A., RA Schrader M.; RT "Dynamin-like protein 1 is involved in peroxisomal fission."; RL J. Biol. Chem. 278:8597-8605(2003). RN [14] RP MUTAGENESIS OF SER-39 AND THR-59, FUNCTION, AND SUBCELLULAR LOCATION. RX MEDLINE=22615981; PubMed=12618434; DOI=10.1074/jbc.M212031200; RA Li X., Gould S.J.; RT "The dynamin-like GTPase DLP1 is essential for peroxisome division and RT is recruited to peroxisomes in part by PEX11."; RL J. Biol. Chem. 278:17012-17020(2003). RN [15] RP FUNCTION OF STRUCTURAL DOMAINS, OLIGOMERIZATION, SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF LYS-38 AND LYS-679. RX PubMed=15208300; DOI=10.1074/jbc.M404105200; RA Zhu P.P., Patterson A., Stadler J., Seeburg D.P., Sheng M., RA Blackstone C.; RT "Intra- and intermolecular domain interactions of the C-terminal RT GTPase effector domain of the multimeric dynamin-like GTPase Drp1."; RL J. Biol. Chem. 279:35967-35974(2004). RN [16] RP UBIQUITINATION BY MARCH5, AND INTERACTION WITH MARCH5. RX PubMed=16874301; DOI=10.1038/sj.emboj.7601249; RA Yonashiro R., Ishido S., Kyo S., Fukuda T., Goto E., Matsuki Y., RA Ohmura-Hoshino M., Sada K., Hotta H., Yamamura H., Inatome R., RA Yanagi S.; RT "A novel mitochondrial ubiquitin ligase plays a critical role in RT mitochondrial dynamics."; RL EMBO J. 25:3618-3626(2006). RN [17] RP UBIQUITINATION BY MARCH5, AND INTERACTION WITH MARCH5. RX PubMed=16936636; DOI=10.1038/sj.embor.7400790; RA Nakamura N., Kimura Y., Tokuda M., Honda S., Hirose S.; RT "MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to RT change mitochondrial morphology."; RL EMBO Rep. 7:1019-1022(2006). RN [18] RP FUNCTION. RX PubMed=17015472; DOI=10.1128/MCB.02282-05; RA Parone P.A., James D.I., Da Cruz S., Mattenberger Y., Donze O., RA Barja F., Martinou J.C.; RT "Inhibiting the mitochondrial fission machinery does not prevent RT Bax/Bak-dependent apoptosis."; RL Mol. Cell. Biol. 26:7397-7408(2006). RN [19] RP PHOSPHORYLATION, AND FUNCTION. RX PubMed=17301055; DOI=10.1074/jbc.M607279200; RA Taguchi N., Ishihara N., Jofuku A., Oka T., Mihara K.; RT "Mitotic phosphorylation of dynamin-related GTPase Drp1 participates RT in mitochondrial fission."; RL J. Biol. Chem. 282:11521-11529(2007). RN [20] RP PHOSPHORYLATION AT SER-637, FUNCTION, SUBUNIT, AND MUTAGENESIS OF RP SER-637. RX PubMed=17553808; DOI=10.1074/jbc.C700083200; RA Chang C.R., Blackstone C.; RT "Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates RT its GTPase activity and mitochondrial morphology."; RL J. Biol. Chem. 282:21583-21587(2007). RN [21] RP SUBCELLULAR LOCATION. RX PubMed=17606867; DOI=10.1083/jcb.200611064; RA Karbowski M., Neutzner A., Youle R.J.; RT "The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 RT dependent mitochondrial division."; RL J. Cell Biol. 178:71-84(2007). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa RT cells and high confident phosphopeptide identification by cross- RT validation of MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18187866; DOI=10.2116/analsci.24.161; RA Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; RT "Automated phosphoproteome analysis for cultured cancer cells by two- RT dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; RL Anal. Sci. 24:161-166(2008). RN [24] RP PHOSPHORYLATION AT SER-637, FUNCTION, INTERACTION WITH FIS1, AND RP MUTAGENESIS OF SER-637. RX PubMed=18695047; DOI=10.1083/jcb.200802164; RA Han X.J., Lu Y.F., Li S.A., Kaitsuka T., Sato Y., Tomizawa K., RA Nairn A.C., Takei K., Matsui H., Matsushita M.; RT "CaM kinase I alpha-induced phosphorylation of Drp1 regulates RT mitochondrial morphology."; RL J. Cell Biol. 182:573-585(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND MASS RP SPECTROMETRY. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548 AND SER-616, AND RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [27] RP PHOSPHORYLATION AT SER-616 AND SER-637, INTERACTION WITH PPP3CA, RP DEPHOSPHORYLATION, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP SER-616 AND SER-637. RX PubMed=18838687; DOI=10.1073/pnas.0808249105; RA Cereghetti G.M., Stangherlin A., Martins de Brito O., Chang C.R., RA Blackstone C., Bernardi P., Scorrano L.; RT "Dephosphorylation by calcineurin regulates translocation of Drp1 to RT mitochondria."; RL Proc. Natl. Acad. Sci. U.S.A. 105:15803-15808(2008). RN [28] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-616, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [29] RP SUMOYLATION BY MUL1. RX PubMed=19407830; DOI=10.1038/embor.2009.86; RA Braschi E., Zunino R., McBride H.M.; RT "MAPL is a new mitochondrial SUMO E3 ligase that regulates RT mitochondrial fission."; RL EMBO Rep. 10:748-754(2009). RN [30] RP SUMOYLATION AT LYS-532; LYS-535; LYS-558; LYS-568; LYS-594; LYS-597; RP LYS-606 AND LYS-608, INTERACTION WITH UBE2I, FUNCTION, AND MUTAGENESIS RP OF LYS-38; LYS-532; LYS-535; LYS-558; LYS-568; LYS-594; LYS-597; RP LYS-606 AND LYS-608. RX PubMed=19638400; DOI=10.1096/fj.09-136630; RA Figueroa-Romero C., Iniguez-Lluhi J.A., Stadler J., Chang C.R., RA Arnoult D., Keller P.J., Hong Y., Blackstone C., Feldman E.L.; RT "SUMOylation of the mitochondrial fission protein Drp1 occurs at RT multiple nonconsensus sites within the B domain and is linked to its RT activity cycle."; RL FASEB J. 23:3917-3927(2009). RN [31] RP SUMOYLATION, DESUMOYLATION, AND FUNCTION. RX PubMed=19411255; DOI=10.1074/jbc.M901902200; RA Zunino R., Braschi E., Xu L., McBride H.M.; RT "Translocation of SenP5 from the nucleoli to the mitochondria RT modulates DRP1-dependent fission during mitosis."; RL J. Biol. Chem. 284:17783-17795(2009). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND MASS RP SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [33] RP S-NITROSYLATION AT CYS-644, FUNCTION, ASSOCIATION WITH ALZHEIMER RP DISEASE, AND MUTAGENESIS OF CYS-300; CYS-345; CYS-361; CYS-367; RP CYS-431; CYS-446; CYS-470; CYS-505 AND CYS-644. RX PubMed=19342591; DOI=10.1126/science.1171091; RA Cho D.H., Nakamura T., Fang J., Cieplak P., Godzik A., Gu Z., RA Lipton S.A.; RT "S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial RT fission and neuronal injury."; RL Science 324:102-105(2009). RN [34] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-283, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [35] RP POSSIBLE FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20688057; DOI=10.1016/j.yexcr.2010.07.020; RA Bonekamp N.A., Vormund K., Jacob R., Schrader M.; RT "Dynamin-like protein 1 at the Golgi complex: A novel component of the RT sorting/targeting machinery en route to the plasma membrane."; RL Exp. Cell Res. 316:3454-3467(2010). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [37] RP INTERACTION WITH MID49 AND MID51. RX PubMed=21508961; DOI=10.1038/embor.2011.54; RA Palmer C.S., Osellame L.D., Laine D., Koutsopoulos O.S., Frazier A.E., RA Ryan M.T.; RT "MiD49 and MiD51, new components of the mitochondrial fission RT machinery."; RL EMBO Rep. 12:565-573(2011). RN [38] RP INTERACTION WITH MID51. RX PubMed=21701560; DOI=10.1038/emboj.2011.198; RA Zhao J., Liu T., Jin S., Wang X., Qu M., Uhlen P., Tomilin N., RA Shupliakov O., Lendahl U., Nister M.; RT "Human MIEF1 recruits Drp1 to mitochondrial outer membranes and RT promotes mitochondrial fusion rather than fission."; RL EMBO J. 30:2762-2778(2011). RN [39] RP VARIANT ASP-395, FUNCTION, AND CHARACTERIZATION OF VARIANT ASP-395. RX PubMed=17460227; DOI=10.1056/NEJMoa064436; RA Waterham H.R., Koster J., van Roermund C.W., Mooyer P.A., RA Wanders R.J., Leonard J.V.; RT "A lethal defect of mitochondrial and peroxisomal fission."; RL N. Engl. J. Med. 356:1736-1741(2007). CC -!- FUNCTION: Functions in mitochondrial and peroxisomal division. CC Mediates membrane fission through oligomerization into ring-like CC structures which wrap around the scission site to constict and CC sever the mitochondrial membrane through a GTP hydrolysis- CC dependent mechanism. Required for normal brain development. CC Facilitates developmentally-regulated apoptosis during neural tube CC development. Required for a normal rate of cytochrome c release CC and caspase activation during apoptosis. Also required for CC mitochondrial fission during mitosis. May be involved in vesicle CC transport. CC -!- FUNCTION: Isoform 1 and isoform 4 inhibit peroxisomal division CC when overexpressed. CC -!- CATALYTIC ACTIVITY: GTP + H(2)O = GDP + phosphate. 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. Can self-assemble in multimeric ring-like structures. CC Interacts with BCL2L1; the interaction stimulates the GTPase CC activity of DMN1L in synapses and increases the number of axonal CC mitochondria and the size and number of synaptic vesicle clusters. CC Interacts with FIS1 (By similarity). Interacts with GSK3B and CC MARCH5. Interacts (via the GTPase and B domains) with UBE2I; the CC interaction promotes sumoylation of DNM1L, mainly in ite B domain. CC Interacts with PPP3CA; the interaction dephosphorylates DNM1L and CC regulates its transition to mitochondria. Interacts witn MID49 and CC MID51. CC -!- INTERACTION: CC P03372:ESR1; NbExp=2; IntAct=EBI-724571, EBI-78473; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Golgi apparatus. CC Endomembrane system; Peripheral membrane protein. Note=Mainly CC cytosolic. Translocated to the mitochondrial membrane through CC interaction with FIS1. Colocalized with MARCH5 at mitochondrial CC membrane. Localizes to mitochondria at sites of division. CC Associated with peroxisomal membranes, partly recruited there by CC PEX11B. May also be associated with endoplasmic reticulum tubules CC and cytoplasmic vesicles and found to be perinuclear. In some cell CC types, localizes to the Golgi complex. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=HdynIV-WT, DLP1F; CC IsoId=O00429-1; Sequence=Displayed; CC Name=4; Synonyms=HdynIV-11, DLP1c; CC IsoId=O00429-2; Sequence=VSP_013688; CC Name=2; Synonyms=DLP1a; CC IsoId=O00429-3; Sequence=VSP_013686; CC Name=3; Synonyms=HdynIV-37, DLP1b; CC IsoId=O00429-4; Sequence=VSP_013685; CC Name=5; Synonyms=HdynIV-26; CC IsoId=O00429-5; Sequence=VSP_013687; CC Note=No experimental confirmation available; CC Name=6; CC IsoId=O00429-6; Sequence=VSP_039097; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels CC found in skeletal muscles, heart, kidney and brain. Isoform 1 is CC brain-specific. Isoform 2 and isoform 3 are predominantly CC expressed in testis and skeletal muscles respectively. Isoform 4 CC is weakly expressed in brain, heart and kidney. Isoform 5 is CC dominantly expressed in liver, heart and kidney. Isoform 6 is CC expressed in neurons. CC -!- DOMAIN: The GED domain folds back to interact, in cis, with the CC GTP-binding domain and middle domain, and interacts, in trans, CC with the GED domains of other DNM1L molecules, and is thus CC critical for activating GTPase activity and for DNM1L CC dimerization. CC -!- PTM: Phosphorylation/dephosphorylation events on two sites near CC the GED domain regulate mitochondrial fission. Phosphorylation on CC Ser-637 inhibits mitochondrial fissin probably through preventing CC intramolecular interaction. Dephosphorylated on this site by CC PPP3CA which promotes mitochondrial fission. Phosphorylation on CC Ser-616 also promotes mitochondrial fission. 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. CC -!- PTM: S-nitrosylation increases DNM1L dimerization, mitochondrial CC fission and causes neuronal damage. CC -!- PTM: Ubiquitination by MARCH5 affects mitochondrial morphology. CC -!- DISEASE: Note=May be associated with Alzheimer disease through CC beta-amyloid-induced increased S-nitrosylation of DNM1L, which CC triggers, directly or indirectly, excessive mitochondrial fission, CC synaptic loss and neuronal damage. CC -!- SIMILARITY: Belongs to the dynamin family. CC -!- SIMILARITY: Contains 1 GED domain. 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; AB006965; BAA22193.1; -; mRNA. DR EMBL; AF061795; AAC35283.1; -; mRNA. DR EMBL; AF000430; AAC23724.1; -; mRNA. DR EMBL; AF151685; AAD39541.1; -; mRNA. DR EMBL; AK299926; BAG61760.1; -; mRNA. DR EMBL; AK291094; BAF83783.1; -; mRNA. DR EMBL; AC084824; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC087588; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC024590; AAH24590.1; -; mRNA. DR IPI; IPI00037283; -. DR IPI; IPI00146935; -. DR IPI; IPI00473085; -. DR IPI; IPI00555883; -. DR IPI; IPI00871742; -. DR IPI; IPI00942042; -. DR PIR; JC5695; JC5695. DR RefSeq; NP_005681.2; NM_005690.3. DR RefSeq; NP_036192.2; NM_012062.3. DR RefSeq; NP_036193.2; NM_012063.2. DR UniGene; Hs.556296; -. DR ProteinModelPortal; O00429; -. DR SMR; O00429; 1-730. DR IntAct; O00429; 5. DR MINT; MINT-1394198; -. DR STRING; O00429; -. DR PhosphoSite; O00429; -. DR PRIDE; O00429; -. DR Ensembl; ENST00000266481; ENSP00000266481; ENSG00000087470. DR Ensembl; ENST00000381000; ENSP00000370388; ENSG00000087470. DR GeneID; 10059; -. DR KEGG; hsa:10059; -. DR UCSC; uc001rld.2; human. DR UCSC; uc001rle.2; human. DR UCSC; uc001rlf.2; human. DR UCSC; uc001rlh.2; human. DR CTD; 10059; -. DR GeneCards; GC12P032732; -. DR H-InvDB; HIX0010537; -. DR HGNC; HGNC:2973; DNM1L. DR HPA; CAB009952; -. DR MIM; 603850; gene. DR neXtProt; NX_O00429; -. DR PharmGKB; PA27441; -. DR eggNOG; COG0699; -. DR GeneTree; ENSGT00630000089767; -. DR HOVERGEN; HBG107833; -. DR KO; K01528; -. DR OrthoDB; EOG4SN1N7; -. DR PhylomeDB; O00429; -. DR Reactome; REACT_578; Apoptosis. DR NextBio; 38007; -. DR PMAP-CutDB; O00429; -. DR ArrayExpress; O00429; -. DR Bgee; O00429; -. DR CleanEx; HS_DNM1L; -. DR Genevestigator; O00429; -. DR GermOnline; ENSG00000087470; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0006921; P:cellular component disassembly involved in apoptosis; TAS:Reactome. DR GO; GO:0003374; P:dynamin polymerization involved in mitochondrial fission; IDA:UniProtKB. DR GO; GO:0090149; P:membrane fission involved in mitochondrial fission; IDA:UniProtKB. DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptosis; IMP:HGNC. DR GO; GO:0016559; P:peroxisome fission; IDA:UniProtKB. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; TAS:BHF-UCL. DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:UniProtKB. DR InterPro; IPR022812; Dynamin. DR InterPro; IPR000375; Dynamin_central. DR InterPro; IPR001401; Dynamin_GTPase. DR InterPro; IPR019762; Dynamin_GTPase_CS. DR InterPro; IPR003130; GED. DR InterPro; IPR020850; GTPase_effector_domain_GED. 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 PROSITE; PS00410; DYNAMIN; 1. DR PROSITE; PS51388; GED; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm; KW Golgi apparatus; GTP-binding; Hydrolase; Isopeptide bond; Membrane; KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; KW S-nitrosylation; Ubl conjugation. FT CHAIN 1 736 Dynamin-1-like protein. FT /FTId=PRO_0000206566. FT DOMAIN 644 735 GED. FT NP_BIND 32 39 GTP (By similarity). FT NP_BIND 146 150 GTP (By similarity). FT NP_BIND 215 218 GTP (By similarity). FT REGION 1 343 GTPase domain. FT REGION 344 489 Middle domain. FT REGION 448 685 Interaction with GSK3B. FT REGION 502 569 B domain. FT MOD_RES 1 1 N-acetylmethionine. FT MOD_RES 283 283 N6-acetyllysine. FT MOD_RES 529 529 Phosphoserine (By similarity). FT MOD_RES 548 548 Phosphoserine. FT MOD_RES 616 616 Phosphoserine; by CDK1. FT MOD_RES 637 637 Phosphoserine; by CAMK1 and PKA. FT MOD_RES 644 644 S-nitrosocysteine. FT CROSSLNK 532 532 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 535 535 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 558 558 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 568 568 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 594 594 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO) FT (Probable). FT CROSSLNK 597 597 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 606 606 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO) FT (Probable). FT CROSSLNK 608 608 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 83 83 N -> NDPATWKNSRHLSK (in isoform 6). FT /FTId=VSP_039097. FT VAR_SEQ 533 569 Missing (in isoform 3). FT /FTId=VSP_013685. FT VAR_SEQ 533 558 Missing (in isoform 2). FT /FTId=VSP_013686. FT VAR_SEQ 544 569 Missing (in isoform 5). FT /FTId=VSP_013687. FT VAR_SEQ 559 569 Missing (in isoform 4). FT /FTId=VSP_013688. FT VARIANT 71 71 S -> T (in dbSNP:rs1064610). FT /FTId=VAR_022446. FT VARIANT 395 395 A -> D (in one newborn; with FT microcephaly, abnormal brain development, FT optic atrophy, hypoplasia, persistent FT lactic acidemia and a mildly elevated FT plasma concentration of very-long-chain FT fatty acids. Defects observed in both FT mitochondrial and peroxisomal fission). FT /FTId=VAR_063704. FT VARIANT 426 426 E -> D (in dbSNP:rs2389105). FT /FTId=VAR_030489. FT MUTAGEN 38 38 K->A: Loss of GTPase activity. Impairs FT mitochondrial division and induces FT changes in peroxisome morphology. No FT effect on oligomerization. Increase in FT sumoylation by SUMO3. FT MUTAGEN 38 38 K->E: Overexpression delays protein FT secretion. FT MUTAGEN 39 39 S->I: Decreased localization to the FT perinuclear region. FT MUTAGEN 39 39 S->N: Reduces peroxisomal abundance. FT MUTAGEN 41 41 V->F: Temperature-sensitive. Impairs FT mitochondrial division. FT MUTAGEN 59 59 T->A: Impairs mitochondrial division. FT Reduces peroxisomal abundance. FT MUTAGEN 281 281 G->D: Temperature-sensitive. Impairs FT mitochondrial division. FT MUTAGEN 300 300 C->A: No effect on S-nitrosylation. FT MUTAGEN 345 345 C->A: No effect on S-nitrosylation. FT MUTAGEN 361 361 C->A: No effect on S-nitrosylation. FT MUTAGEN 367 367 C->A: No effect on S-nitrosylation. FT MUTAGEN 431 431 C->A: No effect on S-nitrosylation. FT MUTAGEN 446 446 C->A: No effect on S-nitrosylation. FT MUTAGEN 470 470 C->A: No effect on S-nitrosylation. FT MUTAGEN 505 505 C->A: No effect on S-nitrosylation. FT MUTAGEN 532 532 K->R: Some loss of sumoylation in B FT domain. Complete loss of sumoylation in B FT domain; when associated with R-535; R-558 FT and R-568. FT MUTAGEN 535 535 K->R: Some loss of sumoylation in B FT domain. Complete loss of sumoylation in B FT domain; when associated with R-532; R-558 FT and R-568. FT MUTAGEN 558 558 K->R: Some loss of sumoylation in B FT domain. Complete loss of sumoylation in B FT domain; when associated with R-532; R-535 FT and R-568. FT MUTAGEN 568 568 K->R: Some loss of sumoylation in B FT domain. Complete loss of sumoylation in B FT domain; when associated with R-532; R-535 FT and R-558. FT MUTAGEN 594 594 K->R: Some loss of sumoylation in the GED FT domain; Complete loss of sumoylation in FT the GED domain; when associated with R- FT 597; R-606 and R-608. FT MUTAGEN 597 597 K->R: Some loss of sumoylation in the GED FT domain; Complete loss of sumoylation in FT the GED domain; when associated with R- FT 594; R-606 and R-608. FT MUTAGEN 606 606 K->R: Some loss of sumoylation in the GED FT domain; Complete loss of sumoylation in FT the GED domain; when associated with R- FT 594; R-597 and R-608. FT MUTAGEN 608 608 K->R: Some loss of sumoylation in the GED FT domain; Complete loss of sumoylation in FT the GED domain; when associated with R- FT 594; R-597 and R-606. FT MUTAGEN 616 616 S->A: Little effect on mitochondrial FT morphology. Translocated to mitochondria. FT MUTAGEN 637 637 S->A: Abolishes phosphorylation. Promotes FT mitochondrial fission and cell FT vulnerability to apoptotic insults. FT Mostly mitochondrial. Disrupts, in vitro, FT binding to FIS1. FT MUTAGEN 637 637 S->D: Impairs intramolecular, but not FT intermolecular interactions. Slight FT reduction in GTPase activity. Inhibits FT mitochondrial fission. Retained in FT cytoplasm. FT MUTAGEN 644 644 C->A: Abolishes S-nitrosylation. Reduced FT dimerization and no enhancement of GTPase FT activity. FT MUTAGEN 679 679 K->A: Diminishes intermolecular FT interaction between GTP-middle domain and FT GED domain but no effect on FT oligomerization. Marked reduction in FT GTPase activity, in vitro. Decreased FT mitochondrial division. FT CONFLICT 208 208 R -> C (in Ref. 2; AAC35283 and 4; FT AAD39541). SQ SEQUENCE 736 AA; 81877 MW; F9521A376B785B71 CRC64; MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL LPRGTGIVTR RPLILQLVHV SQEDKRKTTG EENGVEAEEW GKFLHTKNKL YTDFDEIRQE IENETERISG NNKGVSPEPI HLKIFSPNVV 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 ARELPSAVSR DKSSKVPSAL APASQEPSPA ASAEADGKLI QDSRRETKNV ASGGGGVGDG VQEPTTGNWR GMLKTSKAEE LLAEEKSKPI PIMPASPQKG HAVNLLDVPV PVARKLSARE QRDCEVIERL IKSYFLIVRK NIQDSVPKAV MHFLVNHVKD TLQSELVGQL YKSSLLDDLL TESEDMAQRR KEAADMLKAL QGASQIIAEI RETHLW //