DNM1L_HUMAN
ID DNM1L_HUMAN Reviewed; 736 AA.
AC O00429; A8K4X9; B4DGC9; B4DSU8; G8JLD5; J3KPI2; O14541; O60709; Q59GN9;
AC Q7L6B3; Q8TBT7; Q9BWM1; Q9Y5J2;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 196.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC TISSUE=Hepatoma;
RX PubMed=9348079; DOI=10.1093/oxfordjournals.jbchem.a021784;
RA Shin H.-W., Shinotsuka C., Torii S., Murakami K., Nakayama K.;
RT "Identification and subcellular localization of a novel mammalian dynamin-
RT 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 SPECIFICITY,
RP INTERACTION WITH GSK3B, AND REGION.
RC TISSUE=Liver;
RX 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 kinase
RT 3beta.";
RL Biochem. Biophys. Res. Commun. 249:697-703(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-71, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-38, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=9570752; DOI=10.1242/jcs.111.10.1341;
RA Imoto M., Tachibana I., Urrutia R.;
RT "Identification and functional characterization of a novel human protein
RT 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, TISSUE
RP SPECIFICITY, AND INTERACTION WITH GSK3B.
RC TISSUE=Brain;
RX PubMed=10749171; DOI=10.1089/104454900314573;
RA Chen C.-H., Howng S.-L., Hwang S.-L., Chou C.-K., Liao C.-H., Hong Y.-R.;
RT "Differential expression of four human dynamin-like protein variants in
RT brain tumors.";
RL DNA Cell Biol. 19:189-194(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 6 AND 7).
RC TISSUE=Amygdala, and 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 MRNA] (ISOFORM 8).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., 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., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., 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., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP MUTAGENESIS OF SER-39, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
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 [10]
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 [11]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX 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 [12]
RP OLIGOMERIZATION.
RX PubMed=9915810; DOI=10.1074/jbc.274.5.2780;
RA Shin H.-W., Takatsu H., Mukai H., Munekata E., Murakami K., 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 [13]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-38; VAL-41; THR-59 AND
RP GLY-281, AND OLIGOMERIZATION.
RX PubMed=11514614; DOI=10.1091/mbc.12.8.2245;
RA Smirnova E., Griparic L., Shurland D.-L., van der Bliek A.M.;
RT "Dynamin-related protein Drp1 is required for mitochondrial division in
RT mammalian cells.";
RL Mol. Biol. Cell 12:2245-2256(2001).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-38.
RX PubMed=12499366; DOI=10.1074/jbc.m211761200;
RA Koch A., Thiemann M., Grabenbauer M., Yoon Y., McNiven M.A., Schrader M.;
RT "Dynamin-like protein 1 is involved in peroxisomal fission.";
RL J. Biol. Chem. 278:8597-8605(2003).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-39 AND THR-59.
RX 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 is
RT recruited to peroxisomes in part by PEX11.";
RL J. Biol. Chem. 278:17012-17020(2003).
RN [16]
RP OLIGOMERIZATION, SUBCELLULAR LOCATION, DOMAIN, REGION, AND MUTAGENESIS OF
RP 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., Blackstone C.;
RT "Intra- and intermolecular domain interactions of the C-terminal GTPase
RT effector domain of the multimeric dynamin-like GTPase Drp1.";
RL J. Biol. Chem. 279:35967-35974(2004).
RN [17]
RP UBIQUITINATION BY MARCHF5, AND INTERACTION WITH MARCHF5.
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., Yanagi S.;
RT "A novel mitochondrial ubiquitin ligase plays a critical role in
RT mitochondrial dynamics.";
RL EMBO J. 25:3618-3626(2006).
RN [18]
RP UBIQUITINATION BY MARCHF5, AND INTERACTION WITH MARCHF5.
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 change
RT mitochondrial morphology.";
RL EMBO Rep. 7:1019-1022(2006).
RN [19]
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., Barja F.,
RA Martinou J.C.;
RT "Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-
RT dependent apoptosis.";
RL Mol. Cell. Biol. 26:7397-7408(2006).
RN [20]
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 in
RT mitochondrial fission.";
RL J. Biol. Chem. 282:11521-11529(2007).
RN [21]
RP PHOSPHORYLATION AT SER-637, FUNCTION, SUBUNIT, AND MUTAGENESIS OF 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 its
RT GTPase activity and mitochondrial morphology.";
RL J. Biol. Chem. 282:21583-21587(2007).
RN [22]
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 [23]
RP FUNCTION, VARIANT EMPF1 ASP-395, AND CHARACTERIZATION OF VARIANT EMPF1
RP ASP-395.
RX PubMed=17460227; DOI=10.1056/nejmoa064436;
RA Waterham H.R., Koster J., van Roermund C.W., Mooyer P.A., Wanders R.J.,
RA Leonard J.V.;
RT "A lethal defect of mitochondrial and peroxisomal fission.";
RL N. Engl. J. Med. 356:1736-1741(2007).
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., Nairn A.C.,
RA Takei K., Matsui H., Matsushita M.;
RT "CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial
RT morphology.";
RL J. Cell Biol. 182:573-585(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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; SER-607 AND SER-616, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT 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 mitochondrial
RT 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 OF
RP LYS-38; LYS-532; LYS-535; LYS-558; LYS-568; LYS-594; LYS-597; LYS-606 AND
RP LYS-608.
RX PubMed=19638400; DOI=10.1096/fj.09-136630;
RA Figueroa-Romero C., Iniguez-Lluhi J.A., Stadler J., Chang C.R., Arnoult D.,
RA Keller P.J., Hong Y., Blackstone C., Feldman E.L.;
RT "SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple
RT nonconsensus sites within the B domain and is linked to its activity
RT 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 modulates
RT DRP1-dependent fission during mitosis.";
RL J. Biol. Chem. 284:17783-17795(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 DISEASE,
RP AND MUTAGENESIS OF CYS-300; CYS-345; CYS-361; CYS-367; CYS-431; CYS-446;
RP 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., 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 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 [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(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., Buerckstuemmer T.,
RA 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 MIEF2 AND MIEF1.
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 machinery.";
RL EMBO Rep. 12:565-573(2011).
RN [38]
RP INTERACTION WITH MIEF1.
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 promotes
RT mitochondrial fusion rather than fission.";
RL EMBO J. 30:2762-2778(2011).
RN [39]
RP INTERACTION WITH RALBP1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT
RP SER-616 BY CDK1.
RX PubMed=21822277; DOI=10.1038/ncb2310;
RA Kashatus D.F., Lim K.H., Brady D.C., Pershing N.L., Cox A.D., Counter C.M.;
RT "RALA and RALBP1 regulate mitochondrial fission at mitosis.";
RL Nat. Cell Biol. 13:1108-1115(2011).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [41]
RP FUNCTION, INTERACTION WITH PGAM5, AND SUBCELLULAR LOCATION.
RX PubMed=22265414; DOI=10.1016/j.cell.2011.11.030;
RA Wang Z., Jiang H., Chen S., Du F., Wang X.;
RT "The mitochondrial phosphatase PGAM5 functions at the convergence point of
RT multiple necrotic death pathways.";
RL Cell 148:228-243(2012).
RN [42]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [43]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23921378; DOI=10.1074/jbc.m113.479873;
RA Palmer C.S., Elgass K.D., Parton R.G., Osellame L.D., Stojanovski D.,
RA Ryan M.T.;
RT "MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment
RT and are specific for mitochondrial fission.";
RL J. Biol. Chem. 288:27584-27593(2013).
RN [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-529 AND SER-616, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [45]
RP FUNCTION, INTERACTION WITH MIEF2 AND MIEF1, PHOSPHORYLATION AT SER-637, AND
RP MUTAGENESIS OF SER-637.
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 [46]
RP INTERACTION WITH BCL2L1, AND FUNCTION.
RX PubMed=23792689; DOI=10.1038/ncb2791;
RA Li H., Alavian K.N., Lazrove E., Mehta N., Jones A., Zhang P.,
RA Licznerski P., Graham M., Uo T., Guo J., Rahner C., Duman R.S.,
RA Morrison R.S., Jonas E.A.;
RT "A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during
RT endocytosis.";
RL Nat. Cell Biol. 15:773-785(2013).
RN [47]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [48]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-616 AND SER-637.
RX PubMed=26122121; DOI=10.1093/brain/awv182;
RA Shahni R., Cale C.M., Anderson G., Osellame L.D., Hambleton S.,
RA Jacques T.S., Wedatilake Y., Taanman J.W., Chan E., Qasim W., Plagnol V.,
RA Chalasani A., Duchen M.R., Gilmour K.C., Rahman S.;
RT "Signal transducer and activator of transcription 2 deficiency is a novel
RT disorder of mitochondrial fission.";
RL Brain 138:2834-2846(2015).
RN [49]
RP FUNCTION, INTERACTION WITH MIEF2, AND SUBUNIT.
RX PubMed=23530241; DOI=10.1073/pnas.1300855110;
RA Koirala S., Guo Q., Kalia R., Bui H.T., Eckert D.M., Frost A., Shaw J.M.;
RT "Interchangeable adaptors regulate mitochondrial dynamin assembly for
RT membrane scission.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1342-E1351(2013).
RN [50]
RP FUNCTION, AND PHOSPHORYLATION AT SER-637.
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 [51]
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).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (3.48 ANGSTROMS), FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF 401-GLY--PRO-404; GLU-490 AND LYS-668,
RP LIPID-BINDING, AND REGION.
RX PubMed=23584531; DOI=10.1038/emboj.2013.74;
RA Frohlich C., Grabiger S., Schwefel D., Faelber K., Rosenbaum E., Mears J.,
RA Rocks O., Daumke O.;
RT "Structural insights into oligomerization and mitochondrial remodelling of
RT dynamin 1-like protein.";
RL EMBO J. 32:1280-1292(2013).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-327 AND 711-736 IN COMPLEX WITH
RP GTP ANALOGS, CATALYTIC ACTIVITY, MUTAGENESIS OF GLN-34; LYS-38; SER-39;
RP THR-59; ASP-146; GLY-149; LYS-216 AND ASP-218, ACTIVITY REGULATION, AND
RP SUBUNIT.
RX PubMed=23977156; DOI=10.1371/journal.pone.0071835;
RA Wenger J., Klinglmayr E., Frohlich C., Eibl C., Gimeno A., Hessenberger M.,
RA Puehringer S., Daumke O., Goettig P.;
RT "Functional mapping of human dynamin-1-like GTPase domain based on x-ray
RT structure analyses.";
RL PLoS ONE 8:E71835-E71835(2013).
RN [54] {ECO:0007744|PDB:5WP9}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.22 ANGSTROMS) (ISOFORM 2) IN COMPLEX
RP WITH MIEF2, MUTAGENESIS OF ASP-190; ASP-221 AND SER-637, AND
RP CHARACTERIZATION OF VARIANT EMPF1 ASP-362.
RX PubMed=29899447; DOI=10.1038/s41586-018-0211-2;
RA Kalia R., Wang R.Y., Yusuf A., Thomas P.V., Agard D.A., Shaw J.M.,
RA Frost A.;
RT "Structural basis of mitochondrial receptor binding and constriction by
RT DRP1.";
RL Nature 558:401-405(2018).
RN [55]
RP VARIANT EMPF1 ASP-362, AND CHARACTERIZATION OF VARIANT EMPF1 ASP-362.
RX PubMed=26604000; DOI=10.1038/ejhg.2015.243;
RG Care4Rare Consortium;
RA Vanstone J.R., Smith A.M., McBride S., Naas T., Holcik M., Antoun G.,
RA Harper M.E., Michaud J., Sell E., Chakraborty P., Tetreault M.,
RA Majewski J., Baird S., Boycott K.M., Dyment D.A., MacKenzie A., Lines M.A.;
RT "DNM1L-related mitochondrial fission defect presenting as refractory
RT epilepsy.";
RL Eur. J. Hum. Genet. 24:1084-1088(2016).
RN [56]
RP VARIANT EMPF1 CYS-403, CHARACTERIZATION OF VARIANTS EMPF1 ASP-395 AND
RP CYS-403, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=27145208; DOI=10.1002/ajmg.a.37721;
RA Fahrner J.A., Liu R., Perry M.S., Klein J., Chan D.C.;
RT "A novel de novo dominant negative mutation in DNM1L impairs mitochondrial
RT fission and presents as childhood epileptic encephalopathy.";
RL Am. J. Med. Genet. A 170:2002-2011(2016).
RN [57]
RP VARIANT EMPF1 SER-362, CHARACTERIZATION OF VARIANT EMPF1 SER-362, AND
RP FUNCTION.
RX PubMed=26992161; DOI=10.1002/ajmg.a.37624;
RA Sheffer R., Douiev L., Edvardson S., Shaag A., Tamimi K., Soiferman D.,
RA Meiner V., Saada A.;
RT "Postnatal microcephaly and pain insensitivity due to a de novo
RT heterozygous DNM1L mutation causing impaired mitochondrial fission and
RT function.";
RL Am. J. Med. Genet. A 170:1603-1607(2016).
RN [58]
RP VARIANT EMPF1 SER-406, CHARACTERIZATION OF VARIANT EMPF1 SER-406, AND
RP FUNCTION.
RX PubMed=27301544; DOI=10.1111/cge.12805;
RA Zaha K., Matsumoto H., Itoh M., Saitsu H., Kato K., Kato M., Ogata S.,
RA Murayama K., Kishita Y., Mizuno Y., Kohda M., Nishino I., Ohtake A.,
RA Okazaki Y., Matsumoto N., Nonoyama S.;
RT "DNM1L-related encephalopathy in infancy with Leigh syndrome-like phenotype
RT and suppression-burst.";
RL Clin. Genet. 90:472-474(2016).
RN [59]
RP VARIANT EMPF1 GLY-36, CHARACTERIZATION OF VARIANT EMPF1 GLY-36, AND
RP FUNCTION.
RX PubMed=27328748; DOI=10.1002/humu.23033;
RA Nasca A., Legati A., Baruffini E., Nolli C., Moroni I., Ardissone A.,
RA Goffrini P., Ghezzi D.;
RT "Biallelic Mutations in DNM1L are Associated with a Slowly Progressive
RT Infantile Encephalopathy.";
RL Hum. Mutat. 37:898-903(2016).
RN [60]
RP INVOLVEMENT IN OPA5, VARIANTS OPA5 ALA-2 AND GLU-192, CHARACTERIZATION OF
RP VARIANTS OPA5 ALA-2 AND GLU-192, AND SUBCELLULAR LOCATION.
RX PubMed=28969390; DOI=10.1093/brain/awx219;
RA Gerber S., Charif M., Chevrollier A., Chaumette T., Angebault C.,
RA Kane M.S., Paris A., Alban J., Quiles M., Delettre C., Bonneau D.,
RA Procaccio V., Amati-Bonneau P., Reynier P., Leruez S., Calmon R.,
RA Boddaert N., Funalot B., Rio M., Bouccara D., Meunier I., Sesaki H.,
RA Kaplan J., Hamel C.P., Rozet J.M., Lenaers G.;
RT "Mutations in DNM1L, as in OPA1, result indominant optic atrophy despite
RT opposite effectson mitochondrial fusion and fission.";
RL Brain 140:2586-2596(2017).
CC -!- FUNCTION: Functions in mitochondrial and peroxisomal division
CC (PubMed:9570752, PubMed:9786947, PubMed:11514614, PubMed:12499366,
CC PubMed:17301055, PubMed:17553808, PubMed:17460227, PubMed:18695047,
CC PubMed:18838687, PubMed:19638400, PubMed:19411255, PubMed:19342591,
CC PubMed:23921378, PubMed:23283981, PubMed:23530241, PubMed:29478834,
CC PubMed:32484300, PubMed:27145208, PubMed:26992161, PubMed:27301544,
CC PubMed:27328748). Mediates membrane fission through oligomerization
CC into membrane-associated tubular structures that wrap around the
CC scission site to constrict and sever the mitochondrial membrane through
CC a GTP hydrolysis-dependent mechanism (PubMed:23530241,
CC PubMed:23584531). The specific recruitment at scission sites is
CC mediated by membrane receptors like MFF, MIEF1 and MIEF2 for
CC mitochondrial membranes (PubMed:23921378, PubMed:23283981,
CC PubMed:29899447). 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:29899447). 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
CC (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748).
CC Through its function in mitochondrial division, ensures the survival of
CC at least some types of postmitotic neurons, including Purkinje cells,
CC by suppressing oxidative damage (By similarity). Required for normal
CC brain development, including that of cerebellum (PubMed:17460227,
CC PubMed:27145208, PubMed:26992161, PubMed:27301544, PubMed:27328748).
CC Facilitates developmentally regulated apoptosis during neural tube
CC formation (By similarity). Required for a normal rate of cytochrome c
CC release and caspase activation during apoptosis; this requirement may
CC depend upon the cell type and the physiological apoptotic cues (By
CC similarity). Required for formation of endocytic vesicles
CC (PubMed:9570752, PubMed:20688057, PubMed:23792689). Proposed to
CC 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 (PubMed:17015472, PubMed:23792689).
CC Required for programmed necrosis execution (PubMed:22265414). Rhythmic
CC control of its activity following phosphorylation at Ser-637 is
CC essential for the circadian control of mitochondrial ATP production
CC (PubMed:29478834). {ECO:0000250|UniProtKB:Q8K1M6,
CC ECO:0000269|PubMed:11514614, ECO:0000269|PubMed:12499366,
CC ECO:0000269|PubMed:17015472, ECO:0000269|PubMed:17301055,
CC ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:17553808,
CC ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687,
CC ECO:0000269|PubMed:19342591, ECO:0000269|PubMed:19411255,
CC ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:20688057,
CC ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981,
CC ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531,
CC ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23921378,
CC ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208,
CC ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748,
CC ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:29899447,
CC ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:9570752,
CC ECO:0000269|PubMed:9786947}.
CC -!- FUNCTION: [Isoform 1]: Inhibits peroxisomal division when
CC overexpressed. {ECO:0000269|PubMed:12618434}.
CC -!- FUNCTION: [Isoform 4]: Inhibits peroxisomal division when
CC overexpressed. {ECO:0000269|PubMed:12618434}.
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:23977156, ECO:0000269|PubMed:9422767};
CC -!- ACTIVITY REGULATION: GTPase activity is increased by binding to
CC phospholipid membranes. {ECO:0000269|PubMed:23977156}.
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 inhinited by C11orf65/MFI. Interacts with
CC FIS1. Interacts with MIEF2 and MIEF1; GTP-dependent, regulates GTP
CC hydrolysis and DNM1L oligomerization. Interacts with PGAM5; this
CC interaction leads to dephosphorylation at Ser-656 and activation of
CC GTPase activity and eventually to mitochondria fragmentation. Interacts
CC with RALBP1; during mitosis, recruits DNM1L to the mitochondrion and
CC mediates its activation by the mitotic kinase cyclin B-CDK1
CC (PubMed:21822277). {ECO:0000250|UniProtKB:Q8K1M6,
CC ECO:0000269|PubMed:10749171, ECO:0000269|PubMed:16874301,
CC ECO:0000269|PubMed:16936636, ECO:0000269|PubMed:17553808,
CC ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687,
CC ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:21508961,
CC ECO:0000269|PubMed:21701560, ECO:0000269|PubMed:21822277,
CC ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981,
CC ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531,
CC ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23977156,
CC ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:9731200}.
CC -!- INTERACTION:
CC O00429; Q9NVI7: ATAD3A; NbExp=4; IntAct=EBI-724571, EBI-352007;
CC O00429; Q9NVI7-2: ATAD3A; NbExp=5; IntAct=EBI-724571, EBI-5456381;
CC O00429; O00429: DNM1L; NbExp=2; IntAct=EBI-724571, EBI-724571;
CC O00429; P03372: ESR1; NbExp=2; IntAct=EBI-724571, EBI-78473;
CC O00429; Q9Y3D6: FIS1; NbExp=2; IntAct=EBI-724571, EBI-3385283;
CC O00429; Q5S007: LRRK2; NbExp=14; IntAct=EBI-724571, EBI-5323863;
CC O00429; Q9GZY8: MFF; NbExp=3; IntAct=EBI-724571, EBI-11420856;
CC O00429; Q9NQG6: MIEF1; NbExp=11; IntAct=EBI-724571, EBI-740987;
CC O00429; Q96C03: MIEF2; NbExp=5; IntAct=EBI-724571, EBI-750153;
CC O00429; Q9Y512: SAMM50; NbExp=3; IntAct=EBI-724571, EBI-748409;
CC O00429; Q14160: SCRIB; NbExp=2; IntAct=EBI-724571, EBI-357345;
CC O00429-3; O00429-3: DNM1L; NbExp=8; IntAct=EBI-6896746, EBI-6896746;
CC O00429-3; Q5S007: LRRK2; NbExp=2; IntAct=EBI-6896746, EBI-5323863;
CC O00429-3; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-6896746, EBI-6447163;
CC O00429-3; O95563: MPC2; NbExp=3; IntAct=EBI-6896746, EBI-719403;
CC O00429-3; P21980-2: TGM2; NbExp=3; IntAct=EBI-6896746, EBI-25842075;
CC O00429-3; O43257: ZNHIT1; NbExp=3; IntAct=EBI-6896746, EBI-347522;
CC O00429-4; O00429-4: DNM1L; NbExp=2; IntAct=EBI-4420450, EBI-4420450;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Golgi apparatus. Endomembrane
CC system; Peripheral membrane protein. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:26122121, ECO:0000269|PubMed:27145208,
CC ECO:0000269|PubMed:28969390}; Peripheral membrane protein. Peroxisome.
CC Membrane, clathrin-coated pit {ECO:0000250}. Cytoplasmic vesicle,
CC secretory vesicle, synaptic vesicle membrane
CC {ECO:0000250|UniProtKB:O35303}. Note=Mainly cytosolic. Recruited by
CC RALA and RALBP1 to mitochondrion during mitosis (PubMed:21822277).
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 (By similarity). 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 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q8K1M6,
CC ECO:0000269|PubMed:21822277}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
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 Name=6;
CC IsoId=O00429-6; Sequence=VSP_039097;
CC Name=7;
CC IsoId=O00429-7; Sequence=VSP_054544, VSP_054545;
CC Name=8;
CC IsoId=O00429-8; Sequence=VSP_039097, VSP_013688;
CC Name=9;
CC IsoId=O00429-9; Sequence=VSP_039097, VSP_013685;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels found in
CC skeletal muscles, heart, kidney and brain. Isoform 1 is brain-specific.
CC Isoform 2 and isoform 3 are predominantly expressed in testis and
CC skeletal muscles respectively. Isoform 4 is weakly expressed in brain,
CC heart and kidney. Isoform 5 is dominantly expressed in liver, heart and
CC kidney. Isoform 6 is expressed in neurons.
CC {ECO:0000269|PubMed:10749171, ECO:0000269|PubMed:9422767,
CC ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9731200,
CC ECO:0000269|PubMed:9786947}.
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:0000269|PubMed:15208300}.
CC -!- PTM: Phosphorylation/dephosphorylation events on two sites near the GED
CC domain regulate mitochondrial fission (PubMed:17301055,
CC PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:23283981,
CC PubMed:29478834). Phosphorylation on Ser-637 by CAMK1 and PKA inhibits
CC the GTPase activity, leading to a defect in mitochondrial fission
CC promoting mitochondrial elongation (PubMed:17553808, PubMed:18695047,
CC PubMed:23283981, PubMed:29478834). Dephosphorylated on this site by
CC PPP3CA which promotes mitochondrial fission (PubMed:18838687).
CC Phosphorylation on Ser-616 by CDK1 and PINK1 activates the GTPase
CC activity and promotes mitochondrial fission (PubMed:18838687,
CC PubMed:32484300, PubMed:21822277). Phosphorylated in a circadian manner
CC at Ser-637 (PubMed:29478834). {ECO:0000269|PubMed:17301055,
CC ECO:0000269|PubMed:17553808, ECO:0000269|PubMed:18695047,
CC ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:21822277,
CC ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:29478834,
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.
CC {ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:19411255,
CC ECO:0000269|PubMed:19638400}.
CC -!- PTM: S-nitrosylation increases DNM1L dimerization, mitochondrial
CC fission and causes neuronal damage. {ECO:0000269|PubMed:19342591}.
CC -!- PTM: Ubiquitination by MARCHF5 affects mitochondrial morphology.
CC {ECO:0000269|PubMed:16874301, ECO:0000269|PubMed:16936636}.
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 -!- DISEASE: Note=May be associated with Alzheimer disease through amyloid-
CC beta-induced increased S-nitrosylation of DNM1L, which triggers,
CC directly or indirectly, excessive mitochondrial fission, synaptic loss
CC and neuronal damage. {ECO:0000269|PubMed:19342591}.
CC -!- DISEASE: Encephalopathy due to defective mitochondrial and peroxisomal
CC fission 1 (EMPF1) [MIM:614388]: A rare autosomal dominant systemic
CC disorder resulting in lack of neurologic development and death in
CC infancy. After birth, infants present in the first week of life with
CC poor feeding and neurologic impairment, including hypotonia, little
CC spontaneous movement, no tendon reflexes, no response to light
CC stimulation, and poor visual fixation. Other features include mildly
CC elevated plasma concentration of very-long-chain fatty acids, lactic
CC acidosis, microcephaly, deep-set eyes, optic atrophy and hypoplasia,
CC and an abnormal gyral pattern in both frontal lobes associated with
CC dysmyelination. {ECO:0000269|PubMed:17460227,
CC ECO:0000269|PubMed:26604000, ECO:0000269|PubMed:26992161,
CC ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27301544,
CC ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29899447}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Optic atrophy 5 (OPA5) [MIM:610708]: A form of optic atrophy,
CC a disease characterized by progressive visual loss in association with
CC a deficiency in the number of nerve fibers which arise in the retina
CC and converge to form the optic disk, optic nerve, optic chiasm and
CC optic tracts. OPA5 is an autosomal dominant non-syndromic form that
CC manifests as slowly progressive visual loss with variable onset from
CC the first to third decades. Additional ocular abnormalities may include
CC central scotoma and dyschromatopsia. {ECO:0000269|PubMed:28969390}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE-
CC ProRule:PRU01055}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92307.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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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; AK294533; BAG57740.1; -; mRNA.
DR EMBL; AB209070; BAD92307.1; ALT_INIT; mRNA.
DR EMBL; AC084824; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024590; AAH24590.1; -; mRNA.
DR CCDS; CCDS61095.1; -. [O00429-6]
DR CCDS; CCDS61096.1; -. [O00429-8]
DR CCDS; CCDS61098.1; -. [O00429-2]
DR CCDS; CCDS61099.1; -. [O00429-7]
DR CCDS; CCDS81680.1; -. [O00429-9]
DR CCDS; CCDS8728.1; -. [O00429-4]
DR CCDS; CCDS8729.1; -. [O00429-1]
DR CCDS; CCDS8730.1; -. [O00429-3]
DR PIR; JC5695; JC5695.
DR RefSeq; NP_001265392.1; NM_001278463.1. [O00429-2]
DR RefSeq; NP_001265393.1; NM_001278464.1. [O00429-6]
DR RefSeq; NP_001265394.1; NM_001278465.1. [O00429-8]
DR RefSeq; NP_001265395.1; NM_001278466.1. [O00429-7]
DR RefSeq; NP_001317309.1; NM_001330380.1. [O00429-9]
DR RefSeq; NP_005681.2; NM_005690.4. [O00429-4]
DR RefSeq; NP_036192.2; NM_012062.4. [O00429-1]
DR RefSeq; NP_036193.2; NM_012063.3. [O00429-3]
DR PDB; 3W6N; X-ray; 2.00 A; A/B=1-329, A/B=709-736.
DR PDB; 3W6O; X-ray; 1.90 A; A/B=1-329, A/B=709-736.
DR PDB; 3W6P; X-ray; 1.70 A; A/B=1-329, A/B=709-736.
DR PDB; 4BEJ; X-ray; 3.48 A; A/B/C/D=1-736.
DR PDB; 4H1U; X-ray; 2.30 A; A=1-327, A=711-736.
DR PDB; 4H1V; X-ray; 2.30 A; A=1-327, A=711-736.
DR PDB; 5WP9; EM; 4.22 A; A/C/E/G/I/K/M/O=1-736.
DR PDBsum; 3W6N; -.
DR PDBsum; 3W6O; -.
DR PDBsum; 3W6P; -.
DR PDBsum; 4BEJ; -.
DR PDBsum; 4H1U; -.
DR PDBsum; 4H1V; -.
DR PDBsum; 5WP9; -.
DR AlphaFoldDB; O00429; -.
DR SMR; O00429; -.
DR BioGRID; 115370; 320.
DR CORUM; O00429; -.
DR DIP; DIP-42704N; -.
DR IntAct; O00429; 227.
DR MINT; O00429; -.
DR STRING; 9606.ENSP00000449089; -.
DR BindingDB; O00429; -.
DR ChEMBL; CHEMBL4523118; -.
DR TCDB; 1.N.6.1.2; the mitochondrial inner/outer membrane fusion (mmf) family.
DR GlyGen; O00429; 4 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O00429; -.
DR MetOSite; O00429; -.
DR PhosphoSitePlus; O00429; -.
DR SwissPalm; O00429; -.
DR BioMuta; DNM1L; -.
DR CPTAC; CPTAC-57; -.
DR EPD; O00429; -.
DR jPOST; O00429; -.
DR MassIVE; O00429; -.
DR MaxQB; O00429; -.
DR PaxDb; O00429; -.
DR PeptideAtlas; O00429; -.
DR PRIDE; O00429; -.
DR ProteomicsDB; 34194; -.
DR ProteomicsDB; 4122; -.
DR ProteomicsDB; 47884; -. [O00429-1]
DR ProteomicsDB; 47885; -. [O00429-2]
DR ProteomicsDB; 47886; -. [O00429-3]
DR ProteomicsDB; 47887; -. [O00429-4]
DR ProteomicsDB; 47888; -. [O00429-5]
DR ProteomicsDB; 47889; -. [O00429-6]
DR Antibodypedia; 4096; 729 antibodies from 38 providers.
DR DNASU; 10059; -.
DR Ensembl; ENST00000266481.10; ENSP00000266481.6; ENSG00000087470.19. [O00429-4]
DR Ensembl; ENST00000358214.9; ENSP00000350948.5; ENSG00000087470.19. [O00429-9]
DR Ensembl; ENST00000381000.8; ENSP00000370388.4; ENSG00000087470.19. [O00429-8]
DR Ensembl; ENST00000414834.6; ENSP00000404160.2; ENSG00000087470.19. [O00429-7]
DR Ensembl; ENST00000452533.6; ENSP00000415131.2; ENSG00000087470.19. [O00429-3]
DR Ensembl; ENST00000547312.5; ENSP00000448610.1; ENSG00000087470.19. [O00429-2]
DR Ensembl; ENST00000549701.6; ENSP00000450399.1; ENSG00000087470.19. [O00429-1]
DR Ensembl; ENST00000553257.6; ENSP00000449089.1; ENSG00000087470.19. [O00429-6]
DR GeneID; 10059; -.
DR KEGG; hsa:10059; -.
DR MANE-Select; ENST00000549701.6; ENSP00000450399.1; NM_012062.5; NP_036192.2.
DR UCSC; uc001rld.4; human. [O00429-1]
DR CTD; 10059; -.
DR DisGeNET; 10059; -.
DR GeneCards; DNM1L; -.
DR HGNC; HGNC:2973; DNM1L.
DR HPA; ENSG00000087470; Low tissue specificity.
DR MalaCards; DNM1L; -.
DR MIM; 603850; gene.
DR MIM; 610708; phenotype.
DR MIM; 614388; phenotype.
DR neXtProt; NX_O00429; -.
DR NIAGADS; ENSG00000087470; -.
DR OpenTargets; ENSG00000087470; -.
DR Orphanet; 98673; Autosomal dominant optic atrophy, classic form.
DR Orphanet; 330050; DNM1L-related encephalopathy due to mitochondrial and peroxisomal fission defect.
DR PharmGKB; PA27441; -.
DR VEuPathDB; HostDB:ENSG00000087470; -.
DR eggNOG; KOG0446; Eukaryota.
DR GeneTree; ENSGT00940000155504; -.
DR HOGENOM; CLU_008964_5_4_1; -.
DR InParanoid; O00429; -.
DR OMA; IMATQFQ; -.
DR PhylomeDB; O00429; -.
DR TreeFam; TF352031; -.
DR BRENDA; 3.6.5.5; 2681.
DR PathwayCommons; O00429; -.
DR Reactome; R-HSA-75153; Apoptotic execution phase.
DR SignaLink; O00429; -.
DR SIGNOR; O00429; -.
DR BioGRID-ORCS; 10059; 487 hits in 1087 CRISPR screens.
DR ChiTaRS; DNM1L; human.
DR GeneWiki; DNM1L; -.
DR GenomeRNAi; 10059; -.
DR Pharos; O00429; Tchem.
DR PRO; PR:O00429; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O00429; protein.
DR Bgee; ENSG00000087470; Expressed in lateral nuclear group of thalamus and 207 other tissues.
DR ExpressionAtlas; O00429; baseline and differential.
DR Genevisible; O00429; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005903; C:brush border; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0030742; F:GTP-dependent protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005096; F:GTPase activator activity; IC:ParkinsonsUK-UCL.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0003374; P:dynamin family protein polymerization involved in mitochondrial fission; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061025; P:membrane fusion; IDA:UniProtKB.
DR GO; GO:0000266; P:mitochondrial fission; IDA:UniProtKB.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0090149; P:mitochondrial membrane fission; IDA:UniProtKB.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070266; P:necroptotic process; IMP:UniProtKB.
DR GO; GO:0016559; P:peroxisome fission; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP: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; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:CACAO.
DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:UniProtKB.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IMP:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; IEA:Ensembl.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:1903578; P:regulation of ATP metabolic process; IEA:Ensembl.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; IGI:ParkinsonsUK-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:UniProtKB.
DR GO; GO:1900063; P:regulation of peroxisome organization; IMP:UniProtKB.
DR GO; GO:1904666; P:regulation of ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR CDD; cd08771; DLP_1; 1.
DR DisProt; DP01537; -. [O00429-3]
DR DisProt; DP01540; -.
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 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Coated pit; Cytoplasm; Cytoplasmic vesicle; Disease variant; 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..736
FT /note="Dynamin-1-like protein"
FT /id="PRO_0000206566"
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:0000269|PubMed:15208300"
FT REGION 448..685
FT /note="Interaction with GSK3B"
FT /evidence="ECO:0000269|PubMed:9731200"
FT REGION 502..569
FT /note="B domain"
FT /evidence="ECO:0000269|PubMed:15208300"
FT REGION 523..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 654..668
FT /note="Important for homodimerization"
FT /evidence="ECO:0000269|PubMed:23584531"
FT BINDING 32..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:23977156"
FT BINDING 215..221
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:23977156"
FT BINDING 246..249
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:23977156"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 597
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8K1M6"
FT MOD_RES 607
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 616
FT /note="Phosphoserine; by CDK1 and PINK1"
FT /evidence="ECO:0000269|PubMed:18838687,
FT ECO:0000269|PubMed:21822277, ECO:0000269|PubMed:26122121,
FT ECO:0000269|PubMed:32484300, ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 637
FT /note="Phosphoserine; by CAMK1 and PKA"
FT /evidence="ECO:0000269|PubMed:17553808,
FT ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687,
FT ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:26122121"
FT MOD_RES 644
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:19342591"
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:0000269|PubMed:19638400"
FT CROSSLNK 535
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19638400"
FT CROSSLNK 558
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19638400"
FT CROSSLNK 568
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19638400"
FT CROSSLNK 594
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19638400"
FT CROSSLNK 597
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 606
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19638400"
FT CROSSLNK 608
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:19638400"
FT VAR_SEQ 1..43
FT /note="MEALIPVINKLQDVFNTVGADIIQLPQIVVVGTQSSGKSSVLE -> MFHKK
FT INGKQQEKKMTLLHGKTQDTFLKGWKQKNGVNFFTPKI (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054544"
FT VAR_SEQ 44..246
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054545"
FT VAR_SEQ 83
FT /note="N -> NDPATWKNSRHLSK (in isoform 6, isoform 8 and
FT isoform 9)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.6"
FT /id="VSP_039097"
FT VAR_SEQ 533..569
FT /note="Missing (in isoform 3 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:10749171,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:9731200"
FT /id="VSP_013685"
FT VAR_SEQ 533..558
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013686"
FT VAR_SEQ 544..569
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10749171"
FT /id="VSP_013687"
FT VAR_SEQ 559..569
FT /note="Missing (in isoform 4 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:10749171, ECO:0000303|Ref.6"
FT /id="VSP_013688"
FT VARIANT 2
FT /note="E -> A (in OPA5; changed localization to
FT mitochondrion; impaired mitochondrial membrane fission;
FT dbSNP:rs1555229948)"
FT /evidence="ECO:0000269|PubMed:28969390"
FT /id="VAR_080869"
FT VARIANT 36
FT /note="S -> G (in EMPF1; autosomal recessive; impaired
FT mitochondrial membrane fission; hypomorphic mutation
FT retaining partial activity in mitochondrial membrane
FT fission; dbSNP:rs879255688)"
FT /evidence="ECO:0000269|PubMed:27328748"
FT /id="VAR_080870"
FT VARIANT 71
FT /note="S -> T (in dbSNP:rs1064610)"
FT /evidence="ECO:0000269|PubMed:10749171,
FT ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9731200"
FT /id="VAR_022446"
FT VARIANT 192
FT /note="A -> E (in OPA5; changed localization to
FT mitochondrion; impaired mitochondrial membrane fission;
FT dbSNP:rs1555119216)"
FT /evidence="ECO:0000269|PubMed:28969390"
FT /id="VAR_080871"
FT VARIANT 362
FT /note="G -> D (in EMPF1; unknown pathological significance;
FT unable to associate with MIEF2 into filaments forming the
FT tubular structures that wrap around the scission site;
FT presence of concentric cristae and/or increased dense
FT granules in some mitochondria; dbSNP:rs879255685)"
FT /evidence="ECO:0000269|PubMed:26604000,
FT ECO:0000269|PubMed:29899447"
FT /id="VAR_076316"
FT VARIANT 362
FT /note="G -> S (in EMPF1; the mutation acts in a dominant-
FT negative manner; defects observed in mitochondrial fission;
FT significant decrease in mitochondrial respiratory chain
FT complex IV activity; dbSNP:rs886037861)"
FT /evidence="ECO:0000269|PubMed:26992161"
FT /id="VAR_076317"
FT VARIANT 395
FT /note="A -> D (in EMPF1; the mutation acts in a dominant-
FT negative manner; defects observed in both mitochondrial and
FT peroxisomal fission; reduced oligomerization, decreased
FT mitochondrial recruitment; dbSNP:rs121908531)"
FT /evidence="ECO:0000269|PubMed:17460227,
FT ECO:0000269|PubMed:27145208"
FT /id="VAR_063704"
FT VARIANT 403
FT /note="R -> C (in EMPF1; the mutation acts in a dominant-
FT negative manner; reduced oligomerization; decreased
FT mitochondrial recruitment; defects observed in
FT mitochondrial fission; dbSNP:rs863223953)"
FT /evidence="ECO:0000269|PubMed:27145208"
FT /id="VAR_076318"
FT VARIANT 406
FT /note="L -> S (in EMPF1; impaired mitochondrial and
FT peroxisomal membrane fission)"
FT /evidence="ECO:0000269|PubMed:27301544"
FT /id="VAR_080872"
FT VARIANT 426
FT /note="E -> D (in dbSNP:rs2389105)"
FT /id="VAR_030489"
FT MUTAGEN 34
FT /note="Q->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:23977156"
FT MUTAGEN 38
FT /note="K->A: Loss of GTPase activity. Impairs mitochondrial
FT division and induces changes in peroxisome morphology. No
FT effect on oligomerization. Increase in sumoylation by
FT SUMO3."
FT /evidence="ECO:0000269|PubMed:11514614,
FT ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:15208300,
FT ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:23977156,
FT ECO:0000269|PubMed:9570752"
FT MUTAGEN 38
FT /note="K->E: Overexpression delays protein secretion.
FT Rescues fragmented or truncated mitochondria in PRKN- or
FT PINK1-depleted cells."
FT /evidence="ECO:0000269|PubMed:11514614,
FT ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:15208300,
FT ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:23977156,
FT ECO:0000269|PubMed:9570752"
FT MUTAGEN 39
FT /note="S->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:12618434,
FT ECO:0000269|PubMed:23977156, ECO:0000269|PubMed:9422767"
FT MUTAGEN 39
FT /note="S->I: Decreased localization to the perinuclear
FT region."
FT /evidence="ECO:0000269|PubMed:12618434,
FT ECO:0000269|PubMed:23977156, ECO:0000269|PubMed:9422767"
FT MUTAGEN 39
FT /note="S->N: Reduces peroxisomal abundance."
FT /evidence="ECO:0000269|PubMed:12618434,
FT ECO:0000269|PubMed:23977156, ECO:0000269|PubMed:9422767"
FT MUTAGEN 41
FT /note="V->F: Temperature-sensitive. Impairs mitochondrial
FT division."
FT /evidence="ECO:0000269|PubMed:11514614"
FT MUTAGEN 59
FT /note="T->A: Abolishes GTP hydrolysis. Impairs
FT mitochondrial division. Reduces peroxisomal abundance."
FT /evidence="ECO:0000269|PubMed:11514614,
FT ECO:0000269|PubMed:12618434, ECO:0000269|PubMed:23977156"
FT MUTAGEN 146
FT /note="D->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:23977156"
FT MUTAGEN 149
FT /note="G->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:23977156"
FT MUTAGEN 190
FT /note="D->A: Unable to homooligomerize. Unable to associate
FT with MIEF2 into filaments forming the tubular structures
FT that wrap around the scission site."
FT /evidence="ECO:0000269|PubMed:29899447"
FT MUTAGEN 216
FT /note="K->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:23977156"
FT MUTAGEN 218
FT /note="D->A: Abolishes GTP hydrolysis."
FT /evidence="ECO:0000269|PubMed:23977156"
FT MUTAGEN 221
FT /note="D->A: Unable to homooligomerize. Unable to associate
FT with MIEF2 into filaments forming the tubular structures
FT that wrap around the scission site."
FT /evidence="ECO:0000269|PubMed:29899447"
FT MUTAGEN 281
FT /note="G->D: Temperature-sensitive. Impairs mitochondrial
FT division."
FT /evidence="ECO:0000269|PubMed:11514614"
FT MUTAGEN 300
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 345
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 361
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 367
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 401..404
FT /note="GPRP->AAAA: Impairs formation of higher order
FT oligomers, but not homodimerization."
FT /evidence="ECO:0000269|PubMed:23584531"
FT MUTAGEN 431
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 446
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 470
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 490
FT /note="E->A: Does not impair homodimerization and formation
FT of higher order oligomers."
FT /evidence="ECO:0000269|PubMed:23584531"
FT MUTAGEN 490
FT /note="E->R: Impairs homodimerization and formation of
FT higher order oligomers."
FT /evidence="ECO:0000269|PubMed:23584531"
FT MUTAGEN 505
FT /note="C->A: No effect on S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 532
FT /note="K->R: Some loss of sumoylation in B domain. Complete
FT loss of sumoylation in B domain; when associated with R-
FT 535; R-558 and R-568."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 535
FT /note="K->R: Some loss of sumoylation in B domain. Complete
FT loss of sumoylation in B domain; when associated with R-
FT 532; R-558 and R-568."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 558
FT /note="K->R: Some loss of sumoylation in B domain. Complete
FT loss of sumoylation in B domain; when associated with R-
FT 532; R-535 and R-568."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 568
FT /note="K->R: Some loss of sumoylation in B domain. Complete
FT loss of sumoylation in B domain; when associated with R-
FT 532; R-535 and R-558."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 594
FT /note="K->R: Some loss of sumoylation in the GED domain;
FT Complete loss of sumoylation in the GED domain; when
FT associated with R-597; R-606 and R-608."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 597
FT /note="K->R: Some loss of sumoylation in the GED domain;
FT Complete loss of sumoylation in the GED domain; when
FT associated with R-594; R-606 and R-608."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 606
FT /note="K->R: Some loss of sumoylation in the GED domain;
FT Complete loss of sumoylation in the GED domain; when
FT associated with R-594; R-597 and R-608."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 608
FT /note="K->R: Some loss of sumoylation in the GED domain;
FT Complete loss of sumoylation in the GED domain; when
FT associated with R-594; R-597 and R-606."
FT /evidence="ECO:0000269|PubMed:19638400"
FT MUTAGEN 616
FT /note="S->A: Loss of activity. Little effect on
FT mitochondrial morphology. Translocated to mitochondria."
FT /evidence="ECO:0000269|PubMed:18838687,
FT ECO:0000269|PubMed:32484300"
FT MUTAGEN 637
FT /note="S->A: Abolishes phosphorylation. Reduces interaction
FT with MIEF1 and MIEF2. Promotes mitochondrial fission and
FT cell vulnerability to apoptotic insults. Mostly
FT mitochondrial. Disrupts, in vitro, binding to FIS1."
FT /evidence="ECO:0000269|PubMed:17553808,
FT ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687,
FT ECO:0000269|PubMed:23283981"
FT MUTAGEN 637
FT /note="S->D: Impairs intramolecular interactions but not
FT homooligomerization. Does not reduce interaction with MIEF1
FT and MIEF2. Impairs formation of higher order oligomers but
FT not homodimerization. Unable to associate with MIEF2 into
FT filaments forming the tubular structures that wrap around
FT the scission site. Slight reduction in GTPase activity.
FT Inhibits mitochondrial fission. Retained in the cytoplasm."
FT /evidence="ECO:0000269|PubMed:17553808,
FT ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687,
FT ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:29899447"
FT MUTAGEN 644
FT /note="C->A: Abolishes S-nitrosylation. Reduced
FT dimerization and no enhancement of GTPase activity."
FT /evidence="ECO:0000269|PubMed:19342591"
FT MUTAGEN 668
FT /note="K->E: Abolishes homodimerization and formation of
FT higher order oligomers."
FT /evidence="ECO:0000269|PubMed:23584531"
FT MUTAGEN 679
FT /note="K->A: Diminishes intramolecular interaction between
FT GTP-middle domain and GED domain but no effect on
FT homooligomerization. Marked reduction in GTPase activity,
FT in vitro. Decreased mitochondrial division."
FT /evidence="ECO:0000269|PubMed:15208300"
FT CONFLICT 208
FT /note="R -> C (in Ref. 2; AAC35283 and 4; AAD39541)"
FT /evidence="ECO:0000305"
FT HELIX 5..18
FT /evidence="ECO:0007829|PDB:3W6P"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:4H1U"
FT STRAND 27..31
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:4H1U"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 104..119
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 130..136
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:4H1U"
FT HELIX 162..174
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 179..186
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:4H1U"
FT STRAND 210..215
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:3W6P"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:4H1V"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 249..253
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 258..272
FT /evidence="ECO:0007829|PDB:3W6P"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 282..317
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 338..355
FT /evidence="ECO:0007829|PDB:3W6P"
FT HELIX 363..371
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 373..380
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 389..399
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 409..420
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 425..440
FT /evidence="ECO:0007829|PDB:4BEJ"
FT TURN 441..443
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 444..446
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 458..493
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 643..673
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 675..690
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 693..699
FT /evidence="ECO:0007829|PDB:4BEJ"
FT HELIX 704..727
FT /evidence="ECO:0007829|PDB:4BEJ"
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
