ID DNM1L_HUMAN Reviewed; 736 AA. AC O00429; O14541; O60709; Q7L6B3; Q8TBT7; Q9BWM1; Q9Y5J2; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 2. DT 25-NOV-2008, entry version 65. DE RecName: Full=Dynamin-1-like protein; DE EC=3.6.5.5; DE AltName: Full=Dynamin-like protein; 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-related protein 1; DE AltName: Full=Dynamin-like protein 4; DE AltName: Full=Dynamin-like protein IV; DE AltName: Full=HdynIV; 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 4), 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; 2; 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] (ISOFORM 3), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 27-736 (ISOFORM 1). RC TISSUE=Lung, and Placenta; 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 [6] 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 [7] 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 [8] 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 [9] 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 [10] 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 [11] 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 [12] 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-616, AND MASS RP SPECTROMETRY. 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 [15] 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). CC -!- FUNCTION: Functions in mitochondrial and peroxisomal division CC probably by regulating membrane fission. Enzyme hydrolyzing GTP CC that oligomerizes to form ring-like structures and is able to CC remodel membranes. May also play a role on organelles of the CC secretory pathway. CC -!- CATALYTIC ACTIVITY: GTP + H(2)O = GDP + phosphate. CC -!- SUBUNIT: Homotetramer; N-terminal part binds to the C-terminal CC part of another DNM1L. Can self-assemble in multimeric ring-like CC structures. Interacts with FIS1 (By similarity). Interacts with CC GSK3B. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Intracytoplasmic CC membrane; Peripheral membrane protein. Note=Mainly cytosolic. Also CC membrane-associated. Localizes to mitochondria at spots of CC division events. Associated with peroxisomal membranes, it is CC recruited in part by PEX11B. May also be associated with CC endoplasmic reticulum tubules and cytoplasmic vesicles and found CC to be perinuclear. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=HdynIV-WT, DLP1F; CC IsoId=O00429-1; Sequence=Displayed; CC Name=2; Synonyms=HdynIV-11, DLP1c; CC IsoId=O00429-2; Sequence=VSP_013688; CC Name=3; Synonyms=DLP1a; CC IsoId=O00429-3; Sequence=VSP_013686; CC Name=4; 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 -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels CC found in skeletal muscles, heart, kidney and brain. Isoform 1 is CC brain-specific while isoform 3 and isoform 4 are predominantly CC expressed in testis and skeletal muscles respectively. Isoform 2 CC is weakly expressed in brain, heart and kidney and isoform 5 is CC dominantly expressed in liver, heart and kidney. CC -!- PTM: Phosphorylated by GSK3B (By similarity). CC -!- MISCELLANEOUS: Isoform 1 and isoform 2 inhibits peroxisomal CC division when overexpressed while isoform 3 and isoform 4 have no CC effect. 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; BC000136; AAH00136.1; -; mRNA. DR EMBL; BC024590; AAH24590.1; -; mRNA. DR PIR; JC5695; JC5695. DR RefSeq; NP_036192.2; -. DR RefSeq; NP_036193.2; -. DR UniGene; Hs.556296; -. DR IntAct; O00429; -. DR PhosphoSite; O00429; -. DR Ensembl; ENSG00000087470; Homo sapiens. DR GeneID; 10059; -. DR H-InvDB; HIX0010537; -. DR HGNC; HGNC:2973; DNM1L. DR HPA; CAB009952; -. DR MIM; 603850; gene. DR PharmGKB; PA27441; -. DR HOVERGEN; O00429; -. DR NextBio; 38007; -. DR ArrayExpress; O00429; -. DR CleanEx; HS_DNM1L; -. DR GermOnline; ENSG00000087470; Homo sapiens. DR GO; GO:0005801; C:cis-Golgi network; TAS:ProtInc. DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0005525; F:GTP binding; IEA:InterPro. DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0043653; P:mitochondrial fragmentation during apoptosis; IMP:HGNC. DR GO; GO:0007006; P:mitochondrial membrane organization; TAS:ProtInc. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR InterPro; IPR000375; Dynamin_central. DR InterPro; IPR001401; Dynamin_GTPase. DR InterPro; IPR003130; 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 Alternative splicing; Cytoplasm; GTP-binding; Hydrolase; Membrane; KW Nucleotide-binding; Phosphoprotein; Polymorphism. 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 N-terminal dimerization domain. FT REGION 448 685 Interaction with GSK3B. FT REGION 542 736 C-terminal dimerization domain. FT MOD_RES 616 616 Phosphoserine. FT VAR_SEQ 533 569 Missing (in isoform 4). FT /FTId=VSP_013685. FT VAR_SEQ 533 558 Missing (in isoform 3). 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 2). FT /FTId=VSP_013688. FT VARIANT 71 71 S -> T (in dbSNP:rs1064610). FT /FTId=VAR_022446. FT VARIANT 426 426 E -> D (in dbSNP:rs2389105). FT /FTId=VAR_030489. FT MUTAGEN 38 38 K->A: Impairs mitochondrial division and FT induces changes in peroxisome morphology. 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 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 //