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Protein

Dynamin-1-like protein

Gene

Dnm1l

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions in mitochondrial and peroxisomal division. Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism. Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage. Required for normal brain development, including that of cerebellum. Facilitates developmentally regulated apoptosis during neural tube formation. Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues. Plays an important role in mitochondrial fission during mitosis. Required for formation of endocytic vesicles. Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles. Required for programmed necrosis execution.6 Publications

Catalytic activityi

GTP + H2O = GDP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi32 – 40GTPBy similarity9
Nucleotide bindingi228 – 234GTPBy similarity7
Nucleotide bindingi259 – 262GTPBy similarity4

GO - Molecular functioni

  • BH2 domain binding Source: CAFA
  • clathrin binding Source: CAFA
  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • GTP-dependent protein binding Source: Ensembl
  • lipid binding Source: UniProtKB-KW
  • microtubule binding Source: GO_Central
  • protein-containing complex binding Source: RGD
  • protein homodimerization activity Source: UniProtKB
  • Rab GTPase binding Source: Ensembl
  • ubiquitin protein ligase binding Source: Ensembl

GO - Biological processi

  • cellular response to lipid Source: RGD
  • cellular response to oxygen-glucose deprivation Source: RGD
  • cellular response to thapsigargin Source: RGD
  • dynamin family protein polymerization involved in mitochondrial fission Source: UniProtKB
  • endocytosis Source: UniProtKB-KW
  • intracellular distribution of mitochondria Source: RGD
  • membrane fusion Source: Ensembl
  • mitochondrial fission Source: UniProtKB
  • mitochondrial fragmentation involved in apoptotic process Source: RGD
  • mitochondrial membrane fission Source: Ensembl
  • mitochondrion morphogenesis Source: RGD
  • necroptotic process Source: UniProtKB
  • negative regulation of mitochondrial fusion Source: CAFA
  • peroxisome fission Source: UniProtKB
  • positive regulation of dendritic spine morphogenesis Source: RGD
  • positive regulation of intrinsic apoptotic signaling pathway Source: Ensembl
  • positive regulation of mitochondrial fission Source: RGD
  • positive regulation of protein secretion Source: Ensembl
  • positive regulation of release of cytochrome c from mitochondria Source: Ensembl
  • positive regulation of synaptic vesicle endocytosis Source: CAFA
  • positive regulation of synaptic vesicle exocytosis Source: CAFA
  • protein complex oligomerization Source: UniProtKB
  • protein homooligomerization Source: RGD
  • protein homotetramerization Source: Ensembl
  • regulation of autophagy of mitochondrion Source: Ensembl
  • regulation of peroxisome organization Source: Ensembl
  • regulation of protein oligomerization Source: Ensembl
  • release of cytochrome c from mitochondria Source: Ensembl
  • response to flavonoid Source: RGD
  • response to hypobaric hypoxia Source: RGD
  • synaptic vesicle recycling via endosome Source: CAFA

Keywordsi

Molecular functionHydrolase
Biological processEndocytosis, Necrosis
LigandGTP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-75153 Apoptotic execution phase

Names & Taxonomyi

Protein namesi
Recommended name:
Dynamin-1-like protein (EC:3.6.5.5)
Alternative name(s):
Dynamin-like protein
Gene namesi
Name:Dnm1l
Synonyms:Dlp1, Drp1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 11

Organism-specific databases

RGDi620416 Dnm1l

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Coated pit, Cytoplasm, Cytoplasmic vesicle, Golgi apparatus, Membrane, Mitochondrion, Mitochondrion outer membrane, Peroxisome, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38K → A: Defective in GTP hydrolysis. Tubulates spherical liposomes. Impairs mitochondrial division. Decreases the BCL2L1-mediated induction of synapse number and size of synaptic vesicle clusters. 2 Publications1
Mutagenesisi71S → A: No effect on mitotic phosphorylation. 1 Publication1
Mutagenesisi139S → A: No effect on mitotic phosphorylation. 1 Publication1
Mutagenesisi149S → A: No effect on mitotic phosphorylation. 1 Publication1
Mutagenesisi231D → N: Defective in GTP-binding. 1 Publication1
Mutagenesisi635S → A: Abolishes mitotic phosphorylation. Reduced mitotic mitochondrial fragmentation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002065681 – 755Dynamin-1-like proteinAdd BLAST755

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei542PhosphoserineBy similarity1
Cross-linki545Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki548Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei561PhosphoserineBy similarity1
Cross-linki571Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki581Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Glycosylationi604O-linked (GlcNAc) threonine1 Publication1
Glycosylationi605O-linked (GlcNAc) threonine1 Publication1
Cross-linki613Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei616N6-acetyllysine; alternateBy similarity1
Cross-linki616Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki625Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei626PhosphoserineBy similarity1
Cross-linki627Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei635Phosphoserine; by CDK1Combined sources1 Publication1
Modified residuei656Phosphoserine; by CAMK1 and PKA1 Publication1
Modified residuei663S-nitrosocysteineBy similarity1

Post-translational modificationi

Phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission. Phosphorylation on Ser-656 inhibits mitochondrial fission probably through preventing intramolecular interaction. Dephosphorylated on this site by PPP3CA which promotes mitochondrial fission. Phosphorylation on Ser-635 also promotes mitochondrial fission (By similarity).By similarity
Sumoylated on various lysine residues within the B domain, probably by MUL1. Sumoylation positively regulates mitochondrial fission. Desumoylated by SENP5 during G2/M transition of mitosis. Appears to be linked to its catalytic activity (By similarity).By similarity
S-nitrosylation increases DNM1L dimerization, mitochondrial fission and causes neuronal damage.By similarity
Ubiquitinated by MARCH5.By similarity
O-GlcNAcylation augments the level of the GTP-bound active form of DRP1 and induces translocation from the cytoplasm to mitochondria in cardiomyocytes. It also decreases phosphorylation at Ser-656.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiO35303
PeptideAtlasiO35303
PRIDEiO35303

PTM databases

iPTMnetiO35303
PhosphoSitePlusiO35303
SwissPalmiO35303

Expressioni

Tissue specificityi

Expressed in all tissues tested (at protein level). Longer isoforms are preferentially expressed in brain.2 Publications

Inductioni

By bezafibrate.1 Publication

Gene expression databases

BgeeiENSRNOG00000001813
GenevisibleiO35303 RN

Interactioni

Subunit structurei

Homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule. Oligomerizes in a GTP-dependent manner to form membrane-associated tubules with a spiral pattern. Can also oligomerize to form multimeric ring-like structures. Interacts with GSK3B and MARCH5. Interacts (via the GTPase and B domains) with UBE2I; the interaction promotes sumoylation of DNM1L, mainly in its B domain. Interacts with PPP3CA; the interaction dephosphorylates DNM1L and regulates its transition to mitochondria. Interacts with BCL2L1 isoform BCL-X(L) and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF. Interacts with FIS1. Interacts with MIEF2 and MIEF1; this regulates GTP hydrolysis and DNM1L oligomerization. Interacts with PGAM5; this interaction leads to dephosphorylation at Ser-656 and activation of GTPase activity and eventually to mitochondria fragmentation.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Bcl2l1P53563-14EBI-1767447,EBI-287204

GO - Molecular functioni

  • BH2 domain binding Source: CAFA
  • clathrin binding Source: CAFA
  • GTP-dependent protein binding Source: Ensembl
  • microtubule binding Source: GO_Central
  • protein homodimerization activity Source: UniProtKB
  • Rab GTPase binding Source: Ensembl
  • ubiquitin protein ligase binding Source: Ensembl

Protein-protein interaction databases

BioGridi250292, 3 interactors
CORUMiO35303
DIPiDIP-29699N
ELMiO35303
IntActiO35303, 5 interactors
MINTiO35303
STRINGi10116.ENSRNOP00000002478

Structurei

3D structure databases

ProteinModelPortaliO35303
SMRiO35303
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 315Dynamin-type GPROSITE-ProRule annotationAdd BLAST294
Domaini663 – 754GEDPROSITE-ProRule annotationAdd BLAST92

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 356N-terminal dimerization domainBy similarityAdd BLAST356
Regioni32 – 39G1 motifPROSITE-ProRule annotation8
Regioni58 – 60G2 motifPROSITE-ProRule annotation3
Regioni159 – 162G3 motifPROSITE-ProRule annotation4
Regioni228 – 231G4 motifPROSITE-ProRule annotation4
Regioni258 – 261G5 motifPROSITE-ProRule annotation4
Regioni357 – 502Middle domainBy similarityAdd BLAST146
Regioni461 – 704Interaction with GSK3BBy similarityAdd BLAST244
Regioni461 – 667Interaction with GSK3BBy similarityAdd BLAST207
Regioni515 – 582B domainBy similarityAdd BLAST68
Regioni555 – 755C-terminal dimerization domainBy similarityAdd BLAST201
Regioni673 – 687Important for homodimerizationBy similarityAdd BLAST15

Domaini

The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization.By similarity

Sequence similaritiesi

Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0446 Eukaryota
COG0699 LUCA
GeneTreeiENSGT00760000119213
HOVERGENiHBG107833
InParanoidiO35303
KOiK17065
OMAiHHIPNRR
OrthoDBiEOG091G02TQ
PhylomeDBiO35303
TreeFamiTF352031

Family and domain databases

CDDicd08771 DLP_1, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR030556 DNM1L
IPR000375 Dynamin_central
IPR001401 Dynamin_GTPase
IPR019762 Dynamin_GTPase_CS
IPR022812 Dynamin_SF
IPR030381 G_DYNAMIN_dom
IPR003130 GED
IPR020850 GED_dom
IPR027417 P-loop_NTPase
IPR011993 PH-like_dom_sf
PANTHERiPTHR11566 PTHR11566, 1 hit
PTHR11566:SF39 PTHR11566:SF39, 1 hit
PfamiView protein in Pfam
PF01031 Dynamin_M, 1 hit
PF00350 Dynamin_N, 1 hit
PF02212 GED, 1 hit
PRINTSiPR00195 DYNAMIN
SMARTiView protein in SMART
SM00053 DYNc, 1 hit
SM00302 GED, 1 hit
SUPFAMiSSF52540 SSF52540, 2 hits
PROSITEiView protein in PROSITE
PS00410 G_DYNAMIN_1, 1 hit
PS51718 G_DYNAMIN_2, 1 hit
PS51388 GED, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35303-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL
60 70 80 90 100
LPRGTGVVTR RPLILQLVHV SPEDKRKTTG EENDPATWKN SRHLSKGVEA
110 120 130 140 150
EEWGKFLHTK NKLYTDFDEI RQEIENETER ISGNNKGVSP EPIHLKVFSP
160 170 180 190 200
NVVNLTLVDL PGMTKVPVGD QPKDIELQIR ELILRFISNP NSIILAVTAA
210 220 230 240 250
NTDMATSEAL KISREVDPDG RRTLAVITKL DLMDAGTDAM DVLMGRVIPV
260 270 280 290 300
KLGIIGVVNR SQLDINNKKS VTDSIRDEYA FLQKKYPSLA NRNGTKYLAR
310 320 330 340 350
TLNRLLMHHI RDCLPELKTR INVLAAQYQS LLNSYGEPVD DKSATLLQLI
360 370 380 390 400
TKFATEYCNT IEGTAKYIET SELCGGARIC YIFHETFGRT LESVDPLGGL
410 420 430 440 450
NTIDILTAIR NATGPRPALF VPEVSFELLV KRQIKRLEEP SLRCVELVHE
460 470 480 490 500
EMQRIIQHCS NYSTQELLRF PKLHDAIVEV VTCLLRKRLP VTNEMVHNLV
510 520 530 540 550
AIELAYINTK HPDFADACGL MNNNIEEQRR NRLARELPSA VSRDKSSKVP
560 570 580 590 600
SALAPASQEP SPAASAEADG KLIQDNRRET KNVASAGGGI GDGGRIGDGG
610 620 630 640 650
QEPTTGNWRG MLKTSKAEEL LAEEKSKPIP IMPASPQKGH AVNLLDVPVP
660 670 680 690 700
VARKLSAREQ RDCEVIERLI KSYFLIVRKN IQDSVPKAVM HFLVNHVKDT
710 720 730 740 750
LQSELVGQLY KSSLLDDLLT ESEDMAQRRK EAADMLKALQ GASQIIAEIR

ETHLW
Length:755
Mass (Da):83,908
Last modified:January 1, 1998 - v1
Checksum:i0568353907794C43
GO
Isoform 2 (identifier: O35303-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     84-96: Missing.
     546-571: Missing.

Show »
Length:716
Mass (Da):79,951
Checksum:iE7A629A401FA7004
GO
Isoform 3 (identifier: O35303-3) [UniParc]FASTAAdd to basket
Also known as: DLP1-37

The sequence of this isoform differs from the canonical sequence as follows:
     84-84: D → GKFQSWN
     546-596: SSKVPSALAPASQEPSPAASAEADGKLIQDNRRETKNVASAGGGIGDGGRI → VASGGGGV

Show »
Length:718
Mass (Da):80,253
Checksum:iBC6D99B05A12B398
GO
Isoform 4 (identifier: O35303-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     84-97: DPATWKNSRHLSKG → GKFQSWR

Note: No experimental confirmation available.
Show »
Length:748
Mass (Da):83,220
Checksum:iFFF210166CD3398E
GO
Isoform 5 (identifier: O35303-5) [UniParc]FASTAAdd to basket
Also known as: DLP1-11

The sequence of this isoform differs from the canonical sequence as follows:
     572-582: Missing.

Show »
Length:744
Mass (Da):82,540
Checksum:i5C1E562180C58035
GO
Isoform 6 (identifier: O35303-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     546-582: Missing.

Note: No experimental confirmation available.
Show »
Length:718
Mass (Da):80,104
Checksum:i459857BD43835FE5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti517A → V in AAB71237 (PubMed:9472031).Curated1
Sequence conflicti600G → V in AAD31278 (PubMed:10679301).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01369684 – 97DPATW…HLSKG → GKFQSWR in isoform 4. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_01369784 – 96Missing in isoform 2. 2 PublicationsAdd BLAST13
Alternative sequenceiVSP_01369884D → GKFQSWN in isoform 3. 2 Publications1
Alternative sequenceiVSP_013699546 – 596SSKVP…DGGRI → VASGGGGV in isoform 3. 2 PublicationsAdd BLAST51
Alternative sequenceiVSP_013700546 – 582Missing in isoform 6. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_013701546 – 571Missing in isoform 2. 2 PublicationsAdd BLAST26
Alternative sequenceiVSP_013702572 – 582Missing in isoform 5. 2 PublicationsAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019043 mRNA Translation: AAB72197.1
AF020207 mRNA Translation: AAB71232.1
AF020208 mRNA Translation: AAB71233.1
AF020209 mRNA Translation: AAB71234.1
AF020210 mRNA Translation: AAB71235.1
AF020211 mRNA Translation: AAB71236.1
AF020212 mRNA Translation: AAB71237.1
AF020213 mRNA Translation: AAB71238.1
AF107048 mRNA Translation: AAD22412.1
AF132727 mRNA Translation: AAD31278.1
BC085843 mRNA Translation: AAH85843.1
RefSeqiNP_446107.2, NM_053655.3 [O35303-2]
XP_006248785.1, XM_006248723.3 [O35303-6]
XP_008767063.1, XM_008768841.2 [O35303-1]
XP_008767064.1, XM_008768842.2 [O35303-4]
XP_008767065.1, XM_008768843.2 [O35303-5]
UniGeneiRn.216851

Genome annotation databases

EnsembliENSRNOT00000002477; ENSRNOP00000002477; ENSRNOG00000001813 [O35303-2]
ENSRNOT00000002478; ENSRNOP00000002478; ENSRNOG00000001813 [O35303-1]
ENSRNOT00000002482; ENSRNOP00000002482; ENSRNOG00000001813 [O35303-6]
GeneIDi114114
KEGGirno:114114

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDNM1L_RAT
AccessioniPrimary (citable) accession number: O35303
Secondary accession number(s): O35318
, O35319, O35320, O35321, O35322, O35323, Q5U2W1, Q792T7, Q9R234, Q9R277
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: January 1, 1998
Last modified: June 20, 2018
This is version 146 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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