DNM1L_BOVIN
ID DNM1L_BOVIN Reviewed; 749 AA.
AC Q2KIA5;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Dynamin-1-like protein;
DE EC=3.6.5.5;
GN Name=DNM1L;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Functions in mitochondrial and peroxisomal division. Mediates
CC membrane fission through oligomerization into membrane-associated
CC tubular structures that wrap around the scission site to constrict and
CC sever the mitochondrial membrane through a GTP hydrolysis-dependent
CC mechanism. The specific recruitment at scission sites is mediated by
CC membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial
CC membranes. While the recruitment by the membrane receptors is GTP-
CC 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. Acts
CC downstream of PINK1 to promote mitochondrial fission in a PRKN-
CC dependent manner. Plays an important role in mitochondrial fission
CC during mitosis (By similarity). Through its function in mitochondrial
CC division, ensures the survival of at least some types of postmitotic
CC neurons, including Purkinje cells, by suppressing oxidative damage (By
CC similarity). Required for normal brain development, including that of
CC cerebellum (By similarity). Facilitates developmentally regulated
CC apoptosis during neural tube formation. Required for a normal rate of
CC cytochrome c release and caspase activation during apoptosis; this
CC requirement may depend upon the cell type and the physiological
CC apoptotic cues (By similarity). Required for formation of endocytic
CC vesicles. Proposed to regulate synaptic vesicle membrane dynamics
CC through association with BCL2L1 isoform Bcl-X(L) which stimulates its
CC GTPase activity in synaptic vesicles; the function may require its
CC recruitment by MFF to clathrin-containing vesicles. Required for
CC programmed necrosis execution. Rhythmic control of its activity
CC following phosphorylation at Ser-650 is essential for the circadian
CC control of mitochondrial ATP production (By similarity).
CC {ECO:0000250|UniProtKB:O00429, ECO:0000250|UniProtKB:Q8K1M6}.
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 -!- 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 (By
CC similarity). {ECO:0000250|UniProtKB:O00429,
CC ECO:0000250|UniProtKB:Q8K1M6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8K1M6}. Golgi apparatus {ECO:0000250}.
CC Endomembrane system {ECO:0000250|UniProtKB:Q8K1M6}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q8K1M6}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q8K1M6}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8K1M6}. Peroxisome
CC {ECO:0000250|UniProtKB:O35303}. Membrane, clathrin-coated pit
CC {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000250|UniProtKB:O35303}. Note=Mainly cytosolic.
CC Recruited by RALA and RALBP1 to mitochondrion during mitosis (By
CC similarity). Translocated to the mitochondrial membrane through O-
CC GlcNAcylation and interaction with FIS1. Colocalized with MARCHF5 at
CC mitochondrial membrane. Localizes to mitochondria at sites of division.
CC Localizes to mitochondria following necrosis induction. Recruited to
CC the mitochondrial outer membrane by interaction with MIEF1.
CC Mitochondrial recruitment is inhibited by C11orf65/MFI (By similarity).
CC Associated with peroxisomal membranes, partly recruited there by
CC PEX11B. May also be associated with endoplasmic reticulum tubules and
CC cytoplasmic vesicles and found to be perinuclear. In some cell types,
CC localizes to the Golgi complex (By similarity). Binds to phospholipid
CC membranes (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O00429,
CC ECO:0000250|UniProtKB:Q8K1M6}.
CC -!- DOMAIN: The GED domain folds back to interact, in cis, with the GTP-
CC binding domain and middle domain, and interacts, in trans, with the GED
CC domains of other DNM1L molecules, and is thus critical for activating
CC GTPase activity and for DNM1L dimerization.
CC {ECO:0000250|UniProtKB:O00429}.
CC -!- PTM: Phosphorylation/dephosphorylation events on two sites near the GED
CC domain regulate mitochondrial fission. Phosphorylation on Ser-650 by
CC CAMK1 and PKA inhibits the GTPase activity, leading to a defect in
CC mitochondrial fission promoting mitochondrial elongation.
CC Dephosphorylated on this site by PPP3CA which promotes mitochondrial
CC fission. Phosphorylation on Ser-629 by CDK1 and PINK1 activates the
CC GTPase activity and promotes mitochondrial fission. Phosphorylated in a
CC circadian manner at Ser-650. {ECO:0000250|UniProtKB:O00429}.
CC -!- PTM: Sumoylated on various lysine residues within the B domain,
CC probably by MUL1. Sumoylation positively regulates mitochondrial
CC fission. Desumoylated by SENP5 during G2/M transition of mitosis.
CC Appears to be linked to its catalytic activity (By similarity).
CC {ECO:0000250}.
CC -!- PTM: S-nitrosylation increases DNM1L dimerization, mitochondrial
CC fission and causes neuronal damage. {ECO:0000250}.
CC -!- PTM: O-GlcNAcylation augments the level of the GTP-bound active form of
CC DNM1L and induces translocation from the cytoplasm to mitochondria in
CC cardiomyocytes. It also decreases phosphorylation at Ser-650 (By
CC similarity). {ECO:0000250|UniProtKB:O35303}.
CC -!- PTM: Ubiquitination by MARCHF5 affects mitochondrial morphology.
CC {ECO:0000250|UniProtKB:O00429}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE-
CC ProRule:PRU01055}.
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DR EMBL; BC112710; AAI12711.1; -; mRNA.
DR RefSeq; NP_001039959.1; NM_001046494.2.
DR AlphaFoldDB; Q2KIA5; -.
DR SMR; Q2KIA5; -.
DR STRING; 9913.ENSBTAP00000037777; -.
DR PaxDb; Q2KIA5; -.
DR PeptideAtlas; Q2KIA5; -.
DR PRIDE; Q2KIA5; -.
DR Ensembl; ENSBTAT00000037956; ENSBTAP00000037777; ENSBTAG00000011395.
DR GeneID; 540892; -.
DR KEGG; bta:540892; -.
DR CTD; 10059; -.
DR VEuPathDB; HostDB:ENSBTAG00000011395; -.
DR VGNC; VGNC:28142; DNM1L.
DR eggNOG; KOG0446; Eukaryota.
DR GeneTree; ENSGT00940000155504; -.
DR HOGENOM; CLU_008964_5_0_1; -.
DR InParanoid; Q2KIA5; -.
DR OMA; IMATQFQ; -.
DR OrthoDB; 264244at2759; -.
DR TreeFam; TF352031; -.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000011395; Expressed in occipital lobe and 105 other tissues.
DR ExpressionAtlas; Q2KIA5; baseline and differential.
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; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:ParkinsonsUK-UCL.
DR GO; GO:0099073; C:mitochondrion-derived vesicle; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:ParkinsonsUK-UCL.
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; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0003374; P:dynamin family protein polymerization involved in mitochondrial fission; ISS: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; IEA:Ensembl.
DR GO; GO:0061025; P:membrane fusion; IEA:Ensembl.
DR GO; GO:0000266; P:mitochondrial fission; ISS:UniProtKB.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0090149; P:mitochondrial membrane fission; IEA:Ensembl.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IEA:Ensembl.
DR GO; GO:0070266; P:necroptotic process; ISS:UniProtKB.
DR GO; GO:0016559; P:peroxisome fission; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IEA:Ensembl.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IEA:Ensembl.
DR GO; GO:0050714; P:positive regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; IEA:Ensembl.
DR GO; GO:1903578; P:regulation of ATP metabolic process; IEA:Ensembl.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:1900063; P:regulation of peroxisome organization; IEA:Ensembl.
DR GO; GO:1904666; P:regulation of ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR CDD; cd08771; DLP_1; 1.
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 2: Evidence at transcript level;
KW Acetylation; Biological rhythms; Coated pit; Cytoplasm;
KW Cytoplasmic vesicle; Endocytosis; Glycoprotein; Golgi apparatus;
KW GTP-binding; Hydrolase; Isopeptide bond; Lipid-binding; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Necrosis; Nucleotide-binding;
KW Peroxisome; Phosphoprotein; Reference proteome; S-nitrosylation; Synapse;
KW Ubl conjugation.
FT CHAIN 1..749
FT /note="Dynamin-1-like protein"
FT /id="PRO_0000284972"
FT DOMAIN 22..315
FT /note="Dynamin-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT DOMAIN 657..748
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 74..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 159..162
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 228..231
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 258..261
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055"
FT REGION 357..502
FT /note="Middle domain"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT REGION 461..698
FT /note="Interaction with GSK3B"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT REGION 515..582
FT /note="B domain"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT REGION 536..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 667..681
FT /note="Important for homodimerization"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT BINDING 32..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT BINDING 228..234
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT BINDING 259..262
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 542
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 561
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 610
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8K1M6"
FT MOD_RES 620
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 629
FT /note="Phosphoserine; by CDK1 and PINK1"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 650
FT /note="Phosphoserine; by CAMK1 and PKA"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT MOD_RES 657
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:O00429"
FT CARBOHYD 598
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 599
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT CROSSLNK 545
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 548
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 571
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 581
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 607
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 610
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 619
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 621
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 749 AA; 83352 MW; BA90863E8BC8265B CRC64;
MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL LPRGTGIVTR
RPLILQLVHV APEDKRKTTG EENDPATWKN SRHLSKGVEA EEWGKFLHTK NKLYTDFDEI
RQEIENETER ISGNNKGVSP EPIHLKIFSP NVVNLTLVDL PGMTKVPVGD QPKDIELQIR
ELILRFISNP NSIILAVTAA NTDMATSEAL KISREVDPDG RRTLAVITKL DLMDAGTDAM
DVLMGRVIPV KLGIIGVVNR SQLDINNKKS VTDSIRDEYA FLQKKYPSLA NRNGTKYLAR
TLNRLLMHHI RDCLPELKTR INVLAAQYQS LLNSYGEPVD DKSATLLQLI TKFATEYCNT
IEGTAKYIET SELCGGARIC YIFHETFGRT LESVDPLGGL NTIDILTAIR NATGPRPALF
VPEVSFELLV KRQIKRLEEP SLRCVELVHE EMQRIIQHCS NYSTQELLRF PKLHDAIVEV
VTCLLRKRLP VTNEMVHNLV AIELAYINTK HPDFADACGL MNNNIEEQRR NRLARELPSA
VSRDKSSKVP SALAPASQEP SPAASAEADG KLIQESRRET KNAASGGGGV GDAVQEPTTG
NWRGMLKTSK AEELLAEEKS KPIPIMPASP QKGHAVNLLD VPVPVARKLS AREQRDCEVI
ERLIKSYFLI VRKNIQDSVP KAVMHFLVNH VKDTLQSELV GQLYKSSLLD DLLTESEDMA
QRRKEAADML KALQGASQII AEIRETHLW
