O00429

PTMD Annotation Information

※ Protein Information

Tag	Content
UniProt Accession	DNM1L_HUMAN; O00429;
Entrez ID	10059
GenBank Protein ID	NM_001278463.1; NM_001278464.1; NM_001278465.1; NM_001278466.1; NM_001330380.1; NM_005690.4; NM_012062.4; NM_012063.3;
GenBank Nucleotide ID	NP_001265392.1; NP_001265393.1; NP_001265394.1; NP_001265395.1; NP_001317309.1; NP_005681.2; NP_036192.2; NP_036193.2;
Protein Name	Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1
Gene Name	DNM1L; DLP1; DRP1
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	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 (view all) Functional Description 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 (PubMed:26992161). 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.;Isoform 1: Inhibits peroxisomal division when overexpressed.;Isoform 4: Inhibits peroxisomal division when overexpressed.
Sequence (Fasta)	MEALIPVINK LQDVFNTVGA DIIQLPQIVV VGTQSSGKSS VLESLVGRDL LPRGTGIVTR 60 RPLILQLVHV SQEDKRKTTG EENGVEAEEW GKFLHTKNKL YTDFDEIRQE IENETERISG 120 NNKGVSPEPI HLKIFSPNVV NLTLVDLPGM TKVPVGDQPK DIELQIRELI LRFISNPNSI 180 ILAVTAANTD MATSEALKIS REVDPDGRRT LAVITKLDLM DAGTDAMDVL MGRVIPVKLG 240 IIGVVNRSQL DINNKKSVTD SIRDEYAFLQ KKYPSLANRN GTKYLARTLN RLLMHHIRDC 300 LPELKTRINV LAAQYQSLLN SYGEPVDDKS ATLLQLITKF ATEYCNTIEG TAKYIETSEL 360 CGGARICYIF HETFGRTLES VDPLGGLNTI DILTAIRNAT GPRPALFVPE VSFELLVKRQ 420 IKRLEEPSLR CVELVHEEMQ RIIQHCSNYS TQELLRFPKL HDAIVEVVTC LLRKRLPVTN 480 EMVHNLVAIE LAYINTKHPD FADACGLMNN NIEEQRRNRL ARELPSAVSR DKSSKVPSAL 540 APASQEPSPA ASAEADGKLI QDSRRETKNV ASGGGGVGDG VQEPTTGNWR GMLKTSKAEE 600 LLAEEKSKPI PIMPASPQKG HAVNLLDVPV PVARKLSARE QRDCEVIERL IKSYFLIVRK 660 NIQDSVPKAV MHFLVNHVKD TLQSELVGQL YKSSLLDDLL TESEDMAQRR KEAADMLKAL 720 QGASQIIAEI RETHLW 737 Fasta Sequence >O00429\|DNM1L; DLP1; DRP1\|Homo sapiens (Human) MEALIPVINKLQDVFNTVGADIIQLPQIVVVGTQSSGKSSVLESLVGRDLLPRGTGIVTRRPLILQLVHVSQEDKRKTTGEENGVEAEEWGKFLHTKNKLYTDFDEIRQEIENETERISGNNKGVSPEPIHLKIFSPNVVNLTLVDLPGMTKVPVGDQPKDIELQIRELILRFISNPNSIILAVTAANTDMATSEALKISREVDPDGRRTLAVITKLDLMDAGTDAMDVLMGRVIPVKLGIIGVVNRSQLDINNKKSVTDSIRDEYAFLQKKYPSLANRNGTKYLARTLNRLLMHHIRDCLPELKTRINVLAAQYQSLLNSYGEPVDDKSATLLQLITKFATEYCNTIEGTAKYIETSELCGGARICYIFHETFGRTLESVDPLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKRLEEPSLRCVELVHEEMQRIIQHCSNYSTQELLRFPKLHDAIVEVVTCLLRKRLPVTNEMVHNLVAIELAYINTKHPDFADACGLMNNNIEEQRRNRLARELPSAVSRDKSSKVPSALAPASQEPSPAASAEADGKLIQDSRRETKNVASGGGGVGDGVQEPTTGNWRGMLKTSKAEELLAEEKSKPIPIMPASPQKGHAVNLLDVPVPVARKLSAREQRDCEVIERLIKSYFLIVRKNIQDSVPKAVMHFLVNHVKDTLQSELVGQLYKSSLLDDLLTESEDMAQRRKEAADMLKALQGASQIIAEIRETHLW

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Serine Phosphorylation	Alzheimer's disease	cell line	P	S40	25192600
1	[Reference]: We identified glycogen synthase kinase (GSK)3?-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation. Moreover, neurons transfected with Ser(40)Ser(44) phosphomimic Drp1 showed increased mitochondria fragmentation and were more vulnerable to amyloid-? (A?)-induced apoptosis.?
2	Serine Phosphorylation	Alzheimer's disease		P	S44	25192600
2	[Reference]: Moreover, neurons transfected with Ser(40)Ser(44) phosphomimic Drp1 showed increased mitochondria fragmentation and were more vulnerable to amyloid-? (A?)-induced apoptosis.
3	Serine Phosphorylation	Pancreatic cancer/carcinoma/adenocarcinoma		U	S616	25658205
3	[Reference]: human pancreatic ductal adenocarcinoma
4	Serine Phosphorylation	Heart failure		U	S616	27739424
4	[Reference]: In human failing hearts, Drp1 phosphorylation at S616 is increased. These results uncover a pathway downstream of chronic ?-AR stimulation that links CaMKII, Drp1 and mPTP to bridge cytosolic stress signal with mitochondrial dysfunction in the heart.

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 7) (view all)	MESH:D000140 ; Acidosis, Lactic OMIM:614388 ; ENCEPHALOPATHY DUE TO DEFECTIVE MITOCHONDRIAL AND PEROXISOMAL FISSION 1 MESH:D008831 ; Microcephaly MESH:D017237 ; Mitochondrial Encephalomyopathies MESH:D017202 ; Myocardial Ischemia MESH:D009896 ; Optic Atrophy MESH:C537126 ; Optic atrophy 5
DisGeNet (Curated) (count: 23) (view all)	C0001125; Acidosis, Lactic C0014306; Enophthalmos C0025958; Microcephaly C0026827; Muscle hypotonia C0029124; Optic Atrophy C0085584; Encephalopathies C0151744; Myocardial Ischemia C0162666; Mitochondrial Encephalomyopathies C0231246; Failure to gain weight C0232466; Feeding difficulties C0234146; Absent reflex C0235659; Reduced fetal movement C0241772; Reflex, Deep Tendon, Absent C0271385; Horizontal Nystagmus C0278124; Absent tendon reflex C0347959; Lactic acidemia C0423224; Sunken eyes C0424688; Small head C1844505; Pointed chin C1844947; Death in early childhood C1858430; Death in infancy C2315100; Pediatric failure to thrive C3280660; ENCEPHALOPATHY, LETHAL, DUE TO DEFECTIVE MITOCHONDRIAL AND PEROXISOMAL FISSION
GWASdb (count: 6)	rs7954206; Amyotrophic lateral sclerosis; amyotrophic lateral sclerosis rs11052187; Alzheimer's disease; Alzheimer's disease rs10771984; Amyotrophic lateral sclerosis; amyotrophic lateral sclerosis rs10844309; Amyotrophic lateral sclerosis; amyotrophic lateral sclerosis rs2293341; Alzheimer's disease (late onset); Alzheimer's disease rs3600; Bipolar disorder and schizophrenia; bipolar disorder\|schizophrenia

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 25) (view all)	126 SGNNKGVSPEPIHLK dbPAF 179 RFISNPNSIILAVTA dbPAF 193 AANTDMATSEALKIS dbPAF 194 ANTDMATSEALKISR dbPAF 330 GEPVDDKSATLLQLI dbPAF 394 LNTIDILTAIRNATG dbPAF 40 TQSSGKSSVLESLVG dbPAF 400 LTAIRNATGPRPALF dbPAF 412 ALFVPEVSFELLVKR dbPAF 44 GKSSVLESLVGRDLL dbPAF 529 RELPSAVSRDKSSKV dbPAF 544 PSALAPASQEPSPAA dbPAF 548 APASQEPSPAASAEA dbPAF 552 QEPSPAASAEADGKL dbPAF 572 RETKNVASGGGGVGD dbPAF 586 DGVQEPTTGNWRGML dbPAF 595 NWRGMLKTSKAEELL dbPAF 607 ELLAEEKSKPIPIMP dbPAF 616 PIPIMPASPQKGHAV dbPAF 637 VPVARKLSAREQRDC dbPAF 684 HVKDTLQSELVGQLY dbPAF 693 LVGQLYKSSLLDDLL dbPAF 724 LKALQGASQIIAEIR dbPAF 78 SQEDKRKTTGEENGV dbPAF 79 QEDKRKTTGEENGVE dbPAF
Acetylation (count: 3)	271 DEYAFLQKKYPSLAN PLMD 283 LANRNGTKYLARTLN PLMD 92 VEAEEWGKFLHTKNK PLMD
Ubiquitination (count: 9) (view all)	133 SPEPIHLKIFSPNVV PLMD 160 VPVGDQPKDIELQIR PLMD 198 MATSEALKISREVDP PLMD 238 MGRVIPVKLGIIGVV PLMD 305 RDCLPELKTRINVLA PLMD 418 VSFELLVKRQIKRLE PLMD 532 PSAVSRDKSSKVPSA PLMD 535 VSRDKSSKVPSALAP PLMD 718 KEAADMLKALQGASQ PLMD
Sumoylation (count: 9) (view all)	38 VGTQSSGKSSVLESL PLMD 532 PSAVSRDKSSKVPSA PLMD 535 VSRDKSSKVPSALAP PLMD 558 ASAEADGKLIQDSRR PLMD 568 QDSRRETKNVASGGG PLMD 594 GNWRGMLKTSKAEEL PLMD 597 RGMLKTSKAEELLAE PLMD 606 EELLAEEKSKPIPIM PLMD 608 LLAEEKSKPIPIMPA PLMD

※ Protein-Protein Interaction

Network

Interaction

A

B

Source

O00429	P03372	IntAct
O00429	P43355	DIP