DNM1

DNM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DYN, 2DYN, 2X2E, 2X2F, 3SNH, 3ZYC, 3ZYS, 4UUD, 4UUK, 5D3Q
Identifiers
Aliases	DNM1, Dynamin-1, DNM, EIEE31, dynamin 1, DEE31
External IDs	OMIM: 602377; MGI: 107384; HomoloGene: 123905; GeneCards: DNM1; OMA:DNM1 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.11 Start 128,191,655 bp[1] End 128,255,248 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 B|2 22.09 cM Start 32,198,483 bp[2] End 32,243,350 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum Brodmann area 10 middle temporal gyrus superior frontal gyrus right frontal lobe frontal pole paraflocculus of cerebellum Parietal Lobe Brodmann area 46 postcentral gyrus Top expressed in CA3 field entorhinal cortex perirhinal cortex dentate gyrus of hippocampal formation granule cell superior frontal gyrus cingulate gyrus cerebellar cortex central gray substance of midbrain pontine nuclei prefrontal cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein dimerization activity GTP binding protein binding hydrolase activity protein kinase binding microtubule binding RNA binding GTPase activity protein C-terminus binding D2 dopamine receptor binding protein-containing complex binding nitric-oxide synthase binding identical protein binding SH3 domain binding Cellular component cytoplasm photoreceptor inner segment myelin sheath synapse membrane coat microtubule cytoskeleton extracellular exosome mitochondrial membranes Golgi apparatus plasma membrane synaptic vesicle varicosity nucleus nucleoplasm postsynaptic density membrane axon cytoplasmic vesicle protein-containing complex dendritic spine dendritic spine head postsynaptic membrane photoreceptor ribbon synapse presynaptic endocytic zone membrane postsynaptic endocytic zone membrane glutamatergic synapse Biological process endocytosis ephrin receptor signaling pathway adult locomotory behavior synaptic transmission, GABAergic toxin transport hearing protein tetramerization endosome organization clathrin-dependent endocytosis mitochondrial fission dynamin family protein polymerization involved in mitochondrial fission membrane fusion synaptic vesicle budding from presynaptic endocytic zone membrane G protein-coupled receptor internalization receptor-mediated endocytosis receptor internalization positive regulation of synaptic vesicle recycling synaptic vesicle endocytosis regulation of synapse structure or activity modulation of chemical synaptic transmission postsynaptic neurotransmitter receptor internalization regulation of synaptic vesicle endocytosis positive regulation of synaptic vesicle endocytosis response to amyloid-beta Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1759 13429 Ensembl ENSG00000106976 ENSMUSG00000026825 UniProt Q05193 P39053 RefSeq (mRNA) NM_001005336 NM_001288737 NM_001288738 NM_001288739 NM_004408 NM_001374269 NM_001301737 NM_010065 NM_001368679 RefSeq (protein) NP_001005336 NP_001275666 NP_001275667 NP_001275668 NP_004399 NP_001361198 NP_001288666 NP_034195 NP_001355608 Location (UCSC) Chr 9: 128.19 – 128.26 Mb Chr 2: 32.2 – 32.24 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dynamin-1 is a protein that in humans is encoded by the DNM1 gene.[5][6]

Function

Dynamin possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the dynamin, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described.[7]

Role in disease

De novo mutations in DNM1 have been associated with a severe form of childhood epilepsy called developmental and epileptic encephalopathy. Most pathogenic variants are missense variants, and have been shown to impair synaptic vesicle endocytosis in a dominant negative manner.[8]

Interactions

DNM1 has been shown to interact with:

• AMPH,[9][10][11][12][13]
• FNBP1,[14]
• Grb2[15][16]
• NCK1,[17]
• PACSIN1,[14][18] and
• SH3GL2.[9][19]

References

1. GRCh38: Ensembl release 89: ENSG00000106976 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026825 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Obar RA, Collins CA, Hammarback JA, Shpetner HS, Vallee RB (October 1990). "Molecular cloning of the microtubule-associated mechanochemical enzyme dynamin reveals homology with a new family of GTP-binding proteins". Nature. 347 (6290): 256–61. Bibcode:1990Natur.347..256O. doi:10.1038/347256a0. PMID 2144893. S2CID 4264539.
6. Newman-Smith ED, Shurland DL, van der Bliek AM (July 1997). "Assignment of the dynamin-1 gene (DNM1) to human chromosome 9q34 by fluorescence in situ hybridization and somatic cell hybrid analysis". Genomics. 41 (2): 286–9. doi:10.1006/geno.1996.4596. PMID 9143509.
7. "Entrez Gene: DNM1 dynamin 1".
8. Dhindsa RS, Bradrick SS, Yao X, Heinzen EL, Petrovski S, Krueger BJ, et al. (June 2015). "Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis". Neurology. Genetics. 1 (1): e4. doi:10.1212/01.NXG.0000464295.65736.da. PMC 4821085. PMID 27066543.
9. Micheva KD, Kay BK, McPherson PS (October 1997). "Synaptojanin forms two separate complexes in the nerve terminal. Interactions with endophilin and amphiphysin". J. Biol. Chem. 272 (43): 27239–45. doi:10.1074/jbc.272.43.27239. PMID 9341169.
10. Wigge P, Köhler K, Vallis Y, Doyle CA, Owen D, Hunt SP, McMahon HT (October 1997). "Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis". Mol. Biol. Cell. 8 (10): 2003–15. doi:10.1091/mbc.8.10.2003. PMC 25662. PMID 9348539.
11. McMahon HT, Wigge P, Smith C (August 1997). "Clathrin interacts specifically with amphiphysin and is displaced by dynamin". FEBS Lett. 413 (2): 319–22. doi:10.1016/s0014-5793(97)00928-9. PMID 9280305. S2CID 42520828.
12. Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW (May 2002). "Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate". J. Biol. Chem. 277 (20): 17597–604. doi:10.1074/jbc.M111101200. PMID 11877424.
13. Grabs D, Slepnev VI, Songyang Z, David C, Lynch M, Cantley LC, De Camilli P (May 1997). "The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence". J. Biol. Chem. 272 (20): 13419–25. doi:10.1074/jbc.272.20.13419. PMID 9148966.
14. Kamioka Y, Fukuhara S, Sawa H, Nagashima K, Masuda M, Matsuda M, Mochizuki N (September 2004). "A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis". J. Biol. Chem. 279 (38): 40091–9. doi:10.1074/jbc.M404899200. PMID 15252009.
15. Miki H, Miura K, Matuoka K, Nakata T, Hirokawa N, Orita S, Kaibuchi K, Takai Y, Takenawa T (February 1994). "Association of Ash/Grb-2 with dynamin through the Src homology 3 domain". J. Biol. Chem. 269 (8): 5489–92. doi:10.1016/S0021-9258(17)37484-7. PMID 8119878.
16. Sastry L, Cao T, King CR (January 1997). "Multiple Grb2-protein complexes in human cancer cells". Int. J. Cancer. 70 (2): 208–13. doi:10.1002/(sici)1097-0215(19970117)70:2<208::aid-ijc12>3.0.co;2-e. PMID 9009162. S2CID 10317185.
17. Wunderlich L, Faragó A, Buday L (January 1999). "Characterization of interactions of Nck with Sos and dynamin". Cell. Signal. 11 (1): 25–9. doi:10.1016/s0898-6568(98)00027-8. PMID 10206341.
18. Modregger J, Ritter B, Witter B, Paulsson M, Plomann M (December 2000). "All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis". J. Cell Sci. 113 (24): 4511–21. doi:10.1242/jcs.113.24.4511. PMID 11082044.
19. Modregger J, Schmidt AA, Ritter B, Huttner WB, Plomann M (February 2003). "Characterization of Endophilin B1b, a brain-specific membrane-associated lysophosphatidic acid acyl transferase with properties distinct from endophilin A1". J. Biol. Chem. 278 (6): 4160–7. doi:10.1074/jbc.M208568200. PMID 12456676.

Further reading

• Sever S (2003). "Dynamin and endocytosis". Curr. Opin. Cell Biol. 14 (4): 463–7. doi:10.1016/S0955-0674(02)00347-2. PMID 12383797.
• Wiejak J, Wyroba E (2003). "Dynamin: characteristics, mechanism of action and function". Cell. Mol. Biol. Lett. 7 (4): 1073–80. PMID 12511974.
• Orth JD, McNiven MA (2003). "Dynamin at the actin-membrane interface". Curr. Opin. Cell Biol. 15 (1): 31–9. doi:10.1016/S0955-0674(02)00010-8. PMID 12517701.
• Timm D, Salim K, Gout I, et al. (1995). "Crystal structure of the pleckstrin homology domain from dynamin". Nat. Struct. Biol. 1 (11): 782–8. doi:10.1038/nsb1194-782. PMID 7634088. S2CID 1454909.
• Downing AK, Driscoll PC, Gout I, et al. (1995). "Three-dimensional solution structure of the pleckstrin homology domain from dynamin". Curr. Biol. 4 (10): 884–91. doi:10.1016/S0960-9822(00)00197-4. PMID 7850421. S2CID 37072095.
• Ferguson KM, Lemmon MA, Schlessinger J, Sigler PB (1994). "Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin". Cell. 79 (2): 199–209. doi:10.1016/0092-8674(94)90190-2. PMID 7954789. S2CID 33767806.
• van der Bliek AM, Redelmeier TE, Damke H, et al. (1993). "Mutations in human dynamin block an intermediate stage in coated vesicle formation". J. Cell Biol. 122 (3): 553–63. doi:10.1083/jcb.122.3.553. PMC 2119674. PMID 8101525.
• Miki H, Miura K, Matuoka K, et al. (1994). "Association of Ash/Grb-2 with dynamin through the Src homology 3 domain". J. Biol. Chem. 269 (8): 5489–92. doi:10.1016/S0021-9258(17)37484-7. PMID 8119878.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Sontag JM, Fykse EM, Ushkaryov Y, et al. (1994). "Differential expression and regulation of multiple dynamins". J. Biol. Chem. 269 (6): 4547–54. doi:10.1016/S0021-9258(17)41812-6. PMID 8308025.
• Grabs D, Slepnev VI, Songyang Z, et al. (1997). "The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence". J. Biol. Chem. 272 (20): 13419–25. doi:10.1074/jbc.272.20.13419. PMID 9148966.
• Ramjaun AR, Micheva KD, Bouchelet I, McPherson PS (1997). "Identification and characterization of a nerve terminal-enriched amphiphysin isoform". J. Biol. Chem. 272 (26): 16700–6. doi:10.1074/jbc.272.26.16700. PMID 9195986.
• Ringstad N, Nemoto Y, De Camilli P (1997). "The SH3p4/Sh3p8/SH3p13 protein family: binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain". Proc. Natl. Acad. Sci. U.S.A. 94 (16): 8569–74. Bibcode:1997PNAS...94.8569R. doi:10.1073/pnas.94.16.8569. PMC 23017. PMID 9238017.
• McMahon HT, Wigge P, Smith C (1997). "Clathrin interacts specifically with amphiphysin and is displaced by dynamin". FEBS Lett. 413 (2): 319–22. doi:10.1016/S0014-5793(97)00928-9. PMID 9280305. S2CID 42520828.
• Wigge P, Köhler K, Vallis Y, et al. (1997). "Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis". Mol. Biol. Cell. 8 (10): 2003–15. doi:10.1091/mbc.8.10.2003. PMC 25662. PMID 9348539.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Witke W, Podtelejnikov AV, Di Nardo A, et al. (1998). "In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly". EMBO J. 17 (4): 967–76. doi:10.1093/emboj/17.4.967. PMC 1170446. PMID 9463375.
• Slepnev VI, Ochoa GC, Butler MH, et al. (1998). "Role of phosphorylation in regulation of the assembly of endocytic coat complexes". Science. 281 (5378): 821–4. Bibcode:1998Sci...281..821S. doi:10.1126/science.281.5378.821. PMID 9694653.