ID DYN1_HUMAN Reviewed; 864 AA. AC Q05193; A6NLM6; Q5SYX0; Q5SYX2; Q6P3T6; Q86VD2; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 18-MAR-2008, sequence version 2. DT 27-MAR-2024, entry version 218. DE RecName: Full=Dynamin-1 {ECO:0000303|PubMed:9922133}; DE EC=3.6.5.5 {ECO:0000269|PubMed:15703209, ECO:0000269|PubMed:20428113, ECO:0000269|PubMed:8910402, ECO:0000269|PubMed:9362482}; DE AltName: Full=Dynamin {ECO:0000303|PubMed:8101525}; DE AltName: Full=Dynamin I {ECO:0000303|PubMed:8910402}; GN Name=DNM1 {ECO:0000312|HGNC:HGNC:2972}; Synonyms=DNM; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF RP 387-466 (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF 726-856 (ISOFORM 3), RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-44, AND VARIANT ASN-744. RX PubMed=8101525; DOI=10.1083/jcb.122.3.553; RA van der Bliek A.M., Redelmeier T.E., Tisdale E.J., Meyerowitz E.M., RA Schmid S.L.; RT "Mutations in human dynamin block an intermediate stage in coated vesicle RT formation."; RL J. Cell Biol. 122:553-563(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain, and PNS; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF LYS-44. RX PubMed=7877694; DOI=10.1038/374190a0; RA Hinshaw J.E., Schmid S.L.; RT "Dynamin self-assembles into rings suggesting a mechanism for coated RT vesicle budding."; RL Nature 374:190-192(1995). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=8910402; DOI=10.1074/jbc.271.45.27979; RA Lin H.C., Gilman A.G.; RT "Regulation of dynamin I GTPase activity by G protein betagamma subunits RT and phosphatidylinositol 4,5-bisphosphate."; RL J. Biol. Chem. 271:27979-27982(1996). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND DOMAIN. RX PubMed=9362482; DOI=10.1093/emboj/16.22.6676; RA Muhlberg A.B., Warnock D.E., Schmid S.L.; RT "Domain structure and intramolecular regulation of dynamin GTPase."; RL EMBO J. 16:6676-6683(1997). RN [7] RP FUNCTION, DOMAIN, AND INTERACTION WITH GRB2. RX PubMed=9922133; DOI=10.1021/bi981180g; RA Scaife R., Venien-Bryan C., Margolis R.L.; RT "Dual function C-terminal domain of dynamin-1: modulation of self-assembly RT by interaction of the assembly site with SH3 domains."; RL Biochemistry 37:17673-17679(1998). RN [8] RP SUBUNIT, AND DOMAIN. RX PubMed=9765310; DOI=10.1074/jbc.273.42.27725; RA Klein D.E., Lee A., Frank D.W., Marks M.S., Lemmon M.A.; RT "The pleckstrin homology domains of dynamin isoforms require RT oligomerization for high affinity phosphoinositide binding."; RL J. Biol. Chem. 273:27725-27733(1998). RN [9] RP DOMAIN, AND FUNCTION. RX PubMed=10074457; DOI=10.1016/s0960-9822(99)80115-8; RA Lee A., Frank D.W., Marks M.S., Lemmon M.A.; RT "Dominant-negative inhibition of receptor-mediated endocytosis by a RT dynamin-1 mutant with a defective pleckstrin homology domain."; RL Curr. Biol. 9:261-264(1999). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=12198492; DOI=10.1038/ncb837; RA Merrifield C.J., Feldman M.E., Wan L., Almers W.; RT "Imaging actin and dynamin recruitment during invagination of single RT clathrin-coated pits."; RL Nat. Cell Biol. 4:691-698(2002). RN [11] RP FUNCTION, AND INTERACTION WITH DNAJC6. RX PubMed=12791276; DOI=10.1016/s1534-5807(03)00157-6; RA Newmyer S.L., Christensen A., Sever S.; RT "Auxilin-dynamin interactions link the uncoating ATPase chaperone machinery RT with vesicle formation."; RL Dev. Cell 4:929-940(2003). RN [12] RP SUBCELLULAR LOCATION, INTERACTION WITH SNX9, FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=15703209; DOI=10.1091/mbc.e04-11-1016; RA Soulet F., Yarar D., Leonard M., Schmid S.L.; RT "SNX9 regulates dynamin assembly and is required for efficient clathrin- RT mediated endocytosis."; RL Mol. Biol. Cell 16:2058-2067(2005). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [14] RP INTERACTION WITH MYO1E. RX PubMed=17257598; DOI=10.1016/j.febslet.2007.01.021; RA Krendel M., Osterweil E.K., Mooseker M.S.; RT "Myosin 1E interacts with synaptojanin-1 and dynamin and is involved in RT endocytosis."; RL FEBS Lett. 581:644-650(2007). RN [15] RP FUNCTION. RX PubMed=19084269; DOI=10.1016/j.cell.2008.11.028; RA Bashkirov P.V., Akimov S.A., Evseev A.I., Schmid S.L., Zimmerberg J., RA Frolov V.A.; RT "GTPase cycle of dynamin is coupled to membrane squeeze and release, RT leading to spontaneous fission."; RL Cell 135:1276-1286(2008). RN [16] RP INTERACTION WITH SNX33. RX PubMed=18353773; DOI=10.1074/jbc.m801531200; RA Schobel S., Neumann S., Hertweck M., Dislich B., Kuhn P.H., Kremmer E., RA Seed B., Baumeister R., Haass C., Lichtenthaler S.F.; RT "A novel sorting nexin modulates endocytic trafficking and alpha-secretase RT cleavage of the amyloid precursor protein."; RL J. Biol. Chem. 283:14257-14268(2008). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP INTERACTION WITH DIAPH1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23325789; DOI=10.1091/mbc.e12-08-0597; RA Li D., Dammer E.B., Lucki N.C., Sewer M.B.; RT "cAMP-stimulated phosphorylation of diaphanous 1 regulates protein RT stability and interaction with binding partners in adrenocortical cells."; RL Mol. Biol. Cell 24:848-857(2013). RN [20] RP FUNCTION, PHOSPHORYLATION AT SER-774, MUTAGENESIS OF SER-774 AND SER-778, RP AND INTERACTION WITH SNX9. RX PubMed=29668686; DOI=10.1371/journal.pbio.2005377; RA Srinivasan S., Burckhardt C.J., Bhave M., Chen Z., Chen P.H., Wang X., RA Danuser G., Schmid S.L.; RT "A noncanonical role for dynamin-1 in regulating early stages of clathrin- RT mediated endocytosis in non-neuronal cells."; RL PLoS Biol. 16:e2005377-e2005377(2018). RN [21] RP INVOLVEMENT IN DEE31A, AND VARIANTS DEE31A PRO-177; ASN-206; TRP-237 AND RP ALA-359. RX PubMed=25262651; DOI=10.1016/j.ajhg.2014.08.013; RG EuroEPINOMICS-RES Consortium; RA Appenzeller S., Balling R., Barisic N., Baulac S., Caglayan H., Craiu D., RA De Jonghe P., Depienne C., Dimova P., Djemie T., Gormley P., Guerrini R., RA Helbig I., Hjalgrim H., Hoffman-Zacharska D., Jahn J., Klein K.M., RA Koeleman B., Komarek V., Krause R., Kuhlenbaumer G., Leguern E., RA Lehesjoki A.E., Lemke J.R., Lerche H., Linnankivi T., Marini C., May P., RA Moller R.S., Muhle H., Pal D., Palotie A., Pendziwiat M., Robbiano A., RA Roelens F., Rosenow F., Selmer K., Serratosa J.M., Sisodiya S., RA Stephani U., Sterbova K., Striano P., Suls A., Talvik T., von Spiczak S., RA Weber Y., Weckhuysen S., Zara F., Abou-Khalil B., Alldredge B.K., RA Andermann E., Andermann F., Amron D., Bautista J.F., Berkovic S.F., RA Bluvstein J., Boro A., Cascino G., Consalvo D., Crumrine P., Devinsky O., RA Dlugos D., Epstein M.P., Fiol M., Fountain N.B., French J., Friedman D., RA Geller E.B., Glauser T., Glynn S., Haas K., Haut S.R., Hayward J., RA Helmers S.L., Joshi S., Kanner A., Kirsch H.E., Knowlton R.C., RA Kossoff E.H., Kuperman R., Kuzniecky R., Lowenstein D.H., McGuire S.M., RA Motika P.V., Novotny E.J., Ottman R., Paolicchi J.M., Parent J., Park K., RA Poduri A., Sadleir L., Scheffer I.E., Shellhaas R.A., Sherr E., Shih J.J., RA Singh R., Sirven J., Smith M.C., Sullivan J., Thio L.L., Venkat A., RA Vining E.P., Von Allmen G.K., Weisenberg J.L., Widdess-Walsh P., RA Winawer M.R., Allen A.S., Berkovic S.F., Cossette P., Delanty N., RA Dlugos D., Eichler E.E., Epstein M.P., Glauser T., Goldstein D.B., Han Y., RA Heinzen E.L., Johnson M.R., Kuzniecky R., Lowenstein D.H., Marson A.G., RA Mefford H.C., Nieh S.E., O'Brien T.J., Ottman R., Petrou S., Petrovski S., RA Poduri A., Ruzzo E.K., Scheffer I.E., Sherr E.; RT "De novo mutations in synaptic transmission genes including DNM1 cause RT epileptic encephalopathies."; RL Am. J. Hum. Genet. 95:360-370(2014). RN [22] RP INVOLVEMENT IN DEE31A. RX PubMed=25533962; DOI=10.1038/nature14135; RG Deciphering Developmental Disorders Study; RT "Large-scale discovery of novel genetic causes of developmental RT disorders."; RL Nature 519:223-228(2015). RN [23] RP STRUCTURE BY NMR OF 511-630. RX PubMed=7850421; DOI=10.1016/s0960-9822(00)00197-4; RA Downing A.K., Driscoll P.C., Gout I., Salim K., Zvelebil M.J., RA Waterfield M.D.; RT "Three-dimensional solution structure of the pleckstrin homology domain RT from dynamin."; RL Curr. Biol. 4:884-891(1994). RN [24] {ECO:0007744|PDB:1DYN} RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 509-633, AND MUTAGENESIS OF LYS-44 RP AND 591-THR--GLN-602. RX PubMed=7954789; DOI=10.1016/0092-8674(94)90190-2; RA Ferguson K.M., Lemmon M.A., Schlessinger J., Sigler P.B.; RT "Crystal structure at 2.2-A resolution of the pleckstrin homology domain RT from human dynamin."; RL Cell 79:199-209(1994). RN [25] {ECO:0007744|PDB:2DYN} RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 509-630. RX PubMed=7634088; DOI=10.1038/nsb1194-782; RA Timm D., Salim K., Gout I., Guruprasad L., Waterfield M., Blundell T.; RT "Crystal structure of the pleckstrin homology domain from dynamin."; RL Nat. Struct. Biol. 1:782-788(1994). RN [26] {ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-320 IN COMPLEX WITH GDP, RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF GLN-40; SER-41 RP AND ASP-180. RX PubMed=20428113; DOI=10.1038/nature09032; RA Chappie J.S., Acharya S., Leonard M., Schmid S.L., Dyda F.; RT "G domain dimerization controls dynamin's assembly-stimulated GTPase RT activity."; RL Nature 465:435-440(2010). RN [27] {ECO:0007744|PDB:5D3Q} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 5-320 IN COMPLEX WITH GDP. RX PubMed=26612256; DOI=10.1016/j.bbrc.2015.11.074; RA Anand R., Eschenburg S., Reubold T.F.; RT "Crystal structure of the GTPase domain and the bundle signalling element RT of dynamin in the GDP state."; RL Biochem. Biophys. Res. Commun. 469:76-80(2016). RN [28] {ECO:0007744|PDB:6DLU, ECO:0007744|PDB:6DLV} RP STRUCTURE BY ELECTRON MICROSCOPY (3.75 ANGSTROMS) OF 1-748 IN COMPLEX WITH RP GTP ANALOG, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-44; ARG-290; RP ASP-291; THR-292; LEU-293; PRO-294; LEU-330; GLN-334; ASP-406; MET-407; RP THR-488 AND LEU-702, AND SUBUNIT. RX PubMed=30069048; DOI=10.1038/s41586-018-0378-6; RA Kong L., Sochacki K.A., Wang H., Fang S., Canagarajah B., Kehr A.D., RA Rice W.J., Strub M.P., Taraska J.W., Hinshaw J.E.; RT "Cryo-EM of the dynamin polymer assembled on lipid membrane."; RL Nature 560:258-262(2018). RN [29] RP VARIANT DEE31A TRP-237. RX PubMed=27476654; DOI=10.1016/j.ajhg.2016.06.003; RG Epi4K Consortium; RT "De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic RT encephalopathies."; RL Am. J. Hum. Genet. 99:287-298(2016). RN [30] RP INVOLVEMENT IN DEE31B. RX PubMed=36553519; DOI=10.3390/genes13122252; RA AlTassan R., AlQudairy H., Alromayan R., Alfalah A., AlHarbi O.A., RA Gonzalez-Alvarez A.C., Arold S.T., Kaya N.; RT "Clinical, Radiological, and Genetic Characterization of a Patient with a RT Novel Homoallelic Loss-of-Function Variant in DNM1."; RL Genes (Basel) 13:0-0(2022). RN [31] RP VARIANTS DEE31B 33-GLN--LEU-864 DEL AND 284-GLN--LEU-864 DEL. RX PubMed=34172529; DOI=10.1136/jmedgenet-2021-107769; RA Yigit G., Sheffer R., Daana M., Li Y., Kaygusuz E., Mor-Shakad H., RA Altmueller J., Nuernberg P., Douiev L., Kaulfuss S., Burfeind P., RA Wollnik B., Brockmann K.; RT "Loss-of-function variants in DNM1 cause a specific form of developmental RT and epileptic encephalopathy only in biallelic state."; RL J. Med. Genet. 59:549-553(2022). CC -!- FUNCTION: Catalyzes the hydrolysis of GTP and utilizes this energy to CC mediate vesicle scission and participates in many forms of endocytosis, CC such as clathrin-mediated endocytosis or synaptic vesicle endocytosis CC as well as rapid endocytosis (RE) (PubMed:8910402, PubMed:20428113, CC PubMed:15703209, PubMed:9362482, PubMed:29668686, PubMed:8101525). CC Associates to the membrane, through lipid binding, and self-assembles CC into rings and stacks of interconnected rings through oligomerization CC to form a helical polymer around the vesicle membrane leading to CC constriction of invaginated coated pits around their necks CC (PubMed:7877694, PubMed:9922133, PubMed:30069048). Self-assembly of the CC helical polymer induces membrane tubules narrowing until the polymer CC reaches a length sufficient to trigger GTP hydrolysis CC (PubMed:19084269). Depending on the curvature imposed on the tubules, CC membrane detachment from the helical polymer upon GTP hydrolysis can CC cause spontaneous hemifission followed by complete fission CC (PubMed:19084269). May play a role in regulating early stages of CC clathrin-mediated endocytosis in non-neuronal cells through its CC activation by dephosphorylation via the signaling downstream of EGFR CC (PubMed:29668686). Controls vesicle size at a step before fission, CC during formation of membrane pits, at hippocampal synapses (By CC similarity). Controls plastic adaptation of the synaptic vesicle CC recycling machinery to high levels of activity (By similarity). CC Mediates rapid endocytosis (RE), a Ca(2+)-dependent and clathrin- and CC K(+)-independent process in chromaffin cells (By similarity). CC Microtubule-associated force-producing protein involved in producing CC microtubule bundles and able to bind and hydrolyze GTP (By similarity). CC Through its interaction with DNAJC6, acts during the early steps of CC clathrin-coated vesicle (CCV) formation (PubMed:12791276). CC {ECO:0000250|UniProtKB:P39053, ECO:0000250|UniProtKB:Q08DF4, CC ECO:0000269|PubMed:12791276, ECO:0000269|PubMed:15703209, CC ECO:0000269|PubMed:19084269, ECO:0000269|PubMed:20428113, CC ECO:0000269|PubMed:29668686, ECO:0000269|PubMed:30069048, CC ECO:0000269|PubMed:7877694, ECO:0000269|PubMed:8101525, CC ECO:0000269|PubMed:8910402, ECO:0000269|PubMed:9362482, CC ECO:0000269|PubMed:9922133}. 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 Evidence={ECO:0000269|PubMed:15703209, ECO:0000269|PubMed:20428113, CC ECO:0000269|PubMed:8910402, ECO:0000269|PubMed:9362482}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000269|PubMed:15703209, ECO:0000269|PubMed:20428113, CC ECO:0000269|PubMed:8910402, ECO:0000269|PubMed:9362482}; CC -!- ACTIVITY REGULATION: GTPase activity is activated by 1-phosphatidyl-1D- CC myo-inositol 4,5-bisphosphate (PubMed:8910402). GTPase activity is CC inhibited by the heterodimer G protein formed by GNB1 and GNG2 with an CC IC(50)=400 nM when DNM1 concentration is 5 nM (PubMed:8910402). CC {ECO:0000269|PubMed:8910402}. CC -!- SUBUNIT: Homodimer; homodimerization is mediated by the dynamin-type G CC domain which promotes assembly-stimulated GTPase activity CC (PubMed:20428113, PubMed:26612256). Homo-tetramer formed from two CC dimers in the absence of lipid (PubMed:30069048, PubMed:9362482). CC Oligomerizes into a helical polymer that self-assembles around the CC vesicle membrane, when associated to the menbrane through lipid binding CC (PubMed:9765310, PubMed:30069048, PubMed:7877694). Interacts (via C- CC terminal proline-rich domain (PRD)) with SNX9 (via SH3 domain); this CC interaction allows regulation of DNM1 self-assembly during late stages CC of endocytic vesicle formation and supports DNM1's early functions in CC accelerating clathrin-coated pits (CCPs) maturation in non neuronals CC cell (PubMed:15703209, PubMed:29668686). Interacts (via C-terminal CC proline-rich domain (PRD)) with MYO1E (via SH3 domain); this CC interaction regulates receptor-mediated endocytosis (PubMed:17257598). CC Interacts with SNX33 (via SH3 domain); this interaction decreases DNM1- CC dependent endocytosis (PubMed:18353773). Interacts with DIAPH1 CC (PubMed:23325789). Interacts with GRB2 (via SH3 domain); this CC interaction mediates disassembly of DNM1 polymers, therefore modulates CC self-assembly (PubMed:9922133). Forms a complex with BIN1 (via SH3 CC domain) and SH3GL2 (via SH3 domain). Forms a complex with SH3GL2 (via CC SH3 domain) and AMPH (via SH3 domain). Forms a complex with SH3GL2 (via CC SH3 domain) and SYNJ1. Interacts with AMPH. Interacts (via C-terminal CC proline-rich domain (PRD)) with SYT1; this interaction facilitates CC vesicle fission during clathrin-mediated endocytosis (CME). Interacts CC (via C-terminal proline-rich domain (PRD)) with PLCG1 (via SH3 domain); CC this interaction stimulates the release of GDP from DNM1 and enhances CC DNM1-dependent endocytosis. Interacts with SNPH; this interaction CC inhibits the binding of DNM1 to AMPH and DNM1-receptor-mediated CC endocytosis (By similarity). Interacts with CAV1. Interacts with CC SH3GLB1 (via SH3 domain). Interacts with PACSIN1 (via SH3 domain), CC PACSIN2 (via SH3 domain) and PACSIN3 (via SH3 domain). Interacts with CC UNC119; this interaction decreases DNM1's GTPase activity and affects CC DNM1's interaction with AMPH (By similarity). Interacts (GTP-bound CC form) with DNAJC6; this interaction allows clathrin-coated vesicle CC (CCV) formation at the plasma membrane (PubMed:12791276). CC {ECO:0000250|UniProtKB:P21575, ECO:0000250|UniProtKB:P39053, CC ECO:0000269|PubMed:12791276, ECO:0000269|PubMed:15703209, CC ECO:0000269|PubMed:17257598, ECO:0000269|PubMed:18353773, CC ECO:0000269|PubMed:20428113, ECO:0000269|PubMed:23325789, CC ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:29668686, CC ECO:0000269|PubMed:30069048, ECO:0000269|PubMed:7877694, CC ECO:0000269|PubMed:9362482, ECO:0000269|PubMed:9765310, CC ECO:0000269|PubMed:9922133}. CC -!- INTERACTION: CC Q05193; Q05193: DNM1; NbExp=13; IntAct=EBI-713135, EBI-713135; CC Q05193; Q96RU3: FNBP1; NbExp=5; IntAct=EBI-713135, EBI-1111248; CC Q05193; P62993: GRB2; NbExp=5; IntAct=EBI-713135, EBI-401755; CC Q05193; P42858: HTT; NbExp=3; IntAct=EBI-713135, EBI-466029; CC Q05193; Q5S007: LRRK2; NbExp=4; IntAct=EBI-713135, EBI-5323863; CC Q05193; P16333: NCK1; NbExp=2; IntAct=EBI-713135, EBI-389883; CC Q05193; P29474: NOS3; NbExp=2; IntAct=EBI-713135, EBI-1391623; CC Q05193; Q8IVI9: NOSTRIN; NbExp=3; IntAct=EBI-713135, EBI-1391643; CC Q05193; Q8WV41: SNX33; NbExp=2; IntAct=EBI-713135, EBI-2481535; CC Q05193; Q9Y5X1: SNX9; NbExp=2; IntAct=EBI-713135, EBI-77848; CC Q05193; Q96JI7: SPG11; NbExp=3; IntAct=EBI-713135, EBI-2822128; CC Q05193-5; P68135: ACTA1; Xeno; NbExp=5; IntAct=EBI-8446026, EBI-367540; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15703209}. CC Membrane, clathrin-coated pit {ECO:0000269|PubMed:15703209, CC ECO:0000269|PubMed:8101525}. Cytoplasmic vesicle CC {ECO:0000250|UniProtKB:P21575, ECO:0000250|UniProtKB:P39053}. CC Presynapse {ECO:0000250|UniProtKB:P21575}. Cytoplasmic vesicle, CC secretory vesicle, chromaffin granule {ECO:0000250|UniProtKB:Q08DF4}. CC Note=Associated to the membrane in an helical polymer shape in a GTP CC bound state (PubMed:30069048). Transiently recruited to endocytic CC clathrin-coated pits (CCPs) at a late stage of clathrin-coated vesicle CC (CCV) formation (PubMed:15703209). {ECO:0000269|PubMed:15703209, CC ECO:0000269|PubMed:30069048}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q05193-1; Sequence=Displayed; CC Name=2; CC IsoId=Q05193-2; Sequence=VSP_031518; CC Name=3; CC IsoId=Q05193-3; Sequence=VSP_031519; CC Name=4; CC IsoId=Q05193-5; Sequence=VSP_031518, VSP_031519; CC -!- DOMAIN: The dynamin-type G mediates homodimerization and plays a role CC in self-assembly. {ECO:0000269|PubMed:20428113, CC ECO:0000269|PubMed:9922133}. CC -!- DOMAIN: The C-terminal proline-rich domain (PRD) mediates interaction CC with SH3-binding partners (By similarity). Is required for DNM1 self- CC assembly (PubMed:7877694). {ECO:0000250|UniProtKB:P21575, CC ECO:0000269|PubMed:7877694}. CC -!- DOMAIN: The PH domain binds phosphoinositides such as 1-phosphatidyl- CC 1D-myo-inositol 4,5-bisphosphate, 1-phosphatidyl-1D-myo-inositol 3,4- CC bisphosphate and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, CC and mediates receptor-mediated endocytosis. CC {ECO:0000269|PubMed:10074457, ECO:0000269|PubMed:9765310}. CC -!- PTM: Phosphorylation at Ser-774 by GSK3B/GSK3-beta leads to CC inactivation of receptor-mediated endocytosis in non-neuronal cells CC (PubMed:29668686). Dephosphorylation at Ser-774, through the EGFR CC downstream signaling, leads to activation and regulates early stages of CC clathrin-mediated endocytosis (CME) (PubMed:29668686). Phosphorylated CC by CDK5 leading to synaptic vesicle endocytosis (SVE) activation (By CC similarity). {ECO:0000250|UniProtKB:P21575, CC ECO:0000269|PubMed:29668686}. CC -!- DISEASE: Developmental and epileptic encephalopathy 31A (DEE31A) CC [MIM:616346]: An autosomal dominant epileptic encephalopathy, a CC heterogeneous group of severe early-onset epilepsies characterized by CC refractory seizures, neurodevelopmental impairment, and poor prognosis. CC Development is normal prior to seizure onset, after which cognitive and CC motor delays become apparent. {ECO:0000269|PubMed:25262651, CC ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:27476654}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 31B (DEE31B) CC [MIM:620352]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE31B is an autosomal recessive form with onset in CC the first months of life. {ECO:0000269|PubMed:34172529, CC ECO:0000269|PubMed:36553519}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase CC superfamily. Dynamin/Fzo/YdjA family. {ECO:0000255|PROSITE- CC ProRule:PRU01055}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA02805.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; 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; L07807; AAA02803.1; -; mRNA. DR EMBL; L07808; AAA02804.1; -; mRNA. DR EMBL; L07809; AAA02805.1; ALT_SEQ; mRNA. DR EMBL; L07810; AAA02806.1; -; mRNA. DR EMBL; AL590708; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC050279; AAH50279.2; -; mRNA. DR EMBL; BC063850; AAH63850.1; -; mRNA. DR CCDS; CCDS43882.1; -. [Q05193-3] DR CCDS; CCDS6895.1; -. [Q05193-1] DR CCDS; CCDS75911.1; -. [Q05193-5] DR CCDS; CCDS75912.1; -. [Q05193-2] DR PIR; A40671; A40671. DR RefSeq; NP_001005336.1; NM_001005336.2. [Q05193-3] DR RefSeq; NP_001275666.1; NM_001288737.1. [Q05193-5] DR RefSeq; NP_001275667.1; NM_001288738.1. [Q05193-5] DR RefSeq; NP_001275668.1; NM_001288739.1. [Q05193-2] DR RefSeq; NP_004399.2; NM_004408.3. [Q05193-1] DR RefSeq; XP_005251825.1; XM_005251768.2. DR RefSeq; XP_005251826.1; XM_005251769.2. DR RefSeq; XP_016869860.1; XM_017014371.1. DR PDB; 1DYN; X-ray; 2.20 A; A/B=510-633. DR PDB; 2DYN; X-ray; 2.30 A; A/B=509-630. DR PDB; 2X2E; X-ray; 2.00 A; A/D=6-320, A/D=726-750. DR PDB; 2X2F; X-ray; 2.00 A; A/D=6-320, A/D=726-750. DR PDB; 3SNH; X-ray; 3.70 A; A=6-746. DR PDB; 3ZYC; X-ray; 2.20 A; A/D=6-320, A/D=726-750. DR PDB; 3ZYS; EM; 12.20 A; A/D=6-320, A/D=726-750, C/F=518-630. DR PDB; 4UUD; EM; 12.50 A; A/B/C/D/E/F/G/H/I/J/K/L=1-864. DR PDB; 4UUK; EM; 12.50 A; A/B/C/D/E/F/G/H/I/J/K/L=1-864. DR PDB; 5D3Q; X-ray; 1.70 A; A/B=5-320, A/B=726-746. DR PDB; 6DLU; EM; 3.75 A; B/P=1-748. DR PDB; 6DLV; EM; 10.10 A; b/c/f/g=1-748. DR PDB; 6S9A; X-ray; 2.00 A; A/B=6-746. DR PDB; 7AX3; EM; 3.74 A; A/A2/B/B2/C/C2/D/D2/E/E2/F/F2/G/G2/H/H2/I/I2/J/J2/K/L/M/N/O/P/Q/R/S/T=1-864. DR PDBsum; 1DYN; -. DR PDBsum; 2DYN; -. DR PDBsum; 2X2E; -. DR PDBsum; 2X2F; -. DR PDBsum; 3SNH; -. DR PDBsum; 3ZYC; -. DR PDBsum; 3ZYS; -. DR PDBsum; 4UUD; -. DR PDBsum; 4UUK; -. DR PDBsum; 5D3Q; -. DR PDBsum; 6DLU; -. DR PDBsum; 6DLV; -. DR PDBsum; 6S9A; -. DR PDBsum; 7AX3; -. DR AlphaFoldDB; Q05193; -. DR BMRB; Q05193; -. DR EMDB; EMD-11932; -. DR EMDB; EMD-2701; -. DR EMDB; EMD-7957; -. DR EMDB; EMD-7958; -. DR SMR; Q05193; -. DR BioGRID; 108099; 134. DR CORUM; Q05193; -. DR DIP; DIP-36242N; -. DR IntAct; Q05193; 54. DR MINT; Q05193; -. DR STRING; 9606.ENSP00000362014; -. DR BindingDB; Q05193; -. DR ChEMBL; CHEMBL4958; -. DR DrugCentral; Q05193; -. DR GlyGen; Q05193; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q05193; -. DR PhosphoSitePlus; Q05193; -. DR BioMuta; DNM1; -. DR DMDM; 172046078; -. DR EPD; Q05193; -. DR jPOST; Q05193; -. DR MassIVE; Q05193; -. DR MaxQB; Q05193; -. DR PaxDb; 9606-ENSP00000362014; -. DR PeptideAtlas; Q05193; -. DR ProteomicsDB; 58309; -. [Q05193-1] DR ProteomicsDB; 58310; -. [Q05193-2] DR ProteomicsDB; 58311; -. [Q05193-3] DR ProteomicsDB; 58313; -. [Q05193-5] DR Pumba; Q05193; -. DR Antibodypedia; 3472; 757 antibodies from 46 providers. DR DNASU; 1759; -. DR Ensembl; ENST00000341179.11; ENSP00000345680.7; ENSG00000106976.22. [Q05193-3] DR Ensembl; ENST00000372923.8; ENSP00000362014.4; ENSG00000106976.22. [Q05193-1] DR Ensembl; ENST00000393594.7; ENSP00000377219.3; ENSG00000106976.22. [Q05193-5] DR Ensembl; ENST00000475805.5; ENSP00000419225.1; ENSG00000106976.22. [Q05193-5] DR Ensembl; ENST00000486160.3; ENSP00000420045.1; ENSG00000106976.22. [Q05193-2] DR Ensembl; ENST00000627543.2; ENSP00000487310.1; ENSG00000106976.22. [Q05193-3] DR GeneID; 1759; -. DR KEGG; hsa:1759; -. DR MANE-Select; ENST00000372923.8; ENSP00000362014.4; NM_004408.4; NP_004399.2. DR UCSC; uc064wcg.1; human. [Q05193-1] DR AGR; HGNC:2972; -. DR CTD; 1759; -. DR DisGeNET; 1759; -. DR GeneCards; DNM1; -. DR HGNC; HGNC:2972; DNM1. DR HPA; ENSG00000106976; Tissue enriched (brain). DR MalaCards; DNM1; -. DR MIM; 602377; gene. DR MIM; 616346; phenotype. DR MIM; 620352; phenotype. DR neXtProt; NX_Q05193; -. DR OpenTargets; ENSG00000106976; -. DR Orphanet; 2382; Lennox-Gastaut syndrome. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR PharmGKB; PA27440; -. DR VEuPathDB; HostDB:ENSG00000106976; -. DR eggNOG; KOG0446; Eukaryota. DR GeneTree; ENSGT00940000155214; -. DR InParanoid; Q05193; -. DR OMA; MQMVQTF; -. DR OrthoDB; 1052588at2759; -. DR PhylomeDB; Q05193; -. DR TreeFam; TF300362; -. DR BRENDA; 3.6.5.5; 2681. DR PathwayCommons; Q05193; -. DR Reactome; R-HSA-166016; Toll Like Receptor 4 (TLR4) Cascade. DR Reactome; R-HSA-177504; Retrograde neurotrophin signalling. DR Reactome; R-HSA-190873; Gap junction degradation. DR Reactome; R-HSA-196025; Formation of annular gap junctions. DR Reactome; R-HSA-2132295; MHC class II antigen presentation. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-HSA-437239; Recycling pathway of L1. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR SignaLink; Q05193; -. DR SIGNOR; Q05193; -. DR BioGRID-ORCS; 1759; 70 hits in 1161 CRISPR screens. DR ChiTaRS; DNM1; human. DR EvolutionaryTrace; Q05193; -. DR GeneWiki; DNM1; -. DR GenomeRNAi; 1759; -. DR Pharos; Q05193; Tbio. DR PRO; PR:Q05193; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q05193; Protein. DR Bgee; ENSG00000106976; Expressed in right hemisphere of cerebellum and 175 other cell types or tissues. DR ExpressionAtlas; Q05193; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW. DR GO; GO:0042583; C:chromaffin granule; IEA:UniProtKB-SubCell. DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0030139; C:endocytic vesicle; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0030117; C:membrane coat; IEA:Ensembl. DR GO; GO:0005874; C:microtubule; IBA:GO_Central. DR GO; GO:0001917; C:photoreceptor inner segment; IEA:Ensembl. DR GO; GO:0098684; C:photoreceptor ribbon synapse; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0098793; C:presynapse; ISS:UniProtKB. DR GO; GO:0098835; C:presynaptic endocytic zone membrane; IEA:Ensembl. DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central. DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:ParkinsonsUK-UCL. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0099049; P:clathrin coat assembly involved in endocytosis; ISS:UniProtKB. DR GO; GO:0006897; P:endocytosis; IMP:BHF-UCL. DR GO; GO:0007032; P:endosome organization; IMP:BHF-UCL. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0031623; P:receptor internalization; IBA:GO_Central. DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:UniProtKB. DR GO; GO:0097494; P:regulation of vesicle size; ISS:UniProtKB. DR GO; GO:0016185; P:synaptic vesicle budding from presynaptic endocytic zone membrane; IEA:Ensembl. DR GO; GO:0048488; P:synaptic vesicle endocytosis; IBA:GO_Central. DR GO; GO:0099050; P:vesicle scission; IDA:UniProtKB. DR CDD; cd08771; DLP_1; 1. DR CDD; cd01256; PH_dynamin; 1. DR DisProt; DP02976; -. DR Gene3D; 1.20.120.1240; Dynamin, middle domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. 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 InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR PANTHER; PTHR11566; DYNAMIN; 1. DR PANTHER; PTHR11566:SF32; DYNAMIN-1; 1. DR Pfam; PF01031; Dynamin_M; 1. DR Pfam; PF00350; Dynamin_N; 1. DR Pfam; PF02212; GED; 1. DR Pfam; PF00169; PH; 1. DR PRINTS; PR00195; DYNAMIN. DR SMART; SM00053; DYNc; 1. DR SMART; SM00302; GED; 1. DR SMART; SM00233; PH; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS00410; G_DYNAMIN_1; 1. DR PROSITE; PS51718; G_DYNAMIN_2; 1. DR PROSITE; PS51388; GED; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR Genevisible; Q05193; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Coated pit; Cytoplasmic vesicle; Disease variant; Endocytosis; Epilepsy; KW GTP-binding; Hydrolase; Membrane; Methylation; Microtubule; Motor protein; KW Nitration; Nucleotide-binding; Phosphoprotein; Reference proteome; Synapse. FT CHAIN 1..864 FT /note="Dynamin-1" FT /id="PRO_0000206563" FT DOMAIN 28..294 FT /note="Dynamin-type G" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT DOMAIN 519..625 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 659..750 FT /note="GED" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00720" FT REGION 38..45 FT /note="G1 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 64..66 FT /note="G2 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 136..139 FT /note="G3 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 205..208 FT /note="G4 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 235..238 FT /note="G5 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01055" FT REGION 767..864 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 767..781 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 782..840 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 41 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0007744|PDB:5D3Q" FT BINDING 43 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0007744|PDB:2X2E, FT ECO:0007744|PDB:2X2F, ECO:0007744|PDB:5D3Q" FT BINDING 44 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:30069048, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F, FT ECO:0007744|PDB:5D3Q, ECO:0007744|PDB:6DLU" FT BINDING 45 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0007744|PDB:2X2E, FT ECO:0007744|PDB:2X2F, ECO:0007744|PDB:5D3Q" FT BINDING 46 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:30069048, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F, FT ECO:0007744|PDB:5D3Q, ECO:0007744|PDB:6DLU" FT BINDING 59 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:26612256, FT ECO:0007744|PDB:5D3Q" FT BINDING 60 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F" FT BINDING 206 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0007744|PDB:2X2E, FT ECO:0007744|PDB:2X2F, ECO:0007744|PDB:5D3Q" FT BINDING 208 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0007744|PDB:2X2E, FT ECO:0007744|PDB:2X2F, ECO:0007744|PDB:5D3Q" FT BINDING 211 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:30069048, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:5D3Q, FT ECO:0007744|PDB:6DLU" FT BINDING 236 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:30069048, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F, FT ECO:0007744|PDB:5D3Q, ECO:0007744|PDB:6DLU" FT BINDING 237 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:30069048, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F, FT ECO:0007744|PDB:5D3Q, ECO:0007744|PDB:6DLU" FT BINDING 239 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000269|PubMed:20428113, FT ECO:0000269|PubMed:26612256, ECO:0000269|PubMed:30069048, FT ECO:0007744|PDB:2X2E, ECO:0007744|PDB:2X2F, FT ECO:0007744|PDB:5D3Q, ECO:0007744|PDB:6DLU" FT MOD_RES 80 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 125 FT /note="3'-nitrotyrosine; alternate" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 125 FT /note="Phosphotyrosine; alternate" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 306 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 347 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21575" FT MOD_RES 354 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 512 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 774 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:29668686" FT MOD_RES 778 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21575" FT MOD_RES 796 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P39053" FT MOD_RES 822 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21575" FT MOD_RES 851 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21575" FT MOD_RES 857 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21575" FT VAR_SEQ 407..444 FT /note="MAFETIVKKQVKKIREPCLKCVDMVISELISTVRQCTK -> LAFEATVKKQ FT VQKLKEPSIKCVDMVVSELTATIRKCSE (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:8101525" FT /id="VSP_031518" FT VAR_SEQ 845..864 FT /note="SRSGQASPSRPESPRPPFDL -> RITISDP (in isoform 3 and FT isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8101525" FT /id="VSP_031519" FT VARIANT 33..864 FT /note="Missing (in DEE31B)" FT /evidence="ECO:0000269|PubMed:34172529" FT /id="VAR_088263" FT VARIANT 177 FT /note="A -> P (in DEE31A; dbSNP:rs587777860)" FT /evidence="ECO:0000269|PubMed:25262651" FT /id="VAR_073710" FT VARIANT 206 FT /note="K -> N (in DEE31A; dbSNP:rs587777861)" FT /evidence="ECO:0000269|PubMed:25262651" FT /id="VAR_073711" FT VARIANT 237 FT /note="R -> W (in DEE31A; dbSNP:rs760270633)" FT /evidence="ECO:0000269|PubMed:25262651, FT ECO:0000269|PubMed:27476654" FT /id="VAR_073712" FT VARIANT 284..864 FT /note="Missing (in DEE31B)" FT /evidence="ECO:0000269|PubMed:34172529" FT /id="VAR_088264" FT VARIANT 359 FT /note="G -> A (in DEE31A; dbSNP:rs587777862)" FT /evidence="ECO:0000269|PubMed:25262651" FT /id="VAR_073713" FT VARIANT 744 FT /note="D -> N (in dbSNP:rs1042007)" FT /evidence="ECO:0000269|PubMed:8101525" FT /id="VAR_048904" FT MUTAGEN 40 FT /note="Q->E: Impairs assembly-stimulated GTPase activity. FT Does not affect basal GTPase activity. Does not affect FT membrane binding. Does not affect self-assembly. Completely FT inhibits receptor internalization." FT /evidence="ECO:0000269|PubMed:20428113" FT MUTAGEN 41 FT /note="S->A: Impairs assembly-stimulated GTPase activity. FT Does not affect basal GTPase activity. Does not affect FT membrane binding. Does not affect self-assembly." FT /evidence="ECO:0000269|PubMed:20428113" FT MUTAGEN 44 FT /note="K->A: Inhibits receptor-mediated endocytosis. FT Significantly decreases endocytosis. Impairs FT receptor-mediated endocytosis. Impairs receptor-mediated FT endocytosis; when associated with 591-K--T-602. Does not FT affect self-assembly into rings and stacks." FT /evidence="ECO:0000269|PubMed:30069048, FT ECO:0000269|PubMed:7877694, ECO:0000269|PubMed:7954789, FT ECO:0000269|PubMed:8101525" FT MUTAGEN 180 FT /note="D->A: Inhibits assembly-stimulated GTPase activity. FT Significantly increases basal GTPase activity Does not FT affect membrane binding. Does not affect self-assembly." FT /evidence="ECO:0000269|PubMed:20428113" FT MUTAGEN 290 FT /note="R->A: Does not significantly affect FT receptor-mediated endocytosis; when associated with A-291 FT and A-292." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 291 FT /note="D->A: Does not significantly affect FT receptor-mediated endocytosis; when associated with A-290 FT and A-292." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 292 FT /note="T->A: Does not significantly affect FT receptor-mediated endocytosis; when associated with A-290 FT and A-291." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 292 FT /note="T->A: Substantially reduces receptor-mediated FT endocytosis; whena ssociated with A-293 and A-294." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 293 FT /note="L->A: Substantially reduces receptor-mediated FT endocytosis; whena ssociated with A-292 and A-294." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 294 FT /note="P->A: Does not significantly affect FT receptor-mediated endocytosis. Substantially reduces FT receptor-mediated endocytosis; whena ssociated with A-292 FT and A-293." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 330 FT /note="L->R: Significantly decreases receptor-mediated FT endocytosis; when associated with R-334 and R-702." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 334 FT /note="Q->R: Significantly decreases receptor-mediated FT endocytosis; when associated with R-330 and R-702." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 406 FT /note="D->R: Significantly decreases receptor-mediated FT endocytosis; when associated with R-407 and W-488." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 407 FT /note="M->R: Significantly decreases receptor-mediated FT endocytosis; when associated with R-406 and W-488." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 488 FT /note="T->W: Significantly decreases receptor-mediated FT endocytosis; when associated with R-406 and W-407." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 591..602 FT /note="TEQRNVYKDYRQ->KDQRNT: Abolishes FT 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate binding. FT Impairs receptor-mediated endocytosis. Impairs FT receptor-mediated endocytosis; when associated with A-44." FT /evidence="ECO:0000269|PubMed:7954789" FT MUTAGEN 702 FT /note="L->R: Significantly decreases endocytosis; when FT associated with R-330 and R-334." FT /evidence="ECO:0000269|PubMed:30069048" FT MUTAGEN 774 FT /note="S->A: Increases clathrin-mediated endocytosis (CME); FT when associated with A-778. Increases interaction with FT SNX9; when associated with A-778." FT /evidence="ECO:0000269|PubMed:29668686" FT MUTAGEN 778 FT /note="S->A: Increases clathrin-mediated endocytosis (CME); FT when associated with A-774. Increases interaction with FT SNX9; when associated with A-774." FT /evidence="ECO:0000269|PubMed:29668686" FT CONFLICT 188 FT /note="K -> E (in Ref. 3; AAH50279)" FT /evidence="ECO:0000305" FT CONFLICT 287 FT /note="N -> D (in Ref. 3; AAH50279)" FT /evidence="ECO:0000305" FT CONFLICT 809 FT /note="L -> M (in Ref. 3; AAH50279)" FT /evidence="ECO:0000305" FT HELIX 9..21 FT /evidence="ECO:0007829|PDB:5D3Q" FT TURN 22..24 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 27..29 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 32..39 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 44..52 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 69..75 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 80..83 FT /evidence="ECO:0007829|PDB:5D3Q" FT TURN 85..88 FT /evidence="ECO:0007829|PDB:6S9A" FT HELIX 94..109 FT /evidence="ECO:0007829|PDB:5D3Q" FT TURN 110..113 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 120..126 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 152..164 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 169..176 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 185..193 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 198..205 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 217..220 FT /evidence="ECO:0007829|PDB:5D3Q" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 239..243 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 248..261 FT /evidence="ECO:0007829|PDB:5D3Q" FT TURN 263..265 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 266..271 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 274..311 FT /evidence="ECO:0007829|PDB:5D3Q" FT HELIX 312..316 FT /evidence="ECO:0007829|PDB:3ZYC" FT STRAND 520..529 FT /evidence="ECO:0007829|PDB:1DYN" FT HELIX 533..535 FT /evidence="ECO:0007829|PDB:1DYN" FT STRAND 537..555 FT /evidence="ECO:0007829|PDB:1DYN" FT STRAND 561..566 FT /evidence="ECO:0007829|PDB:1DYN" FT STRAND 570..574 FT /evidence="ECO:0007829|PDB:1DYN" FT STRAND 579..582 FT /evidence="ECO:0007829|PDB:1DYN" FT STRAND 584..590 FT /evidence="ECO:0007829|PDB:1DYN" FT STRAND 601..609 FT /evidence="ECO:0007829|PDB:1DYN" FT HELIX 610..622 FT /evidence="ECO:0007829|PDB:1DYN" SQ SEQUENCE 864 AA; 97408 MW; 7FCD8CB572FFEAEF CRC64; MGNRGMEDLI PLVNRLQDAF SAIGQNADLD LPQIAVVGGQ SAGKSSVLEN FVGRDFLPRG SGIVTRRPLV LQLVNATTEY AEFLHCKGKK FTDFEEVRLE IEAETDRVTG TNKGISPVPI NLRVYSPHVL NLTLVDLPGM TKVPVGDQPP DIEFQIRDML MQFVTKENCL ILAVSPANSD LANSDALKVA KEVDPQGQRT IGVITKLDLM DEGTDARDVL ENKLLPLRRG YIGVVNRSQK DIDGKKDITA ALAAERKFFL SHPSYRHLAD RMGTPYLQKV LNQQLTNHIR DTLPGLRNKL QSQLLSIEKE VEEYKNFRPD DPARKTKALL QMVQQFAVDF EKRIEGSGDQ IDTYELSGGA RINRIFHERF PFELVKMEFD EKELRREISY AIKNIHGIRT GLFTPDMAFE TIVKKQVKKI REPCLKCVDM VISELISTVR QCTKKLQQYP RLREEMERIV TTHIREREGR TKEQVMLLID IELAYMNTNH EDFIGFANAQ QRSNQMNKKK TSGNQDEILV IRKGWLTINN IGIMKGGSKE YWFVLTAENL SWYKDDEEKE KKYMLSVDNL KLRDVEKGFM SSKHIFALFN TEQRNVYKDY RQLELACETQ EEVDSWKASF LRAGVYPERV GDKEKASETE ENGSDSFMHS MDPQLERQVE TIRNLVDSYM AIVNKTVRDL MPKTIMHLMI NNTKEFIFSE LLANLYSCGD QNTLMEESAE QAQRRDEMLR MYHALKEALS IIGDINTTTV STPMPPPVDD SWLQVQSVPA GRRSPTSSPT PQRRAPAVPP ARPGSRGPAP GPPPAGSALG GAPPVPSRPG ASPDPFGPPP QVPSRPNRAP PGVPSRSGQA SPSRPESPRP PFDL //