ID NSF_CRIGR Reviewed; 744 AA. AC P18708; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 1. DT 27-MAR-2024, entry version 170. DE RecName: Full=Vesicle-fusing ATPase; DE EC=3.6.4.6; DE AltName: Full=N-ethylmaleimide-sensitive fusion protein; DE Short=NEM-sensitive fusion protein; DE AltName: Full=Vesicular-fusion protein NSF; GN Name=NSF; OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; OC Cricetidae; Cricetinae; Cricetulus. OX NCBI_TaxID=10029; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Ovary; RX PubMed=2657434; DOI=10.1038/339355a0; RA Wilson D.W., Wilcox C.A., Flynn G.C., Chen E., Kuang W.-J., Henzel W.J., RA Block M.R., Ullrich A., Rothman J.E.; RT "A fusion protein required for vesicle-mediated transport in both mammalian RT cells and yeast."; RL Nature 339:355-359(1989). RN [2] RP FUNCTION. RX PubMed=2542798; DOI=10.1038/339397a0; RA Beckers C.J.M., Block M.R., Glick B.S., Rothman J.E., Balch W.E.; RT "Vesicular transport between the endoplasmic reticulum and the Golgi stack RT requires the NEM-sensitive fusion protein."; RL Nature 339:397-398(1989). RN [3] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 487-740 IN COMPLEX WITH ATP RP ANALOG. RX PubMed=9727495; DOI=10.1016/s0092-8674(00)81593-7; RA Lenzen C.U., Steinmann D., Whiteheart S.W., Weis W.I.; RT "Crystal structure of the hexamerization domain of N-ethylmaleimide- RT sensitive fusion protein."; RL Cell 94:525-536(1998). RN [4] RP ERRATUM OF PUBMED:9727495. RA Lenzen C.U., Steinmann D., Whiteheart S.W., Weis W.I.; RL Cell 95:289-289(1998). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 478-744 IN COMPLEX WITH ATP AND RP MAGNESIUM. RX PubMed=9731775; DOI=10.1038/1843; RA Yu R.C., Hanson P.I., Jahn R., Bruenger A.T.; RT "Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide RT sensitive factor complexed with ATP."; RL Nat. Struct. Biol. 5:803-811(1998). RN [6] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-205. RX PubMed=10445031; DOI=10.1016/s1097-2765(00)80191-4; RA Yu R.C., Jahn R., Brunger A.T.; RT "NSF N-terminal domain crystal structure: models of NSF function."; RL Mol. Cell 4:97-107(1999). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-203. RX PubMed=10559905; DOI=10.1038/11097; RA May A.P., Misura K.M., Whiteheart S.W., Weis W.I.; RT "Crystal structure of the amino-terminal domain of N-ethylmaleimide- RT sensitive fusion protein."; RL Nat. Cell Biol. 1:175-182(1999). CC -!- FUNCTION: Required for vesicle-mediated transport. Catalyzes the fusion CC of transport vesicles within the Golgi cisternae. Is also required for CC transport from the endoplasmic reticulum to the Golgi stack. Seems to CC function as a fusion protein required for the delivery of cargo CC proteins to all compartments of the Golgi stack independent of vesicle CC origin. Interaction with AMPAR subunit GRIA2 leads to influence GRIA2 CC membrane cycling. {ECO:0000269|PubMed:2542798}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000305|PubMed:9731775}; CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000305|PubMed:9731775}; CC -!- SUBUNIT: Homohexamer. Interacts with GABARAP and GABARAPL2 (By CC similarity). Interacts with GRIA2 (By similarity). Interacts with PLK2, CC leading to disrupt the interaction with GRIA2 (By similarity). CC Interacts with MUSK; may regulate MUSK endocytosis and activity (By CC similarity). Interacts with CDK16 (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC P18708; P18708: NSF; NbExp=5; IntAct=EBI-925742, EBI-925742; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- PTM: Phosphorylation at Ser-569 interferes with homohexamerization. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA33678.1; Type=Erroneous initiation; 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; X15652; CAA33678.1; ALT_INIT; mRNA. DR PIR; S04235; S04235. DR RefSeq; XP_007606206.1; XM_007608016.1. DR PDB; 1D2N; X-ray; 1.75 A; A=487-740. DR PDB; 1NSF; X-ray; 1.90 A; A=478-744. DR PDB; 1QCS; X-ray; 1.90 A; A=1-205. DR PDB; 1QDN; X-ray; 2.30 A; A/B/C=1-203. DR PDB; 3J94; EM; 4.20 A; A/B/C/D/E/F=1-744. DR PDB; 3J95; EM; 7.60 A; A/B/C/D/E/F=1-744. DR PDB; 3J96; EM; 7.60 A; A/B/C/D/E/F=1-744. DR PDB; 3J97; EM; 7.80 A; A/B/C/D/E/F=1-744. DR PDB; 3J98; EM; 8.40 A; A/B/C/D/E/F=1-744. DR PDB; 3J99; EM; 8.20 A; A/B/C/D/E/F=1-744. DR PDB; 6IP2; EM; 3.70 A; A/B/C/D/E/F=1-744. DR PDB; 6MDM; EM; 4.40 A; A/B/C/D/E/F=1-744. DR PDB; 6MDN; EM; 4.40 A; A/B/C/D/E/F=1-723. DR PDB; 6MDO; EM; 3.90 A; A/B/C/D/E/F=1-723. DR PDB; 6MDP; EM; 3.80 A; A/B/C/D/E/F=1-723. DR PDBsum; 1D2N; -. DR PDBsum; 1NSF; -. DR PDBsum; 1QCS; -. DR PDBsum; 1QDN; -. DR PDBsum; 3J94; -. DR PDBsum; 3J95; -. DR PDBsum; 3J96; -. DR PDBsum; 3J97; -. DR PDBsum; 3J98; -. DR PDBsum; 3J99; -. DR PDBsum; 6IP2; -. DR PDBsum; 6MDM; -. DR PDBsum; 6MDN; -. DR PDBsum; 6MDO; -. DR PDBsum; 6MDP; -. DR AlphaFoldDB; P18708; -. DR EMDB; EMD-6204; -. DR EMDB; EMD-6205; -. DR EMDB; EMD-6206; -. DR EMDB; EMD-6207; -. DR EMDB; EMD-6208; -. DR EMDB; EMD-6209; -. DR EMDB; EMD-6210; -. DR EMDB; EMD-9100; -. DR EMDB; EMD-9101; -. DR EMDB; EMD-9102; -. DR EMDB; EMD-9103; -. DR EMDB; EMD-9698; -. DR SMR; P18708; -. DR DIP; DIP-35598N; -. DR IntAct; P18708; 9. DR BindingDB; P18708; -. DR ChEMBL; CHEMBL4739845; -. DR iPTMnet; P18708; -. DR PaxDb; 10029-XP_007606206-1; -. DR Ensembl; ENSCGRT00001028633.1; ENSCGRP00001024387.1; ENSCGRG00001022331.1. DR GeneID; 100770898; -. DR CTD; 4905; -. DR eggNOG; KOG0741; Eukaryota. DR GeneTree; ENSGT00530000064085; -. DR OrthoDB; 553800at2759; -. DR EvolutionaryTrace; P18708; -. DR Proteomes; UP000694386; Unplaced. DR Proteomes; UP001108280; Genome assembly. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl. DR GO; GO:0030496; C:midbody; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:Ensembl. DR GO; GO:0140545; F:ATP-dependent protein disaggregase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0000149; F:SNARE binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0017075; F:syntaxin-1 binding; IEA:Ensembl. DR GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl. DR GO; GO:0001921; P:positive regulation of receptor recycling; IEA:Ensembl. DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl. DR GO; GO:0035494; P:SNARE complex disassembly; IDA:ParkinsonsUK-UCL. DR CDD; cd19504; RecA-like_NSF-SEC18_r1-like; 1. DR Gene3D; 1.10.8.60; -; 2. DR Gene3D; 2.40.40.20; -; 1. DR Gene3D; 3.10.330.10; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR041569; AAA_lid_3. DR InterPro; IPR009010; Asp_de-COase-like_dom_sf. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR003960; ATPase_AAA_CS. DR InterPro; IPR004201; Cdc48_dom2. DR InterPro; IPR029067; CDC48_domain_2-like_sf. DR InterPro; IPR003338; CDC4_N-term_subdom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR039812; Vesicle-fus_ATPase. DR PANTHER; PTHR23078:SF3; VESICLE-FUSING ATPASE; 1. DR PANTHER; PTHR23078; VESICULAR-FUSION PROTEIN NSF; 1. DR Pfam; PF00004; AAA; 2. DR Pfam; PF17862; AAA_lid_3; 1. DR Pfam; PF02933; CDC48_2; 1. DR Pfam; PF02359; CDC48_N; 1. DR PRINTS; PR00830; ENDOLAPTASE. DR SMART; SM00382; AAA; 2. DR SMART; SM01072; CDC48_2; 1. DR SMART; SM01073; CDC48_N; 1. DR SUPFAM; SSF50692; ADC-like; 1. DR SUPFAM; SSF54585; Cdc48 domain 2-like; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS00674; AAA; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; KW Direct protein sequencing; Hydrolase; Magnesium; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Protein transport; Repeat; Transport. FT CHAIN 1..744 FT /note="Vesicle-fusing ATPase" FT /id="PRO_0000084562" FT BINDING 505..510 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:9731775, FT ECO:0000305|PubMed:9727495" FT BINDING 545..552 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:9731775, FT ECO:0000305|PubMed:9727495" FT BINDING 550 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:9731775" FT MOD_RES 105 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P46460" FT MOD_RES 207 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P46459" FT MOD_RES 259 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P46460" FT MOD_RES 569 FT /note="Phosphoserine; by CDK16" FT /evidence="ECO:0000250|UniProtKB:P46460" FT STRAND 4..10 FT /evidence="ECO:0007829|PDB:1QCS" FT HELIX 14..18 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 22..24 FT /evidence="ECO:0007829|PDB:1QCS" FT TURN 26..28 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 34..40 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 43..51 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 59..62 FT /evidence="ECO:0007829|PDB:1QCS" FT HELIX 64..70 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 77..83 FT /evidence="ECO:0007829|PDB:1QCS" FT HELIX 87..90 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 91..102 FT /evidence="ECO:0007829|PDB:1QCS" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:1QCS" FT HELIX 114..125 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 135..140 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 143..154 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 173..176 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 182..187 FT /evidence="ECO:0007829|PDB:1QCS" FT STRAND 194..200 FT /evidence="ECO:0007829|PDB:1QCS" FT TURN 500..502 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 512..530 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 535..542 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 549..560 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 563..568 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 570..572 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 578..593 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 595..602 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 605..608 FT /evidence="ECO:0007829|PDB:1D2N" FT TURN 613..616 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 620..629 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 639..647 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 649..654 FT /evidence="ECO:0007829|PDB:1D2N" FT TURN 658..660 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 661..666 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 670..672 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 673..683 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 688..698 FT /evidence="ECO:0007829|PDB:1D2N" FT STRAND 701..705 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 707..717 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 722..724 FT /evidence="ECO:0007829|PDB:1D2N" FT HELIX 725..735 FT /evidence="ECO:0007829|PDB:1D2N" SQ SEQUENCE 744 AA; 82536 MW; F3E0CEB2CF1BD582 CRC64; MAGRSMQAAR CPTDELSLSN CAVVSEKDYQ SGQHVIVRTS PNHKYIFTLR THPSVVPGSV AFSLPQRKWA GLSIGQEIEV ALYSFDKAKQ CIGTMTIEID FLQKKNIDSN PYDTDKMAAE FIQQFNNQAF SVGQQLVFSF NDKLFGLLVK DIEAMDPSIL KGEPASGKRQ KIEVGLVVGN SQVAFEKAEN SSLNLIGKAK TKENRQSIIN PDWNFEKMGI GGLDKEFSDI FRRAFASRVF PPEIVEQMGC KHVKGILLYG PPGCGKTLLA RQIGKMLNAR EPKVVNGPEI LNKYVGESEA NIRKLFADAE EEQRRLGANS GLHIIIFDEI DAICKQRGSM AGSTGVHDTV VNQLLSKIDG VEQLNNILVI GMTNRPDLID EALLRPGRLE VKMEIGLPDE KGRLQILHIH TARMRGHQLL SADVDIKELA VETKNFSGAE LEGLVRAAQS TAMNRHIKAS TKVEVDMEKA ESLQVTRGDF LASLENDIKP AFGTNQEDYA SYIMNGIIKW GDPVTRVLDD GELLVQQTKN SDRTPLVSVL LEGPPHSGKT ALAAKIAEES NFPFIKICSP DKMIGFSETA KCQAMKKIFD DAYKSQLSCV VVDDIERLLD YVPIGPRFSN LVLQALLVLL KKAPPQGRKL LIIGTTSRKD VLQEMEMLNA FSTTIHVPNI ATGEQLLEAL ELLGNFKDKE RTTIAQQVKG KKVWIGIKKL LMLIEMSLQM DPEYRVRKFL ALLREEGASP LDFD //