NSF_CRIGR
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 03-AUG-2022, entry version 163.
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};
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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 SMR; P18708; -.
DR DIP; DIP-35598N; -.
DR IntAct; P18708; 9.
DR STRING; 10029.XP_007606206.1; -.
DR BindingDB; P18708; -.
DR ChEMBL; CHEMBL4739845; -.
DR iPTMnet; P18708; -.
DR Ensembl; ENSCGRT00001028633; ENSCGRP00001024387; ENSCGRG00001022331.
DR GeneID; 100770898; -.
DR KEGG; cge:100770898; -.
DR CTD; 4905; -.
DR eggNOG; KOG0741; Eukaryota.
DR GeneTree; ENSGT00530000064085; -.
DR OrthoDB; 197562at2759; -.
DR EvolutionaryTrace; P18708; -.
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 Gene3D; 3.40.50.300; -; 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; PTHR23078; 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 SMART; SM00382; AAA; 2.
DR SMART; SM01072; CDC48_2; 1.
DR SMART; SM01073; CDC48_N; 1.
DR SUPFAM; SSF50692; SSF50692; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF54585; SSF54585; 1.
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
