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Protein

Vesicle-fusing ATPase

Gene

NSF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seems to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack independent of vesicle origin. Interaction with AMPAR subunit GRIA2 leads to influence GRIA2 membrane cycling (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Cofactori

Mg2+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi550MagnesiumBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi505 – 510ATPBy similarity6
Nucleotide bindingi545 – 552ATPBy similarity8

GO - Molecular functioni

  • ATPase activity Source: ParkinsonsUK-UCL
  • ATPase activity, coupled Source: Ensembl
  • ATP binding Source: UniProtKB-KW
  • ionotropic glutamate receptor binding Source: ParkinsonsUK-UCL
  • metal ion binding Source: UniProtKB-KW
  • PDZ domain binding Source: UniProtKB
  • protein-containing complex binding Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL
  • Rab GTPase binding Source: ParkinsonsUK-UCL
  • SNARE binding Source: ParkinsonsUK-UCL
  • syntaxin-1 binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • COPII vesicle coating Source: Reactome
  • ER to Golgi vesicle-mediated transport Source: Reactome
  • exocytosis Source: UniProtKB
  • intracellular protein transport Source: CACAO
  • plasma membrane fusion Source: UniProtKB
  • positive regulation of protein catabolic process Source: CACAO
  • positive regulation of receptor recycling Source: UniProtKB
  • potassium ion transport Source: Ensembl
  • regulation of exocytosis Source: ParkinsonsUK-UCL
  • retrograde vesicle-mediated transport, Golgi to ER Source: Reactome
  • SNARE complex disassembly Source: ParkinsonsUK-UCL
  • vesicle-mediated transport Source: ParkinsonsUK-UCL

Keywordsi

Molecular functionHydrolase
Biological processProtein transport, Transport
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-204005 COPII (Coat Protein 2) Mediated Vesicle Transport
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors
R-HSA-6807878 COPI-mediated anterograde transport
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-6811438 Intra-Golgi traffic
R-HSA-6811440 Retrograde transport at the Trans-Golgi-Network
SIGNORiP46459

Protein family/group databases

TCDBi1.F.1.1.1 the synaptosomal vesicle fusion pore (svf-pore) family

Names & Taxonomyi

Protein namesi
Recommended name:
Vesicle-fusing ATPase (EC:3.6.4.6)
Alternative name(s):
N-ethylmaleimide-sensitive fusion protein
Short name:
NEM-sensitive fusion protein
Vesicular-fusion protein NSF
Gene namesi
Name:NSF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000073969.18
HGNCiHGNC:8016 NSF
MIMi601633 gene
neXtProtiNX_P46459

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi4905
OpenTargetsiENSG00000073969
PharmGKBiPA31793

Chemistry databases

ChEMBLiCHEMBL2311231

Polymorphism and mutation databases

BioMutaiNSF
DMDMi257051048

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000845631 – 744Vesicle-fusing ATPaseAdd BLAST744

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei105N6-acetyllysineBy similarity1
Modified residuei207PhosphoserineCombined sources1
Modified residuei259PhosphotyrosineBy similarity1
Modified residuei569Phosphoserine; by CDK16By similarity1

Post-translational modificationi

Phosphorylation at Ser-569 interferes with homohexamerization.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP46459
MaxQBiP46459
PaxDbiP46459
PeptideAtlasiP46459
PRIDEiP46459

2D gel databases

UCD-2DPAGEiP46459

PTM databases

iPTMnetiP46459
PhosphoSitePlusiP46459
SwissPalmiP46459

Miscellaneous databases

PMAP-CutDBiP46459

Expressioni

Gene expression databases

BgeeiENSG00000073969
CleanExiHS_NSF
ExpressionAtlasiP46459 baseline and differential
GenevisibleiP46459 HS

Organism-specific databases

HPAiCAB009324
CAB013645
HPA003154
HPA071089

Interactioni

Subunit structurei

Homohexamer. Interacts with GABARAP and GABARAPL2. Interacts with GRIA2. Interacts with PLK2, leading to disrupt the interaction with GRIA2. Interacts with MUSK; may regulate MUSK endocytosis and activity (By similarity). Interacts with CDK16 (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • ionotropic glutamate receptor binding Source: ParkinsonsUK-UCL
  • PDZ domain binding Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL
  • Rab GTPase binding Source: ParkinsonsUK-UCL
  • SNARE binding Source: ParkinsonsUK-UCL
  • syntaxin-1 binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi110960, 72 interactors
IntActiP46459, 51 interactors
MINTiP46459
STRINGi9606.ENSP00000381293

Structurei

3D structure databases

ProteinModelPortaliP46459
SMRiP46459
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0741 Eukaryota
COG0464 LUCA
GeneTreeiENSGT00530000064085
HOGENOMiHOG000198544
HOVERGENiHBG000324
InParanoidiP46459
KOiK06027
OMAiIDWVPIG
OrthoDBiEOG091G02LU
PhylomeDBiP46459
TreeFamiTF300371

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR009010 Asp_de-COase-like_dom_sf
IPR003959 ATPase_AAA_core
IPR003960 ATPase_AAA_CS
IPR004201 Cdc48_dom2
IPR029067 CDC48_domain_2-like_sf
IPR003338 CDC4_N-term_subdom
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00004 AAA, 2 hits
PF02933 CDC48_2, 1 hit
PF02359 CDC48_N, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 2 hits
SM01072 CDC48_2, 1 hit
SM01073 CDC48_N, 1 hit
SUPFAMiSSF50692 SSF50692, 1 hit
SSF52540 SSF52540, 2 hits
SSF54585 SSF54585, 1 hit
PROSITEiView protein in PROSITE
PS00674 AAA, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P46459-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGRSMQAAR CPTDELSLTN CAVVNEKDFQ SGQHVIVRTS PNHRYTFTLK
60 70 80 90 100
THPSVVPGSI AFSLPQRKWA GLSIGQEIEV SLYTFDKAKQ CIGTMTIEID
110 120 130 140 150
FLQKKSIDSN PYDTDKMAAE FIQQFNNQAF SVGQQLVFSF NEKLFGLLVK
160 170 180 190 200
DIEAMDPSIL KGEPATGKRQ KIEVGLVVGN SQVAFEKAEN SSLNLIGKAK
210 220 230 240 250
TKENRQSIIN PDWNFEKMGI GGLDKEFSDI FRRAFASRVF PPEIVEQMGC
260 270 280 290 300
KHVKGILLYG PPGCGKTLLA RQIGKMLNAR EPKVVNGPEI LNKYVGESEA
310 320 330 340 350
NIRKLFADAE EEQRRLGANS GLHIIIFDEI DAICKQRGSM AGSTGVHDTV
360 370 380 390 400
VNQLLSKIDG VEQLNNILVI GMTNRPDLID EALLRPGRLE VKMEIGLPDE
410 420 430 440 450
KGRLQILHIH TARMRGHQLL SADVDIKELA VETKNFSGAE LEGLVRAAQS
460 470 480 490 500
TAMNRHIKAS TKVEVDMEKA ESLQVTRGDF LASLENDIKP AFGTNQEDYA
510 520 530 540 550
SYIMNGIIKW GDPVTRVLDD GELLVQQTKN SDRTPLVSVL LEGPPHSGKT
560 570 580 590 600
ALAAKIAEES NFPFIKICSP DKMIGFSETA KCQAMKKIFD DAYKSQLSCV
610 620 630 640 650
VVDDIERLLD YVPIGPRFSN LVLQALLVLL KKAPPQGRKL LIIGTTSRKD
660 670 680 690 700
VLQEMEMLNA FSTTIHVPNI ATGEQLLEAL ELLGNFKDKE RTTIAQQVKG
710 720 730 740
KKVWIGIKKL LMLIEMSLQM DPEYRVRKFL ALLREEGASP LDFD
Length:744
Mass (Da):82,594
Last modified:September 1, 2009 - v3
Checksum:iBF545A2A0C7EC2F7
GO
Isoform 2 (identifier: P46459-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: Missing.
     739-744: Missing.

Note: No experimental confirmation available.
Show »
Length:644
Mass (Da):71,584
Checksum:iACC3C42259713D42
GO

Sequence cautioni

The sequence AAA17411 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22A → S in AAA17411 (Ref. 1) Curated1
Sequence conflicti22A → S in AAF70545 (Ref. 2) Curated1
Sequence conflicti25N → S in BAF82893 (PubMed:14702039).Curated1
Sequence conflicti107I → N in AAA17411 (Ref. 1) Curated1
Sequence conflicti107I → N in AAF70545 (Ref. 2) Curated1
Sequence conflicti107I → N in AAF04745 (Ref. 3) Curated1
Sequence conflicti130F → Y in AAA17411 (Ref. 1) Curated1
Sequence conflicti130F → Y in AAF70545 (Ref. 2) Curated1
Sequence conflicti130F → Y in AAF04745 (Ref. 3) Curated1
Sequence conflicti154A → S in AAA17411 (Ref. 1) Curated1
Sequence conflicti154A → S in AAF70545 (Ref. 2) Curated1
Sequence conflicti154A → S in AAF04745 (Ref. 3) Curated1
Sequence conflicti237S → F in AAA17411 (Ref. 1) Curated1
Sequence conflicti237S → F in AAF70545 (Ref. 2) Curated1
Sequence conflicti237S → F in AAF04745 (Ref. 3) Curated1
Sequence conflicti251K → I in AAA17411 (Ref. 1) Curated1
Sequence conflicti251K → I in AAF70545 (Ref. 2) Curated1
Sequence conflicti251K → I in AAF04745 (Ref. 3) Curated1
Sequence conflicti427K → R in BAF82893 (PubMed:14702039).Curated1
Sequence conflicti571D → E in AAF04745 (Ref. 3) Curated1
Sequence conflicti639K → M in BAF82893 (PubMed:14702039).Curated1
Sequence conflicti686F → L in AAA17411 (Ref. 1) Curated1
Sequence conflicti686F → L in AAF70545 (Ref. 2) Curated1
Sequence conflicti686F → L in AAF04745 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029580476T → M. Corresponds to variant dbSNP:rs155733Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564201 – 94Missing in isoform 2. 1 PublicationAdd BLAST94
Alternative sequenceiVSP_056421739 – 744Missing in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U03985 mRNA Translation: AAA17411.1 Different initiation.
AF135168 mRNA Translation: AAF70545.1
AF102846 mRNA Translation: AAF04745.2
AK290204 mRNA Translation: BAF82893.1
AK294001 mRNA Translation: BAG57363.1
AC004098 Genomic DNA No translation available.
AC138645 Genomic DNA No translation available.
AC138688 Genomic DNA No translation available.
AC217769 Genomic DNA No translation available.
AC217778 Genomic DNA No translation available.
AC217780 Genomic DNA No translation available.
BC030613 mRNA Translation: AAH30613.1
CCDSiCCDS42354.1 [P46459-1]
PIRiG01234
RefSeqiNP_006169.2, NM_006178.3 [P46459-1]
UniGeneiHs.431279

Genome annotation databases

EnsembliENST00000398238; ENSP00000381293; ENSG00000073969 [P46459-1]
ENST00000611398; ENSP00000478614; ENSG00000278174 [P46459-1]
ENST00000620290; ENSP00000481714; ENSG00000276262 [P46459-1]
GeneIDi4905
KEGGihsa:4905
UCSCiuc002iku.4 human [P46459-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNSF_HUMAN
AccessioniPrimary (citable) accession number: P46459
Secondary accession number(s): A8K2D9
, B4DFA2, Q8N6D7, Q9UKZ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: September 1, 2009
Last modified: April 25, 2018
This is version 183 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health