P46459 (NSF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

NSF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	744 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Seem 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.
Catalytic activity	ATP + H2O = ADP + phosphate.
Cofactor	Binds 1 magnesium ion per subunit By similarity.
Subunit structure	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.
Subcellular location	Cytoplasm.
Post-translational modification	Phosphorylation at Ser-569 interferes with homohexamerization By similarity.
Sequence similarities	Belongs to the AAA ATPase family.
Sequence caution	The sequence AAA17411.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	exocytosis Traceable author statement PubMed 15613468. Source: UniProtKB plasma membrane fusion Traceable author statement PubMed 15613468. Source: UniProtKB positive regulation of receptor recycling Inferred from direct assay PubMed 15613468. Source: UniProtKB potassium ion transport Inferred from electronic annotation. Source: Compara protein transport Inferred from electronic annotation. Source: UniProtKB-KW synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay PubMed 15613468. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity, coupled Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein complex binding Inferred from direct assay PubMed 15613468. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 744	744	Vesicle-fusing ATPase		PRO_0000084563
Regions
	Nucleotide binding	505 – 510	6	ATP By similarity
	Nucleotide binding	545 – 552	8	ATP By similarity
Sites
	Metal binding	550	1	Magnesium By similarity
Amino acid modifications
	Modified residue	259	1	Phosphotyrosine By similarity
	Modified residue	569	1	Phosphoserine; by CDK16 By similarity
Natural variations
	Natural variant	476	1	T → M. Corresponds to variant rs155733 [ dbSNP | Ensembl ].		VAR_029580
Experimental info
	Sequence conflict	22	1	A → S in AAA17411. Ref.1
	Sequence conflict	22	1	A → S in AAF70545. Ref.2
	Sequence conflict	25	1	N → S in BAF82893. Ref.4
	Sequence conflict	107	1	I → N in AAA17411. Ref.1
	Sequence conflict	107	1	I → N in AAF70545. Ref.2
	Sequence conflict	107	1	I → N in AAF04745. Ref.3
	Sequence conflict	130	1	F → Y in AAA17411. Ref.1
	Sequence conflict	130	1	F → Y in AAF70545. Ref.2
	Sequence conflict	130	1	F → Y in AAF04745. Ref.3
	Sequence conflict	154	1	A → S in AAA17411. Ref.1
	Sequence conflict	154	1	A → S in AAF70545. Ref.2
	Sequence conflict	154	1	A → S in AAF04745. Ref.3
	Sequence conflict	237	1	S → F in AAA17411. Ref.1
	Sequence conflict	237	1	S → F in AAF70545. Ref.2
	Sequence conflict	237	1	S → F in AAF04745. Ref.3
	Sequence conflict	251	1	K → I in AAA17411. Ref.1
	Sequence conflict	251	1	K → I in AAF70545. Ref.2
	Sequence conflict	251	1	K → I in AAF04745. Ref.3
	Sequence conflict	427	1	K → R in BAF82893. Ref.4
	Sequence conflict	571	1	D → E in AAF04745. Ref.3
	Sequence conflict	639	1	K → M in BAF82893. Ref.4
	Sequence conflict	686	1	F → L in AAA17411. Ref.1
	Sequence conflict	686	1	F → L in AAF70545. Ref.2
	Sequence conflict	686	1	F → L in AAF04745. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P46459 [UniParc]. Last modified September 1, 2009. Version 3. Checksum: BF545A2A0C7EC2F7	FASTA	744	82,594
	10 20 30 40 50 60 MAGRSMQAAR CPTDELSLTN CAVVNEKDFQ SGQHVIVRTS PNHRYTFTLK THPSVVPGSI 70 80 90 100 110 120 AFSLPQRKWA GLSIGQEIEV SLYTFDKAKQ CIGTMTIEID FLQKKSIDSN PYDTDKMAAE 130 140 150 160 170 180 FIQQFNNQAF SVGQQLVFSF NEKLFGLLVK DIEAMDPSIL KGEPATGKRQ KIEVGLVVGN 190 200 210 220 230 240 SQVAFEKAEN SSLNLIGKAK TKENRQSIIN PDWNFEKMGI GGLDKEFSDI FRRAFASRVF 250 260 270 280 290 300 PPEIVEQMGC KHVKGILLYG PPGCGKTLLA RQIGKMLNAR EPKVVNGPEI LNKYVGESEA 310 320 330 340 350 360 NIRKLFADAE EEQRRLGANS GLHIIIFDEI DAICKQRGSM AGSTGVHDTV VNQLLSKIDG 370 380 390 400 410 420 VEQLNNILVI GMTNRPDLID EALLRPGRLE VKMEIGLPDE KGRLQILHIH TARMRGHQLL 430 440 450 460 470 480 SADVDIKELA VETKNFSGAE LEGLVRAAQS TAMNRHIKAS TKVEVDMEKA ESLQVTRGDF 490 500 510 520 530 540 LASLENDIKP AFGTNQEDYA SYIMNGIIKW GDPVTRVLDD GELLVQQTKN SDRTPLVSVL 550 560 570 580 590 600 LEGPPHSGKT ALAAKIAEES NFPFIKICSP DKMIGFSETA KCQAMKKIFD DAYKSQLSCV 610 620 630 640 650 660 VVDDIERLLD YVPIGPRFSN LVLQALLVLL KKAPPQGRKL LIIGTTSRKD VLQEMEMLNA 670 680 690 700 710 720 FSTTIHVPNI ATGEQLLEAL ELLGNFKDKE RTTIAQQVKG KKVWIGIKKL LMLIEMSLQM 730 740 DPEYRVRKFL ALLREEGASP LDFD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and localization of a brain N-ethylmaleimide-sensitive factor involved in vesicular transport." Hong R., Moriyama Y., Mori H., Futai M., Yamamoto A., Tashiro Y., Fukui T., Tagaya M. Submitted (DEC-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	Bui T.D., Lu L., Hong W. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The regulation of hNSF gene expression." Zhang R., Liu Z., Wu M. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U03985 mRNA. Translation: AAA17411.1. Different initiation. AF135168 mRNA. Translation: AAF70545.1. AF102846 mRNA. Translation: AAF04745.2. AK290204 mRNA. Translation: BAF82893.1. 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.
IPI	IPI00006451.
PIR	G01234.
RefSeq	NP_006169.2. NM_006178.3.
UniGene	Hs.431279.
3D structure databases
ProteinModelPortal	P46459.
SMR	P46459. Positions 1-742.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-389N.
IntAct	P46459. 29 interactions.
MINT	MINT-1369243.
STRING	9606.ENSP00000381293.
Protein family/group databases
TCDB	1.F.1.1.1. synaptosomal vesicle fusion pore (SVF-Pore) family.
PTM databases
PhosphoSite	P46459.
Polymorphism databases
DMDM	257051048.
2D gel databases
UCD-2DPAGE	P46459.
Proteomic databases
PaxDb	P46459.
PRIDE	P46459.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000398238; ENSP00000381293; ENSG00000073969.
GeneID	4905.
KEGG	hsa:4905.
UCSC	uc002iku.3. human.
Organism-specific databases
CTD	4905.
GeneCards	GC17P044668.
H-InvDB	HIX0013914. HIX0013915.
HGNC	HGNC:8016. NSF.
HPA	CAB009324. CAB013645. HPA003154.
MIM	601633. gene.
neXtProt	NX_P46459.
PharmGKB	PA31793.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0464.
HOGENOM	HOG000198544.
HOVERGEN	HBG000324.
InParanoid	P46459.
KO	K06027.
OMA	IFTLRTH.
OrthoDB	EOG4DZ1TR.
PhylomeDB	P46459.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	P46459.
Bgee	P46459.
CleanEx	HS_NSF.
Genevestigator	P46459.
GermOnline	ENSG00000073969. Homo sapiens.
Family and domain databases
Gene3D	2.40.40.20. 1 hit.
InterPro	IPR003593. AAA+_ATPase. IPR009010. Asp_de-COase-like_dom. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. IPR004201. Cdc48_dom2. IPR003338. CDC4_N-term_subdom. [Graphical view]
Pfam	PF00004. AAA. 2 hits. PF02933. CDC48_2. 1 hit. PF02359. CDC48_N. 1 hit. [Graphical view]
SMART	SM00382. AAA. 2 hits. SM01072. CDC48_2. 1 hit. SM01073. CDC48_N. 1 hit. [Graphical view]
SUPFAM	SSF50692. Asp_decarb_fold. 1 hit.
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NSF. human.
GenomeRNAi	4905.
NextBio	18875.
PMAP-CutDB	P46459.
SOURCE	Search...

Entry information

Entry name

NSF_HUMAN

Accession

Primary (citable) accession number: P46459
Secondary accession number(s): A8K2D9, Q8N6D7, Q9UKZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	September 1, 2009
Last modified:	May 1, 2013
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.