P46462 (TERA_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transitional endoplasmic reticulum ATPase
Short name=TER ATPase
EC=3.6.4.6

Alternative name(s):
15S Mg(2+)-ATPase p97 subunit
Valosin-containing protein
Short name=VCP

Gene names

Name:

Vcp

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	806 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage By similarity. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Ref.6 Ref.8
Catalytic activity	ATP + H2O = ADP + phosphate.
Subunit structure	Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. Interacts with NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with RHBDD1 (via C-terminus domain) By similarity. Interacts with VIMP/SELS and SYVN1, as well as with DERL1, DERL2 and DERL3; which probably transfer misfolded proteins from the ER to VCP. Interacts with SVIP. Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Directly interacts with UBXD2 and RNF19A. Interacts with CASR. Interacts with UBXN6, UBE4B and YOD1. Interacts with clathrin. Interacts with RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of the endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts directly with AMFR/gp78 (via its VIM). Interacts with METTL21D. Interacts with SPRTN; leading to recruitment to stalled replication forks By similarity. Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Binds to a heterodimer of NPLOC4 and UFD1L, binding to this heterodimer inhibits Golgi-membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Part of a ternary complex containing NPLOC4, UFD1L and VCP. Ref.4 Ref.5 Ref.7 Ref.8 Ref.9
Subcellular location	Cytoplasm › cytosol. Nucleus. Endoplasmic reticulum By similarity. Note: Recruited to the cytoplasmic surface of the endoplasmic reticulum via interaction with AMFR/gp78. Following DNA double-strand breaks, recruited to the sites of damage. Recruited to stalled replication forks via interaction with SPRTN By similarity. Ref.5
Post-translational modification	Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells. Ref.10 ISGylated By similarity.
Sequence similarities	Belongs to the AAA ATPase family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Transport
Cellular component	Cytoplasm Endoplasmic reticulum Nucleus
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Acetylation Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ER to Golgi vesicle-mediated transport Inferred from mutant phenotype Ref.1. Source: RGD ER-associated protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara aggresome assembly Inferred from electronic annotation. Source: Compara double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype PubMed 16103111. Source: RGD positive regulation of protein complex assembly Inferred from electronic annotation. Source: Compara protein N-linked glycosylation via asparagine Inferred from sequence or structural similarity. Source: UniProtKB protein homooligomerization Inferred from direct assay Ref.1. Source: RGD protein ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB retrograde protein transport, ER to cytosol Inferred from electronic annotation. Source: Compara translesion synthesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.5. Source: RGD endoplasmic reticulum Inferred from direct assay Ref.1. Source: RGD nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell proteasome complex Inferred from electronic annotation. Source: Compara site of double-strand break Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ADP binding Inferred from mutant phenotype PubMed 18332143. Source: RGD ATP binding Inferred from direct assay Ref.1. Source: BHF-UCL ATPase activity Inferred from direct assay Ref.1. Source: RGD identical protein binding Inferred from direct assay Ref.1. Source: BHF-UCL lipid binding Inferred from electronic annotation. Source: UniProtKB-KW receptor binding Inferred from direct assay PubMed 16103111. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Nsfl1c	O35987	4	EBI-399011,EBI-1993760

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 806	805	Transitional endoplasmic reticulum ATPase		PRO_0000084575
Regions
	Nucleotide binding	247 – 253	7	ATP By similarity
	Region	797 – 806	10	Interaction with UBXN6 By similarity
Sites
	Binding site	348	1	ATP By similarity
	Binding site	384	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	3	1	Phosphoserine By similarity
	Modified residue	7	1	Phosphoserine By similarity
	Modified residue	37	1	Phosphoserine By similarity
	Modified residue	315	1	N6,N6,N6-trimethyllysine; by METTL21D By similarity
	Modified residue	436	1	Phosphothreonine By similarity
	Modified residue	770	1	Phosphoserine By similarity
	Modified residue	775	1	Phosphoserine By similarity
	Modified residue	787	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P46462 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 501B721D205EBA8A	FASTA	806	89,349
	10 20 30 40 50 60 MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK 70 80 90 100 110 120 GKKRREAVCI VLSDDTCSDE KIRMNRVVRN NLRVRLGDVI SIQPCPDVKY GKRIHVLPID 130 140 150 160 170 180 DTVEGITGNL FEVYLKPYFL EAYRPIRKGD IFLVRGGMRA VEFKVVETDP SPYCIVAPDT 190 200 210 220 230 240 VIHCEGEPIK REDEEESLNE VGYDDIGGCR KQLAQIKEMV ELPLRHPALF KAIGVKPPRG 250 260 270 280 290 300 ILLYGPPGTG KTLIARAVAN ETGAFFFLIN GPEIMSKLAG ESESNLRKAF EEAEKNAPAI 310 320 330 340 350 360 IFIDELDAIA PKREKTHGEV ERRIVSQLLT LMDGLKQRAH VIVMAATNRP NSIDPALRRF 370 380 390 400 410 420 GRFDREVDIG IPDATGRLEI LQIHTKNMKL ADDVDLEQVA NETHGHVGAD LAALCSEAAL 430 440 450 460 470 480 QAIRKKMDLI DLEDETIDAE VMNSLAVTMD DFRWALSQSN PSALRETVVE VPQVTWEDIG 490 500 510 520 530 540 GLEDVKRELQ ELVQYPVEHP DKFLKFGMTP SKGVLFYGPP GCGKTLLAKA IANECQANFI 550 560 570 580 590 600 SIKGPELLTM WFGESEANVR EIFDKARQAA PCVLFFDELD SIAKARGGNI GDGGGAADRV 610 620 630 640 650 660 INQILTEMDG MSTKKNVFII GATNRPDIID PAILRPGRLD QLIYIPLPDE KSRVAILKAN 670 680 690 700 710 720 LRKSPVAKDV DLEFLAKMTN GFSGADLTEI CQRACKLAIR ESIESEIRRE RERQTNPSAM 730 740 750 760 770 780 EVEEDDPVPE IRRDHFEEAM RFARRSVSDN DIRKYEMFAQ TLQQSRGFGS FRFPSGNQGG 790 800 AGPSQGSGGG TGGNVYTEDN DDDLYG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the principal ATPase associated with transitional endoplasmic reticulum of rat liver." Zhang L., Ashendel C.L., Becker G.W., Morre D.J. J. Cell Biol. 127:1871-1883(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Strain: Sprague-Dawley. Tissue: Liver.
[2]	"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: Prostate.
[3]	Lubec G., Diao W. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 46-53; 149-155; 192-210; 218-225; 240-251; 296-312; 366-386; 454-465; 616-638; 669-677 AND 701-709, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus.
[4]	"Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro." Rabouille C., Kondo H., Newman R., Hui N., Freemont P., Warren G. Cell 92:603-610(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STX5A.
[5]	"A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways." Meyer H.H., Shorter J.G., Seemann J., Pappin D., Warren G. EMBO J. 19:2181-2192(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NPLOC4; UFD1L; NSFL1C AND UBE4B, SUBCELLULAR LOCATION.
[6]	"Role of p97 and syntaxin 5 in the assembly of transitional endoplasmic reticulum." Roy L., Bergeron J.J.M., Lavoie C., Hendriks R., Gushue J., Fazel A., Pelletier A., Morre D.J., Subramaniam V.N., Hong W., Paiement J. Mol. Biol. Cell 11:2529-2542(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Phospholipid species act as modulators in p97/p47-mediated fusion of Golgi membranes." Pecheur E.-I., Martin I., Maier O., Bakowsky U., Ruysschaert J.-M., Hoekstra D. Biochemistry 41:9813-9823(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MEMBRANES.
[8]	"Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1-Npl4." Meyer H.H., Wang Y., Warren G. EMBO J. 21:5645-5652(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NSFL1C; NAP1L4 AND UFD1L.
[9]	"VCIP135, a novel essential factor for p97/p47-mediated membrane fusion, is required for Golgi and ER assembly in vivo." Uchiyama K., Jokitalo E., Kano F., Murata M., Zhang X., Canas B., Newman R., Rabouille C., Pappin D., Freemont P., Kondo H. J. Cell Biol. 159:855-866(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VCIP135.
[10]	"The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle." Uchiyama K., Jokitalo E., Lindman M., Jackman M., Kano F., Murata M., Zhang X., Kondo H. J. Cell Biol. 161:1067-1079(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U11760 mRNA. Translation: AAC52154.1. BC060518 mRNA. Translation: AAH60518.1.
IPI	IPI00212014.
PIR	A55190.
RefSeq	NP_446316.1. NM_053864.2.
UniGene	Rn.98891.
3D structure databases
ProteinModelPortal	P46462.
SMR	P46462. Positions 18-763.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46462. 4 interactions.
MINT	MINT-1954391.
STRING	10116.ENSRNOP00000040121.
PTM databases
PhosphoSite	P46462.
2D gel databases
World-2DPAGE	0004:P46462.
Proteomic databases
PaxDb	P46462.
PRIDE	P46462.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000046102; ENSRNOP00000040121; ENSRNOG00000034242.
GeneID	116643.
KEGG	rno:116643.
UCSC	RGD:621595. rat.
Organism-specific databases
CTD	7415.
RGD	621595. Vcp.
Phylogenomic databases
eggNOG	COG0464.
GeneTree	ENSGT00700000104534.
HOGENOM	HOG000223224.
HOVERGEN	HBG001226.
InParanoid	P46462.
KO	K13525.
OrthoDB	EOG45TCMK.
Gene expression databases
Genevestigator	P46462.
GermOnline	ENSRNOG00000034242. Rattus norvegicus.
Family and domain databases
Gene3D	2.40.40.20. 1 hit.
InterPro	IPR003593. AAA+_ATPase. IPR009010. Asp_de-COase-like_dom. IPR005938. ATPase_AAA_CDC48. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. IPR004201. Cdc48_dom2. IPR003338. CDC4_N-term_subdom. IPR015415. Vps4_C. [Graphical view]
PANTHER	PTHR23077:SF18. PTHR23077:SF18. 1 hit.
Pfam	PF00004. AAA. 2 hits. PF02933. CDC48_2. 1 hit. PF02359. CDC48_N. 1 hit. PF09336. Vps4_C. 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.
TIGRFAMs	TIGR01243. CDC48. 1 hit.
PROSITE	PS00674. AAA. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	619375.

Entry information

Entry name

TERA_RAT

Accession

Primary (citable) accession number: P46462

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 127 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program