P55072 (TERA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:

VCP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 By similarity. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Ref.13
Subunit structure	Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. 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. Interacts with NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis By similarity. Interacts with SELS/VIMP 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. Ref.9 Ref.12 Ref.13 Ref.14 Ref.16 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.30 Ref.32 Ref.36
Subcellular location	Cytoplasm › cytosol. Nucleus. Note: Present in the neuronal hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients. Present in the Lewy bodies specifically found in neurons from Parkinson disease patients. Ref.13
Post-translational modification	Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.17 Ref.18 Ref.25 Ref.26 Ref.29 Ref.33 Ref.34 ISGylated. Ref.15
Involvement in disease	Defects in VCP are the cause of inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) [MIM:167320]; also known as muscular dystrophy, limb-girdle, with Paget disease of bone or pagetoid amyotrophic lateral sclerosis or pagetoid neuroskeletal syndrome or lower motor neuron degeneration with Paget-like bone disease. IBMPFD features adult-onset proximal and distal muscle weakness (clinically resembling limb girdle muscular dystrophy), early-onset Paget disease of bone in most cases and premature frontotemporal dementia. Ref.36 Ref.38 Ref.39 Ref.40 Ref.41 Defects in VCP are the cause of amyotrophic lateral sclerosis type 14 with or without frontotemporal dementia (ALS14) [MIM:613954]. ALS14 is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS14 may develop frontotemporal dementia. Ref.42
Sequence similarities	Belongs to the AAA ATPase family.

Ontologies

Keywords
Biological process	Transport Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Disease	Amyotrophic lateral sclerosis Disease mutation Neurodegeneration
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	ER-associated protein catabolic process Traceable author statement Ref.14. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB double-strand break repair Inferred from direct assay. Source: UniProtKB endoplasmic reticulum unfolded protein response Traceable author statement Ref.14. Source: UniProtKB positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: BHF-UCL positive regulation of protein complex assembly Inferred from direct assay. Source: BHF-UCL protein ubiquitination Non-traceable author statement Ref.14. Source: UniProtKB regulation of apoptotic process Traceable author statement. Source: UniProtKB retrograde protein transport, ER to cytosol Inferred from direct assay Ref.14. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay Ref.14. Source: UniProtKB endoplasmic reticulum Inferred from direct assay Ref.14. Source: UniProtKB microsome Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB proteasome complex Inferred from direct assay. Source: BHF-UCL
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity Traceable author statement Ref.14. Source: UniProtKB lipid binding Inferred from electronic annotation. Source: UniProtKB-KW polyubiquitin binding Inferred from direct assay. Source: BHF-UCL protein domain specific binding Inferred from physical interaction Ref.12. Source: UniProtKB protein phosphatase binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AMFR	Q9UKV5-1	6	EBI-355164,EBI-1046379
ASPSCR1	Q9BZE9	2	EBI-355164,EBI-1993677
ATXN3	P54252	5	EBI-355164,EBI-946046
ATXN3	P54252-1	10	EBI-355164,EBI-946068
CHEK2	O96017	2	EBI-355164,EBI-1180783
FCHSD2	O94868	2	EBI-355164,EBI-1215612
UBXN4	Q92575	2	EBI-355164,EBI-723441
UBXN6	Q9BZV1	7	EBI-355164,EBI-1993899

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7 Ref.8

Chain

2 – 806

805

Transitional endoplasmic reticulum ATPase

PRO_0000084572

Regions

Nucleotide binding

247 – 253

7

ATP

Region

797 – 806

10

Interaction with UBXN6

Sites

Binding site

348

1

ATP

Binding site

384

1

ATP

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8 Ref.31

Modified residue

3

1

Phosphoserine Ref.29 Ref.33

Modified residue

7

1

Phosphoserine By similarity

Modified residue

37

1

Phosphoserine Ref.33

Modified residue

282

1

Phosphoserine Ref.33

Modified residue

284

1

Phosphoserine Ref.33

Modified residue

436

1

Phosphothreonine Ref.29

Modified residue

457

1

Phosphoserine Ref.33

Modified residue

509

1

Phosphothreonine Ref.29

Modified residue

702

1

Phosphoserine Ref.26

Modified residue

705

1

Phosphoserine Ref.26

Modified residue

746

1

Phosphoserine Ref.33

Modified residue

748

1

Phosphoserine Ref.33

Modified residue

770

1

Phosphoserine Ref.34

Modified residue

775

1

Phosphoserine Ref.34

Modified residue

784

1

Phosphoserine Ref.25

Modified residue

787

1

Phosphoserine Ref.29

Modified residue

805

1

Phosphotyrosine Ref.17 Ref.18

Natural variations

Natural variant

95

1

R → G in IBMPFD; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP. Ref.36 Ref.38 Ref.41

VAR_033016

Natural variant

155

1

R → C in IBMPFD; also in one patient without evidence of Paget disease of the bone. Ref.38 Ref.39

VAR_033017

Natural variant

155

1

R → H in ALS14 and IBMPFD; ALS14 patients do not manifest frontotemporal dementia; properly assembles into a hexameric structure and shows normal ATPase activity; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP. Ref.36 Ref.38 Ref.41 Ref.42

VAR_033018

Natural variant

155

1

R → P in IBMPFD. Ref.38

VAR_033019

Natural variant

159

1

R → G in ALS14. Ref.42

VAR_065910

Natural variant

159

1

R → H in IBMPFD; without frontotemporal dementia. Ref.40

VAR_033020

Natural variant

191

1

R → Q in ALS14 and IBMPFD. Ref.38 Ref.42

VAR_033021

Natural variant

232

1

A → E in IBMPFD. Ref.38

VAR_033022

Natural variant

592

1

D → N in ALS14; ALS14 patients do not show frontotemporal dementia. Ref.42

VAR_065911

Experimental info

Mutagenesis

53

1

R → A: Minor effect on affinity for ATP and ADP. Ref.36

Mutagenesis

86

1

R → A: Strongly increased affinity for ATP. Strongly reduced affinity for ADP. Ref.36

Mutagenesis

524

1

K → A: Impairs catalytic activity of RNF19A toward SOD1 mutant. Ref.13

Sequence conflict

169

1

D → H in AAI21795. Ref.6

Sequence conflict

312

1

K → I in BAG35235. Ref.3

Secondary structure

1

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806

Helix Strand Turn

Details...

Beta strand

25 – 29

5

Beta strand

38 – 41

4

Helix

43 – 49

7

Beta strand

56 – 60

5

Beta strand

67 – 73

7

Beta strand

81 – 83

3

Helix

86 – 91

6

Beta strand

99 – 104

6

Beta strand

113 – 119

7

Helix

120 – 122

3

Helix

130 – 133

4

Helix

135 – 139

5

Turn

140 – 142

3

Beta strand

144 – 147

4

Beta strand

151 – 154

4

Beta strand

161 – 176

16

Beta strand

181 – 183

3

Helix

191 – 198

8

Helix

210 – 219

10

Helix

221 – 225

5

Helix

227 – 232

6

Beta strand

242 – 244

3

Helix

252 – 261

10

Beta strand

265 – 269

5

Turn

273 – 276

4

Helix

282 – 295

14

Beta strand

298 – 305

8

Helix

306 – 309

4

Helix

320 – 332

13

Beta strand

341 – 346

6

Helix

350 – 352

3

Helix

355 – 358

4

Beta strand

366 – 368

3

Helix

378 – 384

7

Turn

385 – 387

3

Helix

396 – 401

6

Helix

410 – 424

15

Turn

425 – 429

5

Helix

439 – 444

6

Helix

449 – 456

8

Helix

459 – 465

7

Helix

466 – 468

3

Sequences

	Sequence		Length	Mass (Da)
	P55072 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 501B721D3A77BA8A	FASTA	806	89,322
	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 TGGSVYTEDN DDDLYG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence analysis of a human P1 clone containing the XRCC9 DNA repair gene." Lamerdin J.E., McCready P.M., Skowronski E., Adamson A.W., Burkhart-Schultz K., Gordon L., Kyle A., Ramirez M., Stilwagen S., Phan H., Velasco N., Garnes J., Danganan L., Poundstone P., Christensen M., Georgescu A., Avila J., Liu S. , Attix C., Andreise T., Trankheim M., Amico-Keller G., Coefield J., Duarte S., Lucas S., Bruce R., Thomas P., Quan G., Kronmiller B., Arellano A., Montgomery M., Ow D., Nolan M., Trong S., Kobayashi A., Olsen A.O., Carrano A.V. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pituitary.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[7]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-25. Tissue: Platelet.
[8]	Bienvenut W.V., Claeys D. Submitted (NOV-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-18; 148-155; 278-287; 296-312; 366-377; 466-487; 587-599; 639-651 AND 669-677, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Platelet.
[9]	"Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein." Pleasure I.T., Black M.M., Keen J.H. Nature 365:459-462(1993) [PubMed: 8413590] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-41 AND 233-238, INTERACTION WITH CLATHRIN. Tissue: Glial tumor.
[10]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 46-53; 66-81; 96-109; 148-155; 240-251; 323-336; 454-502; 530-560; 600-614; 639-651; 678-693; 714-732 AND 754-766, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[11]	"Characterization of different mRNA types expressed in human brain." Dmitrenko V.V., Garifulin O.M., Kavsan V.M. Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 388-483. Tissue: Fetal brain.
[12]	"A novel UBA and UBX domain protein that binds polyubiquitin and VCP and is a substrate for SAPKs." McNeill H., Knebel A., Arthur J.S., Cuenda A., Cohen P. Biochem. J. 384:391-400(2004) [PubMed: 15362974] [Abstract] Cited for: INTERACTION WITH NGLY1.
[13]	"Physical and functional interaction between dorfin and valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders." Ishigaki S., Hishikawa N., Niwa J., Iemura S., Natsume T., Hori S., Kakizuka A., Tanaka K., Sobue G. J. Biol. Chem. 279:51376-51385(2004) [PubMed: 15456787] [Abstract] Cited for: FUNCTION, INTERACTION WITH RNF19A, MASS SPECTROMETRY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-524.
[14]	"A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol." Ye Y., Shibata Y., Yun C., Ron D., Rapoport T.A. Nature 429:841-847(2004) [PubMed: 15215856] [Abstract] Cited for: INTERACTION WITH VIMP.
[15]	"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells." Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E. Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed: 16139798] [Abstract] Cited for: ISGYLATION.
[16]	"The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway." Schulze A., Standera S., Buerger E., Kikkert M., van Voorden S., Wiertz E., Koning F., Kloetzel P.-M., Seeger M. J. Mol. Biol. 354:1021-1027(2005) [PubMed: 16289116] [Abstract] Cited for: INTERACTION WITH SYVN1 AND DERL1.
[17]	"Phosphoproteome analysis of HeLa cells using stable isotope labeling with amino acids in cell culture (SILAC)." Amanchy R., Kalume D.E., Iwahori A., Zhong J., Pandey A. J. Proteome Res. 4:1661-1671(2005) [PubMed: 16212419] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-805, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-805, MASS SPECTROMETRY.
[19]	"Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane." Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A. Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005) [PubMed: 16186510] [Abstract] Cited for: INTERACTION WITH DERL1; AMFR; SYVN1 AND SELS.
[20]	"Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane." Lilley B.N., Ploegh H.L. Proc. Natl. Acad. Sci. U.S.A. 102:14296-14301(2005) [PubMed: 16186509] [Abstract] Cited for: INTERACTION WITH DERL1 AND DERL2.
[21]	"Calcium-sensing receptor ubiquitination and degradation mediated by the E3 ubiquitin ligase dorfin." Huang Y., Niwa J., Sobue G., Breitwieser G.E. J. Biol. Chem. 281:11610-11617(2006) [PubMed: 16513638] [Abstract] Cited for: INTERACTION WITH CASR AND RNF19A.
[22]	"Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation." Oda Y., Okada T., Yoshida H., Kaufman R.J., Nagata K., Mori K. J. Cell Biol. 172:383-393(2006) [PubMed: 16449189] [Abstract] Cited for: INTERACTION WITH DERL1; DERL2 AND DERL3.
[23]	"Characterization of erasin (UBXD2): a new ER protein that promotes ER-associated protein degradation." Liang J., Yin C., Doong H., Fang S., Peterhoff C., Nixon R.A., Monteiro M.J. J. Cell Sci. 119:4011-4024(2006) [PubMed: 16968747] [Abstract] Cited for: INTERACTION WITH UBXD2.
[24]	"The RBCC gene RFP2 (Leu5) encodes a novel transmembrane E3 ubiquitin ligase involved in ERAD." Lerner M., Corcoran M., Cepeda D., Nielsen M.L., Zubarev R., Ponten F., Uhlen M., Hober S., Grander D., Sangfelt O. Mol. Biol. Cell 18:1670-1682(2007) [PubMed: 17314412] [Abstract] Cited for: INTERACTION WITH TRIM13.
[25]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-784, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[26]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-702 AND SER-705, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Ubiquitin ligase Kf-1 is involved in the endoplasmic reticulum-associated degradation pathway." Maruyama Y., Yamada M., Takahashi K., Yamada M. Biochem. Biophys. Res. Commun. 374:737-741(2008) [PubMed: 18675248] [Abstract] Cited for: INTERACTION WITH RNF103.
[28]	"Ubxd1 is a novel co-factor of the human p97 ATPase." Madsen L., Andersen K.M., Prag S., Moos T., Semple C.A., Seeger M., Hartmann-Petersen R. Int. J. Biochem. Cell Biol. 40:2927-2942(2008) [PubMed: 18656546] [Abstract] Cited for: INTERACTION WITH UBXN6.
[29]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; THR-436; THR-509 AND SER-787, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[30]	"Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD system." Takahata M., Bohgaki M., Tsukiyama T., Kondo T., Asaka M., Hatakeyama S. Mol. Immunol. 45:2045-2054(2008) [PubMed: 18022694] [Abstract] Cited for: INTERACTION WITH TRIM21.
[31]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[32]	"The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER." Ernst R., Mueller B., Ploegh H.L., Schlieker C. Mol. Cell 36:28-38(2009) [PubMed: 19818707] [Abstract] Cited for: INTERACTION WITH YOD1.
[33]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-37; SER-282; SER-284; SER-457; SER-746 AND SER-748, MASS SPECTROMETRY.
[34]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-770 AND SER-775, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[35]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]	"A novel ATP-dependent conformation in p97 N-D1 fragment revealed by crystal structures of disease-related mutants." Tang W.K., Li D., Li C.C., Esser L., Dai R., Guo L., Xia D. EMBO J. 29:2217-2229(2010) [PubMed: 20512113] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-481 IN COMPLEX WITH ATP ANALOG, CHARACTERIZATION OF VARIANTS IBMPFD GLY-95 AND HIS-155, MUTAGENESIS OF ARG-53 AND ARG-86, SUBUNIT.
[37]	"Structure and function of the PLAA/Ufd3-p97/Cdc48 complex." Qiu L., Pashkova N., Walker J.R., Winistorfer S., Allali-Hassani A., Akutsu M., Piper R., Dhe-Paganon S. J. Biol. Chem. 285:365-372(2010) [PubMed: 19887378] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 797-806 IN COMPLEX WITH PLAA.
[38]	"Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein." Watts G.D.J., Wymer J., Kovach M.J., Mehta S.G., Mumm S., Darvish D., Pestronk A., Whyte M.P., Kimonis V.E. Nat. Genet. 36:377-381(2004) [PubMed: 15034582] [Abstract] Cited for: VARIANTS IBMPFD GLY-95; CYS-155; HIS-155; PRO-155; GLN-191 AND GLU-232.
[39]	"Mutant valosin-containing protein causes a novel type of frontotemporal dementia." Schroeder R., Watts G.D.J., Mehta S.G., Evert B.O., Broich P., Fliessbach K., Pauls K., Hans V.H., Kimonis V., Thal D.R. Ann. Neurol. 57:457-461(2005) [PubMed: 15732117] [Abstract] Cited for: VARIANT IBMPFD CYS-155.
[40]	"Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene." Haubenberger D., Bittner R.E., Rauch-Shorny S., Zimprich F., Mannhalter C., Wagner L., Mineva I., Vass K., Auff E., Zimprich A. Neurology 65:1304-1305(2005) [PubMed: 16247064] [Abstract] Cited for: VARIANT IBMPFD HIS-159.
[41]	"Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation." Weihl C.C., Dalal S., Pestronk A., Hanson P.I. Hum. Mol. Genet. 15:189-199(2006) [PubMed: 16321991] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS IBMPFD GLY-95 AND HIS-155.
[42]	"Exome sequencing reveals VCP mutations as a cause of familial ALS." Johnson J.O., Mandrioli J., Benatar M., Abramzon Y., Van Deerlin V.M., Trojanowski J.Q., Gibbs J.R., Brunetti M., Gronka S., Wuu J., Ding J., McCluskey L., Martinez-Lage M., Falcone D., Hernandez D.G., Arepalli S., Chong S., Schymick J.C. , Rothstein J., Landi F., Wang Y.D., Calvo A., Mora G., Sabatelli M., Monsurro M.R., Battistini S., Salvi F., Spataro R., Sola P., Borghero G., Galassi G., Scholz S.W., Taylor J.P., Restagno G., Chio A., Traynor B.J. Neuron 68:857-864(2010) [PubMed: 21145000] [Abstract] Cited for: VARIANTS ALS14 HIS-155; GLY-159; GLN-191 AND ASN-592.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC004472 Genomic DNA. Translation: AAC07984.1.
AF100752 mRNA. Translation: AAD43016.1.
AK312310 mRNA. Translation: BAG35235.1.
AL353795 Genomic DNA. Translation: CAH70993.1.
CH471071 Genomic DNA. Translation: EAW58404.1.
BC110913 mRNA. Translation: AAI10914.1.
BC121794 mRNA. Translation: AAI21795.1.
Z70768 mRNA. Translation: CAA94809.1.

IPI

IPI00022774.

PIR

T02243.

RefSeq

NP_009057.1. NM_007126.3.

UniGene

Hs.529782.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EBB	X-ray	1.90	E/F/G/H	797-806	[»]
3HU1	X-ray	2.81	A/B/C/D/E/F	1-481	[»]
3HU2	X-ray	2.85	A/B/C/D/E/F	1-481	[»]
3HU3	X-ray	2.20	A/B	1-481	[»]
3QC8	X-ray	2.20	A	21-196	[»]
3QQ7	X-ray	2.65	A	2-187	[»]
3QQ8	X-ray	2.00	A	2-187	[»]
3TIW	X-ray	1.80	A/B	1-187	[»]

ProteinModelPortal

P55072.

SMR

P55072. Positions 10-763.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33543N.

IntAct

P55072. 39 interactions.

MINT

MINT-272884.

STRING

P55072.

Protein family/group databases

TCDB

3.A.16.1.1. endoplasmic reticular retrotranslocon (ER-RT) family.

PTM databases

PhosphoSite

P55072.

Polymorphism databases

DMDM

6094447.

2D gel databases

DOSAC-COBS-2DPAGE

P55072.

OGP

P55072.

REPRODUCTION-2DPAGE

IPI00022774.
P55072.

Proteomic databases

PRIDE

P55072.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000358901; ENSP00000351777; ENSG00000165280.

GeneID

7415.

KEGG

hsa:7415.

UCSC

uc003zvy.2. human.

Organism-specific databases

CTD

7415.

GeneCards

GC09M035056.

H-InvDB

HIX0201346.

HGNC

HGNC:12666. VCP.

HPA

CAB005593.
HPA012728.
HPA012814.

MIM

167320. phenotype.
601023. gene.
613954. phenotype.

neXtProt

NX_P55072.

Orphanet

803. Amyotrophic lateral sclerosis.
52430. Inclusion body myopathy with Paget disease of bone and frontotemporal dementia.

PharmGKB

PA37289.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13782.

HOGENOM

HBG597299.

HOVERGEN

HBG001226.

InParanoid

P55072.

OMA

SFRFPSS.

OrthoDB

EOG45TCMK.

PhylomeDB

P55072.

Gene expression databases

ArrayExpress

P55072.

Bgee

P55072.

CleanEx

HS_VCP.

Genevestigator

P55072.

GermOnline

ENSG00000165280. Homo sapiens.

Family and domain databases

InterPro

IPR009010. Asp_de-COase-like_fold.
IPR003593. ATPase_AAA+_core.
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]

Gene3D

G3DSA:2.40.40.20. Asp_decarboxylase-like_fold. 1 hit.

KO

K13525.

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

29034.

SOURCE

Search...

Entry information

Entry name

TERA_HUMAN

Accession

Primary (citable) accession number: P55072
Secondary accession number(s): B2R5T8 , Q0V924, Q2TAI5, Q969G7, Q9UCD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 129 of the entry and version 4 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.