ID:TERA_HUMAN DESCRIPTION: RecName: Full=Transitional endoplasmic reticulum ATPase; Short=TER ATPase; AltName: Full=15S Mg(2+)-ATPase p97 subunit; AltName: Full=Valosin-containing protein; Short=VCP; 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 (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. 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. SUBUNIT: 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 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 RHBDD1 (via C-terminus domain). INTERACTION: Q9UKV5-1:AMFR; NbExp=6; IntAct=EBI-355164, EBI-1046379; Q9BZE9:ASPSCR1; NbExp=2; IntAct=EBI-355164, EBI-1993677; P54252:ATXN3; NbExp=5; IntAct=EBI-355164, EBI-946046; P54252-1:ATXN3; NbExp=10; IntAct=EBI-355164, EBI-946068; O96017:CHEK2; NbExp=2; IntAct=EBI-355164, EBI-1180783; O94868:FCHSD2; NbExp=2; IntAct=EBI-355164, EBI-1215612; Q92575:UBXN4; NbExp=2; IntAct=EBI-355164, EBI-723441; Q9BZV1:UBXN6; NbExp=7; IntAct=EBI-355164, EBI-1993899; SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum. 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. 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. PTM: Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: ISGylated. 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. DISEASE: 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. SIMILARITY: Belongs to the AAA ATPase family. CAUTION: It is unclear how it participates to the recruitment of TP53BP1 at DNA damage sites. According to a first report, participates in the recruitment of TP53BP1 by promoting ubiquitination and removal of L3MBTL1 from DNA damage sites (PubMed:22120668). According to a second report, it acts by removing 'Lys-48'-linked ubiquitination from sites of DNA damage (PubMed:22020440). WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/VCP";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P55072
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006281 DNA repair GO:0006302 double-strand break repair GO:0006457 protein folding GO:0006511 ubiquitin-dependent protein catabolic process GO:0006734 NADH metabolic process GO:0006888 ER to Golgi vesicle-mediated transport GO:0006914 autophagy GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006974 cellular response to DNA damage stimulus GO:0010498 proteasomal protein catabolic process GO:0010918 positive regulation of mitochondrial membrane potential GO:0016236 macroautophagy GO:0016567 protein ubiquitination GO:0016579 protein deubiquitination GO:0018279 protein N-linked glycosylation via asparagine GO:0019079 viral genome replication GO:0019985 translesion synthesis GO:0030433 ER-associated ubiquitin-dependent protein catabolic process GO:0030968 endoplasmic reticulum unfolded protein response GO:0030970 retrograde protein transport, ER to cytosol GO:0031334 positive regulation of protein complex assembly GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032510 endosome to lysosome transport via multivesicular body sorting pathway GO:0034214 protein hexamerization GO:0036503 ERAD pathway GO:0042981 regulation of apoptotic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043312 neutrophil degranulation GO:0045184 establishment of protein localization GO:0045732 positive regulation of protein catabolic process GO:0046034 ATP metabolic process GO:0051260 protein homooligomerization GO:0055085 transmembrane transport GO:0070842 aggresome assembly GO:0070987 error-free translesion synthesis GO:0071712 ER-associated misfolded protein catabolic process GO:0072389 flavin adenine dinucleotide catabolic process GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0097352 autophagosome maturation GO:1903006 positive regulation of protein K63-linked deubiquitination GO:1903007 positive regulation of Lys63-specific deubiquitinase activity GO:1903715 regulation of aerobic respiration GO:1903862 positive regulation of oxidative phosphorylation GO:2000158 positive regulation of ubiquitin-specific protease activity GO:2001171 positive regulation of ATP biosynthetic process
BC012195 - Homo sapiens valosin-containing protein, mRNA (cDNA clone IMAGE:2822943), **** WARNING: chimeric clone ****. BC017171 - Homo sapiens valosin-containing protein, mRNA (cDNA clone IMAGE:2822943), **** WARNING: chimeric clone ****. BC021055 - Homo sapiens cDNA clone IMAGE:2822943, **** WARNING: chimeric clone ****. AL137377 - Homo sapiens mRNA; cDNA DKFZp434K0126 (from clone DKFZp434K0126). BC007562 - Homo sapiens valosin-containing protein, mRNA (cDNA clone IMAGE:2988964), partial cds. BC110913 - Homo sapiens valosin-containing protein, mRNA (cDNA clone MGC:131997 IMAGE:6502535), complete cds. FJ224344 - Homo sapiens epididymis luminal protein 220 (HEL-220) mRNA, complete cds. JD189210 - Sequence 170234 from Patent EP1572962. JD307220 - Sequence 288244 from Patent EP1572962. JD127173 - Sequence 108197 from Patent EP1572962. JD189192 - Sequence 170216 from Patent EP1572962. JD474078 - Sequence 455102 from Patent EP1572962. BC122550 - Homo sapiens valosin-containing protein, mRNA (cDNA clone MGC:148092 IMAGE:40108357), complete cds. BC121794 - Homo sapiens valosin-containing protein, mRNA (cDNA clone MGC:148093 IMAGE:40108360), complete cds. JD250686 - Sequence 231710 from Patent EP1572962. AF100752 - Homo sapiens transitional endoplasmic reticulum ATPase mRNA, complete cds. FJ224352 - Homo sapiens epididymis secretory protein Li 70 (HEL-S-70) mRNA, complete cds. BC096751 - Homo sapiens cDNA clone IMAGE:5296598, containing frame-shift errors. JD290020 - Sequence 271044 from Patent EP1572962. JD457102 - Sequence 438126 from Patent EP1572962. JD141110 - Sequence 122134 from Patent EP1572962. JD106530 - Sequence 87554 from Patent EP1572962. JD347338 - Sequence 328362 from Patent EP1572962. JD146531 - Sequence 127555 from Patent EP1572962. JD197377 - Sequence 178401 from Patent EP1572962. AK312310 - Homo sapiens cDNA, FLJ92615, highly similar to Homo sapiens valosin-containing protein (VCP), mRNA. KJ901823 - Synthetic construct Homo sapiens clone ccsbBroadEn_11217 VCP gene, encodes complete protein. KR710108 - Synthetic construct Homo sapiens clone CCSBHm_00009656 VCP (VCP) mRNA, encodes complete protein. KR710109 - Synthetic construct Homo sapiens clone CCSBHm_00009658 VCP (VCP) mRNA, encodes complete protein. KJ901824 - Synthetic construct Homo sapiens clone ccsbBroadEn_11218 VCP gene, encodes complete protein. AH009961 - Homo sapiens chromosome 9 valosin-containing protein (VCP) mRNA, partial cds. AB385152 - Synthetic construct DNA, clone: pF1KB5676, Homo sapiens VCP gene for transitional endoplasmic reticulum ATPase, complete cds, without stop codon, in Flexi system. AK307735 - Homo sapiens cDNA, FLJ97683. JD026265 - Sequence 7289 from Patent EP1572962. Z70768 - H.sapiens mRNA for P97. LF211620 - JP 2014500723-A/19123: Polycomb-Associated Non-Coding RNAs. LF382057 - JP 2014500723-A/189560: Polycomb-Associated Non-Coding RNAs. JD408442 - Sequence 389466 from Patent EP1572962. JD458810 - Sequence 439834 from Patent EP1572962. JD523650 - Sequence 504674 from Patent EP1572962. MA447197 - JP 2018138019-A/19123: Polycomb-Associated Non-Coding RNAs. MA617634 - JP 2018138019-A/189560: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P55072 (Reactome details) participates in the following event(s):
R-HSA-6781953 YOD1 binds VCP R-HSA-8932276 VCPKMT (METTL21D) transfers 3xCH3 from 3xAdoMet to VCP R-HSA-5324632 Dissociation of cytosolic HSF1:HSP90:HDAC6:PTGES3 upon sensing protein aggregates R-HSA-5688834 ATXN3 binds VCP R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins R-HSA-6798751 Exocytosis of azurophil granule lumen proteins R-HSA-6798748 Exocytosis of secretory granule lumen proteins R-HSA-8943083 US11:HLA binds DERL1:TMEM129:Ub:UBE2J2,UBE2K:VIMP:VCP R-HSA-5362441 C-terminal Hh fragments are recruited to SEL1:SYVN1 at the ER membrane R-HSA-5387386 Hh processing variants are recruited to SEL1:SYVN at the ER membrane R-HSA-5362459 VCP-catalyzed ATP hydrolysis promotes the translocation of Hh-C into the cytosol R-HSA-5387389 Hh processing variants are translocated to the cytosol in a VCP-dependent manner R-HSA-8866551 CFTR binds components of the ERAD machinery for ubiquitination and degradation R-HSA-8866857 CFTR F508del binds components of the ERAD machinery for ubiquitination and degradation R-HSA-8866542 VCP-catalyzed ATP hydrolysis promotes the translocation of misfolded CFTR into the cytosol R-HSA-8866854 VCP-catalyzed ATP hydrolysis promotes the translocation of CFTR F508del into the cytosol R-HSA-5654985 SPRTN recruits VCP to monoUb:K164-PCNA associated with POLH R-HSA-5362412 SYVN1 ubiquitinates Hh C-terminal fragments R-HSA-5483238 Hh processing variants are ubiquitinated R-HSA-8850594 Deglycosylation complex hydrolyses N-glycans from unfolded glycoproteins R-HSA-8866546 RNF5 and RNF185 ubiquitinate misfolded CFTR R-HSA-8866856 RNF5 and RNF185 ubiquitinate CFTR F508del R-HSA-5654989 SPRTN:VCP-mediated release of POLH from monoUb:K164-PCNA R-HSA-5689896 Ovarian tumor domain proteases R-HSA-8876725 Protein methylation R-HSA-3371511 HSF1 activation R-HSA-5688426 Deubiquitination R-HSA-597592 Post-translational protein modification R-HSA-5689877 Josephin domain DUBs R-HSA-6798695 Neutrophil degranulation R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins R-HSA-3371556 Cellular response to heat stress R-HSA-5358346 Hedgehog ligand biogenesis R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD R-HSA-382556 ABC-family proteins mediated transport R-HSA-5678895 Defective CFTR causes cystic fibrosis R-HSA-392499 Metabolism of proteins R-HSA-110320 Translesion Synthesis by POLH R-HSA-168249 Innate Immune System R-HSA-8852135 Protein ubiquitination R-HSA-2262752 Cellular responses to stress R-HSA-5358351 Signaling by Hedgehog R-HSA-5387390 Hh mutants abrogate ligand secretion R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle R-HSA-382551 Transport of small molecules R-HSA-5619084 ABC transporter disorders R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-168256 Immune System R-HSA-8953897 Cellular responses to external stimuli R-HSA-162582 Signal Transduction R-HSA-5663202 Diseases of signal transduction R-HSA-446203 Asparagine N-linked glycosylation R-HSA-5619115 Disorders of transmembrane transporters R-HSA-73893 DNA Damage Bypass R-HSA-1643685 Disease R-HSA-73894 DNA Repair
GeneReviews article(s) related to gene VCP: als-overview (Amyotrophic Lateral Sclerosis Overview) ibmpfd (Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia)
Gene Model Information
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Methods, Credits, and Use Restrictions
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US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
