VCP valosin containing protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: VCPprovided by HGNC
Official Full Name: valosin containing proteinprovided by HGNC
Primary source: HGNC:HGNC:12666
See related: Ensembl:ENSG00000165280 MIM:601023; AllianceGenome:HGNC:12666
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: p97; TERA; CDC48; FTDALS6
Summary: This gene encodes a member of the AAA ATPase family of proteins. The encoded protein plays a role in protein degradation, intracellular membrane fusion, DNA repair and replication, regulation of the cell cycle, and activation of the NF-kappa B pathway. This protein forms a homohexameric complex that interacts with a variety of cofactors and extracts ubiquitinated proteins from lipid membranes or protein complexes. Mutations in this gene cause IBMPFD (inclusion body myopathy with paget disease of bone and frontotemporal dementia), ALS (amyotrophic lateral sclerosis) and Charcot-Marie-Tooth disease in human patients. [provided by RefSeq, Aug 2017]
Expression: Ubiquitous expression in appendix (RPKM 60.7), thyroid (RPKM 56.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p13.3

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (35056064..35072625, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (35075243..35091804, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (35056061..35072622, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.
Title: ALS-related p97 R155H mutation disrupts lysophagy in iPSC-derived motor neurons.
Bone scan findings of Paget's disease of bone in patients with VCP Multisystem Proteinopathy 1.
Title: Bone scan findings of Paget's disease of bone in patients with VCP Multisystem Proteinopathy 1.
Proteomics analysis of serum and urine identifies VCP and CTSA as potential biomarkers associated with multiple myeloma.
Title: Proteomics analysis of serum and urine identifies VCP and CTSA as potential biomarkers associated with multiple myeloma.
Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.
Title: Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.
p97/VCP Promotes the Recycling of Endocytic Cargo.
Title: p97/VCP Promotes the Recycling of Endocytic Cargo.
An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP.
Title: An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP.
The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP.
Title: The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP.
Nuclear VCP drives colorectal cancer progression by promoting fatty acid oxidation.
Title: Nuclear VCP drives colorectal cancer progression by promoting fatty acid oxidation.
Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.
Title: Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.
Novel variants, muscle imaging, and myopathological changes in Chinese patients with VCP-related multisystem proteinopathy.
Title: Novel variants, muscle imaging, and myopathological changes in Chinese patients with VCP-related multisystem proteinopathy.

Submit: New GeneRIF Correction See all GeneRIFs (319)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Amyotrophic lateral sclerosis MedGen: C0002736 GeneReviews: Amyotrophic Lateral Sclerosis Overview	Compare labs
Charcot-Marie-Tooth disease type 2Y MedGen: C5569026 OMIM: 616687 GeneReviews: Not available	Compare labs
Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 MedGen: C5436279 OMIM: 613954 GeneReviews: Amyotrophic Lateral Sclerosis Overview	Compare labs
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia MedGen: C1833662 GeneReviews: Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia	Compare labs
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 MedGen: C4551951 OMIM: 167320 GeneReviews: Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with VCP; predicted interaction to be within the endoplasmic reticulum to Golgi transport	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 is identified to have a physical interaction with valosin containing protein (VCP) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed
Vpu	vpu	A functional ER-associated degradation pathway is required for Vpu-induced tetherin degradation. P97 ATPase (VCP) knockdown partially impairs Vpu-mediated tetherin degradation	PubMed
	vpu	The VCP-UFD1L-NPL4 complex is required for HIV-1 Vpu-induced CD4 degradation in the ER-associated degradation pathway. The ATPase activity of VCP and ubiquitin binding to UFD1L are important for CD4 degradation by Vpu	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-13566 (e-PCR)
- UniSTS:66324

STS-R69121 (e-PCR)
- UniSTS:29727

D9S1791 (e-PCR), detects polymorphism
- UniSTS:56137

A002I21 (e-PCR)
- UniSTS:346

RH15902 (e-PCR)
- UniSTS:24168

RH11835 (e-PCR)
- UniSTS:32704

RH102684 (e-PCR)
- UniSTS:97018

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ADP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP hydrolysis activity	TAS Traceable Author Statement more info	PubMed
enables BAT3 complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables K48-linked polyubiquitin modification-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables MHC class I protein binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	HDA more info	PubMed
enables deubiquitinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables polyubiquitin modification-dependent protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables polyubiquitin modification-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-like protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-modified protein reader activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-specific protease binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ATP metabolic process	IEA Inferred from Electronic Annotation more info
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair	NAS Non-traceable Author Statement more info	PubMed
involved_in ERAD pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ERAD pathway	TAS Traceable Author Statement more info	PubMed
involved_in NADH metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in aggresome assembly	IEA Inferred from Electronic Annotation more info
involved_in autophagosome maturation	IBA Inferred from Biological aspect of Ancestor more info
involved_in autophagosome maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to arsenite ion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to heat	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to misfolded protein	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum stress-induced pre-emptive quality control	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport	IEA Inferred from Electronic Annotation more info
involved_in endoplasmic reticulum unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in endosome to lysosome transport via multivesicular body sorting pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of protein localization	TAS Traceable Author Statement more info	PubMed
involved_in flavin adenine dinucleotide catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in interstrand cross-link repair	ISS Inferred from Sequence or Structural Similarity more info
involved_in macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic spindle disassembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ATP biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of Lys63-specific deubiquitinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of mitochondrial membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of oxidative phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein K63-linked deubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in proteasomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	NAS Non-traceable Author Statement more info	PubMed
involved_in protein-DNA covalent cross-linking repair	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of aerobic respiration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in regulation of protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of synapse organization	IEA Inferred from Electronic Annotation more info
involved_in retrograde protein transport, ER to cytosol	IBA Inferred from Biological aspect of Ancestor more info
involved_in retrograde protein transport, ER to cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in retrograde protein transport, ER to cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retrograde protein transport, ER to cytosol	ISO Inferred from Sequence Orthology more info
involved_in stress granule disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in stress granule disassembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in translesion synthesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in viral genome replication	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of ATPase complex	IEA Inferred from Electronic Annotation more info
part_of Derlin-1 retrotranslocation complex	IDA Inferred from Direct Assay more info	PubMed
part_of VCP-NPL4-UFD1 AAA ATPase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of VCP-NPL4-UFD1 AAA ATPase complex	IPI Inferred from Physical Interaction more info	PubMed
part_of VCP-NPL4-UFD1 AAA ATPase complex	ISS Inferred from Sequence or Structural Similarity more info
part_of VCP-NPL4-UFD1 AAA ATPase complex	TAS Traceable Author Statement more info	PubMed
part_of VCP-NSFL1C complex	IPI Inferred from Physical Interaction more info	PubMed
part_of VCP-NSFL1C complex	ISS Inferred from Sequence or Structural Similarity more info
located_in azurophil granule lumen	TAS Traceable Author Statement more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
located_in cytoplasmic stress granule	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISS Inferred from Sequence or Structural Similarity more info
located_in lipid droplet	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	TAS Traceable Author Statement more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in secretory granule lumen	TAS Traceable Author Statement more info
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: transitional endoplasmic reticulum ATPase

Names: 15S Mg(2+)-ATPase p97 subunit; TER ATPase

NP_001341856.1

EC 3.6.4.6

NP_001341857.1

EC 3.6.4.6

NP_009057.1

EC 3.6.4.6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007887.1 RefSeqGene

Range

5001..21675

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_657

mRNA and Protein(s)

NM_001354927.2 → NP_001341856.1 transitional endoplasmic reticulum ATPase isoform 2

Status: REVIEWED

Source sequence(s)

AL353795, BU689324

Consensus CDS

CCDS94403.1

UniProtKB/TrEMBL

A0A7P0T8A3, C9IZA5, C9JUP7

Related

ENSP00000392088.2, ENST00000448530.6

Conserved Domains (1) summary

TIGR01243
Location:1 → 719

CDC48; AAA family ATPase, CDC48 subfamily
NM_001354928.2 → NP_001341857.1 transitional endoplasmic reticulum ATPase isoform 2

Status: REVIEWED

Source sequence(s)

AL353795, BU689324

Consensus CDS

CCDS94403.1

UniProtKB/TrEMBL

A0A7P0T8A3, C9IZA5, C9JUP7

Related

ENSP00000399456.2, ENST00000417448.2

Conserved Domains (1) summary

TIGR01243
Location:1 → 719

CDC48; AAA family ATPase, CDC48 subfamily
NM_007126.5 → NP_009057.1 transitional endoplasmic reticulum ATPase isoform 1

See identical proteins and their annotated locations for NP_009057.1

Status: REVIEWED

Source sequence(s)

BC007562, BC110913, BU689324, DA880782

Consensus CDS

CCDS6573.1

UniProtKB/Swiss-Prot

B2R5T8, P55072, Q0V924, Q2TAI5, Q969G7, Q9UCD5, V9HW80

UniProtKB/TrEMBL

A0A7I2V540

Related

ENSP00000351777.6, ENST00000358901.11

Conserved Domains (1) summary

TIGR01243
Location:25 → 764

CDC48; AAA family ATPase, CDC48 subfamily