Seroatlas · Human Serome Atlas

VCP

Transitional endoplasmic reticulum ATPase

Also known as: CDC48, IBMPFD, p97, TERA, TERA_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P55072
Gene
VCP
Ensembl
ENSG00000165280
Chromosome
9
Canonical length
806 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters
Subcellular location
Nucleoplasm,Primary cilium tip,Primary cilium transition zone,Basal body,Cytosol
Quaternary structure
Homohexamer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

806 residues, UniProt reviewed canonical sequence.

>P55072|VCP
     1  MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK
    61  GKKRREAVCI VLSDDTCSDE KIRMNRVVRN NLRVRLGDVI SIQPCPDVKY GKRIHVLPID
   121  DTVEGITGNL FEVYLKPYFL EAYRPIRKGD IFLVRGGMRA VEFKVVETDP SPYCIVAPDT
   181  VIHCEGEPIK REDEEESLNE VGYDDIGGCR KQLAQIKEMV ELPLRHPALF KAIGVKPPRG
   241  ILLYGPPGTG KTLIARAVAN ETGAFFFLIN GPEIMSKLAG ESESNLRKAF EEAEKNAPAI
   301  IFIDELDAIA PKREKTHGEV ERRIVSQLLT LMDGLKQRAH VIVMAATNRP NSIDPALRRF
   361  GRFDREVDIG IPDATGRLEI LQIHTKNMKL ADDVDLEQVA NETHGHVGAD LAALCSEAAL
   421  QAIRKKMDLI DLEDETIDAE VMNSLAVTMD DFRWALSQSN PSALRETVVE VPQVTWEDIG
   481  GLEDVKRELQ ELVQYPVEHP DKFLKFGMTP SKGVLFYGPP GCGKTLLAKA IANECQANFI
   541  SIKGPELLTM WFGESEANVR EIFDKARQAA PCVLFFDELD SIAKARGGNI GDGGGAADRV
   601  INQILTEMDG MSTKKNVFII GATNRPDIID PAILRPGRLD QLIYIPLPDE KSRVAILKAN
   661  LRKSPVAKDV DLEFLAKMTN GFSGADLTEI CQRACKLAIR ESIESEIRRE RERQTNPSAM
   721  EVEEDDPVPE IRRDHFEEAM RFARRSVSDN DIRKYEMFAQ TLQQSRGFGS FRFPSGNQGG
   781  AGPSQGSGGG TGGSVYTEDN DDDLYG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VCP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.3
Highest tissue expression
198 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 198 nTPM
  • heart muscle: 134 nTPM
  • tongue: 126 nTPM
  • adrenal gland: 104 nTPM
  • liver: 99 nTPM
  • esophagus: 97 nTPM

Single-cell type

  • syncytiotrophoblasts: 721 nCPM
  • cytotrophoblasts: 330 nCPM
  • esophageal apical cells: 271 nCPM
  • migrating cytotrophoblasts: 237 nCPM
  • alveolar cells type 1: 234 nCPM
  • esophageal suprabasal cells: 220 nCPM

Immune cell

  • basophil: 143 nTPM
  • total PBMC: 112 nTPM
  • T-reg: 91 nTPM
  • non-classical monocyte: 81 nTPM
  • myeloid DC: 76 nTPM
  • eosinophil: 75 nTPM

Brain region

  • choroid plexus: 93 nTPM
  • pons: 87 nTPM
  • white matter: 86 nTPM
  • hypothalamus: 81 nTPM
  • medulla oblongata: 78 nTPM
  • thalamus: 77 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VCP.

Disease | AllUniProt

Conditions VCP is implicated in, by any mechanism.

  • Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1) MIM:167320
  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (FTDALS6) MIM:613954
  • Charcot-Marie-Tooth disease, axonal, type 2Y (CMT2Y) MIM:616687

Disease | GeneticClinVar

51 pathogenic / likely-pathogenic of 789 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Frontotemporal dementia and/or amyotrophic lateral sclerosis 6
  • Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
  • Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1
  • Inborn genetic diseases
  • Charcot-Marie-Tooth disease type 2Y

ReferencesPubMed · IEDB

Publications for VCP from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

5 publications

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.13
gnomAD pLI
1
gnomAD missense Z
5.41
DepMap mean gene effect
-2.51
DepMap dependency class
pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of VCP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads VCP as an antibody target. Whether an autoantibody or antibody against VCP could matter depends on whether native VCP is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

VCP is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label VCP as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/VCP. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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