InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: VCP

Summary

InnateDB Protein

IDBP-61419.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

VCP

Protein Name

valosin containing protein

Synonyms

ALS14; HEL-220; HEL-S-70; IBMPFD; IBMPFD1; p97; TERA;

Species

Homo sapiens

Ensembl Protein

ENSP00000351777

InnateDB Gene

IDBG-61415 (VCP)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000250, ECO:0000269PubMed:15456787, ECO:0000269PubMed:16168377, ECO:0000269PubMed:22020440, ECO:0000269PubMed:22120668, ECO:0000269PubMed:22607976, ECO:0000269PubMed:23042605, ECO:0000269PubMed:23042607}.

Subcellular Localization

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. Recruited to stalled replication forks via interaction with SPRTN.

Disease Associations

Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1) [MIM:167320]: An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. {ECO:0000269PubMed:15034582, ECO:0000269PubMed:15732117, ECO:0000269PubMed:16247064}. Note=The disease is caused by mutations affecting the gene represented in this entry.Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia (ALS14) [MIM:613954]: 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. {ECO:0000269PubMed:21145000}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 644 experimentally validated interaction(s) in this database.
They are also associated with 36 interaction(s) predicted by orthology.

Experimentally validated
Total	644 [view]
Protein-Protein	640 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	36 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005102	receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008289	lipid binding
GO:0009378	four-way junction helicase activity
GO:0016787	hydrolase activity
GO:0016887	ATPase activity
GO:0019903	protein phosphatase binding
GO:0019904	protein domain specific binding
GO:0031593	polyubiquitin binding
GO:0032403	protein complex binding
GO:0035800	deubiquitinase activator activity
GO:0042802	identical protein binding
GO:0043531	ADP binding
GO:0044822	poly(A) RNA binding
GO:1990381	ubiquitin-specific protease binding

Biological Process

GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006302	double-strand break repair
GO:0006310	DNA recombination
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006888	ER to Golgi vesicle-mediated transport
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0016567	protein ubiquitination
GO:0018279	protein N-linked glycosylation via asparagine
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:0034214	protein hexamerization
GO:0042981	regulation of apoptotic process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0045184	establishment of protein localization
GO:0045732	positive regulation of protein catabolic process
GO:0051260	protein homooligomerization
GO:0070842	aggresome assembly
GO:1903006	positive regulation of protein K63-linked deubiquitination
GO:1903007	positive regulation of Lys63-specific deubiquitinase activity

Cellular Component

GO:0000502	proteasome complex
GO:0000836	Hrd1p ubiquitin ligase complex
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005811	lipid particle
GO:0005829	cytosol
GO:0035861	site of double-strand break
GO:0043231	intracellular membrane-bounded organelle
GO:0043234	protein complex
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR003338 CDC48, N-terminal subdomain
IPR003593 AAA+ ATPase domain
IPR003959 ATPase, AAA-type, core
IPR004201 CDC48, domain 2
IPR005938 AAA ATPase, CDC48 family
IPR008824 DNA helicase, Holliday junction RuvB type, N-terminal
IPR009010 Aspartate decarboxylase-like domain
IPR011704 ATPase, dynein-related, AAA domain
IPR015415 Vps4 oligomerisation, C-terminal
IPR027417 P-loop containing nucleoside triphosphate hydrolase
IPR029067 CDC48 domain 2-like

PFAM