Protein: P55072 | MoonDB v2.0

UniprotKB AC	UniprotKB ID	Gene name	Full name	Species	Curated set
P55072 (Uniprot)	TERA_HUMAN	VCP	Transitional endoplasmic reticulum ATPase	human	No

Protein Function

Uniprot: 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 UFD1, 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-UFD1-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. 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. Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). 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 (PubMed:22020440, PubMed:22120668). 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 (PubMed:23042607, PubMed:23042605). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). Acts as a negative regulator of type I interferon production by interacting with DDX58/RIG-I: interaction takes place when DDX58/RIG-I is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of DDX58/RIG-I (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). more..

MoonDB Dissimilar Functions

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GO ID 1	Function 1	Module ID 1	GO ID 2	Function 2	Module ID 2	Association Probability (PrOnto)	Interaction Probability (PrOnto)
GO:0010646	regulation of cell communication	284	GO:0006725	cellular aromatic compound metabolic process	57	4.64e-30	1.07e-07
GO:0033036	macromolecule localization	517	GO:0006725	cellular aromatic compound metabolic process	57	1.29e-20	6.46e-74
GO:0033036	macromolecule localization	517	GO:0043170	macromolecule metabolic process	531	2.48e-08	1.95e-27

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MoonDB Network Modules

Biological Processes

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Module ID (MoonGO)	GO ID (BP)	GO Name
57	GO:0006139	nucleobase-containing compound metabolic process
177	GO:0044267	cellular protein metabolic process
284	GO:0009966	regulation of signal transduction
517	GO:0008104	protein localization
517	GO:0019538	protein metabolic process
531	GO:0019538	protein metabolic process
555	GO:0006464	cellular protein modification process
555	GO:0060255	regulation of macromolecule metabolic process
555	GO:0007165	signal transduction
560	GO:0006464	cellular protein modification process

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Cellular Components

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Module ID (MoonGO)	GO ID (CC)	GO Name
57	GO:0005634	nucleus
177	GO:0005634	nucleus
256	GO:0043232	intracellular non-membrane-bounded organelle
256	GO:0005634	nucleus
284	GO:0005829	cytosol
284	GO:0005886	plasma membrane
517	GO:0005829	cytosol
517	GO:0012505	endomembrane system
517	GO:0031982	vesicle
555	GO:0005634	nucleus

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Protein GO Annotations

Biological Processes

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GO ID (BP)	GO Name	Evidence Code (GO EC)
GO:0006281	DNA repair	NAS
GO:0006302	double-strand break repair	IDA
GO:0006457	protein folding	TAS
GO:0006479	protein methylation	TAS
GO:0006734	NADH metabolic process	IMP
GO:0006888	ER to Golgi vesicle-mediated transport	IEA
GO:0006914	autophagy	IMP
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process	ISS
GO:0006974	cellular response to DNA damage stimulus	IDA
GO:0010498	proteasomal protein catabolic process	IMP

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Cellular Components

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GO ID (CC)	GO Name	Evidence Code (GO EC)
GO:0000502	proteasome complex	IDA
GO:0005576	extracellular region	TAS
GO:0005634	nucleus	IDA
GO:0005654	nucleoplasm	TAS
GO:0005737	cytoplasm	IDA
GO:0005783	endoplasmic reticulum	IDA
GO:0005789	endoplasmic reticulum membrane	TAS
GO:0005811	lipid droplet	IDA
GO:0005829	cytosol	TAS
GO:0034098	VCP-NPL4-UFD1 AAA ATPase complex	TAS

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Dissimilar Cellular Components (PrOnto)

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GO ID 1	Component 1	GO ID 2	Component 2	Association Probability (PrOnto)	Interaction Probability (PrOnto)
GO:0005576	extracellular region	GO:0005634	nucleus	4.48e-91	1.28e-107
GO:0005576	extracellular region	GO:0005654	nucleoplasm	6.62e-72	7.68e-98
GO:0005576	extracellular region	GO:0043231	intracellular membrane-bounded organelle	1.18e-59	7.46e-19
GO:0005634	nucleus	GO:0005783	endoplasmic reticulum	8.26e-33	3.22e-89
GO:0005634	nucleus	GO:0005789	endoplasmic reticulum membrane	1.61e-25	3.10e-56
GO:0005634	nucleus	GO:0070062	extracellular exosome	6.30e-13	4.54e-26
GO:0005654	nucleoplasm	GO:0005783	endoplasmic reticulum	1.84e-53	1.21e-118
GO:0005654	nucleoplasm	GO:0005789	endoplasmic reticulum membrane	1.09e-31	5.14e-59
GO:0005654	nucleoplasm	GO:0070062	extracellular exosome	3.37e-20	1.23e-35
GO:0005789	endoplasmic reticulum membrane	GO:0005829	cytosol	4.27e-12	7.53e-04

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All Protein Interactions

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Interactor	Also a MoonDB EMF protein
1433Z_HUMAN	Yes: P63104 (MoonDB)
AMFR_HUMAN	No
ANKZ1_HUMAN	No
ASPC1_HUMAN	No
ATG5_HUMAN	No
ATX3_HUMAN	No
BUD23_HUMAN	No
CEP19_HUMAN	Yes: Q96LK0 (MoonDB)
DGCR6_HUMAN	No
DPYL1_HUMAN	No

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Publications Associated

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PMID	Article Title
8413590	Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein.
10931946	Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.
12665801	Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.
14702039	Complete sequencing and characterization of 21,243 full-length human cDNAs.
15034582	Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein.
15164053	DNA sequence and analysis of human chromosome 9.
15215856	A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol.
15362974	A novel UBA and UBX domain protein that binds polyubiquitin and VCP and is a substrate for SAPKs.
15456787	Physical and functional interaction between dorfin and valosin-containing protein that are colocalized in ubiquitylated inclusions in neurodegenerative disorders.
15489334	The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

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OMIM Diseases Associated

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OMIM ID	Disease Name
167320	Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1
613954	Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia
616687	Charcot-Marie-Tooth disease 2Y

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Protein Domains Associated

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Domain Name	Domain ID	Source
AAA	PF00004	Pfam
AAA	PS00674	PROSITE
AAA	SM00382	SMART
AAA+_ATPase	IPR003593	InterPro
AAA_ATPase_CDC48	IPR005938	InterPro
Asp_de-COase-like_dom_sf	IPR009010	InterPro
ATPase_AAA_core	IPR003959	InterPro
ATPase_AAA_CS	IPR003960	InterPro
CDC48	TIGR01243	TIGRFAMs
CDC48_2	PF02933	Pfam

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