======= VCP =======
== Gene Information ==
* **Official Symbol**: VCP
* **Official Name**: valosin containing protein
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7415|7415]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P55072|P55072]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=VCP&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20VCP|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/601023|Open OMIM]]
== Function Summary ==
* **Entrez 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].
* **UniProt Summary**: 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). {ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:27753622}.
|AAA|
|CDC48 N|
|CDC48 2|
|flavin adenine dinucleotide catabolic process|
|positive regulation of Lys63-specific deubiquitinase activity|
|ATPase complex|
|flavin-containing compound catabolic process|
|VCP-NSFL1C complex|
|spindle disassembly|
|positive regulation of protein K63-linked deubiquitination|
|positive regulation of ubiquitin-specific protease activity|
|mitotic spindle disassembly|
|deubiquitinase activator activity|
|flavin adenine dinucleotide metabolic process|
|regulation of protein K63-linked deubiquitination|
|endoplasmic reticulum stress-induced pre-emptive quality control|
|cellular response to arsenite ion|
|response to arsenite ion|
|regulation of ubiquitin-specific protease activity|
|BAT3 complex binding|
|stress granule disassembly|
|aggresome assembly|
|inclusion body assembly|
|K48-linked polyubiquitin modification-dependent protein binding|
|positive regulation of protein deubiquitination|
|endosome to lysosome transport via multivesicular body sorting pathway|
|flavin-containing compound metabolic process|
|VCP-NPL4-UFD1 AAA ATPase complex|
|regulation of aerobic respiration|
|positive regulation of mitochondrial membrane potential|
|Derlin-1 retrotranslocation complex|
|positive regulation of oxidative phosphorylation|
|regulation of protein deubiquitination|
|ER-associated misfolded protein catabolic process|
|positive regulation of ATP biosynthetic process|
|protein hexamerization|
|positive regulation of membrane potential|
|ribonucleoprotein complex disassembly|
|coenzyme catabolic process|
|ubiquitin-specific protease binding|
|regulation of ATP biosynthetic process|
|endoplasmic reticulum to cytosol transport|
|retrograde protein transport, ER to cytosol|
|cellular response to arsenic-containing substance|
|MHC class I protein binding|
|error-free translesion synthesis|
|positive regulation of purine nucleotide biosynthetic process|
|positive regulation of nucleotide biosynthetic process|
|ubiquitin-like protein ligase binding|
|cellular response to misfolded protein|
|endosome transport via multivesicular body sorting pathway|
|protein exit from endoplasmic reticulum|
|response to misfolded protein|
|viral genome replication|
|protein quality control for misfolded or incompletely synthesized proteins|
|polyubiquitin modification-dependent protein binding|
|regulation of cellular respiration|
|regulation of oxidative phosphorylation|
|response to arsenic-containing substance|
|autophagosome maturation|
|protein N-linked glycosylation via asparagine|
|peptidyl-asparagine modification|
|multivesicular body sorting pathway|
|NADH metabolic process|
|ADP binding|
|regulation of purine nucleotide biosynthetic process|
|regulation of nucleotide biosynthetic process|
|translesion synthesis|
|positive regulation of nucleotide metabolic process|
|positive regulation of ATP metabolic process|
|positive regulation of purine nucleotide metabolic process|
|DNA synthesis involved in DNA repair|
|postreplication repair|
|endosome to lysosome transport|
|proteasome complex|
|site of double-strand break|
|cofactor catabolic process|
|organelle disassembly|
|nucleotide catabolic process|
|cytoplasmic stress granule|
|cellular response to heat|
|regulation of mitochondrial membrane potential|
|ubiquitin-dependent ERAD pathway|
|nucleoside phosphate catabolic process|
|mitotic spindle organization|
|protein N-linked glycosylation|
|lipid droplet|
|positive regulation of proteasomal ubiquitin-dependent protein catabolic process|
|protein phosphatase binding|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|ERAD pathway|
|azurophil granule lumen|
|positive regulation of ubiquitin-dependent protein catabolic process|
|microtubule cytoskeleton organization involved in mitosis|
|positive regulation of proteasomal protein catabolic process|
|endoplasmic reticulum unfolded protein response|
|lysosomal transport|
|nucleobase-containing small molecule biosynthetic process|
|DNA biosynthetic process|
|response to heat|
|secretory granule lumen|
|regulation of purine nucleotide metabolic process|
|regulation of nucleotide metabolic process|
|regulation of ATP metabolic process|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|ficolin-1-rich granule lumen|
|cellular response to unfolded protein|
|organophosphate catabolic process|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of protein modification by small protein conjugation or removal|
|positive regulation of small molecule metabolic process|
|positive regulation of cellular protein catabolic process|
|vacuolar transport|
|positive regulation of canonical Wnt signaling pathway|
|cellular response to topologically incorrect protein|
|positive regulation of cysteine-type endopeptidase activity|
|regulation of ubiquitin-dependent protein catabolic process|
|spindle organization|
|lipid binding|
|regulation of generation of precursor metabolites and energy|
|macroautophagy|
|response to unfolded protein|
|positive regulation of endopeptidase activity|
|positive regulation of Wnt signaling pathway|
|response to temperature stimulus|
|double-strand break repair|
|regulation of proteasomal protein catabolic process|
|response to topologically incorrect protein|
|positive regulation of peptidase activity|
|viral life cycle|
|ATP metabolic process|
|endoplasmic reticulum to Golgi vesicle-mediated transport|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of proteolysis involved in cellular protein catabolic process|
|positive regulation of protein catabolic process|
|regulation of synapse organization|
|regulation of synapse structure or activity|
|endosomal transport|
|regulation of protein modification by small protein conjugation or removal|
|protein folding|
|ATPase activity|
|protein-containing complex disassembly|
|regulation of cysteine-type endopeptidase activity|
|protein domain specific binding|
|ribonucleoprotein complex subunit organization|
|regulation of cellular protein catabolic process|
|positive regulation of protein complex assembly|
|coenzyme metabolic process|
|response to endoplasmic reticulum stress|
|macromolecule glycosylation|
|protein glycosylation|
|process utilizing autophagic mechanism|
|autophagy|
|glycosylation|
|regulation of canonical Wnt signaling pathway|
|protein deubiquitination|
|ubiquitin protein ligase binding|
|protein modification by small protein removal|
|glycoprotein biosynthetic process|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|protein homooligomerization|
|glutamatergic synapse|
|proteasomal protein catabolic process|
|positive regulation of proteolysis|
|regulation of Wnt signaling pathway|
|positive regulation of cellular catabolic process|
|Golgi vesicle transport|
|nucleobase-containing compound catabolic process|
|regulation of protein catabolic process|
|glycoprotein metabolic process|
|cellular component disassembly|
|regulation of endopeptidase activity|
|regulation of small molecule metabolic process|
|regulation of membrane potential|
|positive regulation of catabolic process|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|cofactor metabolic process|
|aromatic compound catabolic process|
|regulation of peptidase activity|
|nucleotide metabolic process|
|nucleoside phosphate metabolic process|
|regulation of protein complex assembly|
|microtubule cytoskeleton organization|
|organic cyclic compound catabolic process|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|DNA repair|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|protein complex oligomerization|
|positive regulation of cellular component biogenesis|
|myeloid cell activation involved in immune response|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|response to inorganic substance|
|nucleobase-containing small molecule metabolic process|
|modification-dependent macromolecule catabolic process|
|myeloid leukocyte activation|
|small molecule biosynthetic process|
|proteolysis involved in cellular protein catabolic process|
|protein-containing complex|
|mitotic cell cycle process|
|carbohydrate derivative biosynthetic process|
|cellular protein catabolic process|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|microtubule-based process|
|protein catabolic process|
|mitotic cell cycle|
|intracellular membrane-bounded organelle|
|protein ubiquitination|
|positive regulation of cell death|
|perinuclear region of cytoplasm|
|viral process|
|regulated exocytosis|
|regulation of proteolysis|
|DNA metabolic process|
|leukocyte mediated immunity|
|positive regulation of hydrolase activity|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|symbiotic process|
|exocytosis|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|peptidyl-amino acid modification|
|organophosphate metabolic process|
|cellular macromolecule catabolic process|
|leukocyte activation|
|endoplasmic reticulum membrane|
|regulation of cellular component biogenesis|
|protein modification by small protein conjugation or removal|
|intracellular protein transport|
|regulation of catabolic process|
|cell cycle process|
|response to organonitrogen compound|
|secretion by cell|
|endoplasmic reticulum|
|carbohydrate derivative metabolic process|
|export from cell|
|macromolecule catabolic process|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|organonitrogen compound catabolic process|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|immune effector process|
|nucleobase-containing compound biosynthetic process|
|cytoskeleton organization|
|secretion|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|proteolysis|
|regulation of hydrolase activity|
|transmembrane transport|
|organic cyclic compound biosynthetic process|
|cell cycle|
|RNA binding|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|ATP binding|
|protein transport|
|intracellular transport|
|peptide transport|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|amide transport|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|cellular nitrogen compound biosynthetic process|
|positive regulation of signal transduction|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|small molecule metabolic process|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|establishment of localization in cell|
|regulation of protein modification process|
|nitrogen compound transport|
|protein-containing complex subunit organization|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-1.96|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|-1.88|
|[[:results:exp126|GSK461364A 0.1μM R03 exp126]]|-1.87|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|-1.85|
|[[:results:exp67|BVD-523 15μM R02 exp67]]|-1.71|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|1.78|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|1.81|
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|1.84|
|[[:results:exp10|CCCP 0.1μM R00 exp10]]|1.97|
|[[:results:exp179|Combretastatin A4 0.002 to 0.003μM day4 R04 exp179]]|2.03|
|[[:results:exp46|HMS-I1 1μM R01 exp46]]|2.05|
|[[:results:exp409|THZ531 0.11μM R07 exp409]]|2.38|
|[[:results:exp13|Chloramphenicol 20μM R00 exp13]]|2.63|
|[[:results:exp23|Nocodazole 0.02μM R00 exp23]]|2.81|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|3.26|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 739/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|28/28|
|blood|28/28|
|bone|26/26|
|breast|33/33|
|central nervous system|56/56|
|cervix|4/4|
|colorectal|17/17|
|esophagus|13/13|
|fibroblast|1/1|
|gastric|16/16|
|kidney|21/21|
|liver|20/20|
|lung|75/75|
|lymphocyte|16/16|
|ovary|26/26|
|pancreas|24/24|
|peripheral nervous system|16/16|
|plasma cell|15/15|
|prostate|1/1|
|skin|24/24|
|soft tissue|9/9|
|thyroid|2/2|
|upper aerodigestive|22/22|
|urinary tract|29/29|
|uterus|5/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 427
* **Expression level (log2 read counts)**: 8.61
{{:chemogenomics:nalm6 dist.png?nolink |}}