Transitional endoplasmic reticulum ATPase (Q01853)

Uniprot ID Q01853
Protein Name Transitional endoplasmic reticulum ATPase
Gene Name Vcp
Species Mus musculus (Mouse)
Signal peptide(a) N Secretome P(b) 0.262
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 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. 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. Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation. Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy. 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. May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation. May more particularly play a role in caveolins sorting in cells. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. .
GO - Molecular function
  • ADP binding : IMP:CAFA
  • ATP binding : IDA:ParkinsonsUK-UCL
  • ATPase activity : IDA:ParkinsonsUK-UCL
  • BAT3 complex binding : ISO:MGI
  • deubiquitinase activator activity : ISO:MGI
  • identical protein binding : IMP:CAFA
  • K48-linked polyubiquitin modification-dependent protein binding : IDA:ParkinsonsUK-UCL
  • lipid binding : IEA:UniProtKB-KW
  • MHC class I protein binding : IDA:ParkinsonsUK-UCL
  • polyubiquitin modification-dependent protein binding : IDA:BHF-UCL
  • protein domain specific binding : ISO:MGI
  • protein phosphatase binding : ISO:MGI
  • protein-containing complex binding : ISO:MGI
  • signaling receptor binding : ISO:MGI
  • ubiquitin protein ligase binding : ISO:MGI
  • ubiquitin-like protein ligase binding : ISO:MGI
  • ubiquitin-specific protease binding : IPI:ParkinsonsUK-UCL
GO - Biological process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process : IDA:MGI
  • aggresome assembly : IGI:MGI
  • ATP metabolic process : IDA:ParkinsonsUK-UCL
  • autophagosome maturation : ISS:UniProtKB
  • autophagy : ISS:UniProtKB
  • cellular response to DNA damage stimulus : ISS:UniProtKB
  • double-strand break repair : ISS:UniProtKB
  • endoplasmic reticulum stress-induced pre-emptive quality control : ISS:UniProtKB
  • endosome to lysosome transport via multivesicular body sorting pathway : ISS:UniProtKB
  • ER to Golgi vesicle-mediated transport : ISO:MGI
  • ER-associated misfolded protein catabolic process : ISO:MGI
  • ERAD pathway : ISS:UniProtKB
  • flavin adenine dinucleotide catabolic process : ISO:MGI
  • macroautophagy : ISS:UniProtKB
  • NADH metabolic process : ISO:MGI
  • positive regulation of ATP biosynthetic process : ISO:MGI
  • positive regulation of canonical Wnt signaling pathway : ISO:MGI
  • positive regulation of Lys63-specific deubiquitinase activity : ISO:MGI
  • positive regulation of mitochondrial membrane potential : IMP:ParkinsonsUK-UCL
  • positive regulation of oxidative phosphorylation : ISO:MGI
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process : ISO:MGI
  • positive regulation of protein catabolic process : ISO:MGI
  • positive regulation of protein complex assembly : ISO:MGI
  • positive regulation of protein K63-linked deubiquitination : ISO:MGI
  • proteasomal protein catabolic process : ISS:UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process : IMP:UniProtKB
  • protein hexamerization : IDA:ParkinsonsUK-UCL
  • protein homooligomerization : ISO:MGI
  • protein N-linked glycosylation via asparagine : ISS:UniProtKB
  • protein ubiquitination : ISS:UniProtKB
  • regulation of aerobic respiration : ISO:MGI
  • retrograde protein transport, ER to cytosol : IMP:ParkinsonsUK-UCL
  • translesion synthesis : ISS:UniProtKB
  • ubiquitin-dependent ERAD pathway : ISS:UniProtKB
  • ubiquitin-dependent protein catabolic process : IGI:MGI
  • viral genome replication : ISO:MGI
(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.