| IED ID | IndEnz0002011698 |
| Enzyme Type ID | protease011698 |
| Protein Name |
Transitional endoplasmic reticulum ATPase TER ATPase EC 3.6.4.6 15S Mg 2+ -ATPase p97 subunit Valosin-containing protein VCP |
| Gene Name | Vcp |
| Organism | Rattus norvegicus (Rat) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MASGADSKGDDLSTAILKQKNRPNRLIVDEAINEDNSVVSLSQPKMDELQLFRGDTVLLKGKKRREAVCIVLSDDTCSDEKIRMNRVVRNNLRVRLGDVISIQPCPDVKYGKRIHVLPIDDTVEGITGNLFEVYLKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCIVAPDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKTLIARAVANETGAFFFLINGPEIMSKLAGESESNLRKAFEEAEKNAPAIIFIDELDAIAPKREKTHGEVERRIVSQLLTLMDGLKQRAHVIVMAATNRPNSIDPALRRFGRFDREVDIGIPDATGRLEILQIHTKNMKLADDVDLEQVANETHGHVGADLAALCSEAALQAIRKKMDLIDLEDETIDAEVMNSLAVTMDDFRWALSQSNPSALRETVVEVPQVTWEDIGGLEDVKRELQELVQYPVEHPDKFLKFGMTPSKGVLFYGPPGCGKTLLAKAIANECQANFISIKGPELLTMWFGESEANVREIFDKARQAAPCVLFFDELDSIAKARGGNIGDGGGAADRVINQILTEMDGMSTKKNVFIIGATNRPDIIDPAILRPGRLDQLIYIPLPDEKSRVAILKANLRKSPVAKDVDLEFLAKMTNGFSGADLTEICQRACKLAIRESIESEIRRERERQTNPSAMEVEEDDPVPEIRRDHFEEAMRFARRSVSDNDIRKYEMFAQTLQQSRGFGSFRFPSGNQGGAGPSQGSGGGTGGNVYTEDNDDDLYG |
| Enzyme Length | 806 |
| Uniprot Accession Number | P46462 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 348; /note=ATP 1; /evidence=ECO:0000250|UniProtKB:P55072; BINDING 384; /note=ATP 1; /evidence=ECO:0000250|UniProtKB:P55072 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6; Evidence={ECO:0000250|UniProtKB:P55072}; |
| DNA Binding | |
| EC Number | 3.6.4.6 |
| Enzyme Function | 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) (PubMed:10930451, PubMed:12411482). Vesicle budding from the tER is an ATP-dependent process (PubMed:10930451, PubMed:12411482). 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 (PubMed:10930451, PubMed:12411482). 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. Plays a role in the regulation of stress granules (SGs) clearance process upon arsenite-induced response (By similarity). 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. Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis. Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex. 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 (By similarity). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (By similarity). May more particularly play a role in caveolins sorting in cells (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (By similarity). {ECO:0000250|UniProtKB:P23787, ECO:0000250|UniProtKB:P55072, ECO:0000269|PubMed:10930451, ECO:0000269|PubMed:12411482}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 247..253; /note=ATP 1; /evidence=ECO:0000250|UniProtKB:P55072; NP_BIND 521..526; /note=ATP 2; /evidence=ECO:0000250|UniProtKB:Q01853 |
| Features | Binding site (2); Chain (1); Compositional bias (1); Cross-link (2); Initiator methionine (1); Modified residue (18); Motif (1); Nucleotide binding (2); Region (3) |
| Keywords | ATP-binding;Acetylation;Autophagy;Cytoplasm;DNA damage;DNA repair;Direct protein sequencing;Endoplasmic reticulum;Hydrolase;Isopeptide bond;Lipid-binding;Methylation;Nucleotide-binding;Nucleus;Phosphoprotein;Reference proteome;Transport;Ubl conjugation |
| Interact With | O35987 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10811609}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P55072}. Nucleus {ECO:0000269|PubMed:10811609}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:P55072}. Note=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. Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains. Colocalizes with TIA1, ZFAND1 and G3BP1 in cytoplasmic stress granules (SGs) in response to arsenite-induced stress treatment (By similarity). {ECO:0000250|UniProtKB:P55072}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 3; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:22673903"; MOD_RES 7; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:22673903"; MOD_RES 13; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 37; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 315; /note="N6,N6,N6-trimethyllysine; by VCPKMT"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 436; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 462; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 502; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:Q01853"; MOD_RES 505; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:Q01853"; MOD_RES 668; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:Q01853"; MOD_RES 668; /note="N6-succinyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:Q01853"; MOD_RES 702; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 754; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:Q01853"; MOD_RES 770; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 775; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 787; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P55072"; MOD_RES 805; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q01853" |
| Post Translational Modification | PTM: Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells. {ECO:0000269|PubMed:12810701}.; PTM: ISGylated. {ECO:0000250|UniProtKB:P55072}.; PTM: Methylation at Lys-315 catalyzed by VCPKMT is increased in the presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity. {ECO:0000250|UniProtKB:P55072}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 15215856; 16027165; 16103111; 16396496; 16601695; 18332143; 19562802; 19834914; 19935650; 20691684; 22105171; 22206666; 23444373; 9214505; |
| Motif | MOTIF 802..806; /note=PIM motif; /evidence=ECO:0000250|UniProtKB:P55072 |
| Gene Encoded By | |
| Mass | 89,349 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:13065 |
| Cross Reference Brenda | 3.6.4.6; |