P46462 · TERA_RAT
- ProteinTransitional endoplasmic reticulum ATPase
- GeneVcp
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids806 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139).
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. Involved in clearance process by mediating G3BP1 extraction from stress granules (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. Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (By similarity).
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 RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (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).
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. Mediates the endoplasmic reticulum-associated degradation of CHRNA3 in cortical neurons as part of the STUB1-VCP-UBXN2A complex (PubMed:26265139).
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. Involved in clearance process by mediating G3BP1 extraction from stress granules (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. Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (By similarity).
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 RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (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).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphate
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTransitional endoplasmic reticulum ATPase
- EC number
- Short namesTER ATPase
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP46462
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000084575 | 2-806 | Transitional endoplasmic reticulum ATPase | |||
Sequence: ASGADSKGDDLSTAILKQKNRPNRLIVDEAINEDNSVVSLSQPKMDELQLFRGDTVLLKGKKRREAVCIVLSDDTCSDEKIRMNRVVRNNLRVRLGDVISIQPCPDVKYGKRIHVLPIDDTVEGITGNLFEVYLKPYFLEAYRPIRKGDIFLVRGGMRAVEFKVVETDPSPYCIVAPDTVIHCEGEPIKREDEEESLNEVGYDDIGGCRKQLAQIKEMVELPLRHPALFKAIGVKPPRGILLYGPPGTGKTLIARAVANETGAFFFLINGPEIMSKLAGESESNLRKAFEEAEKNAPAIIFIDELDAIAPKREKTHGEVERRIVSQLLTLMDGLKQRAHVIVMAATNRPNSIDPALRRFGRFDREVDIGIPDATGRLEILQIHTKNMKLADDVDLEQVANETHGHVGADLAALCSEAALQAIRKKMDLIDLEDETIDAEVMNSLAVTMDDFRWALSQSNPSALRETVVEVPQVTWEDIGGLEDVKRELQELVQYPVEHPDKFLKFGMTPSKGVLFYGPPGCGKTLLAKAIANECQANFISIKGPELLTMWFGESEANVREIFDKARQAAPCVLFFDELDSIAKARGGNIGDGGGAADRVINQILTEMDGMSTKKNVFIIGATNRPDIIDPAILRPGRLDQLIYIPLPDEKSRVAILKANLRKSPVAKDVDLEFLAKMTNGFSGADLTEICQRACKLAIRESIESEIRRERERQTNPSAMEVEEDDPVPEIRRDHFEEAMRFARRSVSDNDIRKYEMFAQTLQQSRGFGSFRFPSGNQGGAGPSQGSGGGTGGNVYTEDNDDDLYG | ||||||
Modified residue | 3 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 7 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 8 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 13 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 18 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 37 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 315 | N6,N6,N6-trimethyllysine; by VCPKMT | ||||
Sequence: K | ||||||
Modified residue | 436 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 462 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 502 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 505 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 668 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 668 | N6-succinyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 702 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 754 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 770 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 775 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 787 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 805 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells.
ISGylated.
Methylation at Lys-315 catalyzed by VCPKMT is increased in the presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. Interacts with NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with RHBDD1 (via C-terminal domain). Interacts with SELENOS and SYVN1, as well as with DERL1 (via SHP-box motif), DERL2 and DERL3; which probably transfer misfolded proteins from the ER to VCP. Interacts with SVIP. Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Part of a complex composed of STUB1/CHIP, VCP/p97, CHRNA3, and UBXN2A that modulates the ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of CHRNA3 (PubMed:26265139).
Within the complex UBXN2A acts as a scaffold protein required for the interaction of CHRNA3 with VCP/p97, this interaction also inhibits CHRNA3 ubiquitination by STUB1/CHIP and subsequently ERAD (PubMed:26265139).
Interacts with UBXN2A (via UBX domain); the interaction is required for the interaction of CHRNA3 in the STUB1-VCP-UBXN2A complex (PubMed:26265139).
Directly interacts with UBXN4 and RNF19A. Interacts with CASR. Interacts with UBE4B and YOD1. Interacts with clathrin. Interacts with RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of the endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts directly with AMFR/gp78 (via its VIM). Interacts with SPRTN; leading to recruitment to stalled replication forks. Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Binds to a heterodimer of NPLOC4 and UFD1, binding to this heterodimer inhibits Golgi-membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Part of a ternary complex containing NPLOC4, UFD1 and VCP. Interacts with WASHC5. Interacts with UBOX5. Interacts (via N-terminus) with UBXN7, UBXN8, and probably several other UBX domain-containing proteins (via UBX domains); the interactions are mutually exclusive with VIM-dependent interactions such as those with AMFR and SELENOS. Forms a complex with UBQLN1 and UBXN4 (By similarity).
Interacts (via the PIM motif) with RNF31 (via the PUB domain) (By similarity).
Interacts with RIGI and RNF125; interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (By similarity).
Interacts with BAG6 (By similarity).
Interacts with UBXN10 (By similarity).
Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (By similarity).
Forms a ternary complex with CAV1 and UBXN6. Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (By similarity).
Interacts with ANKZF1 (By similarity).
Interacts with ubiquitin-binding protein FAF1 (By similarity).
Interacts with ZFAND2B (via VIM motif); the interaction is direct (By similarity).
Interacts with ZFAND1 (via its ubiquitin-like region); this interaction occurs in an arsenite-dependent manner (By similarity).
Interacts with CCDC47 (By similarity).
Interacts with LMBR1L and UBAC2 (By similarity).
Interacts with ATXN3 (By similarity).
Interacts with TEX264; bridging VCP to covalent DNA-protein cross-links (DPCs) (By similarity).
Within the complex UBXN2A acts as a scaffold protein required for the interaction of CHRNA3 with VCP/p97, this interaction also inhibits CHRNA3 ubiquitination by STUB1/CHIP and subsequently ERAD (PubMed:26265139).
Interacts with UBXN2A (via UBX domain); the interaction is required for the interaction of CHRNA3 in the STUB1-VCP-UBXN2A complex (PubMed:26265139).
Directly interacts with UBXN4 and RNF19A. Interacts with CASR. Interacts with UBE4B and YOD1. Interacts with clathrin. Interacts with RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of the endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts directly with AMFR/gp78 (via its VIM). Interacts with SPRTN; leading to recruitment to stalled replication forks. Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Binds to a heterodimer of NPLOC4 and UFD1, binding to this heterodimer inhibits Golgi-membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Part of a ternary complex containing NPLOC4, UFD1 and VCP. Interacts with WASHC5. Interacts with UBOX5. Interacts (via N-terminus) with UBXN7, UBXN8, and probably several other UBX domain-containing proteins (via UBX domains); the interactions are mutually exclusive with VIM-dependent interactions such as those with AMFR and SELENOS. Forms a complex with UBQLN1 and UBXN4 (By similarity).
Interacts (via the PIM motif) with RNF31 (via the PUB domain) (By similarity).
Interacts with RIGI and RNF125; interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (By similarity).
Interacts with BAG6 (By similarity).
Interacts with UBXN10 (By similarity).
Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (By similarity).
Forms a ternary complex with CAV1 and UBXN6. Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (By similarity).
Interacts with ANKZF1 (By similarity).
Interacts with ubiquitin-binding protein FAF1 (By similarity).
Interacts with ZFAND2B (via VIM motif); the interaction is direct (By similarity).
Interacts with ZFAND1 (via its ubiquitin-like region); this interaction occurs in an arsenite-dependent manner (By similarity).
Interacts with CCDC47 (By similarity).
Interacts with LMBR1L and UBAC2 (By similarity).
Interacts with ATXN3 (By similarity).
Interacts with TEX264; bridging VCP to covalent DNA-protein cross-links (DPCs) (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P46462 | Nsfl1c O35987 | 12 | EBI-399011, EBI-1993760 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 708-727 | Disordered | ||||
Sequence: RRERERQTNPSAMEVEEDDP | ||||||
Compositional bias | 768-794 | Polar residues | ||||
Sequence: FGSFRFPSGNQGGAGPSQGSGGGTGGN | ||||||
Region | 768-806 | Disordered | ||||
Sequence: FGSFRFPSGNQGGAGPSQGSGGGTGGNVYTEDNDDDLYG | ||||||
Region | 797-806 | Interaction with UBXN6 | ||||
Sequence: TEDNDDDLYG | ||||||
Motif | 802-806 | PIM motif | ||||
Sequence: DDLYG |
Domain
The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31.
Sequence similarities
Belongs to the AAA ATPase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length806
- Mass (Da)89,349
- Last updated2007-01-23 v3
- Checksum501B721D205EBA8A
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 768-794 | Polar residues | ||||
Sequence: FGSFRFPSGNQGGAGPSQGSGGGTGGN |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U11760 EMBL· GenBank· DDBJ | AAC52154.1 EMBL· GenBank· DDBJ | mRNA | ||
BC060518 EMBL· GenBank· DDBJ | AAH60518.1 EMBL· GenBank· DDBJ | mRNA |