TERA_BOVIN
ID TERA_BOVIN Reviewed; 806 AA.
AC Q3ZBT1;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Transitional endoplasmic reticulum ATPase;
DE Short=TER ATPase;
DE EC=3.6.4.6 {ECO:0000250|UniProtKB:P55072};
DE AltName: Full=15S Mg(2+)-ATPase p97 subunit;
DE AltName: Full=Valosin-containing protein;
DE Short=VCP;
GN Name=VCP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Necessary for the fragmentation of Golgi stacks during
CC mitosis and for their reassembly after mitosis. Involved in the
CC formation of the transitional endoplasmic reticulum (tER). The transfer
CC of membranes from the endoplasmic reticulum to the Golgi apparatus
CC occurs via 50-70 nm transition vesicles which derive from part-rough,
CC part-smooth transitional elements of the endoplasmic reticulum (tER).
CC Vesicle budding from the tER is an ATP-dependent process. The ternary
CC complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins
CC and is necessary for the export of misfolded proteins from the ER to
CC the cytoplasm, where they are degraded by the proteasome. The NPLOC4-
CC UFD1-VCP complex regulates spindle disassembly at the end of mitosis
CC and is necessary for the formation of a closed nuclear envelope.
CC Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of
CC the VCP/p97-AMFR/gp78 complex that participates in the final step of
CC the sterol-mediated ubiquitination and endoplasmic reticulum-associated
CC degradation (ERAD) of HMGCR. Involved in endoplasmic reticulum stress-
CC induced pre-emptive quality control, a mechanism that selectively
CC attenuates the translocation of newly synthesized proteins into the
CC endoplasmic reticulum and reroutes them to the cytosol for proteasomal
CC degradation. Plays a role in the regulation of stress granules (SGs)
CC clearance process upon arsenite-induced response (By similarity). Also
CC involved in DNA damage response: recruited to double-strand breaks
CC (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the
CC recruitment of TP53BP1 at DNA damage sites. Recruited to stalled
CC replication forks by SPRTN: may act by mediating extraction of DNA
CC polymerase eta (POLH) to prevent excessive translesion DNA synthesis
CC and limit the incidence of mutations induced by DNA damage. Together
CC with SPRTN metalloprotease, involved in the repair of covalent DNA-
CC protein cross-links (DPCs) during DNA synthesis. Involved in
CC interstrand cross-link repair in response to replication stress by
CC mediating unloading of the ubiquitinated CMG helicase complex. Required
CC for cytoplasmic retrotranslocation of stressed/damaged mitochondrial
CC outer-membrane proteins and their subsequent proteasomal degradation.
CC Essential for the maturation of ubiquitin-containing autophagosomes and
CC the clearance of ubiquitinated protein by autophagy. Acts as a negative
CC regulator of type I interferon production by interacting with
CC DDX58/RIG-I: interaction takes place when DDX58/RIG-I is ubiquitinated
CC via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit
CC RNF125 and promote ubiquitination and degradation of DDX58/RIG-I. May
CC play a role in the ubiquitin-dependent sorting of membrane proteins to
CC lysosomes where they undergo degradation. May more particularly play a
CC role in caveolins sorting in cells. By controlling the steady-state
CC expression of the IGF1R receptor, indirectly regulates the insulin-like
CC growth factor receptor signaling pathway.
CC {ECO:0000250|UniProtKB:P23787, ECO:0000250|UniProtKB:P46462,
CC ECO:0000250|UniProtKB:P55072}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6;
CC Evidence={ECO:0000250|UniProtKB:P55072};
CC -!- SUBUNIT: Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter,
CC that displays 6-fold radial symmetry. Part of a ternary complex
CC containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds
CC to one end of a VCP homohexamer. The complex binds to membranes
CC enriched in phosphatidylethanolamine-containing lipids and promotes
CC Golgi membrane fusion. Binds to a heterodimer of NPLOC4 and UFD1,
CC binding to this heterodimer inhibits Golgi-membrane fusion. Interaction
CC with VCIP135 leads to dissociation of the complex via ATP hydrolysis by
CC VCP. Part of a ternary complex containing NPLOC4, UFD1 and VCP.
CC Interacts with NSFL1C-like protein p37; the complex has membrane fusion
CC activity and is required for Golgi and endoplasmic reticulum
CC biogenesis. Interacts with SELENOS and SYVN1, as well as with DERL1
CC (via SHP-box motif), DERL2 and DERL3; which probably transfer misfolded
CC proteins from the ER to VCP. Interacts with SVIP. Component of a
CC complex required to couple retrotranslocation, ubiquitination and
CC deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B.
CC Directly interacts with UBXN4 and RNF19A. Interacts with CASR.
CC Interacts with UBE4B and YOD1. Interacts with clathrin. Interacts with
CC RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-
CC AMFR/gp78 complex that participates in the final step of the
CC endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts
CC directly with AMFR/gp78 (via its VIM). Interacts with RHBDD1 (via C-
CC terminal domain). Interacts with SPRTN; leading to recruitment to
CC stalled replication forks. Interacts with WASHC5. Interacts with UBOX5.
CC Interacts (via N-terminus) with UBXN7, UBXN8, and probably several
CC other UBX domain-containing proteins (via UBX domains); the
CC interactions are mutually exclusive with VIM-dependent interactions
CC such as those with AMFR and SELENOS. Forms a complex with UBQLN1 and
CC UBXN4. Interacts (via the PIM motif) with RNF31 (via the PUB domain).
CC Interacts with DDX58/RIG-I and RNF125; interaction takes place when
CC DDX58/RIG-I is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD
CC domains, leading to recruit RNF125 and promote ubiquitination and
CC degradation of DDX58/RIG-I. Interacts with BAG6. Interacts with UBXN10.
CC Interacts with UBXN6; the interaction with UBXN6 is direct and
CC competitive with UFD1. Forms a ternary complex with CAV1 and UBXN6.
CC Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in
CC macroautophagy. Interacts with ANKZF1. Interacts with ubiquitin-binding
CC protein FAF1. Interacts with ZFAND2B (via VIM motif); the interaction
CC is direct. Interacts with ZFAND1 (via its ubiquitin-like region); this
CC interaction occurs in an arsenite-dependent manner (By similarity).
CC Interacts with CCDC47 (By similarity). Interacts with LMBR1L and UBAC2
CC (By similarity). Interacts with ATXN3 (By similarity). Interacts with
CC TEX264; bridging VCP to covalent DNA-protein cross-links (DPCs) (By
CC similarity). {ECO:0000250|UniProtKB:P46462,
CC ECO:0000250|UniProtKB:P55072, ECO:0000250|UniProtKB:Q01853}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P55072}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P55072}. Nucleus {ECO:0000250|UniProtKB:P55072}.
CC Cytoplasm, Stress granule {ECO:0000250|UniProtKB:P55072}.
CC Note=Recruited to the cytoplasmic surface of the endoplasmic reticulum
CC via interaction with AMFR/gp78. Following DNA double-strand breaks,
CC recruited to the sites of damage. Recruited to stalled replication
CC forks via interaction with SPRTN. Recruited to damaged lysosomes
CC decorated with K48-linked ubiquitin chains. Colocalizes with TIA1,
CC ZFAND1 and G3BP1 in cytoplasmic stress granules (SGs) in response to
CC arsenite-induced stress treatment (By similarity).
CC {ECO:0000250|UniProtKB:P55072}.
CC -!- DOMAIN: The PIM (PUB-interaction motif) motif mediates interaction with
CC the PUB domain of RNF31. {ECO:0000250|UniProtKB:P55072}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P55072}.
CC -!- PTM: Methylation at Lys-315 catalyzed by VCPKMT is increased in the
CC presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity.
CC {ECO:0000250|UniProtKB:P55072}.
CC -!- PTM: Phosphorylated by tyrosine kinases in response to T-cell antigen
CC receptor activation. Phosphorylated in mitotic cells.
CC {ECO:0000250|UniProtKB:P46462}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
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DR EMBL; BC103125; AAI03126.1; -; mRNA.
DR RefSeq; NP_001029466.1; NM_001034294.2.
DR AlphaFoldDB; Q3ZBT1; -.
DR SMR; Q3ZBT1; -.
DR IntAct; Q3ZBT1; 1.
DR STRING; 9913.ENSBTAP00000019970; -.
DR PaxDb; Q3ZBT1; -.
DR PeptideAtlas; Q3ZBT1; -.
DR PRIDE; Q3ZBT1; -.
DR GeneID; 507345; -.
DR KEGG; bta:507345; -.
DR CTD; 7415; -.
DR eggNOG; KOG0730; Eukaryota.
DR InParanoid; Q3ZBT1; -.
DR OrthoDB; 194195at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0097352; P:autophagosome maturation; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:1903843; P:cellular response to arsenite ion; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0061857; P:endoplasmic reticulum stress-induced pre-emptive quality control; ISS:UniProtKB.
DR GO; GO:0032510; P:endosome to lysosome transport via multivesicular body sorting pathway; ISS:UniProtKB.
DR GO; GO:0036503; P:ERAD pathway; ISS:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; ISS:UniProtKB.
DR GO; GO:1905634; P:regulation of protein localization to chromatin; ISS:UniProtKB.
DR GO; GO:0035617; P:stress granule disassembly; ISS:UniProtKB.
DR GO; GO:0019985; P:translesion synthesis; ISS:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR005938; AAA_ATPase_CDC48.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR009010; Asp_de-COase-like_dom_sf.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR004201; Cdc48_dom2.
DR InterPro; IPR029067; CDC48_domain_2-like_sf.
DR InterPro; IPR003338; CDC4_N-term_subdom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015415; Vps4_C.
DR Pfam; PF00004; AAA; 2.
DR Pfam; PF17862; AAA_lid_3; 2.
DR Pfam; PF02933; CDC48_2; 1.
DR Pfam; PF02359; CDC48_N; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR SMART; SM00382; AAA; 2.
DR SMART; SM01072; CDC48_2; 1.
DR SMART; SM01073; CDC48_N; 1.
DR SUPFAM; SSF50692; SSF50692; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF54585; SSF54585; 1.
DR TIGRFAMs; TIGR01243; CDC48; 1.
DR PROSITE; PS00674; AAA; 2.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Autophagy; Cytoplasm; DNA damage; DNA repair;
KW Endoplasmic reticulum; Hydrolase; Isopeptide bond; Lipid-binding;
KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transport; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT CHAIN 2..806
FT /note="Transitional endoplasmic reticulum ATPase"
FT /id="PRO_0000280706"
FT REGION 708..727
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 768..806
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 797..806
FT /note="Interaction with UBXN6"
FT /evidence="ECO:0000250"
FT MOTIF 802..806
FT /note="PIM motif"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT COMPBIAS 768..794
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 247..253
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 348
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 384
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT BINDING 521..526
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 315
FT /note="N6,N6,N6-trimethyllysine; by VCPKMT"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 436
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 502
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 505
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 668
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 668
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 702
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 754
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 787
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT MOD_RES 805
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01853"
FT CROSSLNK 8
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P55072"
FT CROSSLNK 18
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P55072"
SQ SEQUENCE 806 AA; 89330 MW; 1D366BF671119B70 CRC64;
MASGADSKGD DLSTAILKQK NRPNRLIVDE AINEDNSVVS LSQPKMDELQ LFRGDTVLLK
GKKRREAVCI VLSDDTCSDE KIRMNRVVRN NLRVHLGDVI SIQPCPDVKY GKRIHVLPID
DTVEGITGNL FEVYLKPYFL EAYRPIRKGD IFLVRGGMRA VEFKVVETDP SPYCIVAPDT
VIHCEGEPIK REDEEESLNE VGYDDIGGCR KQLAQIKEMV ELPLRHPALF KAIGVKPPRG
ILLYGPPGTG KTLIARAVAN ETGAFFFLIN GPEIMSKLAG ESESNLRKAF EEAEKNAPAI
IFIDELDAIA PKREKTHGEV ERRIVSQLLT LMDGLKQRAH VIVMAATNRP NSIDPALRRF
GRFDREVDIG IPDATGRLEI LQIHTKNMKL ADDVDLEQVA NETHGHVGAD LAALCSEAAL
QAIRKKMDLI DLEDETIDAE VMNSLAVTMD DFRWALSQSN PSALRETVVE VPQVTWEDIG
GLEDVKRELQ ELVQYPVEHP DKFLKFGMTP SKGVLFYGPP GCGKTLLAKA IANECQANFI
SIKGPELLTM WFGESEANVR EIFDKARQAA PCVLFFDELD SIAKARGGNI GDGGGAADRV
INQILTEMDG MSTKKNVFII GATNRPDIID PAILRPGRLD QLIYIPLPDE KSRVAILKAN
LRKSPVAKDV DLEFLAKMTN GFSGADLTEI CQRACKLAIR ESIESEIRRE RERQTNPSAM
EVEEDDPVPE IRRDHFEEAM RFARRSVSDN DIRKYEMFAQ TLQQSRGFGS FRFPSGNQGG
AGPSQGSGGG TGGNVYTEDN DDDLYG
