Search Results

Overview

Uniprot IDP46462
Protein NameTransitional endoplasmic reticulum ATPase
Gene NameVcp
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
18 DLSTAILKQKNRPNR
231 LRHPALFKAIGVKPP
312 ELDAIAPKREKTHGE
502 YPVEHPDKFLKFGMT
505 EHPDKFLKFGMTPSK
658 KSRVAILKANLRKSP
754 VSDNDIRKYEMFAQT

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)

Protein Sequence

10 MASGADSKGD 20 DLSTAILKQK 30 NRPNRLIVDE 40 AINEDNSVVS 50 LSQPKMDELQ 60 LFRGDTVLLK 70 GKKRREAVCI 80 VLSDDTCSDE 90 KIRMNRVVRN 100 NLRVRLGDVI 110 SIQPCPDVKY 120 GKRIHVLPID 130 DTVEGITGNL 140 FEVYLKPYFL 150 EAYRPIRKGD 160 IFLVRGGMRA 170 VEFKVVETDP 180 SPYCIVAPDT 190 VIHCEGEPIK 200 REDEEESLNE 210 VGYDDIGGCR 220 KQLAQIKEMV 230 ELPLRHPALF 240 KAIGVKPPRG 250 ILLYGPPGTG 260 KTLIARAVAN 270 ETGAFFFLIN 280 GPEIMSKLAG 290 ESESNLRKAF 300 EEAEKNAPAI 310 IFIDELDAIA 320 PKREKTHGEV 330 ERRIVSQLLT 340 LMDGLKQRAH 350 VIVMAATNRP 360 NSIDPALRRF 370 GRFDREVDIG 380 IPDATGRLEI 390 LQIHTKNMKL 400 ADDVDLEQVA 410 NETHGHVGAD 420 LAALCSEAAL 430 QAIRKKMDLI 440 DLEDETIDAE 450 VMNSLAVTMD 460 DFRWALSQSN 470 PSALRETVVE 480 VPQVTWEDIG 490 GLEDVKRELQ 500 ELVQYPVEHP 510 DKFLKFGMTP 520 SKGVLFYGPP 530 GCGKTLLAKA 540 IANECQANFI 550 SIKGPELLTM 560 WFGESEANVR 570 EIFDKARQAA 580 PCVLFFDELD 590 SIAKARGGNI 600 GDGGGAADRV 610 INQILTEMDG 620 MSTKKNVFII 630 GATNRPDIID 640 PAILRPGRLD 650 QLIYIPLPDE 660 KSRVAILKAN 670 LRKSPVAKDV 680 DLEFLAKMTN 690 GFSGADLTEI 700 CQRACKLAIR 710 ESIESEIRRE 720 RERQTNPSAM 730 EVEEDDPVPE 740 IRRDHFEEAM 750 RFARRSVSDN 760 DIRKYEMFAQ 770 TLQQSRGFGS 780 FRFPSGNQGG 790 AGPSQGSGGG 800 TGGNVYTEDN DDDLYG

Gene Ontology

Classification GO ID Description
Molecular Function GO:0031593 polyubiquitin modification-dependent protein binding
Cellular Component GO:1904949 ATPase complex
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0010494 cytoplasmic stress granule
Cellular Component GO:0000153 cytoplasmic ubiquitin ligase complex
Cellular Component GO:0005829 cytosol
Cellular Component GO:0036513 Derlin-1 retrotranslocation complex
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0005811 lipid droplet
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0000502 proteasome complex
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0035861 site of double-strand break
Cellular Component GO:0045202 synapse
Cellular Component GO:0034098 VCP-NPL4-UFD1 AAA ATPase complex
Cellular Component GO:1990730 VCP-NSFL1C complex
Molecular Function GO:0043531 ADP binding
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:1904288 BAT3 complex binding
Molecular Function GO:0035800 deubiquitinase activator activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0036435 K48-linked polyubiquitin modification-dependent protein binding
Molecular Function GO:0008289 lipid binding
Molecular Function GO:0042288 MHC class I protein binding
Molecular Function GO:0019904 protein domain specific binding
Molecular Function GO:0019903 protein phosphatase binding
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0044389 ubiquitin-like protein ligase binding
Molecular Function GO:0140036 ubiquitin-modified protein reader activity
Molecular Function GO:1990381 ubiquitin-specific protease binding
Biological Process GO:0070842 aggresome assembly
Biological Process GO:0046034 ATP metabolic process
Biological Process GO:0097352 autophagosome maturation
Biological Process GO:0006914 autophagy
Biological Process GO:1903843 cellular response to arsenite ion
Biological Process GO:0034605 cellular response to heat
Biological Process GO:0071218 cellular response to misfolded protein
Biological Process GO:0140455 cytoplasm protein quality control
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0061857 endoplasmic reticulum stress-induced pre-emptive quality control
Biological Process GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
Biological Process GO:0032510 endosome to lysosome transport via multivesicular body sorting pathway
Biological Process GO:0036503 ERAD pathway
Biological Process GO:0072389 flavin adenine dinucleotide catabolic process
Biological Process GO:0036297 interstrand cross-link repair
Biological Process GO:0016236 macroautophagy
Biological Process GO:0000423 mitophagy
Biological Process GO:0051228 mitotic spindle disassembly
Biological Process GO:0019674 NAD+ metabolic process
Biological Process GO:0035331 negative regulation of hippo signaling
Biological Process GO:0120186 negative regulation of protein localization to chromatin
Biological Process GO:0045879 negative regulation of smoothened signaling pathway
Biological Process GO:2001171 positive regulation of ATP biosynthetic process
Biological Process GO:0090263 positive regulation of canonical Wnt signaling pathway
Biological Process GO:0010918 positive regulation of mitochondrial membrane potential
Biological Process GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction
Biological Process GO:1903862 positive regulation of oxidative phosphorylation
Biological Process GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Process GO:0045732 positive regulation of protein catabolic process
Biological Process GO:1903006 positive regulation of protein K63-linked deubiquitination
Biological Process GO:0031334 positive regulation of protein-containing complex assembly
Biological Process GO:2000060 positive regulation of ubiquitin-dependent protein catabolic process
Biological Process GO:0010498 proteasomal protein catabolic process
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0016567 protein ubiquitination
Biological Process GO:0043335 protein unfolding
Biological Process GO:0106300 protein-DNA covalent cross-linking repair
Biological Process GO:1903715 regulation of aerobic respiration
Biological Process GO:1905634 regulation of protein localization to chromatin
Biological Process GO:0050807 regulation of synapse organization
Biological Process GO:0030970 retrograde protein transport, ER to cytosol
Biological Process GO:0035617 stress granule disassembly
Biological Process GO:0019985 translesion synthesis
Biological Process GO:0006511 ubiquitin-dependent protein catabolic process
Biological Process GO:0019079 viral genome replication

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.

[2] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.