UniProt functional annotation for P55072



	UniProt functional annotation for P55072

UniProt code: P55072.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (PubMed:26565908). Plays a role in the regulation of stress granules (SGs) clearance process upon arsenite-induced response (PubMed:29804830). 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 (PubMed:22020440, PubMed:22120668). 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 (PubMed:23042607, PubMed:23042605). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer- membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). 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 (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250|UniProtKB:P23787, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:21118995, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:22020440, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22607976, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:23335559, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26565908, ECO:0000269|PubMed:26692333, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:32152270}.

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:0000269|PubMed:26471729};

Subunit: Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. 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 (PubMed:26471729). 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 NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with SELENOS and SYVN1, as well as with DERL1, 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. 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 RHBDD1 (via C- terminal domain). Interacts with SPRTN; leading to recruitment to stalled replication forks (PubMed:23042607, PubMed:23042605). 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. Interacts (via the PIM motif) with RNF31 (via the PUB domain) (PubMed:24726327). Interacts with DDX58/RIG-I and RNF125; 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 (PubMed:26471729). Interacts with BAG6 (PubMed:21636303). Interacts with UBXN10 (PubMed:26389662). Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (PubMed:19174149, PubMed:19275885). Forms a ternary complex with CAV1 and UBXN6 (PubMed:21822278, PubMed:18656546, PubMed:19174149). Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (PubMed:27753622). Interacts with ANKZF1 (PubMed:28302725). Interacts with ubiquitin-binding protein FAF1 (PubMed:26842564). Interacts with ZFAND2B (via VIM motif); the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with ZFAND1 (via its ubiquitin-like region); this interaction occurs in an arsenite-dependent manner (PubMed:29804830). Interacts with CCDC47 (By similarity). Interacts with UBAC2 (By similarity). Interacts with LMBR1L (PubMed:31073040). Interacts with ATXN3 (PubMed:30455355). Interacts with TEX264; bridging VCP to covalent DNA-protein cross-links (DPCs) (PubMed:32152270). {ECO:0000250|UniProtKB:P46462, ECO:0000250|UniProtKB:Q01853, ECO:0000269|PubMed:15215856, ECO:0000269|PubMed:15362974, ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16186509, ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:16289116, ECO:0000269|PubMed:16449189, ECO:0000269|PubMed:16513638, ECO:0000269|PubMed:16968747, ECO:0000269|PubMed:17314412, ECO:0000269|PubMed:18022694, ECO:0000269|PubMed:18656546, ECO:0000269|PubMed:18675248, ECO:0000269|PubMed:19174149, ECO:0000269|PubMed:19275885, ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:19822669, ECO:0000269|PubMed:19887378, ECO:0000269|PubMed:20512113, ECO:0000269|PubMed:20833645, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:21914798, ECO:0000269|PubMed:21949850, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:22537386, ECO:0000269|PubMed:22795130, ECO:0000269|PubMed:22902628, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:24160817, ECO:0000269|PubMed:24726327, ECO:0000269|PubMed:26337389, ECO:0000269|PubMed:26389662, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:26842564, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:28302725, ECO:0000269|PubMed:29804830, ECO:0000269|PubMed:30455355, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:8413590, ECO:0000305|PubMed:31073040}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:15456787}. Endoplasmic reticulum {ECO:0000269|PubMed:15215856}. Nucleus {ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:26842564}. Cytoplasm, Stress granule {ECO:0000269|PubMed:29804830}. Note=Present in the neuronal hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients (PubMed:15456787). Present in the Lewy bodies specifically found in neurons from Parkinson disease patients (PubMed:15456787). Recruited to the cytoplasmic surface of the endoplasmic reticulum via interaction with AMFR/gp78 (PubMed:16168377). Following DNA double-strand breaks, recruited to the sites of damage (PubMed:22120668). Recruited to stalled replication forks via interaction with SPRTN (PubMed:23042605). Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains (PubMed:27753622). Colocalizes with TIA1, ZFAND1 and G3BP1 in cytoplasmic stress granules (SGs) in response to arsenite-induced stress treatment (PubMed:29804830). {ECO:0000269|PubMed:15456787, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:22120668, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830}.

Domain: The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31. {ECO:0000269|PubMed:24726327}.

Ptm: Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells. {ECO:0000250|UniProtKB:P46462}.

Ptm: ISGylated. {ECO:0000269|PubMed:16139798}.

Ptm: Methylation at Lys-315 catalyzed by VCPKMT is increased in the presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity. {ECO:0000269|PubMed:22948820, ECO:0000269|PubMed:23349634}.

Disease: Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1) [MIM:167320]: An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. {ECO:0000269|PubMed:15034582, ECO:0000269|PubMed:15732117, ECO:0000269|PubMed:16247064, ECO:0000269|PubMed:16321991, ECO:0000269|PubMed:17935506, ECO:0000269|PubMed:20104022, ECO:0000269|PubMed:20335036, ECO:0000269|PubMed:20512113, ECO:0000269|PubMed:21822278, ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:25125609, ECO:0000269|PubMed:25878907, ECO:0000269|PubMed:27209344, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:29804830}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (FTDALS6) [MIM:613954]: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia (FTD) is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis (ALS) is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS6 is an autosomal dominant form characterized by onset of ALS or FTD in adulthood. Some patients with the disorder may have features of both diseases. {ECO:0000269|PubMed:21145000, ECO:0000269|PubMed:23349634}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Charcot-Marie-Tooth disease 2Y (CMT2Y) [MIM:616687]: An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:25125609, ECO:0000269|PubMed:25878907}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the AAA ATPase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (PubMed:26565908). Plays a role in the regulation of stress granules (SGs) clearance process upon arsenite-induced response (PubMed:29804830). 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 (PubMed:22020440, PubMed:22120668). 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 (PubMed:23042607, PubMed:23042605). Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (PubMed:32152270). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer- membrane proteins and their subsequent proteasomal degradation (PubMed:16186510, PubMed:21118995). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (PubMed:20104022, PubMed:27753622). 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 (PubMed:26471729). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (PubMed:21822278). May more particularly play a role in caveolins sorting in cells (PubMed:21822278, PubMed:23335559). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). {ECO:0000250\|UniProtKB:P23787, ECO:0000269\|PubMed:15456787, ECO:0000269\|PubMed:16168377, ECO:0000269\|PubMed:16186510, ECO:0000269\|PubMed:20104022, ECO:0000269\|PubMed:21118995, ECO:0000269\|PubMed:21822278, ECO:0000269\|PubMed:22020440, ECO:0000269\|PubMed:22120668, ECO:0000269\|PubMed:22607976, ECO:0000269\|PubMed:23042605, ECO:0000269\|PubMed:23042607, ECO:0000269\|PubMed:23335559, ECO:0000269\|PubMed:26471729, ECO:0000269\|PubMed:26565908, ECO:0000269\|PubMed:26692333, ECO:0000269\|PubMed:27753622, ECO:0000269\|PubMed:29804830, ECO:0000269\|PubMed:32152270}.


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:0000269\|PubMed:26471729};
Subunit:		Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. 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 (PubMed:26471729). 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 NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with SELENOS and SYVN1, as well as with DERL1, 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. 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 RHBDD1 (via C- terminal domain). Interacts with SPRTN; leading to recruitment to stalled replication forks (PubMed:23042607, PubMed:23042605). 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. Interacts (via the PIM motif) with RNF31 (via the PUB domain) (PubMed:24726327). Interacts with DDX58/RIG-I and RNF125; 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 (PubMed:26471729). Interacts with BAG6 (PubMed:21636303). Interacts with UBXN10 (PubMed:26389662). Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (PubMed:19174149, PubMed:19275885). Forms a ternary complex with CAV1 and UBXN6 (PubMed:21822278, PubMed:18656546, PubMed:19174149). Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (PubMed:27753622). Interacts with ANKZF1 (PubMed:28302725). Interacts with ubiquitin-binding protein FAF1 (PubMed:26842564). Interacts with ZFAND2B (via VIM motif); the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with ZFAND1 (via its ubiquitin-like region); this interaction occurs in an arsenite-dependent manner (PubMed:29804830). Interacts with CCDC47 (By similarity). Interacts with UBAC2 (By similarity). Interacts with LMBR1L (PubMed:31073040). Interacts with ATXN3 (PubMed:30455355). Interacts with TEX264; bridging VCP to covalent DNA-protein cross-links (DPCs) (PubMed:32152270). {ECO:0000250\|UniProtKB:P46462, ECO:0000250\|UniProtKB:Q01853, ECO:0000269\|PubMed:15215856, ECO:0000269\|PubMed:15362974, ECO:0000269\|PubMed:15456787, ECO:0000269\|PubMed:16168377, ECO:0000269\|PubMed:16186509, ECO:0000269\|PubMed:16186510, ECO:0000269\|PubMed:16289116, ECO:0000269\|PubMed:16449189, ECO:0000269\|PubMed:16513638, ECO:0000269\|PubMed:16968747, ECO:0000269\|PubMed:17314412, ECO:0000269\|PubMed:18022694, ECO:0000269\|PubMed:18656546, ECO:0000269\|PubMed:18675248, ECO:0000269\|PubMed:19174149, ECO:0000269\|PubMed:19275885, ECO:0000269\|PubMed:19818707, ECO:0000269\|PubMed:19822669, ECO:0000269\|PubMed:19887378, ECO:0000269\|PubMed:20512113, ECO:0000269\|PubMed:20833645, ECO:0000269\|PubMed:21636303, ECO:0000269\|PubMed:21822278, ECO:0000269\|PubMed:21914798, ECO:0000269\|PubMed:21949850, ECO:0000269\|PubMed:22120668, ECO:0000269\|PubMed:22537386, ECO:0000269\|PubMed:22795130, ECO:0000269\|PubMed:22902628, ECO:0000269\|PubMed:23042605, ECO:0000269\|PubMed:23042607, ECO:0000269\|PubMed:24160817, ECO:0000269\|PubMed:24726327, ECO:0000269\|PubMed:26337389, ECO:0000269\|PubMed:26389662, ECO:0000269\|PubMed:26471729, ECO:0000269\|PubMed:26842564, ECO:0000269\|PubMed:27753622, ECO:0000269\|PubMed:28302725, ECO:0000269\|PubMed:29804830, ECO:0000269\|PubMed:30455355, ECO:0000269\|PubMed:32152270, ECO:0000269\|PubMed:8413590, ECO:0000305\|PubMed:31073040}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:15456787}. Endoplasmic reticulum {ECO:0000269\|PubMed:15215856}. Nucleus {ECO:0000269\|PubMed:23042605, ECO:0000269\|PubMed:26842564}. Cytoplasm, Stress granule {ECO:0000269\|PubMed:29804830}. Note=Present in the neuronal hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients (PubMed:15456787). Present in the Lewy bodies specifically found in neurons from Parkinson disease patients (PubMed:15456787). Recruited to the cytoplasmic surface of the endoplasmic reticulum via interaction with AMFR/gp78 (PubMed:16168377). Following DNA double-strand breaks, recruited to the sites of damage (PubMed:22120668). Recruited to stalled replication forks via interaction with SPRTN (PubMed:23042605). Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains (PubMed:27753622). Colocalizes with TIA1, ZFAND1 and G3BP1 in cytoplasmic stress granules (SGs) in response to arsenite-induced stress treatment (PubMed:29804830). {ECO:0000269\|PubMed:15456787, ECO:0000269\|PubMed:16168377, ECO:0000269\|PubMed:22120668, ECO:0000269\|PubMed:23042605, ECO:0000269\|PubMed:27753622, ECO:0000269\|PubMed:29804830}.
Domain:		The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31. {ECO:0000269\|PubMed:24726327}.
Ptm:		Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells. {ECO:0000250\|UniProtKB:P46462}.
Ptm:		ISGylated. {ECO:0000269\|PubMed:16139798}.
Ptm:		Methylation at Lys-315 catalyzed by VCPKMT is increased in the presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity. {ECO:0000269\|PubMed:22948820, ECO:0000269\|PubMed:23349634}.
Disease:		Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1) [MIM:167320]: An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. {ECO:0000269\|PubMed:15034582, ECO:0000269\|PubMed:15732117, ECO:0000269\|PubMed:16247064, ECO:0000269\|PubMed:16321991, ECO:0000269\|PubMed:17935506, ECO:0000269\|PubMed:20104022, ECO:0000269\|PubMed:20335036, ECO:0000269\|PubMed:20512113, ECO:0000269\|PubMed:21822278, ECO:0000269\|PubMed:23349634, ECO:0000269\|PubMed:25125609, ECO:0000269\|PubMed:25878907, ECO:0000269\|PubMed:27209344, ECO:0000269\|PubMed:27753622, ECO:0000269\|PubMed:29804830}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (FTDALS6) [MIM:613954]: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia (FTD) is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis (ALS) is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. FTDALS6 is an autosomal dominant form characterized by onset of ALS or FTD in adulthood. Some patients with the disorder may have features of both diseases. {ECO:0000269\|PubMed:21145000, ECO:0000269\|PubMed:23349634}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Charcot-Marie-Tooth disease 2Y (CMT2Y) [MIM:616687]: An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269\|PubMed:25125609, ECO:0000269\|PubMed:25878907}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the AAA ATPase family. {ECO:0000305}.