TERA_HUMAN
Source:
hRBCD
; ID:
IPI00022774
PM19886704
PM23856902
PM22954596
Marked as 'Non-membrane protein'
Confidence:
high (present in two of the MS resources)
Search PubMed for
(RBC AND this entry)
Gene names:
VCP
Protein names and data:
TERA_HUMAN
, Transitional endoplasmic reticulum ATPase; TER ATPase; 3.6.4.6
, 15S Mg(2+)-ATPase p97 subunit; Valosin-containing protein; VCP
Lenght: 806 a.a.
Mass: 89322 Da
fasta formatted sequence
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 UFD1L, 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-UFD1L-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 (By similarity). 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. 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.
Catalytic activity:
ATP + H(2)O = ADP + phosphate.
Disease:
( OMIM:
167320
601023
613954
)
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. Note=The disease is caused by mutations affecting the gene represented in this entry. Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia (ALS14) [MIM:613954]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS14 may develop frontotemporal dementia. Note=The disease is caused by mutations affecting the gene represented in this entry.
Cellular location:
Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus. Note=Present in the neuronal hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients. Present in the Lewy bodies specifically found in neurons from Parkinson disease patients. 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.
Genetic variants
95 - 95
R -> G (in IBMPFD1; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP; abolishes enhancement of K-315 methylation by ASPSCR1). VAR_033016
155 - 155
R -> C (in IBMPFD1; also in one patient without evidence of Paget disease of the bone). VAR_033017
155 - 155
R -> H (in ALS14 and IBMPFD1; ALS14 patients do not manifest frontotemporal dementia; properly assembles into a hexameric structure and shows normal ATPase activity; cultured cells expressing the mutant protein show a marked general increase in the level of ubiquitin-conjugated proteins and impaired protein degradation through the endoplasmic reticulum-associated degradation (ERAD) pathway; shows strongly reduced affinity for ADP and increased affinity for ATP). VAR_033018
155 - 155
R -> P (in IBMPFD1). VAR_033019
159 - 159
R -> G (in ALS14). VAR_065910
159 - 159
R -> H (in IBMPFD1; without frontotemporal dementia; abolishes enhancement of K-315 methylation by ASPSCR1). VAR_033020
191 - 191
R -> Q (in ALS14 and IBMPFD1; abolishes enhancement of K-315 methylation by ASPSCR1). VAR_033021
232 - 232
A -> E (in IBMPFD1). VAR_033022
592 - 592
D -> N (in ALS14; ALS14 patients do not show frontotemporal dementia). VAR_065911
Database cross-references
UniProt:
P55072
Ensembl:
ENST00000358901
MIM:
167320
MIM:
601023
MIM:
613954
neXtProt:
NX_P55072
Antibodypedia:
P55072
(may not find the protein thus also not any antibody)
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