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Literature summary for 3.6.4.6 extracted from

  • Rijal, R.; Arhzaouy, K.; Strucksberg, K.; Cross, M.; Hofmann, A.; Schroeder, R.; Clemen, C.; Eichinger, L.
    Mutant p97 exhibits species-specific changes of its ATPase activity and compromises the UBXD9-mediated monomerisation of p97 hexamers (2016), Eur. J. Cell Biol., 95, 195-207 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of GST-tagged wild-type and mutant p97 in Escherichia coli strain Arctic express RIL, coexpression with GST-tagged human UBXD9 protein in Escherichia coli in strain BL21Gold (DE3) pLysS Homo sapiens
recombinant expression of GST-tagged wild-type and mutant p97 in Escherichia coli strain XL1 Blue, coexpression with GST-tagged Dictyostelium UBXD9 protein Dictyostelium discoideum

Protein Variants

Protein Variants Comment Organism
E219K naturally occurring mutation, constitutes variations in surface-exposed locations Dictyostelium discoideum
E219K naturally occurring mutation, the E219K mutation leads to an almost complete loss of activity Dictyostelium discoideum
R154C naturally occurring mutation, constitutes variations in surface-exposed locations, but does not alter the ATPase activity Dictyostelium discoideum
R154C/E219K naturally occurring mutation, constitutes variations in surface-exposed locations. The E219K mutation leads to an almost complete loss of activity, which is partially recuperated in the R154C/E219K double-mutant indicating p97 inter-domain communication Dictyostelium discoideum
R155C naturally occurring mutation, constitutes variations in surface-exposed locations and leads to increased ATPase activity, and a twofold decreased kd for human protein UBXD9 Homo sapiens
R155H naturally occurring mutation, constitutes variations in surface-exposed locations and leads to increased ATPase activity, no change in the kd value for human protein UBXD9 Homo sapiens
R93C naturally occurring mutation, constitutes variations in surface-exposed locations and leads to increased ATPase activity and a twofold increased kd for human protein UBXD9 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Dictyostelium discoideum 5737
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Dictyostelium discoideum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + H2O Homo sapiens
-
ADP + phosphate
-
?
ATP + H2O Dictyostelium discoideum
-
ADP + phosphate
-
?
additional information Dictyostelium discoideum UBX-domain containing cytoplasmic Dictyostelium protein UBXD9 is identified as p97 interaction partner ?
-
-

Organism

Organism UniProt Comment Textmining
Dictyostelium discoideum Q75JI3
-
-
Homo sapiens P55072
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-tagged wild-type and mutant p97s from Escherichia coli by glutathione affinity and cleavage of the tag by PreScission protease Homo sapiens
recombinant GST-tagged wild-type and mutant p97s from Escherichia coli by glutathione affinity and cleavage of the tag by PreScission protease Dictyostelium discoideum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + H2O
-
Homo sapiens ADP + phosphate
-
?
ATP + H2O
-
Dictyostelium discoideum ADP + phosphate
-
?
additional information UBX-domain containing cytoplasmic Dictyostelium protein UBXD9 is identified as p97 interaction partner Dictyostelium discoideum ?
-
-
additional information UBX-domain containing human protein UBXDTUG/ASPL/UBXD9 is identified as p97 interaction partner Homo sapiens ?
-
-

Subunits

Subunits Comment Organism
homohexamer
-
Homo sapiens
homohexamer domain organization and structural information of Dictyostelium p97, overview. The N-terminal region comprising the CDC48 N and CDC48 2 domains is followed by the D1 and D2 domains and the C-terminal extension Dictyostelium discoideum

Synonyms

Synonyms Comment Organism
ATPase
-
Homo sapiens
ATPase
-
Dictyostelium discoideum
nsfA gen ename Dictyostelium discoideum
p97
-
Homo sapiens
p97
-
Dictyostelium discoideum
triple-A ATPase
-
Homo sapiens
triple-A ATPase
-
Dictyostelium discoideum
VCP
-
Homo sapiens
VCP
-
Dictyostelium discoideum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Homo sapiens
25
-
assay at Dictyostelium discoideum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens
7.5
-
assay at Dictyostelium discoideum

General Information

General Information Comment Organism
evolution human and Dictyostelium p97 share 81% identity and 89% similarity on the amino acid sequence level and have an almost identical order and composition of secondary structure elements Homo sapiens
evolution human and Dictyostelium p97 share 81% identity and 89% similarity on the amino acid sequence level and have an almost identical order and composition of secondary structure elements Dictyostelium discoideum
malfunction heterozygous missense mutations of p97 cause at least five human neurodegenerative disorders, i.e. R93C, R155H, and R155C mutations. All human p97 mutations lead to an increase in ATPase activity. p97 point mutations lead to differences in enzymatic activities and molecular interactions, which in the long-term result in a late-onset and progressive multisystem disease Homo sapiens
malfunction p97 point mutations lead to differences in enzymatic activities and molecularinteractions, which in the long-term result in a late-onset and progressive multisystem disease Dictyostelium discoideum
additional information UBX-domain containing Dictyostelium protein UBXD9 is identified as p97 interaction partner. Dictyostelium UBXD9 protein disassembles wild-type, but to a lesser extent mutant, p97 hexamers very efficiently into monomers. Enzyme p97 structure homology modelling using the crystal structure of mouse p97 (PDB entry 3cf2) as template Dictyostelium discoideum
additional information UBX-domain containing human protein UBXDTUG/ASPL/UBXD9 is identified as p97 interaction partner. Human UBXD9 protein disassembles wild-type, but to a lesser extent mutant, p97 hexamers very efficiently into monomers. Enzyme p97 structure homology modelling using the crystal structure of mouse p97 (PDB entry 3cf2) as template Homo sapiens