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Literature summary for 3.4.21.78 extracted from

  • Martinvalet, D.; Dykxhoorn, D.M.; Ferrini, R.; Lieberman, J.
    Granzyme A cleaves a mitochondrial complex I protein to initiate caspase-independent cell death (2008), Cell, 133, 681-692.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
additional information treating cells with the Hsp90 inhibitor 17-allylaminogeldanamycin does not inhibit GzmA-induced reactive oxygen species, cell death, or SET cleavage and in fact enhances each of these downstream events Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
K562 cells treated with perforin and recombinant human GzmA Homo sapiens

Protein Variants

Protein Variants Comment Organism
S176A mutated active site, does not cleave protein NDUFS3 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information GzmA-mediated reactive oxygen species production and cell death are impaired in pseudo rho0 cells depleted of mitochondrial DNA. Expression of the K56A-NDUFS3 cleavage site mutant in 293T and K562 cells inhibits GzmA-mediated reactive oxygen species production and cell death Homo sapiens
rotenone the complex I inhibitor hinders GzmA-mediated reactive oxygen species production and cell death Homo sapiens
valinomycin pretreatment of K562 cells with 16 nmol valinomycin inhibits GzmA and perforin-induced reactive oxygen species generation Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Homo sapiens 5739
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
protein NDUFS3 + H2O Homo sapiens GzmA cleavage of native Ndufs3 disrupts complex I electron transport ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
protein NDUFS3 + H2O GzmA cleavage of native Ndufs3 disrupts complex I electron transport Homo sapiens ?
-
?
protein NDUFS3 + H2O GzmA accesses the mitochondrial matrix to cleave the complex I protein NDUFS3, an iron-sulfur subunit of the NADH:ubiquinone oxidoreductase complex I, after Lys56 to interfere with NADH oxidation and generate superoxide anions. NDUFS3 is cleaved in cells treated with GzmA and perforin in a dose-dependent manner. Human GzmA cleaves both human and mouse NDUFS3. GzmA induces caspase-independent increased reactive oxygen species Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
Gzma
-
Homo sapiens