Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
No death without life: vital functions of apoptotic effectors.
A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
Endonuclease G preferentially cleaves 5-hydroxymethylcytosine-modified DNA creating a substrate for recombination.
Architecture of the human interactome defines protein communities and disease networks.
Endonuclease G promotes mitochondrial genome cleavage and replication.
Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Endonuclease G is an apoptotic DNase when released from mitochondria.
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EndoG is released from mitochondria and cleaves chromatin into nucleosomal fragments without caspases, including in DFF-deficient mouse cells.
"Once released from mitochondria, endoG cleaves chromatin DNA into nucleosomal fragments independently of caspases"
Action of recombinant human apoptotic endonuclease G on naked DNA and chromatin substrates: cooperation with exonuclease and DNase I.
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Purified recombinant human EndoG reproduces large-fragment then internucleosomal cleavage on isolated nuclei, aided by exonuclease and DNase I.
"The addition of the protein to isolated nuclei from non-apoptotic cells first induces higher order chromatin cleavage into DNA fragments"
Mitochondrial endonuclease G is important for apoptosis in C. elegans.
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Worm CPS-6 is a mitochondrial EndoG homolog whose loss impairs apoptotic DNA degradation and delays cell-corpse appearance.
"Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation"
Structural insights into apoptotic DNA degradation by CED-3 protease suppressor-6 (CPS-6) from Caenorhabditis elegans.
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The CPS-6 structure shows a Mg-dependent homodimer, and in vivo killing activity tracks the nuclease activity of interface mutants.
"the reduced DNase activity of CPS-6 mutants was positively correlated with its diminished cell killing activity in C. elegans"
Crystal structure of endonuclease G in complex with DNA reveals how it nonspecifically degrades DNA as a homodimer.
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The CPS-6-DNA structure explains sequence-nonspecific cleavage, and the dimer is required for full endonuclease activity.
"Two separate DNA strands are bound at the ββα-metal motifs in the homodimer"
Mammalian mitochondrial endonuclease G. Digestion of R-loops and localization in intermembrane space.
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Submitochondrial fractionation places EndoG in the intermembrane space, not the matrix.
"it exists in the mitochondrial intermembrane space, but not in the matrix where mtDNA replication occurs"
Unleashing a novel function of Endonuclease G in mitochondrial genome instability.
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In human cells EndoG binds G-quadruplex DNA at the 9-bp deletion hotspot and induces breaks; it colocalizes with the matrix marker TFAM.
"Endonuclease G binds to G-quadruplex structures formed at the hotspot and induces DNA breaks"
Purification and properties of the major nuclease from mitochondria of Saccharomyces cerevisiae.
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The major nuclease purified from yeast mitochondria, Nuc1, is located in the inner membrane.
"The enzyme is located in the mitochondrial inner membrane"
Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G.
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Reactive oxygen species dissociate the EndoG homodimer into less active monomers, so the dimer state gates the enzyme; the AIF homolog WAH-1 stabilizes it.
"homodimeric CPS-6-the C. elegans homolog of EndoG-is dissociated into monomers with diminished nuclease activity"
Human Endonuclease G Preferentially Cleaves Oxidatively Damaged DNA.
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Purified human EndoG binds many nucleic acids with similar affinity but preferentially cleaves nicked, gapped and 8-oxoG DNA.
"displays a particularly strong preference for cleaving oxidatively damaged DNA, including nicked and gapped dsDNA, and oxoG-DNA"
Endonuclease G promotes hepatic mitochondrial respiration by selectively increasing mitochondrial tRNA(Thr) production.
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In mouse liver, EndoG cleaves the H-strand transcript 3' end downstream of mt-tRNA(Thr) and, with DHX30, resolves mitochondrial R-loops; loss reduces mt-tRNA(Thr) and respiration in males.
"The MirPro sequence contains multiple C-rich motifs that could be cleaved by EndoG"
Generation and characterization of endonuclease G null mice.
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A null allele that spares the overlapping gene gives viable mice with normal mtDNA and no obvious apoptotic DNA-degradation defect.
"There is also no obvious effect on nuclear DNA degradation in standard apoptosis assays"
Endonuclease G is required for early embryogenesis and normal apoptosis in mice.
Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization.
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In worms, CPS-6 moves from the intermembrane space to the matrix after fertilization to degrade paternal mtDNA.
"CPS-6 relocates from the intermembrane space of paternal mitochondria to the matrix after fertilization to degrade mitochondrial DNA"
Barriers to male transmission of mitochondrial DNA in sperm development.
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Drosophila EndoG is needed for abrupt elimination of mtDNA nucleoids from developing spermatids.
"revealed their abrupt disappearance from developing spermatids in a process requiring the mitochondrial nuclease, Endonuclease G"
Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice.
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Endog-null mice have normal spermatogenesis, fertility and sperm mtDNA copy number.
"our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice"
KU80 suppresses endonuclease G activity to preserve genomic integrity.
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The KU80 C-terminal domain resembles the fly EndoG inhibitor, binds ENDOG and inhibits its nuclease activity.
"The KU80 C-terminal domain (CTD) shares structural homology with Drosophila EndoG inhibitor (EGI), directly binds ENDOG and inhibits its nuclease activity in vitro"
Discovery of an Endonuclease G-inhibitory Ku80-peptide protecting against leukemogenic rearrangements at the MLL breakpoint cluster.
The Drosophila melanogaster Gene cg4930 Encodes a High Affinity Inhibitor for Endonuclease G.
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Fly EndoGI binds dimeric EndoG at subpicomolar affinity and is proposed to protect the nucleus from leaked EndoG.
"We propose that EndoGI protects the cell against low levels of EndoG outside mitochondria"
EXOG, a novel paralog of Endonuclease G in higher eukaryotes.
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Metazoan ENDOG and EXOG arose by duplication of an ancestral mitochondrial endo/exonuclease like yeast Nuc1.
"during metazoan evolution duplication of an ancestral nuclease gene obviously generated the paralogous EndoG- and EXOG-protein subfamilies in higher eukaryotes"
A domain in human EXOG converts apoptotic endonuclease to DNA-repair exonuclease.
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The EXOG Wing domain suppresses endonuclease activity and confers 5' exonuclease activity, distinguishing the paralog from ENDOG.
"A Wing domain, absent in other ββα-Me members, suppresses endonuclease activity"
Endonuclease G mediates α-synuclein cytotoxicity during Parkinson's disease.
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ENDOG depletion reduces α-synuclein-induced death in human neuroblastoma cells; EndoG is needed for neurodegeneration in yeast, worm and fly models.
"EndoG depletion largely reduces α-synuclein-induced cell death in human neuroblastoma cells"
OpenScientist sequence-feature test of whether human ENDOG targets the mitochondrial matrix or the intermembrane space
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ENDOG enters mitochondria by the cleavable-presequence TIM23 route and is not a MIA40 disulfide-relay substrate, which excludes the twin-cysteine class of intermembrane space residents.
"ENDOG is imported via the cleavable-presequence (TOM/TIM23) pathway, not the MIA40 twin-cysteine pathway"
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That route does not settle the compartment, because presequence-imported proteins are sorted to either destination.
"Many IMS proteins (DIABLO/SMAC, HTRA2) are delivered by the same presequence machinery, then arrested or sorted into the IMS"
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The classifier reached only 60 percent accuracy on reference proteins of known sub-compartment, failing on exactly the presequence-bearing intermembrane space proteins that ENDOG resembles, so its matrix lean is not decisive.
"LOO-CV accuracy = 60.0% (9/15)"
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The presequence signature is shared with the EXOG paralog, so it is a family trait rather than a discriminator.
"so the matrix-type signature is a family trait"
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A dual or regulated localization is compatible with every sequence feature computed.
"reconciles all observations and is not excluded by any sequence feature computed here"
OpenScientist computational test of whether mtDNA breakpoints are enriched at ENDOG-preferred G-quadruplex and C-rich motifs
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mtDNA deletion breakpoints are enriched at G-quadruplex and C-rich motifs over GC-matched controls, but the signal is confined to deletions flanked by direct repeats and is absent in non-repeat deletions, so it does not isolate ENDOG cleavage.
"Signal only in DR≥5 bp deletions (fold 1.24); absent in DR<5 bp (fold 0.97, p=0.91)"
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The direct-repeat mechanism accounts for the same localization without ENDOG.
"a mechanism that does not require ENDOG and fully accounts for the observed G/C-rich localization"
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NUMT breakpoints show no such enrichment in the 66,083-genome catalogue or in an independent UCSC set; their own trinucleotide signal looks like end-joining microhomology.
"consistent with non-homologous end joining at the nuclear insertion site rather than ENDOG motif cleavage in mtDNA"
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Coordinate data alone cannot establish that ENDOG made the cuts.
"No ENDOG perturbation data were available; causation cannot be tested from coordinates alone"
Lundep, a sand fly salivary endonuclease increases Leishmania parasite survival in neutrophils and inhibits XIIa contact activation in human plasma.
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A secreted sand-fly member of the same PANTHER family (SF17) is a nonspecific DNase that destroys neutrophil extracellular traps.
"Lundep hydrolyzes both ss- and dsDNA with little sequence specificity"