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WormBase Tree Display for Variation: WBVar01474242

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Name Class

WBVar01474242EvidencePaper_evidenceWBPaper00042171
NamePublic_nameet15
Other_nameZC376.7b.1:c.17G>A
ZC376.7c.1:c.17G>A
ZC376.7c.2:c.17G>A
ZC376.7a.2:c.17G>A
ZC376.7a.1:c.17G>A
CE15205:p.Gly6Glu
ZC376.7b.2:c.17G>A
CE38576:p.Gly6Glu
CE32033:p.Gly6Glu
HGVSgCHROMOSOME_V:g.14194499G>A
Sequence_detailsSMapS_parentSequenceZC376
Flanking_sequencesacagtaccatcaaaatgttttcccgtgtggacgtctcacaacttttggtgcccaggctgt
Mapping_targetZC376
Type_of_mutationSubstitutionga
SeqStatusSequenced
Variation_typeAllele
OriginSpeciesCaenorhabditis elegans
StrainWBStrain00031161
WBStrain00052571
LaboratoryQC
StatusLive
AffectsGeneWBGene00013878
TranscriptZC376.7c.1 (12)
ZC376.7a.2 (12)
ZC376.7b.2 (12)
ZC376.7a.1 (12)
ZC376.7c.2 (12)
ZC376.7b.1 (12)
InteractorWBInteraction000519944
WBInteraction000519945
WBInteraction000536788
WBInteraction000537442
WBInteraction000537446
GeneticsInterpolated_map_positionV6.196
DescriptionPhenotypeWBPhenotype:0000030Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Remark"The statin-resistant mutants also improved the growth of a lethal HMG-CoA reductase null mutant but only when small doses of mevalonate were also provided, suggesting that some residual HMG-CoA reductase activity persists in statin-treated worms (Fig. S1A)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
PenetranceHighPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
DominantPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Variation_effectHypermorph_gain_of_functionPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Affected_byMoleculeWBMol:00004697Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Phenotype_assayGenotypehmgr-1(tm4368)Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
WBPhenotype:0000154Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
RemarkFigure S3BPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBPhenotype:0001171Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
WBPerson2987
RemarkFigure S3APaper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
PenetranceHighPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
DominantPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Variation_effectHypermorph_gain_of_functionPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
WBPhenotype:0001236Paper_evidenceWBPaper00042171
WBPaper00046863
Curator_confirmedWBPerson2987
Remark"the UPRmt reporters hsp-60::GFP and hsp-6::GFP (but not the UPRer reporter hsp-4::GFP) are constitutively expressed in the mutants (Fig. 2C)"Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
atfs-1(et15) resulted in increased expression of the hsp-60::GFP transgene (Figure 5B,5C)Paper_evidenceWBPaper00046863
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0034514PATO:0000460Paper_evidenceWBPaper00046863
Curator_confirmedWBPerson2987
Phenotype_assayGenotypehsp-6::GFPPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
hsp-60::GFPPaper_evidenceWBPaper00042171
WBPaper00046863
Curator_confirmedWBPerson2987
WBPhenotype:0001382Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Remark"The atfs-1(et15) and atfs-1(et18) mutants were also partially resistant to the prenylation inhibitory effects of statins (Fig. 4 D and E)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00003950Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Phenotype_assayGenotypeprotein prenylation reporter (pGLO-1P::GFP-CAAX)Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBPhenotype:0001502Paper_evidenceWBPaper00042171
WBPaper00046863
Curator_confirmedWBPerson488
WBPerson2987
Remark"The isolated mutants are resistant to two statins (fluvastatin and rosuvastatin) and to ibandronate (which inhibits farnesyl diphosphate synthase, i.e., several steps downstream of HMG-CoA reductase) (Fig. 1 B-D)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
"This is consistent with the improved protection of the atfs-1(et15) gof mutant against ethidium bromide (EtBr) (Fig. S4 A-C), which impairs replication and transcription of the mitochondrial genome in cultured cells thus reducing the synthesis of mitochondrially encoded polypeptides (16-19), and the improved respiration of this mutant when challenged with statin (see below)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
"We found that the atfs-1(et15) gof mutant is resistant to gliotoxin, whereas the atfs-1(gk3094) null mutant is hypersensitive (Fig. 4 A-C)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
"Ten of these mutants were characterized in some detail. All were growth-inhibited by 0.5 mM fluvastatin, to which the atfs-1(et15) allele is resistant, and all harbored mutations within the coding region of atfs-1 (Figure 5, D and E)."Paper_evidenceWBPaper00046863
Curator_confirmedWBPerson2987
PenetranceHighPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
DominantPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Variation_effectHypermorph_gain_of_functionPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Affected_byMoleculeWBMol:00007789Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
WBMol:00005361Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00004311Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00003950Paper_evidenceWBPaper00046863
Curator_confirmedWBPerson2987
WBPhenotype:0001719Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Remark"the UPRmt reporters hsp-60::GFP and hsp-6::GFP (but not the UPRer reporter hsp-4::GFP) are constitutively expressed in the mutants (Fig. 2C)"Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
PenetranceHighPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
DominantPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Variation_effectHypermorph_gain_of_functionPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
WBPhenotype:0001990Paper_evidenceWBPaper00048404
Curator_confirmedWBPerson2987
Remark"These gain-of-function mutations in the atfs-1 gene (leading to constitutive mtUPR activation) were sufficient to protect against a severe hypoxic injury, which led to the death of wild-type worms (Figure 2F), indicating that mtUPR activation by ATFS-1 is sufficient to protect against hypoxic injury."Paper_evidenceWBPaper00048404
Curator_confirmedWBPerson2987
EQ_annotationsGO_termGO:0001666PATO:0000460Paper_evidenceWBPaper00048404
Curator_confirmedWBPerson2987
Phenotype_assayTreatmentAnimals were exposed to 20 hours of hypoxia and assayed for survivalPaper_evidenceWBPaper00048404
Curator_confirmedWBPerson2987
WBPhenotype:0002141Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Remark"Indeed, fluvastatin treatment does cause reduced respiration in C. elegans, and the atfs-1(et15) mutant respires normally even in the presence of fluvastatin (Fig. S7A)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00003950Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBPhenotype:0002379Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
PenetranceHighPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
DominantPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Variation_effectHypermorph_gain_of_functionPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson488
Phenotype_not_observedWBPhenotype:0001236Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Remark"the UPRmt reporters hsp-60::GFP and hsp-6::GFP (but not the UPRer reporter hsp-4::GFP) are constitutively expressed in the mutants (Fig. 2C)"Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Phenotype_assayGenotypehsp-4::GFPPaper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBPhenotype:0001502Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Remark"Finally, there is no evidence that the mutant alleles et15-et18 confer general resistance against xenobiotics because they exhibited no resistance to several tested growth inhibitors (Fig. S1 B-D)."Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
"the atfs-1(et15) mutant is not resistant to rotenone, antimycin A, or sodium azide, which are inhibitors of the mitochondrial respiratory chain (25, 26) (Fig. S7 B-D)"Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00003029Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00003638Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00003033Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00004310Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00005355Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
WBMol:00001525Paper_evidenceWBPaper00042171
Curator_confirmedWBPerson2987
ReferenceWBPaper00042171
WBPaper00046863
WBPaper00048404
WBPaper00062005
MethodSubstitution_allele