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WormBase Tree Display for Variation: WBVar00091574

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Name Class

WBVar00091574NamePublic_nameok275
Other_nameF46C3.1.1:c.280-15_1760del
HGVSgCHROMOSOME_X:g.11412305_11414317del
Sequence_detailsSMapS_parentSequenceF46C3
Flanking_sequencesgtgaatccttcgagacttgagcgtgaaatcATTACTTTCCGTATTGGAATAATTAACTAG
Mapping_targetF46C3
Type_of_mutationDeletion
PCR_productOK275_external
OK275_internal
SeqStatusSequenced
Variation_typeAllele
OriginSpeciesCaenorhabditis elegans
StrainWBStrain00031350
LaboratoryRB
PersonWBPerson46
KO_consortium_allele
StatusLive
AffectsGeneWBGene00003970
TranscriptF46C3.1.1VEP_consequencesplice_acceptor_variant,splice_donor_variant,coding_sequence_variant,intron_variant
VEP_impactHIGH
HGVScF46C3.1.1:c.280-15_1760del
cDNA_position?-1836
CDS_position?-1760
Protein_position?-587
Intron_number3-8/13
Exon_number4-9/14
Interactor (38)
IsolationMutagenUV/TMP
GeneticsMapping_dataIn_multi_point4569
DescriptionPhenotypeWBPhenotype:0000119Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
Remark"To examine whether RNF-121 protein level is regulated by the PEK-1 pathway , we performed immunoblot analysis of RNF-121 : : GFP worms treated with tunicamycin and DTT . Although the level of RNF-121 increases after ER stress in wild-type background , it is constantly high in pek-1 ( ok275 ) worms ( Figure 3C ) and does not increase after ER stress . It suggests that PEK-1 pathway activates RNF-121 translation or protein stability under ER stress conditions , whereas inactivation of PEK-1 during development in the pek- 1 ( ok275 ) mutant may cause ER stress and up-regulation of RNF-121 by an alternative pathway ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
Phenotype_assayGenotypeRNF-121 : : GFPPaper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
WBPhenotype:0000135Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
RemarkThe basal expression of both hsp-3 and hsp-4 was increased in the pek-1(ok275) mutant.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBPhenotype:0000136Paper_evidenceWBPaper00036076
WBPaper00041065
Curator_confirmedWBPerson2987
Remark"To determine whether the transcription of rnf-121 is regulated by PEK-1 and the UPR pathway in C . elegans , we performed a real-time PCR analysis of the mutant strains pek-1 ( ok275 ) , ire-1 ( v33 ) , and atf-6 ( ok551 ) , as well as of wild-type worms , treated with the UPR inducers DTT , tunicamycin , and thapsigargin . Although the mRNA levels of hsp-4 were induced upon tunicamycin or DTT treatment and in pek-1 ( ok275 ) and atf-6 ( ok551 ) mutant backgrounds , and abolished in ire-1 ( v33 ) as shown previously ( Shen et al. , 2001 ) , the levels of rnf-121 mRNA were largely unaffected ( Figure 3B ) ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
The pek-1(ok275) mutation resulted in increased mRNA levels of genes F48E8.6 and ZK1098.4 (Table 1)Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000137Paper_evidenceWBPaper00035294
WBPaper00041065
Curator_confirmedWBPerson2987
Remark"In the control wild-type N2 worms, expression of ubiquilin and erasin transcripts increased after 6 h of tunicamycin treatment (Fig. 8). However, the induction of both genes was almost completely attenuated in ire-1(v33) mutant worms, and partially attenuated in the atf-6(ok551) and pek-1(ok275) mutants (Fig. 8). Together, these results indicate that in C. elegans, both ubiquilin and erasin genes are chiefly regulated by ire-1."Paper_evidenceWBPaper00035294
Curator_confirmedWBPerson2987
The pek-1(ok275) mutation resulted in decreased mRNA levels of the gene Y39G10AR.8 (Table 1)Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00035294
Curator_confirmedWBPerson2987
WBPhenotype:0000199Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
Remark"Although less pronounced than gcn-1, loss-of-function mutations in a C. elegans PERK homolog, pek-1 (Shen et_al 2001), also suppressed the ray defect in plx-1/smp-1 smp-2 mutants (Fig 1I; Supplemental Table S2) and reduced P-eIF2α (Fig 2A)"Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
Phenotype_assayGenotypeplx-1(nc37)Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
smp-1(ev715) smp-2(ev709)Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
plx-1(ev724)Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
WBPhenotype:0000273Paper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
RemarkPartial blockage of secondary gene's ability to suppress severe behavioral defects: "pek-1 loss of function partially blocks the ability of neuronal overexpression of xbp-1s in Tau (high)animals to suppress severe behavioral defects observed in a liquid environment" (Figure 4a)Paper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
PenetranceCompletePaper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
Variation_effectLoss_of_function_undetermined_extentPaper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
Phenotype_assayGenotypeaex-3p::hTau (4R1N); myo-2p::gfp; uthls270 [rab-3p::xbp-1s; myo-2p::tdTomato]Paper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
WBPhenotype:0001351Paper_evidenceWBPaper00031700
WBPaper00037064
WBPaper00040453
Curator_confirmedWBPerson2987
Remark"Although less pronounced than gcn-1, loss-of-function mutations in a C. elegans PERK homolog, pek-1 (Shen et_al 2001), also suppressed the ray defect in plx-1/smp-1 smp-2 mutants (Fig 1I; Supplemental Table S2) and reduced P-eIF2α (Fig 2A)"Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
"On the other hand, the significant hypoxic induction of p-eIF2α was blocked in pek-1(ok275), a mutant with normal HP (Fig. 6C)."Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
pek-1(ok275) suppresses the tunicamycin-induced or xbp-1-mutation-induced phosphorylation of eIF2α (Figure 2A, S1A)Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
WBPhenotype:0001724Paper_evidenceWBPaper00005044
WBPaper00032255
WBPaper00036076
Curator_confirmedWBPerson712
WBPerson2987
RemarkOnly 35% of pek-1(ok275) mutants on plates with 2 ug/ml of tunicamycin matured to the L4 stage or older, 31% arrested at or prior to the L3 stage, and 34% were dead. N2 animals were resistant to this concentration.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Mutant animals are more readily killed by tunicamycin.Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
"The ire-1 ( v33 ) and pek-1 ( ok275 ) mutant strains are more sensitive to tunicamycin than the wild-type ( Figure 3A , bars ; Shen et al . , 2001 ) , whereas atf-6 ( ok551 ) worms are less sensitive to tunicamycin ( Shen et al. , 2005 ) , and in our hands are more resistant than the wild type ( Figure 3A , bars ) ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00005044
WBPaper00032255
WBPaper00036076
Curator_confirmedWBPerson712
WBPerson2987
EQ_annotationsLife_stageWBls:0000035PATO:0000460Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Phenotype_not_observedWBPhenotype:0000030Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Remarkpek-1(ok275) mutants were indistinguishable from the wild-type under normal growth conditions.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBPhenotype:0000114Paper_evidenceWBPaper00036076
WBPaper00040397
WBPaper00041065
Curator_confirmedWBPerson2987
Remark"To determine whether the transcription of rnf-121 is regulated by PEK-1 and the UPR pathway in C . elegans , we performed a real-time PCR analysis of the mutant strains pek-1 ( ok275 ) , ire-1 ( v33 ) , and atf-6 ( ok551 ) , as well as of wild-type worms , treated with the UPR inducers DTT , tunicamycin , and thapsigargin . Although the mRNA levels of hsp-4 were induced upon tunicamycin or DTT treatment and in pek-1 ( ok275 ) and atf-6 ( ok551 ) mutant backgrounds , and abolished in ire-1 ( v33 ) as shown previously ( Shen et al. , 2001 ) , the levels of rnf-121 mRNA were largely unaffected ( Figure 3B ) ."Paper_evidenceWBPaper00036076
Curator_confirmedWBPerson2987
pek-1(ok275) did not affect the tunicamycin-induced mRNA expression of uggt-1 and hsp-4Paper_evidenceWBPaper00040397
Curator_confirmedWBPerson2987
The pek-1(ok275) mutation did not affect mRNA levels of genes crt-1, arf-6, 4R79.2, exos-3, rpl-1, cpl-1, or K06A5.8 (Table 1)Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000137Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
Remark"TM (tunicamycin) induction of F48E8.6 did not require ire-1, atf-6, or pek-1, suggesting that its induction did not require any single UPR pathway or that it uses an unconventional UPR pathway (Fig. 1B)."Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
pek-1(ok275) did not affect the tunicamycin-induced expression of crt-1 mRNA (Figure S2)Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00041065
Curator_confirmedWBPerson2987
WBPhenotype:0000298Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
RemarkTable S1Paper_evidenceWBPaper00031700
Curator_confirmedWBPerson2987
WBPhenotype:0000436Paper_evidenceWBPaper00046107
Curator_confirmedWBPerson10038
RemarkFrom the text: "Next, we investigated Venus::UNC-6 in pek-1(ok275) and atf-6(ok551) mutants, to examine whether the other two pathway of the UPR is involved in localization of UNC-6. In pek-1(ok275) and atf-6(ok551) mutants, Venus::UNC-6 was observed throughout the cytosol in the UNC-6-expressing cells, as observed in wild-type worms. In the neurons of these mutants, Venus::UNC-6 showed punctate distribution throughout the cell body cytosol and axons (Fig. 1L-O). The distribution of Venus::UNC-6 in these mutants was similar to that seen in wild-type worms. These facts suggest that only the ire-1/xbp-1 pathway of the UPR plays a role in UNC-6 localization in the neurons."Paper_evidenceWBPaper00046107
Curator_confirmedWBPerson10038
Phenotype_assayGenotypeghIs9[unc-6p::Venus::unc-6; str-3p::dsRed2] IVPaper_evidenceWBPaper00046107
Curator_confirmedWBPerson10038
WBPhenotype:0000520Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
RemarkWild type and mutant worms are healthy adults with similar appearance.Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
WBPhenotype:0001012Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
RemarkAt 16 degrees Celsius, pek-1(ok275) mutants exhibit a wild type growth rate in the presence of Pseudomonas aeruginosa (Figure 5A)Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
Phenotype_assayTemperature16Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
WBPhenotype:0001013Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
RemarkC. elegans lacking the UPR respond normally to attack by the pathogenic bacteria Pseudomonas aeruginosa, which does not make a PFT.Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
WBPhenotype:0001273Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
Remark"Unlike the xbp-1 mutant, the development of the pek-1 mutant at 27C was similar to WT."Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
Phenotype_assayTemperature27Paper_evidenceWBPaper00040453
Curator_confirmedWBPerson2987
WBPhenotype:0001278Paper_evidenceWBPaper00041022
Curator_confirmedWBPerson2987
Remark"While several of the tested genes had an effect (results not shown), hsp-3 stood out for its strong effect, essentially totally blocking the induction of pnlp-29::GFP normally observed upon infection in adult worms (Fig. 2A). A similar abrogation of reporter gene expression was seen in an atf-6 mutant, but not in a pek-1 mutant background (Fig. S1)."Paper_evidenceWBPaper00041022
Curator_confirmedWBPerson2987
Phenotype_assayGenotypePnlp-29::GFPPaper_evidenceWBPaper00041022
Curator_confirmedWBPerson2987
WBPhenotype:0001349Paper_evidenceWBPaper00048983
Curator_confirmedWBPerson2987
Remark"To evaluate whether either GCN-2 or PEK-1 kinases are required for H2S-dependent phosphorylation of eIF2α, we introduced gcn-2(ok886) or pek-1(ok275) deletion alleles into sqrd-1(tm3378) mutant animals. When exposed to H2S, we observed robust phosphorylation of eIF2α in both pek-1; sqrd-1 and gcn-2; sqrd-1 double mutant animals (Fig. 3, A and B)."Paper_evidenceWBPaper00048983
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004296Paper_evidenceWBPaper00048983
Curator_confirmedWBPerson2987
WBPhenotype:0001700Paper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
RemarkQuoted from paper: "C. elegans with a pek-1 loss of function mutation [pek-1 (-/-)] had normal locomotion (Supplementary Fig. 1a)."Paper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
Variation_effectLoss_of_function_undetermined_extentPaper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
Phenotype_assayControl_strainWBStrain00000001Paper_evidenceWBPaper00058677
Curator_confirmedWBPerson10038
WBPhenotype:0001719Paper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
Remarkcrt-1 induction was not affected in atf-6(ok551) and pek-1(ok275) mutantsPaper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
EQ_annotationsLife_stageWBls:0000023PATO:0000460Paper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
Phenotype_assayTreatmentAnalysis of crt-1 expression under TM (30 ug/ml) stressPaper_evidenceWBPaper00030877
Curator_confirmedWBPerson2021
WBPhenotype:0001838Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Remarkpek-1(ok275) mutants were able to activate transcription of both hsp genes to a similar extent as the wild-type.Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBMol:00004908Paper_evidenceWBPaper00005044
Curator_confirmedWBPerson712
WBPhenotype:0001990Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
WBPhenotype:0002058Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
RemarkIn the presence of low to moderate levels of the pore forming toxin (PFT) Cry5B, wild-type worms are slightly intoxicated compared to those found on control no-toxin plates, as evidenced by their smaller sizes and paler appearances. To the same extent seen with wild-type worms, mutant animals are also slightly intoxicated on low to moderate levels of the PFT Cry5B,indicating lack of this gene does not result in overt hypersensitivity or hyper-resistance to Cry5B. Further, no overt difference was observed in sensitivity to PFT in a quantitative dose-dependent lethality assay. Wild type N2 and pek-1(ok275) were both similarly inhibited in their development by increasing percentages of Cry5B.Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
Affected_byMoleculeWBMol:00005329Paper_evidenceWBPaper00032255
Curator_confirmedWBPerson712
WBPhenotype:0002423Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
RemarkTunicamycin (Tm) preconditioning in wild type worms leads to increased tolerance to hypoxia. "A large deletion mutation in pek-1 or gcn-2 did not block Tm preconditioning (Fig. 2D and 3C, E)."Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
"HP (hypoxic preconditioning) consistently provided protection from subsequent harsh hypoxic exposure for wild-type animals (Fig. 4A and B)... the pek-1 deletion mutation had no effect on HP; pek-1(ok275) animals were strongly protected by HP (Fig. 4B)."Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Affected_byMoleculeWBMol:00004565Paper_evidenceWBPaper00037064
Curator_confirmedWBPerson2987
Reference (14)
RemarkSequenced by the C. elegans Gene Knockout ConsortiumPaper_evidenceWBPaper00041807
MethodKO_consortium_allele