ATFS1_CAEEL
ID ATFS1_CAEEL Reviewed; 488 AA.
AC Q23272; E5QCH2; Q52GY6; Q8I4B7;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Stress activated transcription factor atfs-1 {ECO:0000305};
DE Flags: Precursor;
GN Name=atfs-1 {ECO:0000312|WormBase:ZC376.7a};
GN ORFNames=ZC376.7 {ECO:0000312|WormBase:ZC376.7a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF 436-ARG--LYS-441.
RX PubMed=22700657; DOI=10.1126/science.1223560;
RA Nargund A.M., Pellegrino M.W., Fiorese C.J., Baker B.M., Haynes C.M.;
RT "Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR
RT activation.";
RL Science 337:587-590(2012).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF 436-ARG--LYS-441.
RX PubMed=25274306; DOI=10.1038/nature13818;
RA Pellegrino M.W., Nargund A.M., Kirienko N.V., Gillis R., Fiorese C.J.,
RA Haynes C.M.;
RT "Mitochondrial UPR-regulated innate immunity provides resistance to
RT pathogen infection.";
RL Nature 516:414-417(2014).
RN [4] {ECO:0000305}
RP FUNCTION, INDUCTION (ISOFORM B), NUCLEAR LOCALIZATION SIGNAL, AND
RP MUTAGENESIS OF ARG-4 AND 436-ARG--LYS-441.
RX PubMed=25773600; DOI=10.1016/j.molcel.2015.02.008;
RA Nargund A.M., Fiorese C.J., Pellegrino M.W., Deng P., Haynes C.M.;
RT "Mitochondrial and nuclear accumulation of the transcription factor ATFS-1
RT promotes OXPHOS recovery during the UPR(mt).";
RL Mol. Cell 58:123-133(2015).
RN [5] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-4.
RX PubMed=27135930; DOI=10.1038/nature17989;
RA Lin Y.F., Schulz A.M., Pellegrino M.W., Lu Y., Shaham S., Haynes C.M.;
RT "Maintenance and propagation of a deleterious mitochondrial genome by the
RT mitochondrial unfolded protein response.";
RL Nature 533:416-419(2016).
RN [6] {ECO:0000305}
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-6.
RX PubMed=27459203; DOI=10.1371/journal.pone.0159989;
RA Pena S., Sherman T., Brookes P.S., Nehrke K.;
RT "The mitochondrial unfolded protein response protects against anoxia in
RT Caenorhabditis elegans.";
RL PLoS ONE 11:E0159989-E0159989(2016).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, SUMOYLATION AT 342, AND MUTAGENESIS OF
RP LYS-342.
RX PubMed=30642431; DOI=10.7554/elife.41792;
RA Gao K., Li Y., Hu S., Liu Y.;
RT "SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity
RT and lifespan extension.";
RL Elife 8:0-0(2019).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33078707; DOI=10.7554/elife.58815;
RA Littlejohn N.K., Seban N., Liu C.C., Srinivasan S.;
RT "A feedback loop governs the relationship between lipid metabolism and
RT longevity.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: Acts as a transcription factor during mitochondrial stress by
CC activating the mitochondrial unfolded protein response (mtUPR)
CC (PubMed:22700657, PubMed:25274306, PubMed:25773600, PubMed:30642431).
CC Induces nuclear and mitochondrial gene transcription, including genes
CC coding for mitochondrial chaperones and proteins involved in
CC glycolysis, amino acid catabolism and innate immunity (PubMed:22700657,
CC PubMed:25274306, PubMed:25773600). Following mitochondrial stress,
CC restores mitochondrial respiratory capacity by limiting the
CC transcription of oxidative phosphorylation (OXPHOS) machinery genes and
CC by promoting the assembly of OXPHOS complexes via the up-regulation of
CC chaperone and assembly factor genes (PubMed:25773600). Component of a
CC feedback loop involving atfs-1, atgl-1 and hlh-11 (PubMed:33078707).
CC Acts together with flp-7 to negatively regulate the expression of the
CC transcription regulator hlh-11, to promote expression of atgl-1, and
CC thus atgl-1-dependent fat oxidation in response to mitochondrial stress
CC (PubMed:33078707). In addition, functions with hlh-11 to maintain
CC lifespan (PubMed:33078707). Promotes mtDNA maintenance and propagation
CC of deleterious mtDNA (PubMed:27135930). {ECO:0000269|PubMed:22700657,
CC ECO:0000269|PubMed:25274306, ECO:0000269|PubMed:25773600,
CC ECO:0000269|PubMed:27135930, ECO:0000269|PubMed:30642431,
CC ECO:0000269|PubMed:33078707}.
CC -!- INTERACTION:
CC Q23272; Q8IG69: cebp-2; NbExp=2; IntAct=EBI-6748337, EBI-2914231;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:22700657}. Cytoplasm {ECO:0000269|PubMed:22700657}.
CC Nucleus {ECO:0000269|PubMed:22700657, ECO:0000269|PubMed:25274306,
CC ECO:0000269|PubMed:30642431}. Note=In absence of mitochondrial stress,
CC localizes mainly to mitochondria where it is rapidly degraded by
CC protease lonp-1 (PubMed:22700657). Upon mitochondrial stress which
CC causes a reduction in protein mitochondrial import, accumulates in the
CC cytoplasm and translocates into the nucleus to activate transcription
CC of mitochondrial unfolded protein response genes (PubMed:22700657).
CC Similarly, accumulates in the nucleus in response to P.aeruginosa-
CC mediated infection (PubMed:25274306). {ECO:0000269|PubMed:22700657,
CC ECO:0000269|PubMed:25274306}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a {ECO:0000312|WormBase:ZC376.7a};
CC IsoId=Q23272-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:ZC376.7b};
CC IsoId=Q23272-2; Sequence=VSP_059254;
CC Name=c {ECO:0000312|WormBase:ZC376.7c};
CC IsoId=Q23272-3; Sequence=VSP_059254, VSP_059255;
CC Name=d {ECO:0000312|WormBase:ZC376.7d};
CC IsoId=Q23272-4; Sequence=VSP_059253;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:22700657, ECO:0000269|PubMed:25274306}.
CC -!- INDUCTION: [Isoform b]: Induced by mitochondrial stress.
CC {ECO:0000269|PubMed:25773600}.
CC -!- PTM: May be desumoylated by ulp-4. {ECO:0000305|PubMed:30642431}.
CC -!- DISRUPTION PHENOTYPE: Prevents the up-regulation of several innate
CC immune genes following P.aeruginosa-mediated infection
CC (PubMed:25274306). RNAi-mediated knockdown causes a reduction in
CC survival following P.aeruginosa-mediated infection (PubMed:25274306).
CC Prevents the up-regulation of mitochondrial protective genes and
CC increases the transcription of oxidative phosphorylation machinery and
CC tricarboxylic acid cycle genes following mitochondrial stress caused by
CC RNAi-mediated knockdown of protease spg-7 (PubMed:22700657,
CC PubMed:25773600). Assembly of complex I and ATP synthase of the
CC oxidative phosphorylation machinery and oxygen consumption are reduced
CC in a spg-7 RNAi-mediated background (PubMed:25773600). RNAi-mediated
CC knockdown reduces the levels of deleterious mtDNA that occurs in aging
CC cells (PubMed:27135930). Protection from death following anoxia-
CC reperfusion is lost in a spg-7 RNAi-mediated background
CC (PubMed:27459203). RNAi-mediated knockdown does not alter atgl-1
CC expression (PubMed:33078707). However, RNAi-mediated knockdown
CC increases atgl-1 expression in a hlh-11 ok2944 mutant background
CC (PubMed:33078707). RNAi-mediated knockdown reduces the induction of
CC hsp-60, an indicator of mitochondrial stress following overexpression
CC of flp-7 (PubMed:33078707). {ECO:0000269|PubMed:22700657,
CC ECO:0000269|PubMed:25274306, ECO:0000269|PubMed:25773600,
CC ECO:0000269|PubMed:27135930, ECO:0000269|PubMed:27459203,
CC ECO:0000269|PubMed:33078707}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; BX284605; CAB00883.1; -; Genomic_DNA.
DR EMBL; BX284605; CAD54177.1; -; Genomic_DNA.
DR EMBL; BX284605; CAI91180.1; -; Genomic_DNA.
DR EMBL; BX284605; CBY25213.1; -; Genomic_DNA.
DR PIR; T27532; T27532.
DR RefSeq; NP_001024302.1; NM_001029131.3. [Q23272-3]
DR RefSeq; NP_001256571.1; NM_001269642.1. [Q23272-4]
DR RefSeq; NP_506515.1; NM_074114.3. [Q23272-1]
DR RefSeq; NP_872160.1; NM_182360.5. [Q23272-2]
DR AlphaFoldDB; Q23272; -.
DR SMR; Q23272; -.
DR IntAct; Q23272; 3.
DR MINT; Q23272; -.
DR STRING; 6239.ZC376.7a.2; -.
DR PaxDb; Q23272; -.
DR EnsemblMetazoa; ZC376.7a.1; ZC376.7a.1; WBGene00013878. [Q23272-1]
DR EnsemblMetazoa; ZC376.7a.2; ZC376.7a.2; WBGene00013878. [Q23272-1]
DR EnsemblMetazoa; ZC376.7b.1; ZC376.7b.1; WBGene00013878. [Q23272-2]
DR EnsemblMetazoa; ZC376.7b.2; ZC376.7b.2; WBGene00013878. [Q23272-2]
DR EnsemblMetazoa; ZC376.7c.1; ZC376.7c.1; WBGene00013878. [Q23272-3]
DR EnsemblMetazoa; ZC376.7c.2; ZC376.7c.2; WBGene00013878. [Q23272-3]
DR EnsemblMetazoa; ZC376.7d.1; ZC376.7d.1; WBGene00013878. [Q23272-4]
DR GeneID; 179922; -.
DR KEGG; cel:CELE_ZC376.7; -.
DR UCSC; ZC376.7a.1; c. elegans.
DR CTD; 179922; -.
DR WormBase; ZC376.7a; CE15205; WBGene00013878; atfs-1. [Q23272-1]
DR WormBase; ZC376.7b; CE32033; WBGene00013878; atfs-1. [Q23272-2]
DR WormBase; ZC376.7c; CE38576; WBGene00013878; atfs-1. [Q23272-3]
DR WormBase; ZC376.7d; CE45623; WBGene00013878; atfs-1. [Q23272-4]
DR eggNOG; ENOG502TGC0; Eukaryota.
DR GeneTree; ENSGT00530000063801; -.
DR HOGENOM; CLU_571396_0_0_1; -.
DR InParanoid; Q23272; -.
DR OMA; WNHYLES; -.
DR OrthoDB; 973920at2759; -.
DR PRO; PR:Q23272; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00013878; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; HDA:WormBase.
DR GO; GO:0005759; C:mitochondrial matrix; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0034246; F:mitochondrial transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0034514; P:mitochondrial unfolded protein response; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0061063; P:positive regulation of nematode larval development; IGI:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1903108; P:regulation of mitochondrial transcription; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR Pfam; PF07716; bZIP_2; 1.
DR SMART; SM00338; BRLZ; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; DNA-binding; Immunity; Innate immunity;
KW Isopeptide bond; Mitochondrion; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Transit peptide; Unfolded protein response.
FT TRANSIT 1..23
FT /note="Mitochondrion"
FT /evidence="ECO:0000305|PubMed:22700657,
FT ECO:0000305|PubMed:25773600"
FT CHAIN 24..488
FT /note="Stress activated transcription factor atfs-1"
FT /id="PRO_0000442516"
FT DOMAIN 420..483
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 138..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 353..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 425..460
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 462..469
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 436..441
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305|PubMed:22700657,
FT ECO:0000305|PubMed:25274306, ECO:0000305|PubMed:25773600"
FT COMPBIAS 357..373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..400
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 342
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in smo-1)"
FT /evidence="ECO:0000269|PubMed:30642431"
FT VAR_SEQ 1..207
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_059253"
FT VAR_SEQ 114..129
FT /note="Missing (in isoform b and isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059254"
FT VAR_SEQ 205
FT /note="E -> EFQ (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059255"
FT MUTAGEN 4
FT /note="R->C: In et18; reduces its mitochondrial import,
FT constitutively activates the mitochondrial unfolded protein
FT response and up-regulates transcription of several innate
FT immune response genes. Increases resistance to
FT P.aeruginosa-mediated infection. Reduces the levels of
FT deleterious mtDNA."
FT /evidence="ECO:0000269|PubMed:25274306,
FT ECO:0000269|PubMed:27135930"
FT MUTAGEN 6
FT /note="G->E: In et15; probably reduces its mitochondrial
FT import. Constitutively activates the mitochondrial unfolded
FT protein response. Reduced axonal degeneration and death
FT following anoxia-reperfusion."
FT /evidence="ECO:0000269|PubMed:27459203"
FT MUTAGEN 342
FT /note="K->R: Abolishes sumoylation. Does not affect nuclear
FT localization during mitochondrial stress. Enhances
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:30642431"
FT MUTAGEN 436..441
FT /note="RYREKK->AYREAA: Loss of nuclear import. Prevents up-
FT regulation of hsp-60 in response to P.aeruginosa-mediated
FT infection. Assembly of complex I and ATP synthase and
FT oxygen consumption are reduced in a spg-7 RNAi-mediated
FT knockdown background."
FT /evidence="ECO:0000269|PubMed:22700657,
FT ECO:0000269|PubMed:25274306, ECO:0000269|PubMed:25773600"
SQ SEQUENCE 488 AA; 56019 MW; FC332265AF588092 CRC64;
MFSRVGRLTT FGAQAVSNCP FRRDNIYQQP LKVTAPINDQ LTSFAHSFSD SVRHRTTSFG
NDPFLGVPMD DDEVIKELEL LDLDSWHTKP RAPCPAPSDE LELDQFWEGK NVTVCGRDPR
LGKSTDCFEL EAWRPTDSWQ NGSSVGHPHG HQQQQQTCQQ PPTHSSTTET MHDFSNFGDN
MGSPLFQSPS KSAIDQLTGT SRIDEYGMPP QDRKLSKFEM DIEQESKAVD WEAWNHYLES
DDDVFKRPEA FFKEEPMIMT SSDSLMTSST SSPDSGISLY DPMIPPPSSH FPSFNLSSSS
SASNLLRLST PSAPMQQEHR APVRMHHDVD LFSSGPLLCV PKQEDVFDDF IQQRDDDDED
YIPASEARRT SSRLNRKSAT PTYLRRRDSE RSWTPASDDY FPEEHQKFKK RGVVLKPSVD
EETDRRRMLN RIAAVRYREK KRAEKKGRKM EFQEVADRNR ILLQKERQLK REINSMKKEL
RKMGAIIQ
