##gff-version 3 O43524 UniProtKB Chain 1 673 . . . ID=PRO_0000091874;Note=Forkhead box protein O3 O43524 UniProtKB DNA binding 157 251 . . . Note=Fork-head;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00089 O43524 UniProtKB Region 1 153 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O43524 UniProtKB Region 80 108 . . . Note=Required for mitochondrial import;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23283301;Dbxref=PMID:23283301 O43524 UniProtKB Region 231 302 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O43524 UniProtKB Region 300 673 . . . Note=Mediates interaction with CHUK/IKKA and IKBKB/IKKB;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15084260;Dbxref=PMID:15084260 O43524 UniProtKB Region 536 587 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O43524 UniProtKB Motif 242 259 . . . Note=Nuclear localization signal;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:17940099,ECO:0000269|PubMed:29445193;Dbxref=PMID:17940099,PMID:29445193 O43524 UniProtKB Compositional bias 55 69 . . . Note=Acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O43524 UniProtKB Compositional bias 279 302 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O43524 UniProtKB Modified residue 30 30 . . . Note=Phosphoserine%3B by AMPK;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Modified residue 32 32 . . . Note=Phosphothreonine%3B by PKB/AKT1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10102273;Dbxref=PMID:10102273 O43524 UniProtKB Modified residue 46 46 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 149 149 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 179 179 . . . Note=Phosphothreonine%3B by AMPK;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Modified residue 209 209 . . . Note=Phosphoserine%3B by STK4/MST1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16751106;Dbxref=PMID:16751106 O43524 UniProtKB Modified residue 215 215 . . . Note=Phosphoserine%3B by MAPKAPK5;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21329882;Dbxref=PMID:21329882 O43524 UniProtKB Modified residue 230 230 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 242 242 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9WVH4 O43524 UniProtKB Modified residue 253 253 . . . Note=Phosphoserine%3B by PKB/AKT1 and MAPKAPK5;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10102273,ECO:0000269|PubMed:21329882,ECO:0000269|PubMed:30513302;Dbxref=PMID:10102273,PMID:21329882,PMID:30513302 O43524 UniProtKB Modified residue 262 262 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 271 271 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 280 280 . . . Note=Phosphoserine;Ontology_term=ECO:0007744,ECO:0007744,ECO:0007744;evidence=ECO:0007744|PubMed:18669648,ECO:0007744|PubMed:19690332,ECO:0007744|PubMed:23186163;Dbxref=PMID:18669648,PMID:19690332,PMID:23186163 O43524 UniProtKB Modified residue 284 284 . . . Note=Phosphoserine;Ontology_term=ECO:0007744,ECO:0007744;evidence=ECO:0007744|PubMed:18669648,ECO:0007744|PubMed:23186163;Dbxref=PMID:18669648,PMID:23186163 O43524 UniProtKB Modified residue 290 290 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 294 294 . . . Note=Phosphoserine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:30513302;Dbxref=PMID:30513302 O43524 UniProtKB Modified residue 299 299 . . . Note=Phosphoserine%3B by CaMK2A;Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:23805378,ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163,PMID:23805378 O43524 UniProtKB Modified residue 311 311 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:23186163;Dbxref=PMID:23186163 O43524 UniProtKB Modified residue 315 315 . . . Note=Phosphoserine%3B by SGK1;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10102273,ECO:0000269|PubMed:11154281;Dbxref=PMID:10102273,PMID:11154281 O43524 UniProtKB Modified residue 399 399 . . . Note=Phosphoserine%3B by AMPK;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Modified residue 413 413 . . . Note=Phosphoserine%3B by AMPK;Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:17711846,ECO:0007744|PubMed:23186163;Dbxref=PMID:17711846,PMID:23186163 O43524 UniProtKB Modified residue 419 419 . . . Note=N6-methyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Modified residue 421 421 . . . Note=Phosphoserine;Ontology_term=ECO:0007744;evidence=ECO:0007744|PubMed:18220336;Dbxref=PMID:18220336 O43524 UniProtKB Modified residue 551 551 . . . Note=Phosphoserine%3B by MAPKAPK5;Ontology_term=ECO:0000269,ECO:0007744;evidence=ECO:0000269|PubMed:21329882,ECO:0007744|PubMed:23186163;Dbxref=PMID:21329882,PMID:23186163 O43524 UniProtKB Modified residue 555 555 . . . Note=Phosphoserine%3B by AMPK and MAPKAPK5;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:17711846,ECO:0000269|PubMed:21329882;Dbxref=PMID:17711846,PMID:21329882 O43524 UniProtKB Modified residue 588 588 . . . Note=Phosphoserine%3B by AMPK;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Modified residue 626 626 . . . Note=Phosphoserine%3B by AMPK;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Modified residue 644 644 . . . Note=Phosphoserine%3B by IKKB;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15084260;Dbxref=PMID:15084260 O43524 UniProtKB Alternative sequence 1 220 . . . ID=VSP_056225;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:14702039;Dbxref=PMID:14702039 O43524 UniProtKB Mutagenesis 2 148 . . . Note=Loss of localization to the mitochondrion outer membrane and loss of translocation into the mitochondrion following metabolic stress. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Mutagenesis 2 30 . . . Note=Loss of translocation into the mitochondrion following metabolic stress. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Mutagenesis 12 12 . . . Note=In normal cells%2C no defect in mitochondrion import following metabolic stress. In cancer cells%2C defective mitochondrion import following metabolic stress and abolition of ERK-mediated phosphorylation. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Mutagenesis 30 30 . . . Note=Abolishes phosphorylation. Loss of localization to the mitochondrion outer membrane and loss of translocation into the mitochondrion following metabolic stress. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Mutagenesis 32 32 . . . Note=Abolishes YWHAZ-binding%3B when associated with A-253. Exclusively nuclear%2C induces transcription and promotes apoptosis%3B when associated with A-253 and A-315. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10102273;Dbxref=PMID:10102273 O43524 UniProtKB Mutagenesis 80 108 . . . Note=Loss of translocation into the mitochondrion following metabolic stress. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Mutagenesis 179 179 . . . Note=Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene%3B when associated with A-399%3B A-413%3B A-555%3B A-588 and A-626. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Mutagenesis 209 209 . . . Note=Impairs nuclear translocation upon oxidative stress. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16751106;Dbxref=PMID:16751106 O43524 UniProtKB Mutagenesis 242 271 . . . Note=Loss of nuclear import. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:29445193;Dbxref=PMID:29445193 O43524 UniProtKB Mutagenesis 242 242 . . . Note=Slightly decreases DNA affinity. K->A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:17940099,ECO:0000269|PubMed:21841822;Dbxref=PMID:17940099,PMID:21841822 O43524 UniProtKB Mutagenesis 242 242 . . . Note=Reduces acetylation%2C increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation%3B when associated with R-259%3B R-290 and R-569. K->R;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:17940099,ECO:0000269|PubMed:21841822;Dbxref=PMID:17940099,PMID:21841822 O43524 UniProtKB Mutagenesis 245 245 . . . Note=Decreases DNA affinity. K->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17940099;Dbxref=PMID:17940099 O43524 UniProtKB Mutagenesis 253 253 . . . Note=Abolishes YWHAZ-binding%3B when associated with A-32. Exclusively nuclear%2C induces transcription and promotes apoptosis%3B when associated with A-32 and A-315. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10102273;Dbxref=PMID:10102273 O43524 UniProtKB Mutagenesis 259 259 . . . Note=Reduces acetylation%2C increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation%3B when associated with R-242%3B R-290 and R-569. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21841822;Dbxref=PMID:21841822 O43524 UniProtKB Mutagenesis 269 269 . . . Note=Methylation levels similar to wild-type%3B when associated with Arg-270. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Mutagenesis 270 270 . . . Note=Methylation levels similar to wild-type%3B when associated with Arg-269. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Mutagenesis 271 271 . . . Note=Methylation levels strongly reduced. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22820736;Dbxref=PMID:22820736 O43524 UniProtKB Mutagenesis 290 290 . . . Note=Reduces acetylation%2C increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation%3B when associated with R-242%3B R-259 and R-569. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21841822;Dbxref=PMID:21841822 O43524 UniProtKB Mutagenesis 315 315 . . . Note=No effect on YWHAZ-binding. Promotes nuclear translocation. Exclusively nuclear%2C induces transcription and promotes apoptosis%3B when associated with A-32 and A-253. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10102273;Dbxref=PMID:10102273 O43524 UniProtKB Mutagenesis 399 399 . . . Note=Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene%3B when associated with A-179%3B A-413%3B A-555%3B A-588 and A-626. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Mutagenesis 413 413 . . . Note=Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene%3B when associated with A-179%3B A-399%3B A-555%3B A-588 and A-626. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Mutagenesis 555 555 . . . Note=Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene%3B when associated with A-179%3B A-399%3B A-413%3B A-588 and A-626. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Mutagenesis 569 569 . . . Note=Reduces acetylation%2C increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation%3B when associated with R-242%3B R-259 and R-290. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21841822;Dbxref=PMID:21841822 O43524 UniProtKB Mutagenesis 588 588 . . . Note=Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene%3B when associated with A-179%3B A-399%3B A-413%3B A-555 and A-626. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Mutagenesis 626 626 . . . Note=Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene%3B when associated with A-179%3B A-399%3B A-413%3B A-555 and A-588. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17711846;Dbxref=PMID:17711846 O43524 UniProtKB Mutagenesis 644 644 . . . Note=Loss of phosphorylation by IKKB. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:15084260;Dbxref=PMID:15084260 O43524 UniProtKB Sequence conflict 156 163 . . . Note=AWGNLSYA->WGKPVYS;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 238 246 . . . Note=PDGGKSGKA->LMGEERKT;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 253 253 . . . Note=S->T;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 271 271 . . . Note=Missing;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 292 330 . . . Note=PGSPTSRSSDELDAWTDFRSRTNSNASTVSGRLSPIMAS->AWQPHVNAAVMSWMRGRTSVHAPILTPAQSVAACRPSWQV;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 345 361 . . . Note=PMLYSSSASLSPSVSKP->AHALQHVSQPVTFSKQA;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 367 367 . . . Note=P->R;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 371 371 . . . Note=D->E;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Sequence conflict 382 383 . . . Note=LT->AD;Ontology_term=ECO:0000305;evidence=ECO:0000305 O43524 UniProtKB Turn 156 158 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2K86 O43524 UniProtKB Helix 162 169 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Beta strand 172 176 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Helix 180 189 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Beta strand 198 200 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Helix 206 216 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Beta strand 217 229 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Beta strand 233 236 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2UZK O43524 UniProtKB Beta strand 238 240 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2K86 O43524 UniProtKB Beta strand 463 465 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2LQH O43524 UniProtKB Helix 468 477 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2LQH O43524 UniProtKB Turn 478 480 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:2LQH