##gff-version 3 Q12778 UniProtKB Chain 1 655 . . . ID=PRO_0000091872;Note=Forkhead box protein O1 Q12778 UniProtKB DNA binding 159 235 . . . Note=Fork-head;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00089 Q12778 UniProtKB Region 1 63 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Region 116 158 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Region 211 218 . . . Note=DNA-binding;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Region 234 344 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Region 234 237 . . . Note=DNA-binding;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Region 283 563 . . . Note=Sufficient for interaction with NLK;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Region 363 459 . . . Note=Required for interaction with RUNX2;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Region 507 537 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Motif 251 253 . . . Note=Nuclear localization signal Q12778 UniProtKB Motif 462 466 . . . Note=Required for interaction with SIRT1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Compositional bias 28 47 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Compositional bias 118 143 . . . Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Compositional bias 280 330 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite Q12778 UniProtKB Site 158 158 . . . Note=DNA-binding;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Site 165 165 . . . Note=DNA-binding;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Site 225 225 . . . Note=DNA-binding;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Modified residue 24 24 . . . Note=Phosphothreonine%3B by PKB/AKT1 or PKB/AKT2 and SGK1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10358075,ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:11980723;Dbxref=PMID:10358075,PMID:11237865,PMID:11980723 Q12778 UniProtKB Modified residue 212 212 . . . Note=Phosphoserine%3B by STK4/MST1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:18786403,ECO:0000269|PubMed:19221179,ECO:0000269|PubMed:21245099;Dbxref=PMID:18786403,PMID:19221179,PMID:21245099 Q12778 UniProtKB Modified residue 218 218 . . . Note=Phosphoserine%3B by STK4/MST1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Modified residue 234 234 . . . Note=Phosphoserine%3B by STK4/MST1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Modified residue 235 235 . . . Note=Phosphoserine%3B by STK4/MST1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18786403;Dbxref=PMID:18786403 Q12778 UniProtKB Modified residue 245 245 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Modified residue 248 248 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Modified residue 249 249 . . . Note=Phosphoserine%3B by CDK1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18356527;Dbxref=PMID:18356527 Q12778 UniProtKB Modified residue 251 251 . . . Note=Omega-N-methylarginine%3B by PRMT1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Modified residue 253 253 . . . Note=Omega-N-methylarginine%3B by PRMT1;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Modified residue 256 256 . . . Note=Phosphoserine%3B by PKB/AKT1 and SGK1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10358075,ECO:0000269|PubMed:10358076,ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:11980723,ECO:0000269|PubMed:31063815;Dbxref=PMID:10358075,PMID:10358076,PMID:11237865,PMID:11980723,PMID:31063815 Q12778 UniProtKB Modified residue 262 262 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20543840;Dbxref=PMID:20543840 Q12778 UniProtKB Modified residue 265 265 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20543840;Dbxref=PMID:20543840 Q12778 UniProtKB Modified residue 274 274 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20543840;Dbxref=PMID:20543840 Q12778 UniProtKB Modified residue 287 287 . . . Note=Phosphoserine;Ontology_term=ECO:0007744,ECO:0007744,ECO:0007744;evidence=ECO:0007744|PubMed:18669648,ECO:0007744|PubMed:20068231,ECO:0007744|PubMed:21406692;Dbxref=PMID:18669648,PMID:20068231,PMID:21406692 Q12778 UniProtKB Modified residue 298 298 . . . Note=Phosphoserine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Modified residue 319 319 . . . Note=Phosphoserine%3B by PKB/AKT1;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10358075,ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:11980723;Dbxref=PMID:10358075,PMID:11237865,PMID:11980723 Q12778 UniProtKB Modified residue 322 322 . . . Note=Phosphoserine%3B by CK1 and SGK1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11980723;Dbxref=PMID:11980723 Q12778 UniProtKB Modified residue 325 325 . . . Note=Phosphoserine%3B by CK1;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11980723;Dbxref=PMID:11980723 Q12778 UniProtKB Modified residue 329 329 . . . Note=Phosphoserine%3B by DYRK1A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11311120,ECO:0000269|PubMed:11980723;Dbxref=PMID:11311120,PMID:11980723 Q12778 UniProtKB Modified residue 333 333 . . . Note=Phosphothreonine;Ontology_term=ECO:0000250;evidence=ECO:0000250|UniProtKB:Q9R1E0 Q12778 UniProtKB Modified residue 423 423 . . . Note=N6-acetyllysine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25009184;Dbxref=PMID:25009184 Q12778 UniProtKB Mutagenesis 24 24 . . . Note=Abolishes PKB/AKT1-mediated phosphorylation but does not prevent phosphorylation of Ser-256 or Ser-319. Also inhibits binding of 14-3-3 proteins. Nuclear in unstimulated cells%2C and little export to cytoplasm on IGF1 stimulation. Targeted to the nucleus and enhances transactivation%3B when associated with A-319. No effect on interaction with STUB1. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1%3B when associated with A-256 and A-319. T->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:12228231,ECO:0000269|PubMed:19483080;Dbxref=PMID:11237865,PMID:12228231,PMID:19483080 Q12778 UniProtKB Mutagenesis 212 212 . . . Note=Abolishes STK4/MST1-mediated phosphorylation. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19221179;Dbxref=PMID:19221179 Q12778 UniProtKB Mutagenesis 245 245 . . . Note=Disrupts DNA-binding%3B when associated with A-248. K->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12228231;Dbxref=PMID:12228231 Q12778 UniProtKB Mutagenesis 248 248 . . . Note=Disrupts DNA-binding%3B when associated with A-245. K->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12228231;Dbxref=PMID:12228231 Q12778 UniProtKB Mutagenesis 249 249 . . . Note=Impaired phosphorylation by CDK1. S->A;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:18356527,ECO:0000269|PubMed:18786403;Dbxref=PMID:18356527,PMID:18786403 Q12778 UniProtKB Mutagenesis 249 249 . . . Note=No effect on DNA-binding. S->E;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:18356527,ECO:0000269|PubMed:18786403;Dbxref=PMID:18356527,PMID:18786403 Q12778 UniProtKB Mutagenesis 251 253 . . . Note=No targeting to the nucleus and disruption of DNA-binding. RRR->SAS;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12228231;Dbxref=PMID:12228231 Q12778 UniProtKB Mutagenesis 256 256 . . . Note=Completely abolishes PKB/AKT1-mediated phosphorylation at all three sites%2C and inhibits binding of 14-3-3 proteins. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1%3B when associated with or without A-24 and A-319. Nuclear in unstimulated cells%2C and little export to cytoplasm on IGF1 stimulation. Abolishes the ability of IGF1 to suppress transactivation. Prevents T-24 and S-319 phosphorylation. Abolishes interaction with and ubiquitination by STUB1. Enhances transactivation%3B when associated with A-24 and A-319. S->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:12228231,ECO:0000269|PubMed:15668399,ECO:0000269|PubMed:19483080;Dbxref=PMID:11237865,PMID:12228231,PMID:15668399,PMID:19483080 Q12778 UniProtKB Mutagenesis 256 256 . . . Note=Reduces DNA binding%2C promotes nuclear exclusion and partially promotes T-24 and S-319 phosphorylation. Reduces DNA binding%2C does not promote nuclear exclusion but reduces transactivation%3B when associated with A-24 and A-319. S->D;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:12228231,ECO:0000269|PubMed:15668399;Dbxref=PMID:11237865,PMID:12228231,PMID:15668399 Q12778 UniProtKB Mutagenesis 262 262 . . . Note=Inhibits interaction with ATG7 and FOXO1-acetylation-induced autophagic cell death%3B when associated with R-265 and R-274. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12228231;Dbxref=PMID:12228231 Q12778 UniProtKB Mutagenesis 265 265 . . . Note=Inhibits interaction with ATG7 and FOXO1-acetylation-induced autophagic cell death%3B when associated with R-262 and R-274. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12228231;Dbxref=PMID:12228231 Q12778 UniProtKB Mutagenesis 274 274 . . . Note=Inhibits interaction with ATG7 and FOXO1-acetylation-induced autophagic cell death%3B when associated with R-262 and R-265. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:12228231;Dbxref=PMID:12228231 Q12778 UniProtKB Mutagenesis 319 319 . . . Note=Abolishes PKB/AKT1-mediated phosphorylation but does not prevent phosphorylation of Ser-24 or Ser-256. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1%3B when associated with A-24 and A-256. Targeted to the nucleus and enhances transactivation%3B when associated with A-24. No effect on interaction with STUB1. S->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11237865,ECO:0000269|PubMed:12228231,ECO:0000269|PubMed:19483080;Dbxref=PMID:11237865,PMID:12228231,PMID:19483080 Q12778 UniProtKB Mutagenesis 329 329 . . . Note=Targeted to the nucleus and enhances transactivation. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:11311120;Dbxref=PMID:11311120 Q12778 UniProtKB Mutagenesis 423 423 . . . Note=Abolished deacetylation by SIRT6. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25009184;Dbxref=PMID:25009184 Q12778 UniProtKB Mutagenesis 446 446 . . . Note=Does not affect deacetylation by SIRT6. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25009184;Dbxref=PMID:25009184 Q12778 UniProtKB Mutagenesis 463 463 . . . Note=Does not affect deacetylation by SIRT6. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25009184;Dbxref=PMID:25009184 Q12778 UniProtKB Mutagenesis 515 515 . . . Note=Does not affect deacetylation by SIRT6. K->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25009184;Dbxref=PMID:25009184 Q12778 UniProtKB Sequence conflict 131 131 . . . Note=L->V;Ontology_term=ECO:0000305;evidence=ECO:0000305 Q12778 UniProtKB Sequence conflict 343 343 . . . Note=V->M;Ontology_term=ECO:0000305;evidence=ECO:0000305 Q12778 UniProtKB Beta strand 156 158 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Helix 165 175 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Beta strand 176 181 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:5DUI Q12778 UniProtKB Helix 183 193 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Helix 195 197 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Helix 203 219 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Beta strand 223 226 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Turn 230 232 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6 Q12778 UniProtKB Beta strand 236 239 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3CO6