| IED ID | IndEnz0018000614 |
| Enzyme Type ID | peroxidase000614 |
| Protein Name |
Forkhead box protein O4 Fork head domain transcription factor AFX1 |
| Gene Name | FOXO4 AFX AFX1 MLLT7 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MDPGNENSATEAAAIIDLDPDFEPQSRPRSCTWPLPRPEIANQPSEPPEVEPDLGEKVHTEGRSEPILLPSRLPEPAGGPQPGILGAVTGPRKGGSRRNAWGNQSYAELISQAIESAPEKRLTLAQIYEWMVRTVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSWWMLNPEGGKSGKAPRRRAASMDSSSKLLRGRSKAPKKKPSVLPAPPEGATPTSPVGHFAKWSGSPCSRNREEADMWTTFRPRSSSNASSVSTRLSPLRPESEVLAEEIPASVSSYAGGVPPTLNEGLELLDGLNLTSSHSLLSRSGLSGFSLQHPGVTGPLHTYSSSLFSPAEGPLSAGEGCFSSSQALEALLTSDTPPPPADVLMTQVDPILSQAPTLLLLGGLPSSSKLATGVGLCPKPLEAPGPSSLVPTLSMIAPPPVMASAPIPKALGTPVLTPPTEAASQDRMPQDLDLDMYMENLECDMDNIISDLMDEGEGLDFNFEPDP |
| Enzyme Length | 505 |
| Uniprot Accession Number | P98177 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | DNA_BIND 100..188; /note=Fork-head; /evidence=ECO:0000255|PROSITE-ProRule:PRU00089 |
| EC Number | |
| Enzyme Function | FUNCTION: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity. {ECO:0000269|PubMed:10217147, ECO:0000269|PubMed:10783894, ECO:0000269|PubMed:12761217, ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:16054032, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:22972301}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Beta strand (4); Chain (1); DNA binding (1); Helix (5); Modified residue (3); Mutagenesis (3); Region (2); Sequence conflict (7); Turn (1) |
| Keywords | 3D-structure;Acetylation;Activator;Alternative splicing;Cell cycle;Chromosomal rearrangement;Cytoplasm;DNA-binding;Developmental protein;Differentiation;Myogenesis;Nucleus;Pharmaceutical;Phosphoprotein;Proto-oncogene;Reference proteome;Transcription;Transcription regulation;Ubl conjugation |
| Interact With | Itself; Q04864; P31947; Q96EB6; Q13485 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=When phosphorylated, translocated from nucleus to cytoplasm. Dephosphorylation triggers nuclear translocation. Monoubiquitination increases nuclear localization. When deubiquitinated, translocated from nucleus to cytoplasm. |
| Modified Residue | MOD_RES 32; /note="Phosphothreonine; by PKB/AKT1"; /evidence="ECO:0000269|PubMed:16272144"; MOD_RES 197; /note="Phosphoserine; by PKB/AKT1"; /evidence="ECO:0000269|PubMed:10217147, ECO:0000269|PubMed:10518537, ECO:0000269|PubMed:16272144"; MOD_RES 262; /note="Phosphoserine; by PKB/AKT1"; /evidence="ECO:0000269|PubMed:10217147, ECO:0000269|PubMed:10518537, ECO:0000269|PubMed:16272144" |
| Post Translational Modification | PTM: Acetylation by CREBBP/CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity. {ECO:0000269|PubMed:15126506}.; PTM: Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK. {ECO:0000269|PubMed:10217147, ECO:0000269|PubMed:10518537, ECO:0000269|PubMed:16272144}.; PTM: Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors; results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7; deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently, deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity. Hydrogene-peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein stability. {ECO:0000269|PubMed:16964248}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1); NMR spectroscopy (1) |
| Cross Reference PDB | 1E17; 3L2C; |
| Mapped Pubmed ID | 10102273; 10358014; 10358075; 10480625; 10913147; 11313479; 11777915; 11884591; 11923872; 11964479; 12048180; 12192052; 12239572; 12754525; 12857750; 12913110; 12960271; 12964026; 14576824; 14690436; 14701673; 14966295; 15053880; 15084259; 15109499; 15509806; 15538382; 15688004; 15824087; 15905404; 15916963; 15987244; 16215946; 16493026; 16571842; 16840535; 16943287; 17244620; 17611497; 18648506; 18665269; 18692812; 18787071; 18794148; 19244250; 19416966; 19560465; 19648934; 19932102; 20037138; 20136501; 20348951; 20570964; 20921137; 20934750; 20959475; 21123876; 21164521; 21388494; 21389279; 21454807; 21510935; 21525355; 21536589; 21567078; 21613825; 21708191; 21934092; 21940782; 22112832; 22125836; 22285440; 22411791; 22412893; 23333309; 23551888; 23707940; 23770673; 23918930; 24040102; 24353279; 24886657; 24935588; 24983969; 24984152; 25007147; 25053419; 25416956; 25609649; 25648147; 25753202; 25958948; 26463624; 26715362; 26780985; 26797321; 27027443; 27547294; 27911272; 27976702; 28554751; 28699853; 28945225; 28963932; 28973411; 30249393; 30610793; 30643063; 31351930; 31529218; 31712122; 32329448; 32820304; 32847377; 33103284; 33211221; 33238881; 33463054; 33577016; 33649837; 33723462; 34055579; 34320339; 34800438; |
| Motif | |
| Gene Encoded By | |
| Mass | 53,684 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |