Reviewed,
UniProtKB/Swiss-Prot Q12778 (FOXO1_HUMAN)
Last modified
February 9, 2010.
Version 103.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Forkhead box protein O1 Alternative name(s): Forkhead box protein O1A Forkhead in rhabdomyosarcoma | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 655 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Transcription factor. Ref.9 |
| Subunit structure | Interacts with LRPPRC By similarity. |
| Subcellular location | Cytoplasm. Nucleus. Note: Shuttles between cytoplasm and nucleus. Ref.9 Ref.7 |
| Tissue specificity | Ubiquitous. Ref.2 |
| Post-translational modification | Phosphorylated by AKT1; insulin-induced By similarity. IGF1 rapidly induces phosphorylation of Ser-256, Thr-24, and Ser-319. Phosphorylation of Ser-256 decreases DNA-binding activity and promotes the phosphorylation of Thr-24, and Ser-319, permitting phosphorylation of Ser-322 and Ser-325, probably by CK1, leading to nuclear exclusion and loss of function. Phosphorylation of Ser-329 is independent of IGF1 and leads to reduced function. Phosphorylated upon DNA damage, probably by ATM or ATR. |
| Involvement in disease | Chromosomal aberrations involving FOXO1 are a cause of rhabdomyosarcoma 2 (RMS2) [MIM:268220]; also known as alveolar rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3; translocation t(1;13)(p36;q14) with PAX7. The resulting protein is a transcriptional activator. |
| Sequence similarities | Contains 1 fork-head DNA-binding domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Cytoplasm Nucleus |
| Coding sequence diversity | Chromosomal rearrangement |
| Disease | Proto-oncogene |
| Ligand | DNA-binding |
| PTM | Phosphoprotein |
| Technical term | 3D-structure Complete proteome |
| Gene Ontology (GO) | |
| Biological process | anti-apoptosis Inferred from direct assay. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Ref.9Inferred from direct assay. Source: UniProtKB transcriptionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cytosol Ref.9 Inferred from Experiment. Source: Reactome nucleoplasm Ref.9Inferred from Experiment. Source: Reactome |
| Molecular function | protein binding Inferred from physical interaction. Source: IntAct sequence-specific DNA binding Ref.9Inferred from direct assay. Source: UniProtKB transcription activator activity Ref.9Inferred from direct assay. Source: UniProtKB |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| AR | P10275 | 1 | EBI-1108782,EBI-608057 | |
| CDC2 | P06493 | 4 | EBI-1108782,EBI-444308 | |
| ESR1 | P03372 | 1 | EBI-1108782,EBI-78473 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 655 | 655 | Forkhead box protein O1 | PRO_0000091872 | |||||||||||||||||||||
Regions | |||||||||||||||||||||||||
| DNA binding | 159 – 235 | 77 | Fork-head | ||||||||||||||||||||||
| Compositional bias | 91 – 102 | 12 | Poly-Ala | ||||||||||||||||||||||
| Compositional bias | 120 – 130 | 11 | Poly-Pro | ||||||||||||||||||||||
| Compositional bias | 152 – 155 | 4 | Poly-Ser | ||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||
| Modified residue | 24 | 1 | Phosphothreonine; by PKB/AKT1 Ref.6 Ref.8 | ||||||||||||||||||||||
| Modified residue | 256 | 1 | Phosphoserine; by PKB/AKT1 Ref.6 Ref.8 | ||||||||||||||||||||||
| Modified residue | 287 | 1 | Phosphoserine Ref.11 Ref.12 | ||||||||||||||||||||||
| Modified residue | 319 | 1 | Phosphoserine; by PKB/AKT1 Ref.6 Ref.8 | ||||||||||||||||||||||
| Modified residue | 322 | 1 | Phosphoserine; by CK1 Ref.8 | ||||||||||||||||||||||
| Modified residue | 325 | 1 | Phosphoserine; by CK1 Ref.8 | ||||||||||||||||||||||
| Modified residue | 329 | 1 | Phosphoserine; by DYRK1A Ref.7 Ref.8 | ||||||||||||||||||||||
| Modified residue | 467 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||
| Modified residue | 468 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||
| Modified residue | 505 | 1 | Phosphoserine Ref.10 | ||||||||||||||||||||||
| Modified residue | 509 | 1 | Phosphoserine Ref.10 | ||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||
| Mutagenesis | 24 | 1 | T → A: Nuclear targeting and enhanced transactivation; when associated with A-319. Ref.9 | ||||||||||||||||||||||
| Mutagenesis | 245 | 1 | K → A: Disrupts DNA binding; when associated with A-248. | ||||||||||||||||||||||
| Mutagenesis | 248 | 1 | K → A: Disrupts DNA binding; when associated with A-245. | ||||||||||||||||||||||
| Mutagenesis | 251 – 253 | 3 | RRR → SAS: Disrupts DNA binding. | ||||||||||||||||||||||
| Mutagenesis | 256 | 1 | S → A: Nuclear targeting. Abolishes the ability of IGF1 to suppress transactivation. Prevents T-24 and S-319 phosphorylation. Enhances transactivation; when associated with A-24 and A-319. Ref.9 | ||||||||||||||||||||||
| Mutagenesis | 256 | 1 | S → D: Reduces DNA binding, promotes nuclear exclusion and partially promotes T-24 and S-319 phosphorylation. Reduces DNA binding, does not promote nuclear exclusion but reduces transactivation; when associated with A-24 and A-319. Ref.9 | ||||||||||||||||||||||
| Mutagenesis | 319 | 1 | S → A: Nuclear targeting and enhanced transactivation; when associated with A-24. Ref.9 | ||||||||||||||||||||||
| Mutagenesis | 329 | 1 | S → A: Nuclear targeting and enhanced transactivation. Ref.7 | ||||||||||||||||||||||
| Sequence conflict | 131 | 1 | L → V in AAA03629. Ref.1 | ||||||||||||||||||||||
| Sequence conflict | 343 | 1 | V → M in AAH70065. Ref.5 | ||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||
| Beta strand | 156 – 158 | 3 | |||||||||||||||||||||||
| Helix | 165 – 175 | 11 | |||||||||||||||||||||||
| Helix | 183 – 193 | 11 | |||||||||||||||||||||||
| Helix | 195 – 197 | 3 | |||||||||||||||||||||||
| Helix | 203 – 206 | 4 | |||||||||||||||||||||||
| Helix | 210 – 219 | 10 | |||||||||||||||||||||||
| Beta strand | 223 – 226 | 4 | |||||||||||||||||||||||
| Beta strand | 236 – 239 | 4 | |||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma." Galili N., Davis R.J., Fredericks W.J., Mukhopadhyay S., Rauscher F.J. III, Emanuel B.S., Rovera G., Barr F.G. Nat. Genet. 5:230-235(1993) [PubMed: 8275086] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH PAX3. |
| [2] | "Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily." Anderson M.J., Viars C.S., Czekay S., Cavenee W.K., Arden K.C. Genomics 47:187-199(1998) [PubMed: 9479491] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Rhabdomyosarcoma. |
| [3] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | "The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. Ross M.T.Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Placenta. |
| [6] | "Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B." Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P. J. Biol. Chem. 274:17179-17183(1999) [PubMed: 10358075] [Abstract] Cited for: PHOSPHORYLATION AT THR-24; SER-256 AND SER-319. |
| [7] | "The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site." Woods Y.L., Rena G., Morrice N., Barthel A., Becker W., Guo S., Unterman T.G., Cohen P. Biochem. J. 355:597-607(2001) [PubMed: 11311120] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-329, MUTAGENESIS OF SER-329. |
| [8] | "Two novel phosphorylation sites on FKHR that are critical for its nuclear exclusion." Rena G., Woods Y.L., Prescott A.R., Peggie M., Unterman T.G., Williams M.R., Cohen P. EMBO J. 21:2263-2271(2002) [PubMed: 11980723] [Abstract] Cited for: PHOSPHORYLATION AT THR-24; SER-256; SER-319; SER-322; SER-325 AND SER-329. |
| [9] | "Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding." Zhang X., Gan L., Pan H., Guo S., He X., Olson S.T., Mesecar A., Adam S., Unterman T.G. J. Biol. Chem. 277:45276-45284(2002) [PubMed: 12228231] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-24; SER-256 AND SER-319. |
| [10] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505 AND SER-509, MASS SPECTROMETRY. |
| [11] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, MASS SPECTROMETRY. |
| [12] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | U02310 mRNA. Translation: AAA03629.1. AF032885 mRNA. Translation: AAC39591.1. BT007455 mRNA. Translation: AAP36123.1. AL355132, AL133318 Genomic DNA. Translation: CAH70978.1. AL133318, AL355132 Genomic DNA. Translation: CAI16970.1. BC021981 mRNA. Translation: AAH21981.1. BC070065 mRNA. Translation: AAH70065.3. | ||||||||||||||||||||||||
| IPI | IPI00289866. | ||||||||||||||||||||||||
| PIR | S40521. | ||||||||||||||||||||||||
| RefSeq | NP_002006.2. | ||||||||||||||||||||||||
| UniGene | Hs.370666 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| DIP | DIP-35654N. | ||||||||||||||||||||||||
| IntAct | Q12778. 5 interactions. | ||||||||||||||||||||||||
| STRING | Q12778. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | Q12778. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PRIDE | Q12778. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENST00000379561; ENSP00000368880; ENSG00000150907; Homo sapiens. [Genome view] | ||||||||||||||||||||||||
| GeneID | 2308. | ||||||||||||||||||||||||
| KEGG | hsa:2308. | ||||||||||||||||||||||||
| UCSC | uc001uxl.2. human. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 2308. | ||||||||||||||||||||||||
| GeneCards | GC13M040028. | ||||||||||||||||||||||||
| HGNC | HGNC:3819. FOXO1. | ||||||||||||||||||||||||
| HPA | HPA001252. | ||||||||||||||||||||||||
| MIM | 136533. gene. 268220. phenotype. | ||||||||||||||||||||||||
| Orphanet | 99756. Alveolar rhabdomyosarcoma. 780. Rhabdomyosarcoma. | ||||||||||||||||||||||||
| PharmGKB | PA28237. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| eggNOG | prNOG11255. | ||||||||||||||||||||||||
| HOGENOM | HBG714085. | ||||||||||||||||||||||||
| HOVERGEN | Q12778. | ||||||||||||||||||||||||
| InParanoid | Q12778. | ||||||||||||||||||||||||
| OMA | PPHNDIL. | ||||||||||||||||||||||||
| OrthoDB | EOG9QJV6J. | ||||||||||||||||||||||||
| PhylomeDB | Q12778. | ||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||
| Pathway_Interaction_DB | angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling. pi3kciaktpathway. Class I PI3K signaling events mediated by Akt. foxopathway. FoxO family signaling. il6_7pathway. IL6-mediated signaling events. ar_tf_pathway. Regulation of Androgen receptor activity. smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling. hdac_classiii_pathway. Signaling events mediated by HDAC Class III. | ||||||||||||||||||||||||
| Reactome | REACT_11061. Signalling by NGF. REACT_13698. Regulation of beta-cell development. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | Q12778. | ||||||||||||||||||||||||
| Bgee | Q12778. | ||||||||||||||||||||||||
| CleanEx | HS_FOXO1. | ||||||||||||||||||||||||
| Genevestigator | Q12778. | ||||||||||||||||||||||||
| GermOnline | ENSG00000150907. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view] | ||||||||||||||||||||||||
| Gene3D | G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit. | ||||||||||||||||||||||||
| PANTHER | PTHR11829. Fork_box_protein. 1 hit. | ||||||||||||||||||||||||
| Pfam | PF00250. Fork_head. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PRINTS | PR00053. FORKHEAD. | ||||||||||||||||||||||||
| SMART | SM00339. FH. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS00657. FORK_HEAD_1. False negative. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 9375. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | FOXO1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q12778 Secondary accession number(s): O43523, Q5VYC7, Q6NSK6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 13 Human chromosome 13: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


