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Identification
HMDB Protein ID HMDBP08863
Secondary Accession Numbers
  • 14590
Name Forkhead box protein O4
Synonyms
  1. Fork head domain transcription factor AFX1
Gene Name FOXO4
Protein Type Unknown
Biological Properties
General Function Involved in sequence-specific DNA binding transcription factor activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
binding
nucleic acid binding
dna binding
sequence-specific dna binding
sequence-specific dna binding transcription factor activity
Process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
regulation of transcription, dna-dependent
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs FOXO4
Gene Sequence
>1518 bp
ATGGATCCGGGGAATGAGAATTCAGCCACAGAGGCTGCCGCGATCATAGACCTAGATCCC
GACTTCGAACCCCAGAGCCGTCCCCGCTCCTGCACCTGGCCCCTTCCCCGACCAGAGATC
GCTAACCAGCCGTCCGAGCCGCCCGAGGTGGAGCCAGATCTGGGGGAAAAGGTACACACG
GAGGGGCGCTCAGAGCCGATCCTGTTGCCCTCTCGGCTCCCAGAGCCGGCCGGGGGCCCC
CAGCCCGGAATCCTGGGGGCTGTAACAGGTCCTCGGAAGGGAGGCTCCCGCCGGAATGCC
TGGGGAAATCAGTCATATGCAGAACTCATCAGCCAGGCCATTGAAAGCGCCCCGGAGAAG
CGACTGACACTTGCCCAGATCTACGAGTGGATGGTCCGTACTGTACCCTACTTCAAGGAC
AAGGGTGACAGCAACAGCTCAGCAGGATGGAAGAACTCGATCCGCCACAACCTGTCCCTG
CACAGCAAGTTCATCAAGGTTCACAACGAGGCCACCGGCAAAAGCTCTTGGTGGATGCTG
AACCCTGAGGGAGGCAAGAGCGGCAAAGCCCCCCGCCGCCGGGCCGCCTCCATGGATAGC
AGCAGCAAGCTGCTCCGGGGCCGCAGTAAAGCCCCCAAGAAGAAACCATCTGTGCTGCCA
GCTCCACCCGAAGGTGCCACTCCAACGAGCCCTGTCGGCCACTTTGCCAAGTGGTCAGGC
AGCCCTTGCTCTCGAAACCGTGAAGAAGCCGATATGTGGACCACCTTCCGTCCACGAAGC
AGTTCAAATGCCAGCAGTGTCAGCACCCGGCTGTCCCCCTTGAGGCCAGAGTCTGAGGTG
CTGGCGGAGGAAATACCAGCTTCAGTCAGCAGTTATGCAGGGGGTGTCCCTCCCACCCTC
AATGAAGGTCTAGAGCTGTTAGATGGGCTCAATCTCACCTCTTCCCATTCCCTGCTATCT
CGGAGTGGTCTCTCTGGCTTCTCTTTGCAGCATCCTGGGGTTACCGGCCCCTTACACACC
TACAGCAGCTCCCTTTTCAGCCCAGCAGAGGGGCCCCTGTCAGCAGGAGAAGGGTGCTTC
TCCAGCTCCCAGGCTCTGGAGGCCCTGCTCACCTCTGATACGCCACCACCCCCTGCTGAC
GTCCTCATGACCCAGGTAGATCCCATTCTGTCCCAGGCTCCGACTCTTCTGTTGCTGGGG
GGGCTTCCTTCCTCCAGTAAGCTGGCCACGGGCGTCGGCCTGTGTCCCAAGCCCCTAGAG
GCTCCAGGCCCCAGCAGTCTGGTTCCCACCCTTTCTATGATAGCACCACCTCCAGTCATG
GCAAGTGCCCCCATCCCCAAGGCTCTGGGGACTCCTGTGCTCACACCCCCTACTGAAGCT
GCAAGCCAAGACAGAATGCCTCAGGATCTAGATCTTGATATGTATATGGAGAACCTGGAG
TGTGACATGGATAACATCATCAGTGACCTCATGGATGAGGGCGAGGGACTGGACTTCAAC
TTTGAGCCAGATCCCTGA
Protein Properties
Number of Residues 505
Molecular Weight 53683.8
Theoretical pI 4.89
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Forkhead box protein O4
MDPGNENSATEAAAIIDLDPDFEPQSRPRSCTWPLPRPEIANQPSEPPEVEPDLGEKVHT
EGRSEPILLPSRLPEPAGGPQPGILGAVTGPRKGGSRRNAWGNQSYAELISQAIESAPEK
RLTLAQIYEWMVRTVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSWWML
NPEGGKSGKAPRRRAASMDSSSKLLRGRSKAPKKKPSVLPAPPEGATPTSPVGHFAKWSG
SPCSRNREEADMWTTFRPRSSSNASSVSTRLSPLRPESEVLAEEIPASVSSYAGGVPPTL
NEGLELLDGLNLTSSHSLLSRSGLSGFSLQHPGVTGPLHTYSSSLFSPAEGPLSAGEGCF
SSSQALEALLTSDTPPPPADVLMTQVDPILSQAPTLLLLGGLPSSSKLATGVGLCPKPLE
APGPSSLVPTLSMIAPPPVMASAPIPKALGTPVLTPPTEAASQDRMPQDLDLDMYMENLE
CDMDNIISDLMDEGEGLDFNFEPDP
GenBank ID Protein 103472003
UniProtKB/Swiss-Prot ID P98177
UniProtKB/Swiss-Prot Entry Name FOXO4_HUMAN
PDB IDs
GenBank Gene ID NM_005938.3
GeneCard ID FOXO4
GenAtlas ID FOXO4
HGNC ID HGNC:7139
References
General References
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  2. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y: Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
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  5. Obsilova V, Vecer J, Herman P, Pabianova A, Sulc M, Teisinger J, Boura E, Obsil T: 14-3-3 Protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4. Biochemistry. 2005 Aug 30;44(34):11608-17. [PubMed:16114898 ]
  6. Peters U, Haberhausen G, Kostrzewa M, Nolte D, Muller U: AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as candidate genes of X-linked dystonia parkinsonism. Hum Genet. 1997 Oct;100(5-6):569-72. [PubMed:9341872 ]
  7. Borkhardt A, Repp R, Haas OA, Leis T, Harbott J, Kreuder J, Hammermann J, Henn T, Lampert F: Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23). Oncogene. 1997 Jan 16;14(2):195-202. [PubMed:9010221 ]
  8. Yang Z, Whelan J, Babb R, Bowen BR: An mRNA splice variant of the AFX gene with altered transcriptional activity. J Biol Chem. 2002 Mar 8;277(10):8068-75. Epub 2002 Jan 4. [PubMed:11779849 ]
  9. Parry P, Wei Y, Evans G: Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family. Genes Chromosomes Cancer. 1994 Oct;11(2):79-84. [PubMed:7529552 ]
  10. Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM: Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature. 1999 Apr 15;398(6728):630-4. [PubMed:10217147 ]
  11. Takaishi H, Konishi H, Matsuzaki H, Ono Y, Shirai Y, Saito N, Kitamura T, Ogawa W, Kasuga M, Kikkawa U, Nishizuka Y: Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11836-41. [PubMed:10518537 ]
  12. Medema RH, Kops GJ, Bos JL, Burgering BM: AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 2000 Apr 13;404(6779):782-7. [PubMed:10783894 ]
  13. Tang TT, Lasky LA: The forkhead transcription factor FOXO4 induces the down-regulation of hypoxia-inducible factor 1 alpha by a von Hippel-Lindau protein-independent mechanism. J Biol Chem. 2003 Aug 8;278(32):30125-35. Epub 2003 May 21. [PubMed:12761217 ]
  14. Liu ZP, Wang Z, Yanagisawa H, Olson EN: Phenotypic modulation of smooth muscle cells through interaction of Foxo4 and myocardin. Dev Cell. 2005 Aug;9(2):261-70. [PubMed:16054032 ]
  15. Matsuzaki H, Ichino A, Hayashi T, Yamamoto T, Kikkawa U: Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family. J Biochem. 2005 Oct;138(4):485-91. [PubMed:16272144 ]
  16. Yang H, Zhao R, Yang HY, Lee MH: Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. Oncogene. 2005 Mar 10;24(11):1924-35. [PubMed:15688030 ]
  17. van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BM: FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006 Oct;8(10):1064-73. Epub 2006 Sep 10. [PubMed:16964248 ]
  18. Weigelt J, Climent I, Dahlman-Wright K, Wikstrom M: 1H, 13C and 15N resonance assignments of the DNA binding domain of the human forkhead transcription factor AFX. J Biomol NMR. 2000 Jun;17(2):181-2. [PubMed:10921784 ]
  19. Weigelt J, Climent I, Dahlman-Wright K, Wikstrom M: Solution structure of the DNA binding domain of the human forkhead transcription factor AFX (FOXO4). Biochemistry. 2001 May 22;40(20):5861-9. [PubMed:11352721 ]