FBXW7

F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase

PDB rendering based on 2ovp.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsFBXW7 ; AGO; CDC4; FBW6; FBW7; FBX30; FBXO30; FBXW6; SEL-10; SEL10; hAgo; hCdc4
External IDsOMIM: 606278 MGI: 1354695 HomoloGene: 117451 GeneCards: FBXW7 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez5529450754
EnsemblENSG00000109670ENSMUSG00000028086
UniProtQ969H0Q8VBV4
RefSeq (mRNA)NM_001013415NM_001177773
RefSeq (protein)NP_001013433NP_001171244
Location (UCSC)Chr 4:
153.24 – 153.46 Mb		Chr 3:
84.82 – 84.98 Mb
PubMed search

F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.[1][2][3]

Function

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Mutations in this gene are detected in ovarian, breast and colorectal cancer cell lines, implicating the gene's potential role in the pathogenesis of human cancers. Three transcript variants encoding three different isoforms have been found for this gene.[3]

Interactions

FBXW7 has been shown to interact with:

References

  1. ↑ Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Dec 1999). "A family of mammalian F-box proteins". Curr Biol 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037.
  2. ↑ Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E et al. (Sep 2001). "Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor". J Biol Chem 276 (37): 34371–8. doi:10.1074/jbc.M101343200. PMID 11425854.
  3. ↑ 3.0 3.1 "Entrez Gene: FBXW7 F-box and WD repeat domain containing 7".
  4. ↑ Kanei-Ishii C, Nomura T, Takagi T, Watanabe N, Nakayama KI, Ishii S (Nov 2008). "Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation". J. Biol. Chem. 283 (45): 30540–8. doi:10.1074/jbc.M804340200. PMC 2662147. PMID 18765672.
  5. ↑ Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A et al. (Jan 2008). "SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. 22 (2): 252–64. doi:10.1101/gad.1624208. PMC 2192758. PMID 18198341.
  6. ↑ 6.0 6.1 Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A (Mar 2003). "Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity". Neuron 37 (5): 735–49. doi:10.1016/s0896-6273(03)00084-9. PMID 12628165.
  7. ↑ Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A et al. (Nov 2001). "SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation". Mol. Cell. Biol. 21 (21): 7403–15. doi:10.1128/MCB.21.21.7403-7415.2001. PMC 99913. PMID 11585921.

Further reading

  • Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC (1995). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID 7829101. Vancouver style error (help)
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Oberg C, Li J, Pauley A, Wolf E, Gurney M, Lendahl U (2001). "The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog". J. Biol. Chem. 276 (38): 35847–53. doi:10.1074/jbc.M103992200. PMID 11461910.
  • Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW et al. (2001). "Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase". Science 294 (5540): 173–7. doi:10.1126/science.1065203. PMID 11533444.
  • Moberg KH, Bell DW, Wahrer DC, Haber DA, Hariharan IK (2001). "Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines". Nature 413 (6853): 311–6. doi:10.1038/35095068. PMID 11565033.
  • Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI (2001). "Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line". Nature 413 (6853): 316–22. doi:10.1038/35095076. PMID 11565034.
  • Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A et al. (2001). "SEL-10 Is an Inhibitor of Notch Signaling That Targets Notch for Ubiquitin-Mediated Protein Degradation". Mol. Cell. Biol. 21 (21): 7403–15. doi:10.1128/MCB.21.21.7403-7415.2001. PMC 99913. PMID 11585921.
  • Spruck CH, Strohmaier H, Sangfelt O, Müller HM, Hubalek M, Müller-Holzner E et al. (2002). "hCDC4 gene mutations in endometrial cancer". Cancer Res. 62 (16): 4535–9. PMID 12183400. Vancouver style error (help)
  • Li J, Pauley AM, Myers RL, Shuang R, Brashler JR, Yan R et al. (2002). "SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production". J. Neurochem. 82 (6): 1540–8. doi:10.1046/j.1471-4159.2002.01105.x. PMID 12354302.
  • Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A (2003). "Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity". Neuron 37 (5): 735–49. doi:10.1016/S0896-6273(03)00084-9. PMID 12628165.
  • Calhoun ES, Jones JB, Ashfaq R, Adsay V, Baker SJ, Valentine V et al. (2003). "BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) Mutations in Distinct Subsets of Pancreatic Cancer: Potential Therapeutic Targets". Am. J. Pathol. 163 (4): 1255–60. doi:10.1016/S0002-9440(10)63485-2. PMC 1868306. PMID 14507635.
  • Welcker M, Singer J, Loeb KR, Grim J, Bloecher A, Gurien-West M et al. (2003). "Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation". Mol. Cell 12 (2): 381–92. doi:10.1016/S1097-2765(03)00287-9. PMID 14536078.
  • Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV et al. (2003). "Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage". Nature 426 (6962): 87–91. doi:10.1038/nature02082. PMID 14603323.
  • Cassia R, Moreno-Bueno G, Rodríguez-Perales S, Hardisson D, Cigudosa JC, Palacios J (2004). "Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma". J. Pathol. 201 (4): 589–95. doi:10.1002/path.1474. PMID 14648662. Vancouver style error (help)
  • Nateri AS, Riera-Sans L, Da Costa C, Behrens A (2004). "The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling". Science 303 (5662): 1374–8. doi:10.1126/science.1092880. PMID 14739463.