FBXW7

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2OVP, 2OVQ, 2OVR, 5IBK

Identifiers

Aliases

FBXW7, AGO, CDC4, FBW6, FBW7, FBX30, FBXO30, FBXW6, SEL-10, SEL10, hAgo, hCdc4, F-box and WD repeat domain containing 7

External IDs

MGI: 1354695 HomoloGene: 117451 GeneCards: FBXW7

Gene ontology
Molecular function	• protein binding, bridging • protein binding • ubiquitin-protein transferase activator activity • identical protein binding • ubiquitin protein ligase binding • cyclin binding • phosphothreonine binding • ubiquitin-protein transferase activity
Cellular component	• cytoplasm • Parkin-FBXW7-Cul1 ubiquitin ligase complex • SCF ubiquitin ligase complex • nucleoplasm • protein complex • nucleolus • nucleus • cytosol
Biological process	• positive regulation of epidermal growth factor-activated receptor activity • positive regulation of protein targeting to mitochondrion • negative regulation of SREBP signaling pathway • cellular response to UV • negative regulation of triglyceride biosynthetic process • protein stabilization • negative regulation of hepatocyte proliferation • sister chromatid cohesion • cellular response to DNA damage stimulus • regulation of protein localization • positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process • vasculature development • regulation of mitophagy • negative regulation of DNA endoreduplication • positive regulation of ubiquitin-protein transferase activity • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • protein ubiquitination • lipid homeostasis • positive regulation of ERK1 and ERK2 cascade • regulation of cell cycle G1/S phase transition • regulation of lipid storage • viral process • positive regulation of proteasomal protein catabolic process • positive regulation of protein ubiquitination • negative regulation of Notch signaling pathway • protein polyubiquitination
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


55294


50754

Ensembl


ENSG00000109670


ENSMUSG00000028086

UniProt


Q969H0


Q8VBV4

RefSeq (mRNA)


NM_001013415 NM_001257069 NM_018315 NM_033632


NM_001177773 NM_001177774 NM_080428

RefSeq (protein)


NP_001013433.1 NP_060785.2 NP_361014.1


NP_536353.2

Location (UCSC)

Chr 4: 152.32 – 152.54 Mb

Chr 3: 84.82 – 84.98 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.^[3]^[4]^[5]

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.^[5]

Interactions

FBXW7 has been shown to interact with:

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
↑ Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israël A (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.
1 2 "Entrez Gene: FBXW7 F-box and WD repeat domain containing 7".
↑ 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.
↑ Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (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.
1 2 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.
↑ Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (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.

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.
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, Elledge SJ (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, Chui I, Deshaies RJ, Kitajewski J (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, Marth C, Widschwendter M, Reed SI (2002). "hCDC4 gene mutations in endometrial cancer". Cancer Res. 62 (16): 4535–9. PMID 12183400.
Li J, Pauley AM, Myers RL, Shuang R, Brashler JR, Yan R, Buhl AE, Ruble C, Gurney ME (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, Hempen PM, Hilgers W, Yeo CJ, Hruban RH, Kern SE (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, Clurman BE, Roberts JM (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, Hershko A, Pagano M, Draetta GF (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.
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.

PDB gallery

2ovp: Structure of the Skp1-Fbw7 complex

2ovq: Structure of the Skp1-Fbw7-CyclinEdegC complex

2ovr: Structure of the Skp1-Fbw7-CyclinEdegN complex

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FBXW7

Function

Interactions

References

Further reading