FBXW7

FBXW7
Available structures PDB 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	OMIM: 606278; MGI: 1354695; HomoloGene: 117451; GeneCards: FBXW7; OMA:FBXW7 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q31.3 Start 152,320,544 bp[1] End 152,536,092 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F1|3 37.7 cM Start 84,722,575 bp[2] End 84,886,505 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 Achilles tendon epithelium of colon middle temporal gyrus superior frontal gyrus occipital lobe pons parietal lobe primary visual cortex postcentral gyrus Top expressed in prefrontal cortex primary motor cortex barrel cortex visual cortex temporal lobe primary visual cortex amygdala saccule superior frontal gyrus Region I of hippocampus proper More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein-macromolecule adaptor activity protein binding ubiquitin-protein transferase activator activity identical protein binding ubiquitin protein ligase binding cyclin binding phosphothreonine residue binding ubiquitin-protein transferase activity ubiquitin binding Cellular component cytoplasm Parkin-FBXW7-Cul1 ubiquitin ligase complex SCF ubiquitin ligase complex nucleoplasm nucleolus nucleus cytosol mitochondrion endoplasmic reticulum Golgi apparatus perinuclear region of cytoplasm 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 autophagy of mitochondrion negative regulation of DNA endoreduplication positive regulation of ubiquitin-protein transferase activity positive regulation of 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 post-translational protein modification negative regulation of osteoclast development vasculogenesis Notch signaling pathway negative regulation of gene expression ubiquitin recycling lung development protein destabilization proteasome-mediated ubiquitin-dependent protein catabolic process regulation of cell migration involved in sprouting angiogenesis negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding regulation of circadian rhythm rhythmic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55294 50754 Ensembl ENSG00000109670 ENSMUSG00000028086 UniProt Q969H0 Q8VBV4 RefSeq (mRNA) NM_001013415 NM_001257069 NM_018315 NM_033632 NM_001349798 NM_001177773 NM_001177774 NM_080428 RefSeq (protein) NP_001013433 NP_001243998 NP_060785 NP_361014 NP_001336727 NP_001171244 NP_001171245 NP_536353 Location (UCSC) Chr 4: 152.32 – 152.54 Mb Chr 3: 84.72 – 84.89 Mb PubMed search [3] [4]
Wikidata
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F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.^[5][6][7]

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. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers [e.g., cholangiocarcinoma (35%), T-ALL (31%), endometrial carcinoma (16%), colorectal carcinoma (16%), bladder cancer (10%), gastric carcinoma (6%), lung squamous cell carcinoma (5%), etc.]. These findings implicate the gene's potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and multiple myeloma. One possibility is that FBXW7 substrate stabilization is detrimental in these neoplasms. For example, the FBXW7 substrate C/EBPα suppresses AML^[8] and multiple myelomas require constitutive NF-κB signaling; therefore, disruption of FBXW7-mediated ubiquitylation of IκBd in these tumors results in cell death.^[9][10]

Three transcript variants encoding three different isoforms have been found for this gene.^[7]

Interactions

FBXW7 has been shown to interact with:

• MYB,^[11]
• PPARGC1A,^[12]
• Parkin (ligase),^[13] and
• SKP1A.^[13][14]

References

Further reading

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