FBXW7
Summary: 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 and breast cancer cell lines, implicating the gene's potential role in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| F-box and WD repeat domain containing 7 | MIM:606278 | Ensembl:ENSG00000109670 | HGNC:HGNC:16712 | PA28054 | 4q31.3 |
GO terms in FBXW7
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | EXP | GO:0004842 | ubiquitin-protein transferase activity |
| MF | TAS | GO:0004842 | ubiquitin-protein transferase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IDA | GO:0030332 | cyclin binding |
| MF | IPI | GO:0030332 | cyclin binding |
| MF | IDA | GO:0030674 | protein binding, bridging |
| MF | IPI | GO:0031625 | ubiquitin protein ligase binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IBA | GO:0043130 | ubiquitin binding |
| MF | IDA | GO:0050816 | phosphothreonine residue binding |
| MF | IDA | GO:0097027 | ubiquitin-protein transferase activator activity |
| BP | TAS | GO:0000209 | protein polyubiquitination |
| BP | TAS | GO:0001944 | vasculature development |
| BP | IMP | GO:0007062 | sister chromatid cohesion |
| BP | ISS | GO:0010868 | negative regulation of triglyceride biosynthetic process |
| BP | ISS | GO:0010883 | regulation of lipid storage |
| BP | IBA | GO:0010992 | ubiquitin recycling |
| BP | IEA | GO:0016032 | viral process |
| BP | IDA | GO:0016567 | protein ubiquitination |
| BP | IDA | GO:0031146 | SCF-dependent proteasomal ubiquitin-dependent protein catabolic process |
| BP | IDA | GO:0031398 | positive regulation of protein ubiquitination |
| BP | IMP | GO:0032876 | negative regulation of DNA endoreduplication |
| BP | ISS | GO:0032880 | regulation of protein localization |
| BP | IBA | GO:0043161 | proteasome-mediated ubiquitin-dependent protein catabolic process |
| BP | TAS | GO:0043687 | post-translational protein modification |
| BP | IDA | GO:0045741 | positive regulation of epidermal growth factor-activated receptor activity |
| BP | ISS | GO:0045746 | negative regulation of Notch signaling pathway |
| BP | IDA | GO:0050821 | protein stabilization |
| BP | IDA | GO:0051443 | positive regulation of ubiquitin-protein transferase activity |
| BP | ISS | GO:0055088 | lipid homeostasis |
| BP | IMP | GO:0070374 | positive regulation of ERK1 and ERK2 cascade |
| BP | IDA | GO:1901800 | positive regulation of proteasomal protein catabolic process |
| BP | TAS | GO:1902806 | regulation of cell cycle G1/S phase transition |
| BP | IMP | GO:1903146 | regulation of autophagy of mitochondrion |
| BP | IDA | GO:1903378 | positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| BP | IMP | GO:1903955 | positive regulation of protein targeting to mitochondrion |
| BP | IDA | GO:2000060 | positive regulation of ubiquitin-dependent protein catabolic process |
| BP | ISS | GO:2000346 | negative regulation of hepatocyte proliferation |
| BP | ISS | GO:2000639 | negative regulation of SREBP signaling pathway |
| BP | IMP | GO:2001205 | negative regulation of osteoclast development |
| CC | IBA | GO:0005634 | nucleus |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | IEA | GO:0005730 | nucleolus |
| CC | IBA | GO:0005737 | cytoplasm |
| CC | IDA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0019005 | SCF ubiquitin ligase complex |
| CC | IPI | GO:1990452 | Parkin-FBXW7-Cul1 ubiquitin ligase complex |
Gene expression in normal tissue: FBXW7
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in FBXW7
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| kegg | hsa04120 | Ubiquitin mediated proteolysis - Homo sapiens (human) |
| pid | deltanp63pathway | Validated transcriptional targets of deltaNp63 isoforms |
| pid | myc_pathway | C-MYC pathway |
| netpath | Pathway_Notch | Notch |
| netpath | Pathway_TNFalpha | TNFalpha |
| wikipathways | WP2359 | Parkin-Ubiquitin Proteasomal System pathway |
| wikipathways | WP3651 | Pathways Affected in Adenoid Cystic Carcinoma |
| wikipathways | WP61 | Notch Signaling Pathway |
| reactome | R-HSA-1280218 | Adaptive Immune System |
| reactome | R-HSA-157118 | Signaling by NOTCH |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-1980143 | Signaling by NOTCH1 |
| reactome | R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer |
| reactome | R-HSA-2644603 | Signaling by NOTCH1 in Cancer |
| reactome | R-HSA-2644605 | FBXW7 Mutants and NOTCH1 in Cancer |
| reactome | R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants |
| reactome | R-HSA-2644607 | Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling |
| reactome | R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer |
| reactome | R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants |
| reactome | R-HSA-390466 | Chaperonin-mediated protein folding |
| reactome | R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis |
| reactome | R-HSA-391251 | Protein folding |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-5663202 | Diseases of signal transduction |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-8878166 | Transcriptional regulation by RUNX2 |
| reactome | R-HSA-8939902 | Regulation of RUNX2 expression and activity |
| reactome | R-HSA-8951664 | Neddylation |
| reactome | R-HSA-9013694 | Signaling by NOTCH4 |
| reactome | R-HSA-9604323 | Negative regulation of NOTCH4 signaling |
| reactome | R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation |
| reactome | R-HSA-983169 | Class I MHC mediated antigen processing & presentation |
| biocarta | fbw7pathway | cyclin e destruction pathway |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD451 | Serdemetan | 2 |
| iGMDRD100 | Zebularine | 5 |
| iGMDRD562 | Navitoclax | 2 |
| iGMDRD573 | GSK-1904529A | 1 |
| iGMDRD309 | 17AAG | 1 |
| iGMDRD138 | PX 12 | 1 |
| iGMDRD491 | TAE-684 | 1 |
| iGMDRD270 | Ciclosporin | 4 |
| iGMDRD33 | Entinostat | 1 |
| iGMDRD134 | Sorafenib | 1 |
| iGMDRD401 | Afatinib | 2 |
| iGMDRD280 | CYTOCHALASIN B | 6 |
| iGMDRD498 | GW441756X | 1 |
| iGMDRD446 | LY 2183240 | 2 |
| iGMDRD193 | Fqi1 | 3 |
| iGMDRD136 | Nutlin-3 | 1 |
| iGMDRD1008 | SR-II-138A | 1 |
| iGMDRD599 | Salermide | 1 |
| iGMDRD472 | PF-562271 | 1 |
| iGMDRD505 | Pevonedistat | 8 |
| iGMDRD695 | FR-180204 | 2 |
| iGMDRD967 | Panitumumab | 1 |
| iGMDRD68 | Paclitaxel | 1 |
| iGMDRD211 | (1S,3R)-RSL3 | 3 |
| iGMDRD536 | PLX-4720 | 1 |
| iGMDRD499 | PDMP | 3 |
| iGMDRD116 | CD437 | 2 |
| iGMDRD456 | Crizotinib | 2 |
| iGMDRD701 | NVP-AUY922 | 1 |
| iGMDRD84 | Lovastatin acid | 3 |
| iGMDRD792 | Cetuximab | 1 |
| iGMDRD347 | Y-39983 | 1 |
| iGMDRD190 | Nilotinib | 1 |
| iGMDRD369 | TGX-115 | 1 |
| iGMDRD64 | Parbendazole | 3 |
| iGMDRD356 | PNU-74654 | 1 |
| iGMDRD399 | Selumetinib | 5 |
| iGMDRD74 | Idarubicin | 2 |
| iGMDRD133 | Lapatinib | 1 |
| iGMDRD188 | Piperlongumine | 2 |
| iGMDRD506 | Fedratinib | 4 |
| iGMDRD284 | Palbociclib | 1 |
| iGMDRD187 | BRD9876 | 2 |
| iGMDRD198 | AC1LE7KD | 1 |
| iGMDRD748 | PHA-665752 | 1 |
| iGMDRD820 | anti-tubulin agents | 1 |
| iGMDRD546 | BMS-754807 | 1 |
| iGMDRD670 | ML 210 | 4 |
| iGMDRD427 | ABT737 | 3 |
| iGMDRD781 | Sirolimus | 1 |
| iGMDRD409 | Saracatinib | 1 |
| iGMDRD749 | ZINC6718453 | 1 |
| iGMDRD1012 | steroids early setting | 1 |
| iGMDRD993 | QL-XII-61 | 1 |
| iGMDRD286 | Nsc 632839 | 2 |
| iGMDRD77 | Itraconazole | 1 |
| iGMDRD202 | Curcumin | 2 |
| iGMDRD137 | Indisulam | 3 |
| iGMDRD949 | mTOR inhibitor | 1 |
| iGMDRD1011 | Steroid | 1 |
| iGMDRD5 | Tyrphostin AG 1478 | 3 |
| iGMDRD123 | Isoevodiamine | 3 |
| iGMDRD1029 | Tubulin inhibitor | 2 |
| iGMDRD39 | Pyrimethamine | 1 |
| iGMDRD1002 | rTRAIL | 1 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD150 | RITA | 5 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD324 | CI-1040 | 1 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in FBXW7
CLASSFICATION
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