ID:FBXW7_HUMAN DESCRIPTION: RecName: Full=F-box/WD repeat-containing protein 7; AltName: Full=Archipelago homolog; Short=hAgo; AltName: Full=F-box and WD-40 domain-containing protein 7; AltName: Full=F-box protein FBX30; AltName: Full=SEL-10; AltName: Full=hCdc4; FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. Involved in the degradation of cyclin-E, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SUBUNIT: Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7. Interacts with PSEN1, cyclin E, NOTCH1 NICD, NOTCH4 NICD and SKP1. Interacts with MYC (when phosphorylated). Isoform 1 interacts with USP28, leading to counteract ubiquitination of MYC. Isoform 4 interacts (via WD repeats) with SV40 large T antigen (via CPD region). Forms a trimeric complex with NOTCH1 and SGK1. INTERACTION: P01106:MYC; NbExp=2; IntAct=EBI-359574, EBI-447544; SUBCELLULAR LOCATION: Isoform 1: Nucleus, nucleoplasm. SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. SUBCELLULAR LOCATION: Isoform 4: Nucleus, nucleolus. SUBCELLULAR LOCATION: Nucleus (By similarity). TISSUE SPECIFICITY: Isoform 1 is widely expressed. Isoform 4 is expressed in brain. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. SIMILARITY: Contains 1 F-box domain. SIMILARITY: Contains 7 WD repeats. SEQUENCE CAUTION: Sequence=BAA91986.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q969H0
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0030332 cyclin binding GO:0030674 protein binding, bridging GO:0031625 ubiquitin protein ligase binding GO:0042802 identical protein binding GO:0050816 phosphothreonine binding GO:0097027 ubiquitin-protein transferase activator activity
Biological Process: GO:0000209 protein polyubiquitination GO:0001944 vasculature development GO:0006974 cellular response to DNA damage stimulus GO:0007062 sister chromatid cohesion GO:0010868 negative regulation of triglyceride biosynthetic process GO:0010883 regulation of lipid storage GO:0016032 viral process GO:0016567 protein ubiquitination GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0031398 positive regulation of protein ubiquitination GO:0032876 negative regulation of DNA endoreduplication GO:0032880 regulation of protein localization GO:0034644 cellular response to UV GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043687 post-translational protein modification GO:0045741 positive regulation of epidermal growth factor-activated receptor activity GO:0045746 negative regulation of Notch signaling pathway GO:0050821 protein stabilization GO:0051443 positive regulation of ubiquitin-protein transferase activity GO:0055088 lipid homeostasis GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:1901800 positive regulation of proteasomal protein catabolic process GO:1902806 regulation of cell cycle G1/S phase transition GO:1903146 regulation of mitophagy GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway GO:1903955 positive regulation of protein targeting to mitochondrion GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000346 negative regulation of hepatocyte proliferation GO:2000639 negative regulation of SREBP signaling pathway GO:2001205 negative regulation of osteoclast development
BC117244 - Homo sapiens F-box and WD repeat domain containing 7, mRNA (cDNA clone MGC:150853 IMAGE:40125795), complete cds. BC117246 - Homo sapiens F-box and WD repeat domain containing 7, mRNA (cDNA clone MGC:150855 IMAGE:40125797), complete cds. BC143944 - Homo sapiens F-box and WD repeat domain containing 7, mRNA (cDNA clone MGC:177479 IMAGE:9052462), complete cds. CR749305 - Homo sapiens mRNA; cDNA DKFZp686F23254 (from clone DKFZp686F23254). BC014503 - Homo sapiens, clone IMAGE:4860747, mRNA. HQ873864 - Homo sapiens F-box and WD repeat domain containing 7 isoform 1 (FBXW7) mRNA, partial cds, alternatively spliced. HQ873865 - Homo sapiens F-box and WD repeat domain containing 7 isoform 2 (FBXW7) mRNA, partial cds, alternatively spliced. HQ873866 - Homo sapiens F-box and WD repeat domain containing 7 isoform 3 (FBXW7) mRNA, partial cds, alternatively spliced. HQ873867 - Homo sapiens F-box and WD repeat domain containing 7 isoform 4 (FBXW7) mRNA, partial cds, alternatively spliced. HQ873868 - Homo sapiens F-box and WD repeat domain containing 7 isoform 5 (FBXW7) mRNA, partial cds, alternatively spliced. HQ873869 - Homo sapiens F-box and WD repeat domain containing 7 isoform 6 (FBXW7) mRNA, partial cds, alternatively spliced. HQ873870 - Homo sapiens F-box and WD repeat domain containing 7 isoform 7 (FBXW7) mRNA, partial cds, alternatively spliced. AY008274 - Homo sapiens F-box protein SEL10 (SEL10) mRNA, complete cds. BC059373 - Homo sapiens cDNA clone IMAGE:5263248, containing frame-shift errors. BC037320 - Homo sapiens F-box and WD repeat domain containing 7, mRNA (cDNA clone IMAGE:5260084), partial cds. JD506395 - Sequence 487419 from Patent EP1572962. JD454797 - Sequence 435821 from Patent EP1572962. JD314680 - Sequence 295704 from Patent EP1572962. AK299722 - Homo sapiens cDNA FLJ59410 complete cds, highly similar to F-box/WD repeat protein 7. JD234660 - Sequence 215684 from Patent EP1572962. JD213932 - Sequence 194956 from Patent EP1572962. AK223449 - Homo sapiens mRNA for F-box protein FBW7 isoform 2 variant, clone: FCC113E01. AF383178 - Homo sapiens F-box protein FBX30 mRNA, partial cds. AF411972 - Homo sapiens archipelago beta form mRNA, complete cds. AY033553 - Homo sapiens F-box protein FBW7 mRNA, complete cds. AB209725 - Homo sapiens mRNA for F-box protein FBW7 isoform 2 variant protein. AK131383 - Homo sapiens cDNA FLJ16457 fis, clone BRAWH3009017. AK294568 - Homo sapiens cDNA FLJ55681 complete cds, highly similar to F-box/WD repeat protein 7. AK001933 - Homo sapiens cDNA FLJ11071 fis, clone PLACE1004937, moderately similar to SEL-10 PROTEIN. AY049984 - Homo sapiens F-box protein CDC4 (CDC4) mRNA, complete cds. AF411971 - Homo sapiens archipelago alpha form mRNA, complete cds. AK315142 - Homo sapiens cDNA, FLJ96109. HQ258348 - Synthetic construct Homo sapiens clone IMAGE:100072657 F-box and WD repeat domain containing 7 (FBXW7), transcript variant 1 (FBXW7) gene, encodes complete protein. KJ894180 - Synthetic construct Homo sapiens clone ccsbBroadEn_03574 FBXW7 gene, encodes complete protein. AB527140 - Synthetic construct DNA, clone: pF1KB5050, Homo sapiens FBXW7 gene for F-box and WD repeat domain containing 7, without stop codon, in Flexi system. JD067281 - Sequence 48305 from Patent EP1572962. JD228067 - Sequence 209091 from Patent EP1572962. JD301826 - Sequence 282850 from Patent EP1572962. JD200351 - Sequence 181375 from Patent EP1572962. JD462061 - Sequence 443085 from Patent EP1572962. JD200367 - Sequence 181391 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_fbw7Pathway - Cyclin E Destruction Pathway
Reactome (by CSHL, EBI, and GO)
Protein Q969H0 (Reactome details) participates in the following event(s):
R-HSA-390470 Association of CCT/TriC with other substrates during biosynthesis (unknown chaperone) R-HSA-8952620 NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex R-HSA-8956200 MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases R-HSA-8952618 AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis R-HSA-390466 Chaperonin-mediated protein folding R-HSA-8951664 Neddylation R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-391251 Protein folding R-HSA-597592 Post-translational protein modification R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-392499 Metabolism of proteins R-HSA-1280218 Adaptive Immune System R-HSA-168256 Immune System R-HSA-1912385 Phosphorylated NICD1 binds FBXW7 R-NUL-2064853 FBXW7 binds phosphorylated NICD1 R-HSA-1852623 Ubiquitination of NICD1 by FBWX7 R-NUL-2064883 FBXW7 mediates ubiquitination of phosphorylated NICD1 R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling R-HSA-157118 Signaling by NOTCH R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-2644605 FBXW7 Mutants and NOTCH1 in Cancer R-HSA-162582 Signal Transduction R-HSA-5663202 Diseases of signal transduction R-HSA-1643685 Disease R-HSA-9008478 FBXW7 binds RUNX2 and GSK3B R-HSA-9008479 FBXW7 polyubiquitinates RUNX2 R-HSA-1912385 Phosphorylated NICD1 binds FBXW7 R-NUL-2064853 FBXW7 binds phosphorylated NICD1 R-HSA-1852623 Ubiquitination of NICD1 by FBWX7 R-NUL-2064883 FBXW7 mediates ubiquitination of phosphorylated NICD1 R-HSA-8939902 Regulation of RUNX2 expression and activity R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-212436 Generic Transcription Pathway R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling R-HSA-73857 RNA Polymerase II Transcription R-HSA-157118 Signaling by NOTCH R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-2644605 FBXW7 Mutants and NOTCH1 in Cancer R-HSA-74160 Gene expression (Transcription) R-HSA-162582 Signal Transduction R-HSA-5663202 Diseases of signal transduction R-HSA-1643685 Disease
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
