General Information of Drug Therapeutic Target (DTT) (ID: TT29KY7)

DTT Name F-box and WD-40 domain protein 7 (Fbxw7)
Synonyms
hCdc4; hAgo; SEL10; SEL-10; FBX30; FBW7; F-box/WD repeat-containing protein 7; F-box-WD40 repeat protein 6; F-box protein Fbxw6; F-box protein FBX30; F-box protein FBW7; F-box and WD-40 domain-containing protein 7; Archipelago homolog
Gene Name FBXW7
DTT Type
Literature-reported target
[1]
UniProt ID
FBXW7_HUMAN
TTD ID
T21705
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MNQELLSVGSKRRRTGGSLRGNPSSSQVDEEQMNRVVEEEQQQQLRQQEEEHTARNGEVV
GVEPRPGGQNDSQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQ
ESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTKMKRKLDHGSEVRS
FSLGKKPCKVSEYTSTTGLVPCSATPTTFGDLRAANGQGQQRRRITSVQPPTGLQEWLKM
FQSWSGPEKLLALDELIDSCEPTQVKHMMQVIEPQFQRDFISLLPKELALYVLSFLEPKD
LLQAAQTCRYWRILAEDNLLWREKCKEEGIDEPLHIKRRKVIKPGFIHSPWKSAYIRQHR
IDTNWRRGELKSPKVLKGHDDHVITCLQFCGNRIVSGSDDNTLKVWSAVTGKCLRTLVGH
TGGVWSSQMRDNIIISGSTDRTLKVWNAETGECIHTLYGHTSTVRCMHLHEKRVVSGSRD
ATLRVWDIETGQCLHVLMGHVAAVRCVQYDGRRVVSGAYDFMVKVWDPETETCLHTLQGH
TNRVYSLQFDGIHVVSGSLDTSIRVWDVETGNCIHTLTGHQSLTSGMELKDNILVSGNAD
STVKIWDIKTGQCLQTLQGPNKHQSAVTCLQFNKNFVITSSDDGTVKLWDLKTGEFIRNL
VTLESGGSGGVVWRIRASNTKLVCAVGSRNGTEETKLLVLDFDVDMK
Function
Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, and probably PSEN1. Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation. SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1. Involved in bone homeostasis and negative regulation of osteoclast differentiation. Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination. 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.
KEGG Pathway
Ubiquitin mediated proteolysis (hsa04120 )
Reactome Pathway
Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606 )
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling (R-HSA-2644607 )
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862 )
Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471 )
Regulation of RUNX2 expression and activity (R-HSA-8939902 )
Neddylation (R-HSA-8951664 )
Negative regulation of NOTCH4 signaling (R-HSA-9604323 )
Antigen processing (R-HSA-983168 )
NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 )

References

1 BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am J Pathol. 2003 Oct;163(4):1255-60.