Target Information

Target General Information

Target ID

T21705 (Former ID: TTDR00937)

Target 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

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Gene Name

FBXW7

Target Type

Literature-reported target

[1]

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.

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UniProt ID

FBXW7_HUMAN

Sequence

MNQELLSVGSKRRRTGGSLRGNPSSSQVDEEQMNRVVEEEQQQQLRQQEEEHTARNGEVV
GVEPRPGGQNDSQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQ
ESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTKMKRKLDHGSEVRS
FSLGKKPCKVSEYTSTTGLVPCSATPTTFGDLRAANGQGQQRRRITSVQPPTGLQEWLKM
FQSWSGPEKLLALDELIDSCEPTQVKHMMQVIEPQFQRDFISLLPKELALYVLSFLEPKD
LLQAAQTCRYWRILAEDNLLWREKCKEEGIDEPLHIKRRKVIKPGFIHSPWKSAYIRQHR
IDTNWRRGELKSPKVLKGHDDHVITCLQFCGNRIVSGSDDNTLKVWSAVTGKCLRTLVGH
TGGVWSSQMRDNIIISGSTDRTLKVWNAETGECIHTLYGHTSTVRCMHLHEKRVVSGSRD
ATLRVWDIETGQCLHVLMGHVAAVRCVQYDGRRVVSGAYDFMVKVWDPETETCLHTLQGH
TNRVYSLQFDGIHVVSGSLDTSIRVWDVETGNCIHTLTGHQSLTSGMELKDNILVSGNAD
STVKIWDIKTGQCLQTLQGPNKHQSAVTCLQFNKNFVITSSDDGTVKLWDLKTGEFIRNL
VTLESGGSGGVVWRIRASNTKLVCAVGSRNGTEETKLLVLDFDVDMK

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3D Structure

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AlphaFold

HIT2.0 ID

T01N30

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Neurobeachin-like protein 1 (NBEAL1)	PF02138 ; PF15787 ; PF16057 ; PF20426 ; PF14844 More >>	28.906 (37/128)	1.60E-05
Neurobeachin-like protein 2 (NBEAL2)	PF02138 ; PF15787 ; PF16057 ; PF20426 ; PF20425 ; PF14844 More >>	23.718 (37/156)	1.90E-05
Neurobeachin (NBEA)	PF02138 ; PF06469 ; PF15787 ; PF13385 ; PF20426 ; PF20425 ; PF14844 More >>	38.333 (23/60)	2.52E-05
Lipopolysaccharide-responsive and beige-like anchor protein (LRBA)	PF02138 ; PF06469 ; PF15787 ; PF13385 ; PF20426 ; PF20425 ; PF14844 More >>	30.108 (28/93)	3.05E-05
WD repeat and FYVE domain-containing protein 3 (WDFY3)	PF02138 ; PF01363 ; PF14844 More >>	23.671 (49/207)	4.68E-05
Activating molecule in BECN1-regulated autophagy protein 1 (AMBRA1)		30.667 (23/75)	2.38E-04
TBC1 domain family member 31 (TBC1D31)	PF00566	22.222 (60/270)	2.49E-04
NACHT and WD repeat domain-containing protein 2 (NWD2)	PF05729	21.579 (41/190)	7.75E-04
Transducin-like enhancer protein 6 (TLE6)		21.561 (58/269)	4.00E-03
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KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Ubiquitin mediated proteolysis	hsa04120	Affiliated Target
Class: Genetic Information Processing => Folding, sorting and degradation	Pathway Hierarchy

Degree	16	Degree centrality	1.72E-03	Betweenness centrality	5.58E-04
Closeness centrality	2.38E-01	Radiality	1.42E+01	Clustering coefficient	1.42E-01
Neighborhood connectivity	4.93E+01	Topological coefficient	8.73E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 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.

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