FBXW7
entrez
55294
canonical
uniprot
Q969H0
canonical
ensembl
ENSG00000109670
resolver
ensp
ENSP00000281708
resolver
ensp
ENSP00000296555
resolver
ensp
ENSP00000377528
resolver
ensp
ENSP00000474725
resolver
ensp
ENSP00000474751
resolver
ensp
ENSP00000495702
resolver
ensp
ENSP00000495753
resolver
ensp
ENSP00000495905
resolver
ensp
ENSP00000515368
resolver
ensp
ENSP00000515369
resolver
ensp
ENSP00000535717
resolver
ensp
ENSP00000607412
resolver
enst
ENST00000604872
resolver
enst
ENST00000642901
resolver
enst
ENST00000643834
resolver
enst
ENST00000647166
resolver
genesymbol
FBXW7
resolver
genesymbol_syn
FBW7
resolver
genesymbol_syn
FBX30
resolver
genesymbol_syn
SEL10
resolver
hgnc
HGNC:16712
resolver
uniprot
A0A2R8YEM7
resolver
uniprot
B7ZLP9
resolver
uniprot
G0Z2K0
resolver
uniprot
Q68DR0
resolver
uniprot
Q96A16
resolver
uniprot
Q96LE0
resolver
uniprot
Q96RI2
resolver
uniprot
Q9NUX6
resolver
uniprot
S4R3U4
resolver
uniprot_entry
A0A2R8YEM7_HUMAN
resolver
uniprot_entry
FBXW7_HUMAN
resolver
uniprot_entry
G0Z2K0_HUMAN
resolver
uniprot_entry
S4R3U4_HUMAN
resolver
uniprot_sec
B7ZLP9
resolver
uniprot_sec
Q68DR0
resolver
uniprot_sec
Q96A16
resolver
uniprot_sec
Q96LE0
resolver
uniprot_sec
Q96RI2
resolver
uniprot_sec
Q9NUX6
resolver
amino_acid_sequence
MNQELLSVGSKRRRTGGSLRGNPSSSQVDEEQMNRVVEEEQQQQLRQQEEEHTARNGEVVGVEPRPGGQNDSQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTKMKRKLDHGSEVRSFSLGKKPCKVSEYTSTTGLVPCSATPTTFGDLRAANGQGQQRRRITSVQPPTGLQEWLKMFQSWSGPEKLLALDELIDSCEPTQVKHMMQVIEPQFQRDFISLLPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLWREKCKEEGIDEPLHIKRRKVIKPGFIHSPWKSAYIRQHRIDTNWRRGELKSPKVLKGHDDHVITCLQFCGNRIVSGSDDNTLKVWSAVTGKCLRTLVGHTGGVWSSQMRDNIIISGSTDRTLKVWNAETGECIHTLYGHTSTVRCMHLHEKRVVSGSRDATLRVWDIETGQCLHVLMGHVAAVRCVQYDGRRVVSGAYDFMVKVWDPETETCLHTLQGHTNRVYSLQFDGIHVVSGSLDTSIRVWDVETGNCIHTLTGHQSLTSGMELKDNILVSGNADSTVKIWDIKTGQCLQTLQGPNKHQSAVTCLQFNKNFVITSSDDGTVKLWDLKTGEFIRNLVTLESGGSGGVVWRIRASNTKLVCAVGSRNGTEETKLLVLDFDVDMK
uniprot
proteins
disease_involvement
DISEASE: Developmental delay, hypotonia, and impaired language (DEDHIL) [MIM:620012]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, borderline to severe intellectual disability, language difficulties, hypotonia, and gastrointestinal problems. Brain imaging shows variable structural abnormalities affecting the cerebellum, corpus collosum, and white matter. {ECO:0000269|PubMed:35395208}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:17434132, PubMed:22748924, PubMed:26976582, PubMed:28727686, PubMed:34741373, PubMed:35395208). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:17434132, PubMed:22748924, PubMed:26774286, PubMed:26976582, PubMed:28727686, PubMed:34741373). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and probably PSEN1 (PubMed:11565034, PubMed:11585921, PubMed:12354302, PubMed:14739463, PubMed:15103331, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:25775507, PubMed:25897075, PubMed:26976582, PubMed:28007894, PubMed:28727686, PubMed:29149593, PubMed:34102342). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). 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 (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (PubMed:26774286). {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:26976582, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:28007894, ECO:0000269|PubMed:28727686, ECO:0000269|PubMed:29149593, ECO:0000269|PubMed:34102342, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:35395208, ECO:0000305|PubMed:12354302}.
uniprot
proteins
mass_dalton
79663
uniprot
proteins
mutagenesis
MUTAGEN 26; /note="S->A: Abolished phosphorylation by ATM."; /evidence="ECO:0000269|PubMed:26774286"; MUTAGEN 72; /note="S->A: Does not affect phosphorylation by ATM."; /evidence="ECO:0000269|PubMed:26774286"; MUTAGEN 159; /note="S->A: Does not affect interaction with PIN1."; /evidence="ECO:0000269|PubMed:22608923"; MUTAGEN 205; /note="T->A: Impaired interaction with PIN1."; /evidence="ECO:0000269|PubMed:22608923"; MUTAGEN 252..257; /note="ALDELI->DDDEDD: Prevents homodimerization."; /evidence="ECO:0000269|PubMed:17434132"; MUTAGEN 349; /note="S->A: Does not affect interaction with PIN1."; /evidence="ECO:0000269|PubMed:22608923"; MUTAGEN 372; /note="S->A: Does not affect interaction with PIN1."; /evidence="ECO:0000269|PubMed:22608923
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:34741373}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-205 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Phosphorylated by ATM at Ser-26 in response to DNA damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4 (PubMed:26774286). {ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:26774286}.; PTM: Ubiquitinated: autoubiquitinates following phosphorylation at Thr-205 and subsequent interaction with PIN1. Ubiquitination leads to its proteasomal degradation (PubMed:22608923). {ECO:0000269|PubMed:22608923}.
uniprot
proteins
pubmed
10531037
uniprot
proteins
pubmed
11565033
uniprot
proteins
pubmed
11565034
uniprot
proteins
pubmed
11585921
uniprot
proteins
pubmed
12354302
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14739463
uniprot
proteins
pubmed
15103331
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15611062
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17224074
uniprot
proteins
pubmed
17434132
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17558397
uniprot
proteins
pubmed
17873522
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
21147854
uniprot
proteins
pubmed
22608923
uniprot
proteins
pubmed
22748924
uniprot
proteins
pubmed
23082202
uniprot
proteins
pubmed
24000165
uniprot
proteins
pubmed
24344117
uniprot
proteins
pubmed
25775507
uniprot
proteins
pubmed
25897075
uniprot
proteins
pubmed
26774286
uniprot
proteins
pubmed
26976582
uniprot
proteins
pubmed
27238018
uniprot
proteins
pubmed
27458189
uniprot
proteins
pubmed
27837025
uniprot
proteins
pubmed
28007894
uniprot
proteins
pubmed
28727686
uniprot
proteins
pubmed
29149593
uniprot
proteins
pubmed
34102342
uniprot
proteins
pubmed
34741373
uniprot
proteins
pubmed
35395208
uniprot
proteins
sequence_length
707
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleoplasm {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:28007894}. Chromosome {ECO:0000269|PubMed:26774286}. Note=Localizes to site of double-strand breaks following phosphorylation by ATM. {ECO:0000269|PubMed:26774286}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:28007894}.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleolus {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:28007894}.
uniprot
proteins