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Protein

F-box/WD repeat-containing protein 7

Gene

Fbxw7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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:21953459). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination (By similarity). Identified substrates include cyclin-E (CCNE1 or CCNE2), JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1 and probably PSEN1 (By similarity). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (By similarity). SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1 (PubMed:21953459). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

BRENDAi6.3.2.19 3474
ReactomeiR-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/WD repeat-containing protein 7Curated
Alternative name(s):
F-box and WD-40 domain-containing protein 7Imported
F-box protein FBW7Curated
F-box protein Fbxw61 Publication
F-box-WD40 repeat protein 61 Publication
SEL-101 Publication
Gene namesi
Name:Fbxw7Imported
Synonyms:Fbw7Curated, Fbwd6Imported, Fbxw6Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1354695 Fbxw7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Whole body FBW7 knockout is embryonic lethal. Conditional knockout mice in which FBW7 expression is specifically abolished in osteoclats display severe bone resorption, bone fragility and low bone mass.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509951 – 710F-box/WD repeat-containing protein 7Add BLAST710

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei208PhosphothreonineBy similarity1
Modified residuei230Phosphoserine; by SGK1By similarity1

Post-translational modificationi

Phosphorylation at Thr-208 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation.By similarity
Ubiquitinated: autoubiquitinates following phosphorylation at Thr-208 and subsequent interaction with PIN1. Ubiquitination leads to its degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8VBV4
PeptideAtlasiQ8VBV4
PRIDEiQ8VBV4

PTM databases

iPTMnetiQ8VBV4
PhosphoSitePlusiQ8VBV4

Expressioni

Tissue specificityi

Widely expressed with highest levels in brain, heart and testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000028086
ExpressionAtlasiQ8VBV4 baseline and differential
GenevisibleiQ8VBV4 MM

Interactioni

Subunit structurei

Homodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (By similarity). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11735228). Interacts (via F-box domain) with SKP1 (PubMed:11735228). Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1 (By similarity). Interacts with cyclin-E (CCNE1 or CCNE2) (By similarity). Interacts with PSEN1 (By similarity). Forms a trimeric complex with NOTCH1 and SGK1 (By similarity). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD (PubMed:11425854, PubMed:11461910). Interacts with NOTCH2 intracellular domain (N2ICD) (By similarity). Interacts with MYC (when phosphorylated) (By similarity). Interacts with USP28, leading to counteract ubiquitination of MYC (By similarity). Interacts (when phosphorylated at Thr-127) with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity). Interacts with UBE2QL1 (By similarity). Interacts with FAM83D; promotes FBXW7 degradation (By similarity). Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (By similarity). Interacts with JUN (By similarity). Found in a complex with JUN and PRR7 (By similarity). Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (By similarity). Interacts with NFE2L1 (PubMed:21953459).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206088, 22 interactors
DIPiDIP-61083N
IntActiQ8VBV4, 3 interactors
MINTiQ8VBV4
STRINGi10090.ENSMUSP00000103305

Structurei

3D structure databases

ProteinModelPortaliQ8VBV4
SMRiQ8VBV4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini281 – 327F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati381 – 421WD 1Add BLAST41
Repeati423 – 459WD 2Add BLAST37
Repeati462 – 501WD 3Add BLAST40
Repeati503 – 539WD 4Add BLAST37
Repeati542 – 581WD 5Add BLAST40
Repeati583 – 621WD 6Add BLAST39
Repeati625 – 662WD 7Add BLAST38

Domaini

The WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.By similarity
The F-box domain mediates interaction with SKP1.By similarity

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0274 Eukaryota
ENOG410XRWX LUCA
GeneTreeiENSGT00760000119106
HOGENOMiHOG000236264
HOVERGENiHBG051596
InParanoidiQ8VBV4
KOiK10260
OMAiVWRVAFE
OrthoDBiEOG091G04EW
PhylomeDBiQ8VBV4
TreeFamiTF101074

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR020472 G-protein_beta_WD-40_rep
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
PF00400 WD40, 7 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00320 WD40, 8 hits
SUPFAMiSSF50978 SSF50978, 1 hit
SSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
PS00678 WD_REPEATS_1, 5 hits
PS50082 WD_REPEATS_2, 7 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8VBV4-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNQELLSVGS KRRRTGGSLR GNASSSQVDE GQMNRVVEED PQQQARHQEE
60 70 80 90 100
EHTARNGELV GANPRPGDQN DTQQGQVEEN NNRFISVDED SSGNQEEQEE
110 120 130 140 150
DEEHAGEQEE EEEEEEEEEE MDQESDDFDP SDDSSREDEH THNSNVTNCS
160 170 180 190 200
SVSDLPAHQL SSPFYTKTTK MKRKLDHGSE VRSFSLGKKP CKVSDYTSTT
210 220 230 240 250
GLVPCSATPT TFGDLRAANG QGQQRRRITS VQPPTGLQEW LKMFQSWSGP
260 270 280 290 300
EKLLALDELI DSCEPTQVKH MMQVIEPQFQ RDFISLLPKE LALYVLSFLE
310 320 330 340 350
PKDLLQAAQT CRYWRILAED NLLWREKCKE EGIDEPLHIK RRKIIKPGFI
360 370 380 390 400
HSPWKSAYIR QHRIDTNWRR GELKSPKVLK GHDDHVITCL QFCGNRIVSG
410 420 430 440 450
SDDNTLKVWS AVTGKCLRTL VGHTGGVWSS QMRDNIIISG STDRTLKVWN
460 470 480 490 500
AETGECIHTL YGHTSTVRCM HLHEKRVVSG SRDATLRVWD IETGQCLHVL
510 520 530 540 550
MGHVAAVRCV QYDGRRVVSG AYDFMVKVWD PETETCLHTL QGHTNRVYSL
560 570 580 590 600
QFDGIHVVSG SLDTSIRVWD VETGNCIHTL TGHQSLTSGM ELKDNILVSG
610 620 630 640 650
NADSTVKIWD IKTGQCLQTL QGPSKHQSAV TCLQFNKNFV ITSSDDGTVK
660 670 680 690 700
LWDLKTGEFI RNLVTLESGG SGGVVWRIRA SNTKLVCAVG SRNGTEETKL
710
LVLDFDVDMK
Length:710
Mass (Da):79,848
Last modified:April 25, 2018 - v2
Checksum:i9D56F7E81E6E390B
GO
Isoform 2 (identifier: Q8VBV4-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-169: MNQELLSVGS...LSSPFYTKTT → MRVCVPSSVL...FYGTLKMIFY

Show »
Length:629
Mass (Da):70,547
Checksum:i80483A7C2ED61FE7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73Q → R in AAL50052 (Ref. 2) Curated1
Sequence conflicti621Q → E in AAL50052 (Ref. 2) Curated1
Sequence conflicti700L → F in AAL50052 (Ref. 2) Curated1
Sequence conflicti705F → V in AAL50052 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0595301 – 169MNQEL…YTKTT → MRVCVPSSVLVLSCVCWCWG VLLPVPLPNLPFLACLSMST LESVTYLPEKGLYCQRLPSS RTHGGTESLKGKNTENMGFY GTLKMIFY in isoform 2. Add BLAST169

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF391202
, AF391193, AF391194, AF391195, AF391196, AF391197, AF391198, AF391199, AF391200, AF391201 Genomic DNA Translation: AAL40930.1
AF391192 mRNA Translation: AAL40928.1
AF427101 mRNA Translation: AAL50052.1
AC124496 Genomic DNA No translation available.
AC158583 Genomic DNA No translation available.
BC131648 mRNA Translation: AAI31649.1
AK032174 mRNA Translation: BAC27743.1
CCDSiCCDS17440.1 [Q8VBV4-1]
CCDS50940.1 [Q8VBV4-2]
RefSeqiNP_001171244.1, NM_001177773.1 [Q8VBV4-2]
NP_001171245.1, NM_001177774.1 [Q8VBV4-2]
NP_536353.2, NM_080428.3 [Q8VBV4-1]
XP_006501719.1, XM_006501656.3 [Q8VBV4-2]
XP_006501720.1, XM_006501657.3 [Q8VBV4-2]
UniGeneiMm.196475

Genome annotation databases

EnsembliENSMUST00000029727; ENSMUSP00000029727; ENSMUSG00000028086 [Q8VBV4-1]
ENSMUST00000107678; ENSMUSP00000103305; ENSMUSG00000028086 [Q8VBV4-2]
ENSMUST00000107679; ENSMUSP00000103306; ENSMUSG00000028086 [Q8VBV4-2]
GeneIDi50754
KEGGimmu:50754
UCSCiuc008pqk.2 mouse
uc008pql.2 mouse [Q8VBV4-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFBXW7_MOUSE
AccessioniPrimary (citable) accession number: Q8VBV4
Secondary accession number(s): A2RRI5
, D3YUA5, Q8CCS5, Q8VHP4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: April 25, 2018
Last modified: June 20, 2018
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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