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Protein

F-box/WD repeat-containing protein 7

Gene

Fbxw7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Substrate recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. 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), JUN, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation.By similarity

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509951 – 629F-box/WD repeat-containing protein 7Add BLAST629

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei127PhosphothreonineBy similarity1
Modified residuei149Phosphoserine; by SGK1By similarity1

Post-translational modificationi

Phosphorylation at Thr-127 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation.By similarity
Ubiquitinated: autoubiquitinates following phosphorylation at Thr-127 and subsequent interaction with PIN1. Ubiquitination leads to its degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8VBV4.
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. Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11735228). Interacts with PSEN1, cyclin-E (CCNE1 or CCNE2), NOTCH1 intracellular domain/NICD, NOTCH4 intracellular domain/NICD and SKP1 (PubMed:11425854, PubMed:11461910). Interacts with MYC (when phosphorylated). Interacts with USP28, leading to counteract ubiquitination of MYC. Forms a trimeric complex with NOTCH1 and SGK1. 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. Found in a complex with JUN and PRR7. Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (By similarity).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206088. 22 interactors.
DIPiDIP-61083N.
IntActiQ8VBV4. 3 interactors.
MINTiMINT-4609106.
STRINGi10090.ENSMUSP00000103305.

Structurei

3D structure databases

ProteinModelPortaliQ8VBV4.
SMRiQ8VBV4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini200 – 246F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati300 – 340WD 1Add BLAST41
Repeati342 – 378WD 2Add BLAST37
Repeati381 – 420WD 3Add BLAST40
Repeati422 – 458WD 4Add BLAST37
Repeati461 – 500WD 5Add BLAST40
Repeati502 – 540WD 6Add BLAST39
Repeati544 – 581WD 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.
PhylomeDBiQ8VBV4.

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.

Sequencei

Sequence statusi: Complete.

Q8VBV4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVCVPSSVL VLSCVCWCWG VLLPVPLPNL PFLACLSMST LESVTYLPEK
60 70 80 90 100
GLYCQRLPSS RTHGGTESLK GKNTENMGFY GTLKMIFYKM KRKLDHGSEV
110 120 130 140 150
RSFSLGKKPC KVSDYTSTTG LVPCSATPTT FGDLRAANGQ GQQRRRITSV
160 170 180 190 200
QPPTGLQEWL KMFQSWSGPE KLLALDELID SCEPTQVKHM MQVIEPQFQR
210 220 230 240 250
DFISLLPKEL ALYVLSFLEP KDLLQAAQTC RYWRILAEDN LLWREKCKEE
260 270 280 290 300
GIDEPLHIKR RKIIKPGFIH SPWKSAYIRQ HRIDTNWRRG ELKSPKVLKG
310 320 330 340 350
HDDHVITCLQ FCGNRIVSGS DDNTLKVWSA VTGKCLRTLV GHTGGVWSSQ
360 370 380 390 400
MRDNIIISGS TDRTLKVWNA ETGECIHTLY GHTSTVRCMH LHEKRVVSGS
410 420 430 440 450
RDATLRVWDI ETGQCLHVLM GHVAAVRCVQ YDGRRVVSGA YDFMVKVWDP
460 470 480 490 500
ETETCLHTLQ GHTNRVYSLQ FDGIHVVSGS LDTSIRVWDV ETGNCIHTLT
510 520 530 540 550
GHQSLTSGME LKDNILVSGN ADSTVKIWDI KTGQCLQTLQ GPSKHQSAVT
560 570 580 590 600
CLQFNKNFVI TSSDDGTVKL WDLKTGEFIR NLVTLESGGS GGVVWRIRAS
610 620
NTKLVCAVGS RNGTEETKLL VLDFDVDMK
Length:629
Mass (Da):70,547
Last modified:March 1, 2002 - v1
Checksum:i80483A7C2ED61FE7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55Q → R in AAL50052 (Ref. 2) Curated1
Sequence conflicti540Q → E in AAL50052 (Ref. 2) Curated1
Sequence conflicti619L → F in AAL50052 (Ref. 2) Curated1
Sequence conflicti624F → V in AAL50052 (Ref. 2) Curated1

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.
BC131648 mRNA. Translation: AAI31649.1.
AK032174 mRNA. Translation: BAC27743.1.
CCDSiCCDS17440.1.
RefSeqiNP_536353.2. NM_080428.3.
UniGeneiMm.196475.

Genome annotation databases

EnsembliENSMUST00000029727; ENSMUSP00000029727; ENSMUSG00000028086.
GeneIDi50754.
KEGGimmu:50754.
UCSCiuc008pql.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiFBXW7_MOUSE
AccessioniPrimary (citable) accession number: Q8VBV4
Secondary accession number(s): A2RRI5, Q8CCS5, Q8VHP4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2002
Last modified: November 22, 2017
This is version 141 of the entry and version 1 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