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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

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi6.3.2.19. 3474.
ReactomeiREACT_275351. Association of TriC/CCT with target proteins during biosynthesis.
REACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_343568. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1354695. Fbxw7.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • Golgi apparatus Source: MGI
  • integral component of membrane Source: ParkinsonsUK-UCL
  • mitochondrion Source: ParkinsonsUK-UCL
  • nucleolus Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: BHF-UCL
  • Parkin-FBXW7-Cul1 ubiquitin ligase complex Source: ParkinsonsUK-UCL
  • perinuclear region of cytoplasm Source: BHF-UCL
  • protein complex Source: MGI
  • SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 629629F-box/WD repeat-containing protein 7PRO_0000050995Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei127 – 1271PhosphothreonineBy similarity
Modified residuei149 – 1491Phosphoserine; by SGK1By similarity

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

PRIDEiQ8VBV4.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ8VBV4.
ExpressionAtlasiQ8VBV4. baseline and differential.
GenevestigatoriQ8VBV4.

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 with JUN. Interacts (when phosphorylated at Thr-127) with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity).By similarity3 Publications

Protein-protein interaction databases

BioGridi206088. 16 interactions.
DIPiDIP-61083N.
IntActiQ8VBV4. 1 interaction.
MINTiMINT-4609106.

Structurei

3D structure databases

ProteinModelPortaliQ8VBV4.
SMRiQ8VBV4. Positions 185-628.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini200 – 24647F-boxPROSITE-ProRule annotationAdd
BLAST
Repeati300 – 34041WD 1Add
BLAST
Repeati342 – 37837WD 2Add
BLAST
Repeati381 – 42040WD 3Add
BLAST
Repeati422 – 45837WD 4Add
BLAST
Repeati461 – 50040WD 5Add
BLAST
Repeati502 – 54039WD 6Add
BLAST
Repeati544 – 58138WD 7Add
BLAST

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

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiCOG2319.
GeneTreeiENSGT00760000119106.
HOGENOMiHOG000236264.
HOVERGENiHBG051596.
InParanoidiQ8VBV4.
KOiK10260.
OMAiDHVITCM.
OrthoDBiEOG7VX8VF.
PhylomeDBiQ8VBV4.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
IPR020472. G-protein_beta_WD-40_rep.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF00400. WD40. 7 hits.
[Graphical view]
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00256. FBOX. 1 hit.
SM00320. WD40. 8 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
PS00678. WD_REPEATS_1. 5 hits.
PS50082. WD_REPEATS_2. 7 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti55 – 551Q → R in AAL50052 (Ref. 2) Curated
Sequence conflicti540 – 5401Q → E in AAL50052 (Ref. 2) Curated
Sequence conflicti619 – 6191L → F in AAL50052 (Ref. 2) Curated
Sequence conflicti624 – 6241F → V in AAL50052 (Ref. 2) Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8VBV4.
SMRiQ8VBV4. Positions 185-628.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206088. 16 interactions.
DIPiDIP-61083N.
IntActiQ8VBV4. 1 interaction.
MINTiMINT-4609106.

Proteomic databases

PRIDEiQ8VBV4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi55294.
MGIiMGI:1354695. Fbxw7.

Phylogenomic databases

eggNOGiCOG2319.
GeneTreeiENSGT00760000119106.
HOGENOMiHOG000236264.
HOVERGENiHBG051596.
InParanoidiQ8VBV4.
KOiK10260.
OMAiDHVITCM.
OrthoDBiEOG7VX8VF.
PhylomeDBiQ8VBV4.

Enzyme and pathway databases

BRENDAi6.3.2.19. 3474.
ReactomeiREACT_275351. Association of TriC/CCT with target proteins during biosynthesis.
REACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_343568. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

NextBioi307631.
PROiQ8VBV4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VBV4.
ExpressionAtlasiQ8VBV4. baseline and differential.
GenevestigatoriQ8VBV4.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
IPR020472. G-protein_beta_WD-40_rep.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF00400. WD40. 7 hits.
[Graphical view]
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00256. FBOX. 1 hit.
SM00320. WD40. 8 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
PS00678. WD_REPEATS_1. 5 hits.
PS50082. WD_REPEATS_2. 7 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of a mouse gene (Fbxw6) that encodes a homologue of Caenorhabditis elegans SEL-10."
    Maruyama S., Hatakeyama S., Nakayama K., Ishida N., Kawakami K., Nakayama K.
    Genomics 78:214-222(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, INTERACTION WITH SKP1 AND CUL1.
    Strain: 129/Sv.
  2. Ilyin G.P.
    Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 305-629.
    Strain: C57BL/6J.
    Tissue: Olfactory bulb.
  5. "Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor."
    Gupta-Rossi N., Le Bail O., Gonen H., Brou C., Logeat F., Six E., Ciechanover A., Israel A.
    J. Biol. Chem. 276:34371-34378(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NOTCH1 NICD.
  6. "The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog."
    Oeberg C., Li J., Pauley A., Wolf E., Gurney M., Lendahl U.
    J. Biol. Chem. 276:35847-35853(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NOTCH1 NICD.

Entry informationi

Entry nameiFBXW7_MOUSE
AccessioniPrimary (citable) accession number: Q8VBV4
Secondary accession number(s): A2RRI5, Q8CCS5, Q8VHP4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2002
Last modified: May 27, 2015
This is version 120 of the entry and version 1 of the sequence. [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
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.