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Protein

F-box/WD repeat-containing protein 7

Gene

FBXW7

Organism
Bos taurus (Bovine)
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. 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), 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.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-BTA-8951664 Neddylation
R-BTA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/WD repeat-containing protein 7
Alternative name(s):
F-box and WD-40 domain-containing protein 7
Gene namesi
Name:FBXW7By similarity
Synonyms:FBW7By similarity
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 17

Organism-specific databases

VGNCiVGNC:28926 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_00004327051 – 627F-box/WD repeat-containing protein 7Add BLAST627

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei125PhosphothreonineBy similarity1
Modified residuei147PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-125 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation.By similarity
Ubiquitinated: autoubiquitinates following phosphorylation at Thr-125 and subsequent interaction with PIN1 (PubMed:25624101). Ubiquitination leads to its degradation (PubMed:25624101).By similarity1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiF1MNN4

Expressioni

Gene expression databases

BgeeiENSBTAG00000007953

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. Interacts (via F-box domain) with SKP1. Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1. Interacts with cyclin-E (CCNE1 or CCNE2). Interacts with PSEN1. Forms a trimeric complex with NOTCH1 and SGK1. Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD. Interacts with NOTCH2 intracellular domain (N2ICD). Interacts with MYC (when phosphorylated). Interacts with USP28, leading to counteract ubiquitination of MYC. Interacts (when phosphorylated at Thr-125) with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation. Interacts with UBE2QL1. Interacts with FAM83D; promotes FBXW7 degradation. Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN. 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. Interacts with NFE2L1.By similarity
(Microbial infection) In case of infection, interacts with T.annulata PIN1 (TaPIN1); leading to FBXW7 autoubiquitination and subsequent degradation: FBXW7 degradation promotes stabilization of JUN, which promotes cell transformation (PubMed:25624101).1 Publication

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61528N
IntActiF1MNN4, 3 interactors
STRINGi9913.ENSBTAP00000010457

Structurei

3D structure databases

ProteinModelPortaliF1MNN4
SMRiF1MNN4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini198 – 244F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati298 – 338WD 1Sequence analysisAdd BLAST41
Repeati340 – 376WD 2Sequence analysisAdd BLAST37
Repeati379 – 418WD 3Sequence analysisAdd BLAST40
Repeati420 – 456WD 4Sequence analysisAdd BLAST37
Repeati459 – 498WD 5Sequence analysisAdd BLAST40
Repeati500 – 538WD 6Sequence analysisAdd BLAST39
Repeati542 – 579WD 7Sequence analysisAdd 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
HOVERGENiHBG051596
InParanoidiF1MNN4
KOiK10260
OMAiVWRVAFE
OrthoDBiEOG091G04EW
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

Sequencei

Sequence statusi: Complete.

F1MNN4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCVPRSGLIL SCICLYCGVL LPVLLPNLPF LTCLSMSTLE SVTYLPEKGL
60 70 80 90 100
YCQRLPSSRT HGGTESLKGK NPENMGFYGT LKMIFYKMKR KLDHGSEVRS
110 120 130 140 150
FSLGKKPCKV SEYTSTTGLV PCSATPTTFG DLRAANGQGQ QRRRITSVQP
160 170 180 190 200
PTGLQEWLKM FQSWSGPEKL LALDELIDSC EPTQVKHMMQ VIEPQFQRDF
210 220 230 240 250
ISLLPKELAL YVLSFLEPKD LLQAAQTCRY WRILAEDNLL WREKCKEEGI
260 270 280 290 300
DEPLHIKRRK VIKPGFIHSP WKSAYIRQHR IDTNWRRGEL KSPKVLKGHD
310 320 330 340 350
DHVITCLQFC GNRIVSGSDD NTLKVWSAVT GKCLRTLVGH TGGVWSSQMR
360 370 380 390 400
DNIIISGSTD RTLKVWNAET GECIHTLYGH TSTVRCMHLH EKRVVSGSRD
410 420 430 440 450
ATLRVWDIET GQCLHVLMGH VAAVRCVQYD GRRVVSGAYD FMVKVWDPET
460 470 480 490 500
ETCLHTLQGH TNRVYSLQFD GIHVVSGSLD TSIRVWDVET GNCIHTLTGH
510 520 530 540 550
QSLTSGMELK DNILVSGNAD STVKIWDIKT GQCLQTLQGP NKHQSAVTCL
560 570 580 590 600
QFNKNFVITS SDDGTVKLWD LKTGEFIRNL VTLESGGSGG VVWRIRASNT
610 620
KLVCAVGSRN GTEETKLLVL DFDVDMK
Length:627
Mass (Da):70,320
Last modified:November 16, 2011 - v2
Checksum:i948107C1DA95FDFA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57S → N in AAI19947 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DAAA02044177 Genomic DNA No translation available.
BC119946 mRNA Translation: AAI19947.1
RefSeqiNP_001069717.1, NM_001076249.1
UniGeneiBt.24006

Genome annotation databases

EnsembliENSBTAT00000010457; ENSBTAP00000010457; ENSBTAG00000007953
GeneIDi540932
KEGGibta:540932

Similar proteinsi

Entry informationi

Entry nameiFBXW7_BOVIN
AccessioniPrimary (citable) accession number: F1MNN4
Secondary accession number(s): Q0VCX6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 2015
Last sequence update: November 16, 2011
Last modified: June 20, 2018
This is version 62 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

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