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Protein

F-box/WD repeat-containing protein 7

Gene

Fbxw7

Organism
Rattus norvegicus (Rat)
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 brings 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

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

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/WD repeat-containing protein 7Curated
Gene namesi
Name:Fbxw7Imported
OrganismiRattus norvegicus (Rat)Imported
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi2321145. 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_00004420301 – 713F-box/WD repeat-containing protein 7Add BLAST713

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei211PhosphothreonineBy similarity1
Modified residuei233PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-211 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation.By similarity
Ubiquitinated: autoubiquitinates following phosphorylation at Thr-211 and subsequent interaction with PIN1. Ubiquitination leads to its degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiD3Z902.
PeptideAtlasiD3Z902.

Expressioni

Gene expression databases

BgeeiENSRNOG00000010889.
ExpressionAtlasiD3Z902. baseline and differential.

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 with PSEN1, cyclin-E (CCNE1 or CCNE2), NOTCH1 intracellular domain/NICD, NOTCH4 intracellular domain/NICD and SKP1. Interacts with MYC (when phosphorylated). Forms a trimeric complex with NOTCH1 and SGK1. Interacts (when phosphorylated at Thr-211) 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 PRR7 (PubMed:27458189). 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).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000050193.

Structurei

3D structure databases

ProteinModelPortaliD3Z902.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini284 – 330F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati384 – 424WD 1Sequence analysisAdd BLAST41
Repeati426 – 462WD 2Sequence analysisAdd BLAST37
Repeati465 – 504WD 3Sequence analysisAdd BLAST40
Repeati506 – 542WD 4Sequence analysisAdd BLAST37
Repeati545 – 584WD 5Sequence analysisAdd BLAST40
Repeati586 – 624WD 6Sequence analysisAdd BLAST39
Repeati628 – 665WD 7Sequence analysisAdd BLAST38

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili94 – 136Sequence analysisAdd BLAST43

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi96 – 127Glu-richPROSITE-ProRule annotationAdd BLAST32

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

Coiled coil, Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0274. Eukaryota.
ENOG410XRWX. LUCA.
GeneTreeiENSGT00760000119106.
InParanoidiD3Z902.
OrthoDBiEOG091G04EW.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
2.130.10.10. 1 hit.
InterProiView protein in InterPro
IPR011042. 6-blade_b-propeller_TolB-like.
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.

D3Z902-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNQELLSVGS KRRRTGGSLR GNASSSQVDE EQMNRVVEED PQQQPRHQEE
60 70 80 90 100
EHTARNGELV GADPRPGAQN DSQQGQVEEN NNRFVSVDED SSGNQEEQEE
110 120 130 140 150
DEEHAGEQEE EEEEEEEEEE EEEMDQESDD FDQSDDSSRE DEHTHNSNVT
160 170 180 190 200
NCTSVVDLPI NQLSSPFYTK TTKMKRKLDH GSEVRSFSLG KKPCKVSDYT
210 220 230 240 250
STTGLVPCSA TPTTFGDLRA ANGQGQQRRR ITSVQPPTGL QEWLKMFQSW
260 270 280 290 300
SGPEKLLALD ELIDSCEPTQ VKHMMQVIEP QFQRDFISLL PKELALYVLS
310 320 330 340 350
FLEPKDLLQA AQTCRYWRIL AEDNLLWREK CKEEGIDEPL HIKRRKIIKP
360 370 380 390 400
GFIHSPWKSA YIRQHRIDTN WRRGELRSPK VLKGHDDHVI TCLQFCGNRI
410 420 430 440 450
VSGSDDNTLK VWSAVTGKCL RTLVGHTGGV WSSQMRDNII ISGSTDRTLK
460 470 480 490 500
VWNAETGECI HTLYGHTSTV RCMHLHEKRV VSGSRDATLR VWDIETGQCL
510 520 530 540 550
HVLMGHVAAV RCVQYDGRRV VSGAYDFMVK VWDPETETCL HTLQGHTNRV
560 570 580 590 600
YSLQFDGIHV VSGSLDTSIR VWDVETGNCI HTLTGHQSLT SGMELKDNIL
610 620 630 640 650
VSGNADSTVK IWDIKTGQCL QTLQGPSKHQ SAVTCLQFNK NFVITSSDDG
660 670 680 690 700
TVKLWDLKTG EFIRNLVTLE SGGSGGVVWR IRASNTKLVC AVGSRNGTEE
710
TKLLVLDFDV DMK
Length:713
Mass (Da):80,367
Last modified:April 3, 2013 - v2
Checksum:i3B208792FE3790B9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR07012054 Genomic DNA. No translation available.
AABR07012055 Genomic DNA. No translation available.
AABR07012056 Genomic DNA. No translation available.

Genome annotation databases

EnsembliENSRNOT00000052051; ENSRNOP00000050193; ENSRNOG00000010889.

Similar proteinsi

Entry informationi

Entry nameiFBXW7_RAT
AccessioniPrimary (citable) accession number: D3Z902
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2017
Last sequence update: April 3, 2013
Last modified: November 22, 2017
This is version 60 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