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Protein

F-box/WD repeat-containing protein 7

Gene

FBXW7

Organism
Bos taurus (Bovine)
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

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 Componentsi: Chromosome 17, Unassembled WGS sequence

Subcellular locationi

  • Nucleus By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 627627F-box/WD repeat-containing protein 7PRO_0000432705Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei125 – 1251PhosphothreonineBy similarity
Modified residuei147 – 1471PhosphoserineBy similarity

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. Ubiquitination leads to its degradation.By similarity1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiF1MNN4.

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). 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-125) with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity). 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). Interacts with UBE2QL1 (By similarity). Interacts with FAM83D; promotes FBXW7 degradation (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61528N.
STRINGi9913.ENSBTAP00000010457.

Structurei

3D structure databases

ProteinModelPortaliF1MNN4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini198 – 24447F-boxPROSITE-ProRule annotationAdd
BLAST
Repeati298 – 33841WD 1Sequence analysisAdd
BLAST
Repeati340 – 37637WD 2Sequence analysisAdd
BLAST
Repeati379 – 41840WD 3Sequence analysisAdd
BLAST
Repeati420 – 45637WD 4Sequence analysisAdd
BLAST
Repeati459 – 49840WD 5Sequence analysisAdd
BLAST
Repeati500 – 53839WD 6Sequence analysisAdd
BLAST
Repeati542 – 57938WD 7Sequence analysisAdd
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

eggNOGiKOG0274. Eukaryota.
ENOG410XRWX. LUCA.
GeneTreeiENSGT00760000119106.
HOVERGENiHBG051596.
InParanoidiF1MNN4.
KOiK10260.
OMAiMELRNNI.
OrthoDBiEOG7VX8VF.
TreeFamiTF101074.

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti57 – 571S → N in AAI19947 (Ref. 2) Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliF1MNN4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61528N.
STRINGi9913.ENSBTAP00000010457.

Proteomic databases

PaxDbiF1MNN4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000010457; ENSBTAP00000010457; ENSBTAG00000007953.
GeneIDi540932.
KEGGibta:540932.

Organism-specific databases

CTDi55294.

Phylogenomic databases

eggNOGiKOG0274. Eukaryota.
ENOG410XRWX. LUCA.
GeneTreeiENSGT00760000119106.
HOVERGENiHBG051596.
InParanoidiF1MNN4.
KOiK10260.
OMAiMELRNNI.
OrthoDBiEOG7VX8VF.
TreeFamiTF101074.

Miscellaneous databases

NextBioi20878919.

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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Hereford.
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Brain cortex.
  3. Cited for: INTERACTION WITH T.ANNULATA PIN1, UBIQUITINATION.

Entry informationi

Entry nameiFBXW7_BOVIN
AccessioniPrimary (citable) accession number: F1MNN4
Secondary accession number(s): Q0VCX6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 2015
Last sequence update: November 16, 2011
Last modified: May 11, 2016
This is version 45 of the entry and version 2 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. SIMILARITY comments
    Index of protein domains and families

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 one 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.