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Protein

F-box/WD repeat-containing protein 5

Gene

FBXW5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Substrate recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. Substrate recognition component of the SCF(FBXW5) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of SASS6 during S phase, leading to prevent centriole reduplication. The SCF(FBXW5) complex also mediates ubiquitination and degradation of actin-regulator EPS8 during G2 phase, leading to the transient degradation of EPS8 and subsequent cell shape changes required to allow mitotic progression. Substrate-specific adapter of the DCX(FBXW5) E3 ubiquitin-protein ligase complex which mediates the polyubiquitination and subsequent degradation of TSC2. May also act as a negative regulator of MAP3K7/TAK1 signaling in the interleukin-1B (IL1B) signaling pathway.3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Reactome

GO - Biological processi

  • post-translational protein modification Source: Reactome
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein polyubiquitination Source: Reactome
  • protein ubiquitination Source: UniProtKB
  • regulation of centrosome duplication Source: UniProtKB
  • regulation of mitotic nuclear division Source: Ensembl
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ969U6
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/WD repeat-containing protein 5
Alternative name(s):
F-box and WD-40 domain-containing protein 5
Gene namesi
Name:FBXW5
Synonyms:FBW5
ORF Names:PP3971
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000159069.13
HGNCiHGNC:13613 FBXW5
MIMi609072 gene
neXtProtiNX_Q969U6

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

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi151S → A: Impairs phosphorylation by PLK4 and enhances ubiquitination of SASS6. 1 Publication1

Organism-specific databases

DisGeNETi54461
OpenTargetsiENSG00000159069
PharmGKBiPA134928070

Polymorphism and mutation databases

BioMutaiFBXW5
DMDMi44887886

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509921 – 566F-box/WD repeat-containing protein 5Add BLAST566

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei151Phosphoserine; by PLK41 Publication1
Modified residuei284PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-151 by PLK4 during the G1/S transition, leading to inhibit its ability to ubiquitinate SASS6.1 Publication
Ubiquitinated and degraded by the APC/C complex during mitosis and G1 phase.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ969U6
MaxQBiQ969U6
PaxDbiQ969U6
PeptideAtlasiQ969U6
PRIDEiQ969U6
ProteomicsDBi75846
75847 [Q969U6-2]

PTM databases

iPTMnetiQ969U6
PhosphoSitePlusiQ969U6

Expressioni

Developmental stagei

Degraded by the APC/C complex during G1 phase and reaccumulates at the G1/S phase transition.1 Publication

Gene expression databases

BgeeiENSG00000159069
ExpressionAtlasiQ969U6 baseline and differential
GenevisibleiQ969U6 HS

Organism-specific databases

HPAiHPA046615

Interactioni

Subunit structurei

Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXW5) composed of CUL1, SKP1, RBX1 and FBXW5. Component of the DCX(FBXW5) E3 ubiquitin ligase complex, at least composed of (CUL4A or CUL4B), DDB1, FBXW5 and RBX1. Interacts with CDC20, EPS8, TSC1, TSC2 and SASS6. Interacts with TNFAIP8L1; TNFAIP8L1 competes with TSC2 to bind FBXW5 increasing TSC2 stability by preventing its ubiquitination.By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi119967, 46 interactors
DIPiDIP-37971N
IntActiQ969U6, 38 interactors
MINTiQ969U6
STRINGi9606.ENSP00000313034

Structurei

3D structure databases

ProteinModelPortaliQ969U6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 49F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati83 – 125WD 1Add BLAST43
Repeati126 – 178WD 2Add BLAST53
Repeati179 – 238WD 3Add BLAST60
Repeati239 – 281WD 4Add BLAST43
Repeati394 – 447WD 5Add BLAST54
Repeati458 – 501WD 6Add BLAST44
Repeati502 – 539WD 7Add BLAST38

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi303 – 311D-box9

Domaini

The F-box domain mediates interaction with components of SCF (SKP1-CUL1-F-box protein) complexes, while WD repeats mediate interaction with components of DCX (DDB1-CUL4-X-box) complexes.Curated
The D-box (destruction box) mediate the interaction with APC proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.By similarity

Sequence similaritiesi

Belongs to the FBXW5 family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiENOG410IEAX Eukaryota
ENOG410XTK0 LUCA
GeneTreeiENSGT00730000111276
HOVERGENiHBG051595
InParanoidiQ969U6
KOiK10263
OMAiPHQIGFK
OrthoDBiEOG091G04E0
PhylomeDBiQ969U6
TreeFamiTF324320

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
PF00400 WD40, 1 hit
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00320 WD40, 3 hits
SUPFAMiSSF50978 SSF50978, 2 hits
SSF81383 SSF81383, 2 hits
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
PS50082 WD_REPEATS_2, 2 hits
PS50294 WD_REPEATS_REGION, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969U6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDEGGTPLLP DSLVYQIFLS LGPADVLAAG LVCRQWQAVS RDEFLWREQF
60 70 80 90 100
YRYYQVARDV PRHPAAMSWY EEFQRLYDTV PCVEVQTLRE HTDQVLHLSF
110 120 130 140 150
SHSGYQFASC SKDCTVKIWS NDLTISLLHS ADMRPYNWSY TQFSQFNKDD
160 170 180 190 200
SLLLASGVFL GPHNSSSGEI AVISLDSFAL LSRVRNKPYD VFGCWLTETS
210 220 230 240 250
LISGNLHRIG DITSCSVLWL NNAFQDVESE NVNVVKRLFK IQNLNASTVR
260 270 280 290 300
TVMVADCSRF DSPDLLLEAG DPATSPCRIF DLGSDNEEVV AGPAPAHAKE
310 320 330 340 350
GLRHFLDRVL EGRAQPQLSE RMLETKVAEL LAQGHTKPPE RSATGAKSKY
360 370 380 390 400
LIFTTGCLTY SPHQIGIKQI LPHQMTTAGP VLGEGRGSDA FFDALDHVID
410 420 430 440 450
IHGHIIGMGL SPDNRYLYVN SRAWPNGAVV ADPMQPPPIA EEIDLLVFDL
460 470 480 490 500
KTMREVRRAL RAHRAYTPND ECFFIFLDVS RDFVASGAED RHGYIWDRHY
510 520 530 540 550
NICLARLRHE DVVNSVVFSP QEQELLLTAS DDATIKAWRS PRTMRVLQAP
560
RPRPRTFFSW LASQRR
Length:566
Mass (Da):63,922
Last modified:December 1, 2001 - v1
Checksum:i7D389AB6F50193B1
GO
Isoform 2 (identifier: Q969U6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     367-377: IKQILPHQMTT → TPLPPCCPPRS
     378-566: Missing.

Show »
Length:377
Mass (Da):42,185
Checksum:i88369E8BB6758ACE
GO

Sequence cautioni

The sequence AAG17240 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence AAG23772 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence AAH00850 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAI12741 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI12744 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti490D → G in BAB15354 (PubMed:14702039).Curated1
Sequence conflicti508R → Q in BAD92963 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053393340E → K. Corresponds to variant dbSNP:rs7850438Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009479367 – 377IKQILPHQMTT → TPLPPCCPPRS in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_009480378 – 566Missing in isoform 2. 1 PublicationAdd BLAST189

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK026081 mRNA Translation: BAB15354.1
AK315738 mRNA Translation: BAG38093.1
CH471090 Genomic DNA Translation: EAW88307.1
BC000850 mRNA Translation: AAH00850.1 Different initiation.
BC004541 mRNA Translation: AAH04541.2
BC009429 mRNA Translation: AAH09429.1
BC014297 mRNA Translation: AAH14297.1
AL807752 Genomic DNA Translation: CAI12741.1 Sequence problems.
AL807752 Genomic DNA Translation: CAI12743.1
AL807752 Genomic DNA Translation: CAI12744.1 Sequence problems.
AL807752 Genomic DNA Translation: CAI12746.1
BC014130 mRNA Translation: AAH14130.1
AB209726 mRNA Translation: BAD92963.1
AL137631 mRNA Translation: CAB70851.1
AF217998 mRNA Translation: AAG17240.1 Frameshift.
AF258569 mRNA Translation: AAG23772.1 Frameshift.
CCDSiCCDS7014.1 [Q969U6-1]
PIRiT46483
RefSeqiNP_061871.1, NM_018998.3 [Q969U6-1]
UniGeneiHs.522507

Genome annotation databases

EnsembliENST00000325285; ENSP00000313034; ENSG00000159069 [Q969U6-1]
GeneIDi54461
KEGGihsa:54461
UCSCiuc004cjx.4 human [Q969U6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFBXW5_HUMAN
AccessioniPrimary (citable) accession number: Q969U6
Secondary accession number(s): B2RDZ6
, Q59ET5, Q5SPZ8, Q5SPZ9, Q5SQ00, Q5SQ02, Q5SQ03, Q5SQ04, Q8WY79, Q96GJ6, Q9BSU8, Q9H6A8, Q9HBQ6, Q9NSZ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: December 1, 2001
Last modified: June 20, 2018
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

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