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Q969U6 (FBXW5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
F-box/WD repeat-containing protein 5
Alternative name(s):
F-box and WD-40 domain-containing protein 5
Gene names
Name:FBXW5
Synonyms:FBW5
ORF Names:PP3971
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length566 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.10

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.8 Ref.10

Subcellular location

Cytoplasm Ref.10.

Developmental stage

Degraded by the APC/C complex during G1 phase and reaccumulates at the G1/S phase transition. Ref.10

Domain

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 Probable.

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.

Post-translational modification

Phosphorylated at Ser-151 by PLK4 during the G1/S transition, leading to inhibit its ability to ubiquitinate SASS6. Ref.10

Ubiquitinated and degraded by the APC/C complex during mitosis and G1 phase. Ref.10

Sequence similarities

Belongs to the FBXW5 family.

Contains 1 F-box domain.

Contains 3 WD repeats.

Sequence caution

The sequence AAG17240.1 differs from that shown. Reason: Frameshift at several positions.

The sequence AAG23772.1 differs from that shown. Reason: Frameshift at several positions.

The sequence AAH00850.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAI12741.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence CAI12744.1 differs from that shown. Reason: Erroneous gene model prediction.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SKP1P632083EBI-741068,EBI-307486

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q969U6-1)

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.
Isoform 2 (identifier: Q969U6-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 566566F-box/WD repeat-containing protein 5
PRO_0000050992

Regions

Domain3 – 4947F-box
Repeat90 – 12940WD 1
Repeat467 – 50640WD 2
Repeat508 – 54841WD 3
Motif303 – 3119D-box

Amino acid modifications

Modified residue1511Phosphoserine; by PLK4 Ref.10

Natural variations

Alternative sequence367 – 37711IKQILPHQMTT → TPLPPCCPPRS in isoform 2.
VSP_009479
Alternative sequence378 – 566189Missing in isoform 2.
VSP_009480
Natural variant3401E → K.
Corresponds to variant rs7850438 [ dbSNP | Ensembl ].
VAR_053393

Experimental info

Mutagenesis1511S → A: Impairs phosphorylation by PLK4 and enhances ubiquitination of SASS6. Ref.10
Sequence conflict4901D → G in BAB15354. Ref.1
Sequence conflict5081R → Q in BAD92963. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 7D389AB6F50193B1

FASTA56663,922
        10         20         30         40         50         60 
MDEGGTPLLP DSLVYQIFLS LGPADVLAAG LVCRQWQAVS RDEFLWREQF YRYYQVARDV 

        70         80         90        100        110        120 
PRHPAAMSWY EEFQRLYDTV PCVEVQTLRE HTDQVLHLSF SHSGYQFASC SKDCTVKIWS 

       130        140        150        160        170        180 
NDLTISLLHS ADMRPYNWSY TQFSQFNKDD SLLLASGVFL GPHNSSSGEI AVISLDSFAL 

       190        200        210        220        230        240 
LSRVRNKPYD VFGCWLTETS LISGNLHRIG DITSCSVLWL NNAFQDVESE NVNVVKRLFK 

       250        260        270        280        290        300 
IQNLNASTVR TVMVADCSRF DSPDLLLEAG DPATSPCRIF DLGSDNEEVV AGPAPAHAKE 

       310        320        330        340        350        360 
GLRHFLDRVL EGRAQPQLSE RMLETKVAEL LAQGHTKPPE RSATGAKSKY LIFTTGCLTY 

       370        380        390        400        410        420 
SPHQIGIKQI LPHQMTTAGP VLGEGRGSDA FFDALDHVID IHGHIIGMGL SPDNRYLYVN 

       430        440        450        460        470        480 
SRAWPNGAVV ADPMQPPPIA EEIDLLVFDL KTMREVRRAL RAHRAYTPND ECFFIFLDVS 

       490        500        510        520        530        540 
RDFVASGAED RHGYIWDRHY NICLARLRHE DVVNSVVFSP QEQELLLTAS DDATIKAWRS 

       550        560 
PRTMRVLQAP RPRPRTFFSW LASQRR 

« Hide

Isoform 2 [UniParc].

Checksum: 88369E8BB6758ACE
Show »

FASTA37742,185

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORM 1).
Tissue: Cervix, Colon, Ovary, Placenta and Skin.
[5]"Homo sapiens protein coding cDNA."
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-566 (ISOFORM 1).
Tissue: Brain.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 186-566 (ISOFORM 2).
Tissue: Testis.
[7]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 219-566 (ISOFORM 1).
[8]"WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase."
Hu J., Zacharek S., He Y.J., Lee H., Shumway S., Duronio R.J., Xiong Y.
Genes Dev. 22:866-871(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TSC1 AND TSC2, IDENTIFICATION IN A DCX PROTEIN LIGASE COMPLEX.
[9]"An F-box protein, FBXW5, negatively regulates TAK1 MAP3K in the IL-1beta signaling pathway."
Minoda Y., Sakurai H., Kobayashi T., Yoshimura A., Takaesu G.
Biochem. Biophys. Res. Commun. 381:412-417(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication."
Puklowski A., Homsi Y., Keller D., May M., Chauhan S., Kossatz U., Grunwald V., Kubicka S., Pich A., Manns M.P., Hoffmann I., Gonczy P., Malek N.P.
Nat. Cell Biol. 13:1004-1009(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SASS6 AND CDC20, IDENTIFICATION IN A SCF PROTEIN LIGASE COMPLEX, DEVELOPMENTAL STAGE, UBIQUITINATION, PHOSPHORYLATION AT SER-151, MUTAGENESIS OF SER-151.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT46483.
RefSeqNP_061871.1. NM_018998.3.
UniGeneHs.522507.

3D structure databases

ProteinModelPortalQ969U6.
SMRQ969U6. Positions 84-227, 438-540.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119967. 22 interactions.
DIPDIP-37971N.
IntActQ969U6. 8 interactions.
MINTMINT-276597.

PTM databases

PhosphoSiteQ969U6.

Polymorphism databases

DMDM44887886.

Proteomic databases

PaxDbQ969U6.
PRIDEQ969U6.

Protocols and materials databases

DNASU54461.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000325285; ENSP00000313034; ENSG00000159069. [Q969U6-1]
GeneID54461.
KEGGhsa:54461.
UCSCuc004cjx.3. human. [Q969U6-1]

Organism-specific databases

CTD54461.
GeneCardsGC09M139834.
HGNCHGNC:13613. FBXW5.
HPAHPA046615.
MIM609072. gene.
neXtProtNX_Q969U6.
PharmGKBPA134928070.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG81436.
HOVERGENHBG051595.
InParanoidQ969U6.
KOK10263.
OMAVLWLNNA.
OrthoDBEOG7RZ5PB.
PhylomeDBQ969U6.
TreeFamTF324320.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
SignaLinkQ969U6.
UniPathwayUPA00143.

Gene expression databases

BgeeQ969U6.
GenevestigatorQ969U6.

Family and domain databases

Gene3D2.130.10.10. 2 hits.
InterProIPR001810. F-box_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00400. WD40. 2 hits.
[Graphical view]
SMARTSM00256. FBOX. 1 hit.
SM00320. WD40. 3 hits.
[Graphical view]
SUPFAMSSF50978. SSF50978. 2 hits.
SSF81383. SSF81383. 2 hits.
PROSITEPS50181. FBOX. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFBXW5. human.
GeneWikiFBXW5.
GenomeRNAi54461.
NextBio56717.
PROQ969U6.
SOURCESearch...

Entry information

Entry nameFBXW5_HUMAN
AccessionPrimary (citable) accession number: Q969U6
Secondary accession number(s): B2RDZ6 expand/collapse secondary AC list , Q59ET5, Q5SPZ8, Q5SPZ9, Q5SQ00, Q5SQ02, Q5SQ03, Q5SQ04, Q8WY79, Q96GJ6, Q9BSU8, Q9H6A8, Q9HBQ6, Q9NSZ3
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM