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Protein

F-box/WD repeat-containing protein 5

Gene

Fbxw5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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-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. 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 (By similarity). 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.By similarity1 Publication

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

GO - Biological processi

  • centrosome duplication Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1354731. Fbxw5.

Subcellular locationi

  • Cytoplasm By similarity

GO - Cellular componenti

  • Cul4-RING E3 ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 573573F-box/WD repeat-containing protein 5PRO_0000050993Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei151 – 1511Phosphoserine; by PLK4By similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9QXW2.
PaxDbiQ9QXW2.
PRIDEiQ9QXW2.

PTM databases

iPTMnetiQ9QXW2.
PhosphoSiteiQ9QXW2.

Expressioni

Tissue specificityi

Widely expressed in adult and embryonal tissues.1 Publication

Gene expression databases

BgeeiQ9QXW2.
CleanExiMM_FBXW5.
ExpressionAtlasiQ9QXW2. baseline and differential.
GenevisibleiQ9QXW2. MM.

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, TSC1, TSC2 and SASS6 (By similarity). Interacts with EPS8. Interacts with TNFAIP8L1; TNFAIP8L1 competes with TSC2 to bind FBXW5 increasing TSC2 stability by preventing its ubiquitination.By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi205976. 4 interactions.
DIPiDIP-60700N.
STRINGi10090.ENSMUSP00000015239.

Structurei

3D structure databases

ProteinModelPortaliQ9QXW2.
SMRiQ9QXW2. Positions 75-180, 476-542.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 4947F-boxPROSITE-ProRule annotationAdd
BLAST
Repeati90 – 12940WD 1Add
BLAST
Repeati470 – 50940WD 2Add
BLAST
Repeati511 – 55141WD 3Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi308 – 3169D-box

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.By similarity
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
Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 3 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiENOG410IEAX. Eukaryota.
ENOG410XTK0. LUCA.
GeneTreeiENSGT00730000111276.
HOGENOMiHOG000231549.
HOVERGENiHBG051595.
InParanoidiQ9QXW2.
KOiK10263.
OMAiYDIFGTW.
OrthoDBiEOG7RZ5PB.
TreeFamiTF324320.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF00400. WD40. 2 hits.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00320. WD40. 3 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
SSF81383. SSF81383. 2 hits.
PROSITEiPS50181. FBOX. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9QXW2-1) [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
MDEGGLPLLP DSLVYQIFLS LGPADVLAAG LVCRQWQAVS RDEFLWKEQF
60 70 80 90 100
YRYYQVARDV PRHPAATSWY EEFRRLYDMV PCVEVQTLKE HTDQVLHLSF
110 120 130 140 150
SHSGYQFASC SKDCTVKIWN NDLTISLLHS ADMRPYNWSY TQFSQFNQDD
160 170 180 190 200
SLLLASGVFL GPHNSSSGEI AVISLDSFAL LSRVRNKPYD VFGCWLTETS
210 220 230 240 250
LISGNLHRIG DITSCSVLWL NNAFQDVESE NVNVVKRLFK IQNLNASTIR
260 270 280 290 300
TVMVADCSRF DSPDLLLDAS DQAGLPCRVF DLGGDTEEEA TDPGLHTSGS
310 320 330 340 350
DHVKKGLRRV FDSVLDGHGQ LSDCALETKV AELLAQGHTK PPECNDADTR
360 370 380 390 400
NKYLIFTTGC LTYSPHQIGI KQILPHQMTT AGPVLGEGRG SDAFFDALDH
410 420 430 440 450
VIDVHGHIIG MGLSPDNRYL YVNSRAWPPG SVVADPMQPP PIAEEIDLLV
460 470 480 490 500
FDLKTMREVK RALRAHRAYT PNDECFFIFL DVSRDFVASG AEDRHGYIWD
510 520 530 540 550
RHYNICLAKL RHEDVVNSVA FSPQEQELLL TASDDATIKA WRSPRIVRVL
560 570
QAPRPRPRPR PRPFFSWFAS HRR
Length:573
Mass (Da):64,646
Last modified:May 1, 2000 - v1
Checksum:iB71B3B207D3091B1
GO
Isoform 2 (identifier: Q9QXW2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLSAVEFSGGQLVGLARTAMSGTPDYQSLPGVGDEEAWVQSRHWWVSGPSGQNVTM
     530-573: LTASDDATIK...FFSWFASHRR → PDSQRRCHYQ...PPLLLLVCQP

Note: No experimental confirmation available.
Show »
Length:626
Mass (Da):69,687
Checksum:iA1B30E41EB835282
GO

Sequence cautioni

The sequence CAM25630.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MLSAVEFSGGQLVGLARTAM SGTPDYQSLPGVGDEEAWVQ SRHWWVSGPSGQNVTM in isoform 2. 1 PublicationVSP_042293
Alternative sequencei530 – 57344LTASD…ASHRR → PDSQRRCHYQSLAFTTHCSC SAGSTPSPPPSPPPLLLLVC QP in isoform 2. 1 PublicationVSP_042294Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176520 mRNA. Translation: AAF09130.1.
AK019715 mRNA. Translation: BAB31841.1.
AK154911 mRNA. Translation: BAE32921.1.
AL732557 Genomic DNA. Translation: CAM25629.1.
AL732557 Genomic DNA. Translation: CAM25630.1. Sequence problems.
CH466542 Genomic DNA. Translation: EDL08255.1.
BC010776 mRNA. Translation: AAH10776.1.
CCDSiCCDS15778.1. [Q9QXW2-1]
RefSeqiNP_038936.1. NM_013908.4. [Q9QXW2-1]
UniGeneiMm.29170.

Genome annotation databases

EnsembliENSMUST00000015239; ENSMUSP00000015239; ENSMUSG00000015095. [Q9QXW2-1]
GeneIDi30839.
KEGGimmu:30839.
UCSCiuc008isj.1. mouse. [Q9QXW2-1]
uc008isk.1. mouse. [Q9QXW2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176520 mRNA. Translation: AAF09130.1.
AK019715 mRNA. Translation: BAB31841.1.
AK154911 mRNA. Translation: BAE32921.1.
AL732557 Genomic DNA. Translation: CAM25629.1.
AL732557 Genomic DNA. Translation: CAM25630.1. Sequence problems.
CH466542 Genomic DNA. Translation: EDL08255.1.
BC010776 mRNA. Translation: AAH10776.1.
CCDSiCCDS15778.1. [Q9QXW2-1]
RefSeqiNP_038936.1. NM_013908.4. [Q9QXW2-1]
UniGeneiMm.29170.

3D structure databases

ProteinModelPortaliQ9QXW2.
SMRiQ9QXW2. Positions 75-180, 476-542.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205976. 4 interactions.
DIPiDIP-60700N.
STRINGi10090.ENSMUSP00000015239.

PTM databases

iPTMnetiQ9QXW2.
PhosphoSiteiQ9QXW2.

Proteomic databases

MaxQBiQ9QXW2.
PaxDbiQ9QXW2.
PRIDEiQ9QXW2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000015239; ENSMUSP00000015239; ENSMUSG00000015095. [Q9QXW2-1]
GeneIDi30839.
KEGGimmu:30839.
UCSCiuc008isj.1. mouse. [Q9QXW2-1]
uc008isk.1. mouse. [Q9QXW2-2]

Organism-specific databases

CTDi54461.
MGIiMGI:1354731. Fbxw5.

Phylogenomic databases

eggNOGiENOG410IEAX. Eukaryota.
ENOG410XTK0. LUCA.
GeneTreeiENSGT00730000111276.
HOGENOMiHOG000231549.
HOVERGENiHBG051595.
InParanoidiQ9QXW2.
KOiK10263.
OMAiYDIFGTW.
OrthoDBiEOG7RZ5PB.
TreeFamiTF324320.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

ChiTaRSiFbxw5. mouse.
PROiQ9QXW2.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QXW2.
CleanExiMM_FBXW5.
ExpressionAtlasiQ9QXW2. baseline and differential.
GenevisibleiQ9QXW2. MM.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF00400. WD40. 2 hits.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00320. WD40. 3 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
SSF81383. SSF81383. 2 hits.
PROSITEiPS50181. FBOX. 1 hit.
PS50082. WD_REPEATS_2. 2 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH SKP1.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J and NOD.
    Tissue: Testis.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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: Liver.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Testis.
  7. "SCF(Fbxw5) mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression."
    Werner A., Disanza A., Reifenberger N., Habeck G., Becker J., Calabrese M., Urlaub H., Lorenz H., Schulman B., Scita G., Melchior F.
    Nat. Cell Biol. 15:179-188(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EPS8.
  8. "Tnfaip8 l1/Oxi-beta binds to FBXW5, increasing autophagy through activation of TSC2 in a Parkinson's disease model."
    Ha J.Y., Kim J.S., Kang Y.H., Bok E., Kim Y.S., Son J.H.
    J. Neurochem. 129:527-538(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TNFAIP8L1.

Entry informationi

Entry nameiFBXW5_MOUSE
AccessioniPrimary (citable) accession number: Q9QXW2
Secondary accession number(s): A2AJ36
, A2AJ37, E9QMP0, Q3U368
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 120 of the entry and version 1 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.