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Protein

F-box/WD repeat-containing protein 8

Gene

Fbxw8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The Cul7-RING(FBXW8) complex mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradatation, thereby affecting cell proliferation and differentiation. Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions (By similarity).By similarity

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

  • cell proliferation Source: UniProtKB
  • Golgi organization Source: UniProtKB
  • labyrinthine layer blood vessel development Source: MGI
  • positive regulation of dendrite morphogenesis Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • spongiotrophoblast layer development Source: MGI
  • ubiquitin-dependent protein catabolic process Source: MGI
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 8
Alternative name(s):
F-box and WD-40 domain-containing protein 8
Gene namesi
Name:Fbxw8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1923041. Fbxw8.

Subcellular locationi

GO - Cellular componenti

  • 3M complex Source: Ensembl
  • Cul7-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: MGI
  • Golgi apparatus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • SCF ubiquitin ligase complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus

Pathology & Biotechi

Disruption phenotypei

Reduced embryo size and neonatal lethality. Embryos and placentas are smaller and only a third of the expected number of mice survived birth. Mice that survive remain smaller throughout postnatal development.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 598598F-box/WD repeat-containing protein 8PRO_0000050998Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei84 – 841PhosphoserineCombined sources
Modified residuei86 – 861PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8BIA4.
MaxQBiQ8BIA4.
PaxDbiQ8BIA4.
PRIDEiQ8BIA4.

PTM databases

iPTMnetiQ8BIA4.
PhosphoSiteiQ8BIA4.

Expressioni

Tissue specificityi

Widely expressed. Expressed at higher level in skeletal muscle, cartilage and lung.1 Publication

Gene expression databases

BgeeiQ8BIA4.
CleanExiMM_FBXW8.
GenevisibleiQ8BIA4. MM.

Interactioni

Subunit structurei

Part of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN. Interacts with OBSL1, CUL1, CUL2, SKP1, CCT6B, PFDN5, CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8, ARF1, TRIP13, PDCD5 and GORASP1. Interacts with MAP4K1/HPK1 (when autophosphorylated). Associated component of the 3M complex (By similarity). Interacts with CUL7.By similarity1 Publication

Protein-protein interaction databases

BioGridi231155. 6 interactions.
STRINGi10090.ENSMUSP00000047012.

Structurei

3D structure databases

ProteinModelPortaliQ8BIA4.
SMRiQ8BIA4. Positions 119-554.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini113 – 15947F-boxPROSITE-ProRule annotationAdd
BLAST
Repeati197 – 24549WD 1Add
BLAST
Repeati253 – 29442WD 2Add
BLAST
Repeati297 – 33640WD 3Add
BLAST
Repeati430 – 47041WD 4Add
BLAST
Repeati473 – 51038WD 5Add
BLAST

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 5 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiENOG410IQD1. Eukaryota.
ENOG4110ZIH. LUCA.
GeneTreeiENSGT00390000017221.
HOGENOMiHOG000112555.
HOVERGENiHBG051597.
InParanoidiQ8BIA4.
KOiK10264.
OMAiQSPLPVC.
OrthoDBiEOG7N8ZV2.
PhylomeDBiQ8BIA4.
TreeFamiTF332593.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
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.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
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: Q8BIA4-1) [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
MDDHNLEEFR RHWQEELAQS QALRRRRRLE AGERRSPRRP EAGARGEPAS
60 70 80 90 100
GYLGLAQGLL EGAGRPPAPR PGRGGDRKDT SSRSRSPPDR DATEPEPLVD
110 120 130 140 150
QLIRDLNELD DVPFFDVRLP YELAINIFQY LNRRELGLCA QVSKTWKVIA
160 170 180 190 200
EDEVLWYRLC RQEGHLPHSR FSDYTCWKLI LQECLAKEHT LRANWKNRKG
210 220 230 240 250
AVSELEHVPD AVLCDVRSHD GVVIAGYTSG DVRVWDTRTW DYVAPFLESE
260 270 280 290 300
SEEEDPGMQP YVSFVRINSS LAVAAYEDGI LNIWDLRTGR FPIFRFEHDA
310 320 330 340 350
RIQALALSQE KPIVATASAF DVVMLYPNEE GHWHVASEFE VQKLVDYLEI
360 370 380 390 400
VPNTGRYPVA IATAGDLVYL LKADDSARTL HYVYGQPATC LDVSASQVAF
410 420 430 440 450
GVKSLGWVYE GNKILVYSLE AERCLSKLGN ALGDFTCVNI RDSPPNLMVS
460 470 480 490 500
GNMDRRVRIH DLRSDKIALS LSAHQLGVSA VQMDDWKVVS GGEEGLVSVW
510 520 530 540 550
DYRMNQKLWE VHSRHPVRYL SFNSHSLITA NVPYEKVLRN SDLDNFACHR
560 570 580 590
RHRGLIHAYE FAVDQLAFQS PLPVCRLPRD IMAGYSYDLA LSFPHDSI
Length:598
Mass (Da):67,956
Last modified:October 3, 2003 - v2
Checksum:i4FEAF1C4384D3CA5
GO
Isoform 2 (identifier: Q8BIA4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     457-598: Missing.

Show »
Length:456
Mass (Da):51,673
Checksum:i2C90E47D7E946821
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti67 – 671P → T in BAC28712 (PubMed:16141072).Curated
Sequence conflicti171 – 1711F → S in AAH09095 (PubMed:15489334).Curated
Sequence conflicti247 – 2482LE → WS in BAC33128 (PubMed:16141072).Curated
Sequence conflicti280 – 2801I → V in BAC35527 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei457 – 598142Missing in isoform 2. 1 PublicationVSP_008502Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK034447 mRNA. Translation: BAC28712.1.
AK047695 mRNA. Translation: BAC33128.1.
AK047756 mRNA. Translation: BAC33147.1.
AK053794 mRNA. Translation: BAC35527.1.
BC009095 mRNA. Translation: AAH09095.2.
BC024091 mRNA. Translation: AAH24091.1.
CCDSiCCDS19609.1. [Q8BIA4-1]
RefSeqiNP_766309.2. NM_172721.2. [Q8BIA4-1]
UniGeneiMm.221769.

Genome annotation databases

EnsembliENSMUST00000049474; ENSMUSP00000047012; ENSMUSG00000032867. [Q8BIA4-1]
GeneIDi231672.
KEGGimmu:231672.
UCSCiuc008zge.1. mouse. [Q8BIA4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK034447 mRNA. Translation: BAC28712.1.
AK047695 mRNA. Translation: BAC33128.1.
AK047756 mRNA. Translation: BAC33147.1.
AK053794 mRNA. Translation: BAC35527.1.
BC009095 mRNA. Translation: AAH09095.2.
BC024091 mRNA. Translation: AAH24091.1.
CCDSiCCDS19609.1. [Q8BIA4-1]
RefSeqiNP_766309.2. NM_172721.2. [Q8BIA4-1]
UniGeneiMm.221769.

3D structure databases

ProteinModelPortaliQ8BIA4.
SMRiQ8BIA4. Positions 119-554.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi231155. 6 interactions.
STRINGi10090.ENSMUSP00000047012.

PTM databases

iPTMnetiQ8BIA4.
PhosphoSiteiQ8BIA4.

Proteomic databases

EPDiQ8BIA4.
MaxQBiQ8BIA4.
PaxDbiQ8BIA4.
PRIDEiQ8BIA4.

Protocols and materials databases

DNASUi231672.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000049474; ENSMUSP00000047012; ENSMUSG00000032867. [Q8BIA4-1]
GeneIDi231672.
KEGGimmu:231672.
UCSCiuc008zge.1. mouse. [Q8BIA4-1]

Organism-specific databases

CTDi26259.
MGIiMGI:1923041. Fbxw8.

Phylogenomic databases

eggNOGiENOG410IQD1. Eukaryota.
ENOG4110ZIH. LUCA.
GeneTreeiENSGT00390000017221.
HOGENOMiHOG000112555.
HOVERGENiHBG051597.
InParanoidiQ8BIA4.
KOiK10264.
OMAiQSPLPVC.
OrthoDBiEOG7N8ZV2.
PhylomeDBiQ8BIA4.
TreeFamiTF332593.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ8BIA4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BIA4.
CleanExiMM_FBXW8.
GenevisibleiQ8BIA4. MM.

Family and domain databases

Gene3Di2.130.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
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.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 2 hits.
SSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 1 hit.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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.
    Tissue: Corpus striatum, Diencephalon and Eye.
  2. "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).
    Strain: FVB/N.
    Tissue: Liver and Mammary gland.
  3. "Fbxw8 is essential for Cul1-Cul7 complex formation and for placental development."
    Tsunematsu R., Nishiyama M., Kotoshiba S., Saiga T., Kamura T., Nakayama K.I.
    Mol. Cell. Biol. 26:6157-6169(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CUL7.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  5. "Disruption of the Fbxw8 gene results in pre- and postnatal growth retardation in mice."
    Tsutsumi T., Kuwabara H., Arai T., Xiao Y., Decaprio J.A.
    Mol. Cell. Biol. 28:743-751(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84 AND SER-86, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Lung, Spleen and Testis.

Entry informationi

Entry nameiFBXW8_MOUSE
AccessioniPrimary (citable) accession number: Q8BIA4
Secondary accession number(s): Q8BI62
, Q8BI75, Q8BI76, Q8CID8, Q921Z1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: June 8, 2016
This is version 123 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. 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.