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Protein

F-box/WD repeat-containing protein 8

Gene

FBXW8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:21572988). Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2) (PubMed:18498745). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation (PubMed:24362026). Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions (PubMed:24793695).4 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

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ8N3Y1
UniPathwayi
UPA00143

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
F-box only protein 29
Gene namesi
Name:FBXW8
Synonyms:FBW6, FBW8, FBX29, FBXO29, FBXW6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000174989.12
HGNCiHGNC:13597 FBXW8
MIMi609073 gene
neXtProtiNX_Q8N3Y1

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, Golgi apparatus

Pathology & Biotechi

Organism-specific databases

DisGeNETi26259
OpenTargetsiENSG00000174989
PharmGKBiPA28039

Polymorphism and mutation databases

BioMutaiFBXW8
DMDMi296434513

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509971 – 598F-box/WD repeat-containing protein 8Add BLAST598

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei83PhosphoserineBy similarity1
Modified residuei85PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8N3Y1
MaxQBiQ8N3Y1
PaxDbiQ8N3Y1
PeptideAtlasiQ8N3Y1
PRIDEiQ8N3Y1
ProteomicsDBi71847
71848 [Q8N3Y1-2]

PTM databases

iPTMnetiQ8N3Y1
PhosphoSitePlusiQ8N3Y1

Expressioni

Gene expression databases

BgeeiENSG00000174989 Expressed in 127 organ(s), highest expression level in adenohypophysis
CleanExiHS_FBXW8
GenevisibleiQ8N3Y1 HS

Organism-specific databases

HPAiHPA038850
HPA038851

Interactioni

Subunit structurei

Part of a Cul7-RING ubiquitin-protein ligase complex, consisting of CUL7, RBX1, SKP1 and FBXW8. Interacts with GLMN isoform 1. Interacts with CUL7. Interacts with OBSL1, CUL1, CUL2, SKP1, CCT6B, PFDN5, CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8, ARF1, TRIP13, PDCD5 and GORASP1. Interacts with IRS1 (when phosphorylated). Interacts with MAP4K1/HPK1 (when autophosphorylated). Associated component of the 3M complex. Interacts with POUF51 (when phosphorylated on 'Ser-355') (By similarity).By similarity6 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi117645, 52 interactors
CORUMiQ8N3Y1
DIPiDIP-37970N
IntActiQ8N3Y1, 20 interactors
MINTiQ8N3Y1
STRINGi9606.ENSP00000310686

Structurei

3D structure databases

ProteinModelPortaliQ8N3Y1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini113 – 159F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati197 – 245WD 1Add BLAST49
Repeati254 – 294WD 2Add BLAST41
Repeati297 – 336WD 3Add BLAST40
Repeati430 – 470WD 4Add BLAST41
Repeati473 – 510WD 5Add BLAST38

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiENOG410IQD1 Eukaryota
ENOG4110ZIH LUCA
GeneTreeiENSGT00390000017221
HOGENOMiHOG000112555
HOVERGENiHBG051597
InParanoidiQ8N3Y1
KOiK10264
OMAiFEHDARI
OrthoDBiEOG091G0KZ9
PhylomeDBiQ8N3Y1
TreeFamiTF332593

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR011047 Quinoprotein_ADH-like_supfam
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00320 WD40, 5 hits
SUPFAMiSSF50998 SSF50998, 2 hits
SSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 1 hit
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: Q8N3Y1-1) [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
MDDYSLDEFR RRWQEELAQA QAPKKRRRPE AAERRARRPE VGSGRGEQAS
60 70 80 90 100
GDPALAQRLL EGAGRPPAAR ATRAEGQDVA SRSRSPLARE GAGGGEQLVD
110 120 130 140 150
QLIRDLNEMN DVPFFDIQLP YELAINIFQY LDRKELGRCA QVSKTWKVIA
160 170 180 190 200
EDEVLWYRLC QQEGHLPDSS ISDYSCWKLI FQECRAKEHM LRTNWKNRKG
210 220 230 240 250
AVSELEHVPD TVLCDVHSHD GVVIAGYTSG DVRVWDTRTW DYVAPFLESE
260 270 280 290 300
DEEDEPGMQP NVSFVRINSS LAVAAYEDGF LNIWDLRTGK YPVHRFEHDA
310 320 330 340 350
RIQALALSQD DATVATASAF DVVMLSPNEE GYWQIAAEFE VPKLVQYLEI
360 370 380 390 400
VPETRRYPVA VAAAGDLMYL LKAEDSARTL LYAHGPPVTC LDVSANQVAF
410 420 430 440 450
GVQGLGWVYE GSKILVYSLE AGRRLLKLGN VLRDFTCVNL SDSPPNLMVS
460 470 480 490 500
GNMDGRVRIH DLRSGNIALS LSAHQLRVSA VQMDDWKIVS GGEEGLVSVW
510 520 530 540 550
DYRMNQKLWE VYSGHPVQHI SFSSHSLITA NVPYQTVMRN ADLDSFTTHR
560 570 580 590
RHRGLIRAYE FAVDQLAFQS PLPVCRSSCD AMATHYYDLA LAFPYNHV
Length:598
Mass (Da):67,394
Last modified:May 18, 2010 - v2
Checksum:i03B3C283BA46DB6B
GO
Isoform 2 (identifier: Q8N3Y1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     41-106: Missing.

Show »
Length:532
Mass (Da):60,705
Checksum:i921550273E26D2F2
GO

Sequence cautioni

The sequence AAF03129 differs from that shown. Reason: Frameshift at positions 282 and 295.Curated
The sequence AAF03129 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46G → S in AAH37296 (PubMed:15489334).Curated1
Sequence conflicti58R → G in AAH37296 (PubMed:15489334).Curated1
Sequence conflicti380L → I in AAH37296 (PubMed:15489334).Curated1
Sequence conflicti510E → K in AAF03129 (PubMed:10531037).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_060326192R → Q2 PublicationsCorresponds to variant dbSNP:rs4076700Ensembl.1
Natural variantiVAR_057597211T → A. Corresponds to variant dbSNP:rs36021180Ensembl.1
Natural variantiVAR_057598536T → M. Corresponds to variant dbSNP:rs3741466Ensembl.1
Natural variantiVAR_062096563V → M. Corresponds to variant dbSNP:rs56350562Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00850141 – 106Missing in isoform 2. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176707 mRNA Translation: AAF03129.1 Sequence problems.
AC026368 Genomic DNA No translation available.
AC083806 Genomic DNA No translation available.
AC127164 Genomic DNA No translation available.
BC037296 mRNA Translation: AAH37296.1
CCDSiCCDS44988.1 [Q8N3Y1-2]
CCDS9182.1 [Q8N3Y1-1]
RefSeqiNP_036306.1, NM_012174.1 [Q8N3Y1-2]
NP_699179.2, NM_153348.2 [Q8N3Y1-1]
UniGeneiHs.624537
Hs.696428

Genome annotation databases

EnsembliENST00000309909; ENSP00000310686; ENSG00000174989 [Q8N3Y1-1]
ENST00000455858; ENSP00000389144; ENSG00000174989 [Q8N3Y1-2]
GeneIDi26259
KEGGihsa:26259
UCSCiuc001twf.2 human [Q8N3Y1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176707 mRNA Translation: AAF03129.1 Sequence problems.
AC026368 Genomic DNA No translation available.
AC083806 Genomic DNA No translation available.
AC127164 Genomic DNA No translation available.
BC037296 mRNA Translation: AAH37296.1
CCDSiCCDS44988.1 [Q8N3Y1-2]
CCDS9182.1 [Q8N3Y1-1]
RefSeqiNP_036306.1, NM_012174.1 [Q8N3Y1-2]
NP_699179.2, NM_153348.2 [Q8N3Y1-1]
UniGeneiHs.624537
Hs.696428

3D structure databases

ProteinModelPortaliQ8N3Y1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117645, 52 interactors
CORUMiQ8N3Y1
DIPiDIP-37970N
IntActiQ8N3Y1, 20 interactors
MINTiQ8N3Y1
STRINGi9606.ENSP00000310686

PTM databases

iPTMnetiQ8N3Y1
PhosphoSitePlusiQ8N3Y1

Polymorphism and mutation databases

BioMutaiFBXW8
DMDMi296434513

Proteomic databases

EPDiQ8N3Y1
MaxQBiQ8N3Y1
PaxDbiQ8N3Y1
PeptideAtlasiQ8N3Y1
PRIDEiQ8N3Y1
ProteomicsDBi71847
71848 [Q8N3Y1-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309909; ENSP00000310686; ENSG00000174989 [Q8N3Y1-1]
ENST00000455858; ENSP00000389144; ENSG00000174989 [Q8N3Y1-2]
GeneIDi26259
KEGGihsa:26259
UCSCiuc001twf.2 human [Q8N3Y1-1]

Organism-specific databases

CTDi26259
DisGeNETi26259
EuPathDBiHostDB:ENSG00000174989.12
GeneCardsiFBXW8
H-InvDBiHIX0026457
HIX0037115
HGNCiHGNC:13597 FBXW8
HPAiHPA038850
HPA038851
MIMi609073 gene
neXtProtiNX_Q8N3Y1
OpenTargetsiENSG00000174989
PharmGKBiPA28039
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQD1 Eukaryota
ENOG4110ZIH LUCA
GeneTreeiENSGT00390000017221
HOGENOMiHOG000112555
HOVERGENiHBG051597
InParanoidiQ8N3Y1
KOiK10264
OMAiFEHDARI
OrthoDBiEOG091G0KZ9
PhylomeDBiQ8N3Y1
TreeFamiTF332593

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ8N3Y1

Miscellaneous databases

ChiTaRSiFBXW8 human
GeneWikiiFBXW8
GenomeRNAii26259
PROiPR:Q8N3Y1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000174989 Expressed in 127 organ(s), highest expression level in adenohypophysis
CleanExiHS_FBXW8
GenevisibleiQ8N3Y1 HS

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR011047 Quinoprotein_ADH-like_supfam
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00320 WD40, 5 hits
SUPFAMiSSF50998 SSF50998, 2 hits
SSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 1 hit
PS50294 WD_REPEATS_REGION, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiFBXW8_HUMAN
AccessioniPrimary (citable) accession number: Q8N3Y1
Secondary accession number(s): Q9UK95
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: May 18, 2010
Last modified: September 12, 2018
This is version 155 of the entry and version 2 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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