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MGP004835

UniProt Annotations

Entry Information
Gene NameF-box and WD repeat domain containing 8
Protein EntryFBXW8_HUMAN
UniProt IDQ8N3Y1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q8N3Y1-1; Sequence=Displayed; Name=2; IsoId=Q8N3Y1-2; Sequence=VSP_008501;
FunctionSubstrate-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 degradatation, 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). {ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695}.
InteractionP01106:MYC; NbExp=3; IntAct=EBI-914770, EBI-447544;
PathwayProtein modification; protein ubiquitination.
Sequence CautionSequence=AAF03129.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAF03129.1; Type=Frameshift; Positions=282, 295; Evidence={ECO:0000305};
SimilarityContains 1 F-box domain. {ECO:0000255|PROSITE- ProRule:PRU00080}.
SimilarityContains 5 WD repeats. {ECO:0000255|PROSITE- ProRule:PRU00221}.
Subcellular LocationCytoplasm, perinuclear region {ECO:0000269|PubMed:21572988}. Golgi apparatus {ECO:0000269|PubMed:21572988}. Note=Colocalizes with CUL7 at the Golgi apparatus in neurons. {ECO:0000250}.
SubunitPart 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. {ECO:0000269|PubMed:12481031, ECO:0000269|PubMed:12904573, ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026}.
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