FBXW8
entrez
26259
canonical
uniprot
Q8N3Y1
canonical
ensembl
ENSG00000174989
resolver
ensp
ENSP00000310686
resolver
ensp
ENSP00000389144
resolver
ensp
ENSP00000498999
resolver
genesymbol
FBXW8
resolver
genesymbol_syn
FBW6
resolver
genesymbol_syn
FBW8
resolver
genesymbol_syn
FBX29
resolver
genesymbol_syn
FBXO29
resolver
genesymbol_syn
FBXW6
resolver
hgnc
HGNC:13597
resolver
uniprot
Q9UK95
resolver
uniprot_entry
FBXW8_HUMAN
resolver
uniprot_sec
Q9UK95
resolver
amino_acid_sequence
MDDYSLDEFRRRWQEELAQAQAPKKRRRPEAAERRARRPEVGSGRGEQASGDPALAQRLLEGAGRPPAARATRAEGQDVASRSRSPLAREGAGGGEQLVDQLIRDLNEMNDVPFFDIQLPYELAINIFQYLDRKELGRCAQVSKTWKVIAEDEVLWYRLCQQEGHLPDSSISDYSCWKLIFQECRAKEHMLRTNWKNRKGAVSELEHVPDTVLCDVHSHDGVVIAGYTSGDVRVWDTRTWDYVAPFLESEDEEDEPGMQPNVSFVRINSSLAVAAYEDGFLNIWDLRTGKYPVHRFEHDARIQALALSQDDATVATASAFDVVMLSPNEEGYWQIAAEFEVPKLVQYLEIVPETRRYPVAVAAAGDLMYLLKAEDSARTLLYAHGPPVTCLDVSANQVAFGVQGLGWVYEGSKILVYSLEAGRRLLKLGNVLRDFTCVNLSDSPPNLMVSGNMDGRVRIHDLRSGNIALSLSAHQLRVSAVQMDDWKIVSGGEEGLVSVWDYRMNQKLWEVYSGHPVQHISFSSHSLITANVPYQTVMRNADLDSFTTHRRHRGLIRAYEFAVDQLAFQSPLPVCRSSCDAMATHYYDLALAFPYNHV
uniprot
proteins
function
FUNCTION: Substrate-recognition component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:17205132, PubMed:18498745, PubMed:21572988, PubMed:24362026, PubMed:35982156). 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). The Cul7-RING(FBXW8) complex also mediates ubiquitination of phosphorylated cyclin-D1 (CCND1) (PubMed:17205132). The Cul7-RING(FBXW8) complex is however not a major regulator of CCND1 stability during the G1/S transition (By similarity). Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions (PubMed:24793695). {ECO:0000250|UniProtKB:Q8BIA4, ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:35982156}.
uniprot
proteins
mass_dalton
67394
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:18498745}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-85 by mTORC2 promotes FBXW8 stabilization, allowing its translocation to the cytosol in response to insulin. {ECO:0000250|UniProtKB:Q8BIA4}.
uniprot
proteins
pubmed
10531037
uniprot
proteins
pubmed
12481031
uniprot
proteins
pubmed
12904573
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17205132
uniprot
proteins
pubmed
17332328
uniprot
proteins
pubmed
18498745
uniprot
proteins
pubmed
21572988
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24362026
uniprot
proteins
pubmed
24793695
uniprot
proteins
pubmed
35982156
uniprot
proteins
sequence_length
598
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000269|PubMed:21572988}. Golgi apparatus {ECO:0000269|PubMed:21572988}. Cytoplasm {ECO:0000269|PubMed:17205132}. Note=Localizes to the cytosol when phosphorylated at Ser-85, promoting IRS1 ubiquitination. {ECO:0000250|UniProtKB:Q8BIA4}.
uniprot
proteins