P0DL28
uniprot
P0DL28
canonical
amino_acid_sequence
MEDHNLEEFRQRWQEELAHSQVLRRRRRLEAGERRPRRPEAGARGEPASGYLGLAQGLLEGAGRPPAPRPGRTDRKDVSSRSRSPPDRDAAEPEPLVDQLIRDLNEMDDVPFFDVHLPYELAINIFQYLNRRELGLCAQVSKTWKVIAEDEVLWYRLCRQEGHLPHSRFSDYTCWKLILQECLAPVHLIRPSWMNRKGAVSELEHVPDAVLCDVRSHDGVVIAGYTSGEVRVWDTRTWDYVAPFLESESEEEDPGMQPYVSFVRINSSLAVAAYEDGILNVWDLRTGRFPIFRFEHDARIQALALSQEKPVVATASAFDVVMLYPNEEGNWHVASEFEVQKLVDYLEIVPNTGRYPVAIATAGDLVYLLKAEDSARTLHYVYGQPATCLDVSASQVAFGVKSLGWVYEGNKILVYSLEAERCLSKLGNALGDFTCVNIRDSPPNLMVSGNMDRRVRLHDLRTDKIALSLSAHQLGVSAVQMDDWKIVSGGEEGLVSVWDYRMNQKLWEVHSRHPVRYISFNSHSLITANVPYEKVLRNSDLDNFACHRRHRGLIHAYEFAVDQLAFQSPLPICRLPRDTVAGYSYDLALSFPYDSI
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 (By similarity). 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) (By similarity). 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 (By similarity). The Cul7-RING(FBXW8) complex also mediates ubiquitination of phosphorylated cyclin-D1 (CCND1) (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q8BIA4, ECO:0000250|UniProtKB:Q8N3Y1, ECO:0000269|PubMed:21572988}.
uniprot
proteins
mass_dalton
67819
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-84 by mTORC2 promotes FBXW8 stabilization, allowing its translocation to the cytosol in response to insulin. {ECO:0000250|UniProtKB:Q8BIA4}.
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
21572988
uniprot
proteins
sequence_length
596
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000269|PubMed:21572988}. Golgi apparatus {ECO:0000269|PubMed:21572988}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q8BIA4}. Note=Colocalizes with CUL7 at the Golgi apparatus in neurons (PubMed:21572988). Localizes to the cytosol when phosphorylated at Ser-84, promoting IRS1 ubiquitination (By similarity). {ECO:0000250|UniProtKB:Q8BIA4, ECO:0000269|PubMed:21572988}.
uniprot
proteins