Protein: F-box/WD repeat-containing protein 7 (Archipelago homolog) (hAgo) (F-box and WD-40 domain-containing protein 7) (F-box protein FBX30) (SEL-10) (hCdc4) (Q969H0)
Organism: Homo sapiens (Human)
Function: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, RICTOR, and probably PSEN1. Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation. Involved in bone homeostasis and negative regulation of osteoclast differentiation. Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination. Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage. The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining.
Subcellular location: [Isoform 1]: Nucleus, nucleoplasm {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:28007894}. Chromosome {ECO:0000269|PubMed:26774286}. Note=Localizes to site of double-strand breaks following phosphorylation by ATM. {ECO:0000269|PubMed:26774286}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:28007894}.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleolus {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:28007894}.
Interaction partners:
- S-phase kinase-associated protein 1
- E3 ubiquitin-protein ligase RBX1
- Myc proto-oncogene protein
- Cullin-1
- G1/S-specific cyclin-E1
- Transcription factor Jun
- Neurogenic locus notch homolog protein 1
- Friend leukemia integration 1 transcription factor
- S-phase kinase-associated protein 2
- F-box/WD repeat-containing protein 1A
Sequence:
MNQELLSVGSKRRRTGGSLRGNPSSSQVDEEQMNRVVEEEQQQQLRQQEEEHTARNGEVVGVEPRPGGQNDSQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTKMKRKLDHGSEVRSFSLGKKPCKVSEYTSTTGLVPCSATPTTFGDLRAANGQGQQRRRITSVQPPTGLQEWLKMFQSWSGPEKLLALDELIDSCEPTQVKHMMQVIEPQFQRDFISLLPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLWREKCKEEGIDEPLHIKRRKVIKPGFIHSPWKSAYIRQHRIDTNWRRGELKSPKVLKGHDDHVITCLQFCGNRIVSGSDDNTLKVWSAVTGKCLRTLVGHTGGVWSSQMRDNIIISGSTDRTLKVWNAETGECIHTLYGHTSTVRCMHLHEKRVVSGSRDATLRVWDIETGQCLHVLMGHVAAVRCVQYDGRRVVSGAYDFMVKVWDPETETCLHTLQGHTNRVYSLQFDGIHVVSGSLDTSIRVWDVETGNCIHTLTGHQSLTSGMELKDNILVSGNADSTVKIWDIKTGQCLQTLQGPNKHQSAVTCLQFNKNFVITSSDDGTVKLWDLKTGEFIRNLVTLESGGSGGVVWRIRASNTKLVCAVGSRNGTEETKLLVLDFDVDMK