FBXO5
entrez
26271
canonical
uniprot
Q9UKT4
canonical
ensembl
ENSG00000112029
resolver
ensp
ENSP00000229758
resolver
ensp
ENSP00000356210
resolver
genesymbol
FBXO5
resolver
genesymbol_syn
EMI1
resolver
genesymbol_syn
FBX5
resolver
hgnc
HGNC:13584
resolver
uniprot
B3KNX5
resolver
uniprot
Q5TF47
resolver
uniprot
Q8WV29
resolver
uniprot
Q9UGC8
resolver
uniprot_entry
FBX5_HUMAN
resolver
uniprot_sec
B3KNX5
resolver
uniprot_sec
Q5TF47
resolver
uniprot_sec
Q8WV29
resolver
uniprot_sec
Q9UGC8
resolver
amino_acid_sequence
MSRRPCSCALRPPRCSCSASPSAVTAAGRPRPSDSCKEESSTLSVKMKCDFNCNHVHSGLKLVKPDDIGRLVSYTPAYLEGSCKDCIKDYERLSCIGSPIVSPRIVQLETESKRLHNKENQHVQQTLNSTNEIEALETSRLYEDSGYSSFSLQSGLSEHEEGSLLEENFGDSLQSCLLQIQSPDQYPNKNLLPVLHFEKVVCSTLKKNAKRNPKVDREMLKEIIARGNFRLQNIIGRKMGLECVDILSELFRRGLRHVLATILAQLSDMDLINVSKVSTTWKKILEDDKGAFQLYSKAIQRVTENNNKFSPHASTREYVMFRTPLASVQKSAAQTSLKKDAQTKLSNQGDQKGSTYSRHNEFSEVAKTLKKNESLKACIRCNSPAKYDCYLQRATCKREGCGFDYCTKCLCNYHTTKDCSDGKLLKASCKIGPLPGTKKSKKNLRRL
uniprot
proteins
function
FUNCTION: Regulator of APC activity during mitotic and meiotic cell cycle (PubMed:16921029, PubMed:17234884, PubMed:17485488, PubMed:17875940, PubMed:23708001, PubMed:23708605). During mitotic cell cycle plays a role as both substrate and inhibitor of APC-FZR1 complex (PubMed:16921029, PubMed:17234884, PubMed:17485488, PubMed:17875940, PubMed:23708001, PubMed:23708605, PubMed:29875408). During G1 phase, plays a role as substrate of APC-FZR1 complex E3 ligase (PubMed:29875408). Then switches as an inhibitor of APC-FZR1 complex during S and G2 leading to cell-cycle commitment (PubMed:29875408). As APC inhibitor, prevents the degradation of APC substrates at multiple levels: by interacting with APC and blocking access of APC substrates to the D-box coreceptor, formed by FZR1 and ANAPC10; by suppressing ubiquitin ligation and chain elongation by APC by preventing the UBE2C and UBE2S activities (PubMed:16921029, PubMed:23708001, PubMed:23708605). Plays a role in genome integrity preservation by coordinating DNA replication with mitosis through APC inhibition in interphase to stabilize CCNA2 and GMNN in order to promote mitosis and prevent rereplication and DNA damage-induced cellular senescence (PubMed:17234884, PubMed:17485488, PubMed:17875940). During oocyte maturation, plays a role in meiosis through inactivation of APC-FZR1 complex. Inhibits APC through RPS6KA2 interaction that increases FBXO5 affiniy for CDC20 leading to the metaphase arrest of the second meiotic division before fertilization (By similarity). Controls entry into the first meiotic division through inactivation of APC-FZR1 complex (By similarity). Promotes migration and osteogenic differentiation of mesenchymal stem cells (PubMed:29850565). {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:16921029, ECO:0000269|PubMed:17234884, ECO:0000269|PubMed:17485488, ECO:0000269|PubMed:17875940, ECO:0000269|PubMed:23708001, ECO:0000269|PubMed:23708605, ECO:0000269|PubMed:29850565, ECO:0000269|PubMed:29875408}.
uniprot
proteins
mass_dalton
50146
uniprot
proteins
mutagenesis
MUTAGEN 143; /note="E->A: Delays degradation."; /evidence="ECO:0000269|PubMed:15469984"; MUTAGEN 144; /note="D->A: Does not affect protein stability."; /evidence="ECO:0000269|PubMed:17485488"; MUTAGEN 145; /note="S->A: Does not affect protein stability; when associated with A-149."; /evidence="ECO:0000269|PubMed:17485488"; MUTAGEN 145; /note="S->E: Degraded in similar manner to wild-type."; /evidence="ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984"; MUTAGEN 145; /note="S->N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-149."; /evidence="ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984"; MUTAGEN 146; /note="G->V: Does not affect protein stability."; /evidence="ECO:0000269|PubMed:17485488"; MUTAGEN 148; /note="S->A: Degraded in similar manner to wild-type."; /evidence="ECO:0000269|PubMed:15469984"; MUTAGEN 149; /note="S->A: Does not affect protein stability; when associated with A-145."; /evidence="ECO:0000269|PubMed:17485488"; MUTAGEN 149; /note="S->E: Degraded in similar manner to wild-type."; /evidence="ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984"; MUTAGEN 149; /note="S->N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-145."; /evidence="ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984"; MUTAGEN 182; /note="S->A: Shows impaired interaction with BTRC."; /evidence="ECO:0000269|PubMed:12791267"; MUTAGEN 210..216; /note="KRNPKVD->AAAAAAA: Loss of interaction with EVI5."; /evidence="ECO:0000269|PubMed:16439210"; MUTAGEN 322..325; /note="RTPL->ATPA: Does not affect inhibition of UBE2S-catalyzed chain elongation. Efficiently inhibits the degradation of PTTG1 at relatively high concentration. Reduces the competitive ability of FBXO5 to inhibit the association of PTTG1 to APC. Cannot compete with the APC substrate for APC binding. Decreases inhibition of CCNB1 ubiquitination by UBE2C."; /evidence="ECO:0000269|PubMed:23708001, ECO:0000269|PubMed:23708605"; MUTAGEN 339..345; /note="Missing: Impairs CCNB1 ubiquitination by UBE2C; when associated with 356-Y--R-358 del."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 345; /note="L->A: Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with 346-S--T-355 del."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 346..355; /note="Missing: Inhibits CCNB1 ubiquitination by UBE2C. Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with A-345; A-356 and A-358."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 356..358; /note="Missing: Impairs CCNB1 ubiquitination by UBE2C; when associated with 339-K--L-345 del."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 356; /note="Y->A: Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with 346-S--T-355 del."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 358; /note="R->A: Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with 346-S--T-355 del."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 375; /note="L->A: Decreases UBE2C-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 376; /note="K->A: Decreases UBE2C-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 393; /note="R->A: Decreases UBE2C-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 401; /note="C->S: Reduced inhibition of APC. Does not affect the FBXO5-mediated inhibitory activity against ubiquitin chain assembly. Does not affect the FBXO5-mediated inhibitory activity against ubiquitin chain assembly; when associated with S-401. Does not affect inhibition of UBE2S-catalyzed chain elongation. Reduces the competitive ability of FBXO5 to inhibit the association of securin to APC. Can still compete with the APC substrate for APC binding. Fails to inhibit ubiquitin chain assembly by UBE2C or mono-ubiquitination by UBE2D1. Largely abolishes the inhibitory activity against protein degradation. Fails to inactivate APC-FZR1 complex. Allows FBXO5 degradation in the absence of CDK4 inhibitor."; /evidence="ECO:0000269|PubMed:16921029, ECO:0000269|PubMed:23708001, ECO:0000269|PubMed:29875408"; MUTAGEN 406; /note="C->S: Does not affect the inhibitory activity against chain assembly; when associated with S-401."; /evidence="ECO:0000269|PubMed:23708001"; MUTAGEN 409; /note="C->A: Decreases UBE2C-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:23708605"; MUTAGEN 444..445; /note="LR->AA: Loses inhibitory activity on UBE2S-catalyzed chain elongation."; /evidence="ECO:0000269|PubMed:23708001
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by CDK2 and subsequently by PLK1 triggers degradation during early mitosis through ubiquitin-mediated proteolysis by the SCF ubiquitin ligase complex containing the F-box protein BTRC. This degradation is necessary for the activation of APC in late mitosis and subsequent mitotic progression (PubMed:12791267, PubMed:15469984). Phosphorylated by RPS6KA2; increases and stabilizes interaction with CDC20 (By similarity). {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:15469984}.; PTM: Ubiquitinated by the SCF(BTRC) complex following phosphorylation by PLK1 (PubMed:15469984). Undergoes both 'Lys-11' and 'Lys-48'-linked polyubiquitination by APC-FZR1 complex leading to degradation by proteasome during G1 phase (PubMed:29875408). Degraded through the SCF(BTRC) complex; degradation occurs during oocyte maturation, between germinal vesicle breakdown (GVBD) and meiosis I, and is required for the meiosis I-meiosis II transition (By similarity). {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:29875408}.
uniprot
proteins
pubmed
10531035
uniprot
proteins
pubmed
11988738
uniprot
proteins
pubmed
12791267
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15148369
uniprot
proteins
pubmed
15469984
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16439210
uniprot
proteins
pubmed
16921029
uniprot
proteins
pubmed
17234884
uniprot
proteins
pubmed
17485488
uniprot
proteins
pubmed
17875940
uniprot
proteins
pubmed
19211842
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23708001
uniprot
proteins
pubmed
23708605
uniprot
proteins
pubmed
26083744
uniprot
proteins
pubmed
29850565
uniprot
proteins
pubmed
29875408
uniprot
proteins
sequence_length
447
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11988738}. Cytoplasm {ECO:0000269|PubMed:11988738}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:15469984}. Note=In interphase, localizes in a punctate manner in the nucleus and cytoplasm with some perinuclear concentration (PubMed:11988738). In mitotic cells, localizes throughout the cell, particularly at the spindle (PubMed:15469984). {ECO:0000269|PubMed:11988738, ECO:0000269|PubMed:15469984}.
uniprot
proteins