F-box only protein 5; early mitotic inhibitor 1 (FBXO5, EMI1, FBX5)

Function

• regulates progression through early mitosis by inhibiting the anaphase promoting complex/cyclosome (APC)
• binds to the APC activators CDC20 & FZR1/CDH1 to prevent APC activation
• can also bind directly to the APC to inhibit substrate-binding
• phosphorylation by CDK2 & 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 activation of APC in late mitosis & subsequent mitotic progression
• part of a SCF complex (putative)
• interacts with BTRC, FZR1/CDH1 & the N-terminal substrate- binding domain of CDC20
• also interacts with EVI5 which blocks its phosphorylation by PLK1 & prevents its subsequent binding to BTRC & degradation

Structure

• the C-terminal region is required for inhibition of APC activity
• contains 1 F-box domain
• contains 1 IBR-type Zn+2 finger

Compartment

• nucleus, cytoplasm, cytoskeleton, spindle
• in interphase, localizes in a punctate manner in the nucleus & cytoplasm with some perinuclear concentration
• in mitotic cells, localizes throughout the cell, particularly at the spindle

Expression

• accumulates in late G1 phase, levels rise during S phase & drop in early mitosis

More general terms

• F-box only protein
• zinc finger protein

Component of

• SCF-type E3 ligase complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=26271
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:26271
• OMIM: https://mirror.omim.org/entry/606013
• UniProt: http://www.uniprot.org/uniprot/Q9UKT4.html