HGNC Approved Gene Symbol: ZYG11B
Cytogenetic location: 1p32.3 Genomic coordinates (GRCh38): 1:52,726,453-52,827,336 (from NCBI)
ZYG11B is a subunit of a cullin-RING E3 ubiquitin ligase (CLR) complex containing CUL2 (603135) that is involved in protein degradation and mitotic slippage (Balachandran et al., 2016; Timms et al., 2019).
Using immunofluorescence analysis, Balachandran et al. (2016) showed that fluorescence-tagged human ZYG11B localized predominantly to cytoplasm of transfected U2OS cells during interphase and mitosis.
Balachandran et al. (2016) showed that ZYG11A or ZYG11B, the human orthologs of C. elegans Zyg11, were subunits of a CUL2-containing CRL complex (CRL2-ZYG11) that targeted cyclin B1 (CCNB1; 123836) for degradation. This function of the CRL2-ZYG11 complex was redundant with and independent of the anaphase-promoting complex/cyclosome (APC/C; see 608476), as it was required only when cyclin B1 was overexpressed or APC/C was inactive. ZYG11B bound to cyclin B1 and contributed to its degradation in a manner that was distinct from APC/C binding to cyclin B. In addition, both ZYG11A and ZYG11B contributed to mitotic slippage promoted by the CRL2-ZYG11 complex in mammalian cells in which APC/C was inactive.
Timms et al. (2019) identified N-terminal glycine as a potent degron in HEK293T cells that was redundantly targeted for proteasomal degradation by 2 CLR complexes, CUL2-ZYG11B and CUL2-ZER1 (617764). ZYG11B and ZER1 functioned cooperatively and recognized proteins bearing exposed N-terminal glycines for degradation. The recognition motif for ZYG11B was relatively small, comprising just the terminal glycine and the following residue, whereas the recognition motif for ZER1 appeared to extend 3 or more residues along the polypeptide chain and preferentially comprised amino acids with bulky aromatic side chains. Proteolytic cleavage generated downstream fragments bearing N-terminal glycine degrons, and these fragments were also targeted by ZYG11B and ZER1 for further degradation and clearance. ZYG11B and ZER1 also targeted proteins for degradation when they failed to undergo N-myristoylation, which occurs exclusively on N-terminal glycine and shields proteins from degradation.
Gross (2019) mapped the ZYG11B gene to chromosome 1p32.3 based on an alignment of the ZYG11B sequence (GenBank BC029832) with the genomic sequence (GRCh38).
Balachandran, R. S., Heighington, C. S., Starostina, N. G., Anderson, J. W., Owen, D. L., Vasudevan, S., Kipreos, E. T. The ubiquitin ligase CRL2-ZYG11 targets cyclin B1 for degradation in a conserved pathway that facilitates mitotic slippage. J. Cell Biol. 215: 151-166, 2016. [PubMed: 27810909] [Full Text: https://doi.org/10.1083/jcb.201601083]
Gross, M. B. Personal Communication. Baltimore, Md. 11/21/2019.
Timms, R. T., Zhang, Z., Rhee, D. Y., Harper, J. W., Koren, I., Elledge, S. J. A glycine-specific N-degron pathway mediates the quality control of protein N-myristoylation. Science 365: eaaw4912, 2019. Note: Electronic Article. [PubMed: 31273098] [Full Text: https://doi.org/10.1126/science.aaw4912]