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ZYG11-RELATED CELL CYCLE REGULATOR; ZER1

ZYG11-RELATED CELL CYCLE REGULATOR; ZER1

Alternative titles; symbolsZER1, C. ELEGANS, HOMOLOG OFZYG11B-LIKE PROTEIN; ZYG11BLZYGCHROMOSOME 9 OPEN READING FRAME 60; C9ORF60HGNC Approved Gene Symbol: ZER1C...

Alternative titles; symbols

  • ZER1, C. ELEGANS, HOMOLOG OF
  • ZYG11B-LIKE PROTEIN; ZYG11BL
  • ZYG
  • CHROMOSOME 9 OPEN READING FRAME 60; C9ORF60

HGNC Approved Gene Symbol: ZER1

Cytogenetic location: 9q34.11 Genomic coordinates (GRCh38): 9:128,729,785-128,772,485 (from NCBI)

▼ Description
ZER1 is expressed in testis and skeletal muscle and interacts with the CUL2 (603135) E3 ubiquitin ligase (Feral et al., 2001; Vasudevan et al., 2007).

▼ Cloning and Expression
Feral et al. (2001) cloned human ZER1, which they called ZYG, from a testis cDNA library. The putative 776-amino acid protein has a predicted molecular mass of 88 kD. It contains 4 leucine-rich repeats (LRRs), 3 potential N-glycosylation sites, and a potential O-glycosylation site. Database analysis revealed ZYG orthologs in C. elegans and Drosophila. Northern blot analysis revealed strong expression of a 3.1-kb transcript in testis only. A 5-kb transcript was abundant in testis and skeletal muscle, with low levels in other tissues. In situ hybridization on human testis sections showed that ZYG mRNA was mainly expressed in germ cells that undergo meiotic division. Immunohistochemical analysis revealed that ZYG expression was specific to cytoplasm of late pachytene spermatocytes and round spermatids.

Vasudevan et al. (2007) reported that human ZER1 contains an N-terminal VHL (608537)-box motif and a C-terminal armadillo (ARM)-like helicase domain that are both conserved in C. elegans Zer1. Database analysis revealed additional ZER1 orthologs in mouse and sea urchin.

▼ Gene Function
Vasudevan et al. (2007) identified Zer1 in a proteomic screen in C. elegans for proteins that copurified with Cul2 (603135). In HEK293T cells, ZER1 coimmunoprecipitated with endogenous CUL2. Yeast 2-hybrid assays showed that Zer1 interacted with elongin C (ELOC; 600788), an adaptor protein found in multisubunit E3 complexes, in C. elegans. Human ZER1 also interacted with elongin C, but it required coexpression of elongin B (ELOB; 600787) and depended on the ZER1 VHL-box motif. Vasudevan et al. (2007) proposed that ZER1 functions in multisubunit E3 complexes as a substrate recognition subunit for CUL2.

Timms et al. (2019) identified N-terminal glycine as a potent degron in HEK293T cells that was redundantly targeted for proteasomal degradation by 2 cullin-RING E3 ubiquitin ligase (CLR) complexes, CUL2-ZYG11B (618673) and CUL2-ZER1. 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.

▼ Mapping
By genomic sequence analysis, Feral et al. (2001) mapped the ZER1 gene to chromosome 9q32-q34.1.

Gross (2017) mapped the ZER1 gene to chromosome 9q34.11 based on an alignment of the ZER1 sequence (GenBank BC052563) with the genomic sequence (GRCh38).

Tags: 9q34.11