ZNF598
Description
The ZNF598 (zinc finger protein 598, E3 ubiquitin ligase) is a protein-coding gene located on chromosome 16.
Zinc finger protein 598 (ZNF598) is a protein that in humans is encoded by the ZNF598 gene. Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This protein and Grb10-interacting GYF protein 2 have been identified as a components of the mammalian 4EHP (m4EHP) complex. The complex is thought to function as a translation repressor in embryonic development. ZNF598 and its yeast homologue Hel2 are ubiquitin ligases that ubiquitinate the 40S ribosomal subunit during ribosome-associated protein quality control.
ZNF598 is an E3 ubiquitin-protein ligase that plays a critical role in ribosome quality control (RQC), a process that occurs when ribosomes stall during translation, leading to the breakdown of nascent peptide chains. ZNF598 is activated when ribosomes become stalled within an mRNA after the translation of prematurely polyadenylated mRNAs. It acts as a ribosome collision sensor, specifically recognizing and binding to collided di-ribosomes, which form when a trailing ribosome encounters a slower leading ribosome, resulting in the termination of translation. Upon binding to colliding ribosomes, ZNF598 mediates monoubiquitination of the 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, as well as ‘Lys-63‘-linked polyubiquitination of RPS20/uS10. Polyubiquitination of RPS20/uS10 facilitates the recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by the degradation of nascent peptides. The E3 ubiquitin-protein ligase activity of ZNF598 is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3. ZNF598 also functions as an adapter protein, recruiting the 4EHP-GYF2 complex to mRNAs. Independently of its role in RQC, ZNF598 may also act as a negative regulator of interferon-stimulated gene (ISG) expression.
ZNF598 is also known as HEL2.
