E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains (  , ). ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs ( ). Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation ( , ). Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10 ( ). Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides ( ). E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3 . Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs (, ). Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression .
(Microbial infection) Required for poxvirus protein synthesis by mediating ubiquitination of RPS10/eS10 and RPS20/uS10 . Poxvirus encoding mRNAs contain unusual 5' poly(A) leaders and ZNF598 is required for their translational efficiency, possibly via its ability to suppress readthrough or sliding on shorter poly(A) tracts .
Subcellular locations: Cytoplasm, Cytosol