The complex of ISG15 E2 conjugating enzyme UBE2L6 (UBCH8) and ISG15 E3 conjugating enzyme TRIM25 (EFP) doubly ISGylates monoubiquitinated PCNA (MonoUb:K164-PCNA) on lysine residues K164 and K168. Note that PCNA is a homotrimer, meaning ISGylation of K164 (and K168) occurs on a different subunit than that monoubiquitinated on K164. UBA7 (UBE1L) is the ISG15 E1-activating enzyme (Park et al. 2014).
ISG15 transferase activity of UBE2L6:TRIM25:DNA polymerase Y:MonoUb:K164-PCNA:RPA:RFC:TLS-DNA Template [nucleoplasm]