E3 ubiquitin ligase that conjugates ubiquitin to ADP- ribosylated cysteine residues, independently of lysine side chains or free N-termini (PubMed:40681873). For example, PARP7 generates an ADP- ribosyl degron within the DNA-binding domain of the androgen receptor (AR), which is recognized by DTX2 and targeted for proteasomal degradation (PubMed:40681873). Functions in genome stability maintenance by acting as an ADP-ribosylation-dependent regulator of DNA double-strand break repair (PubMed:38992439). Mechanistically, recognizes PARylated substrates generated in response to DNA damage and promotes their ubiquitination via its RING and DTC domains (PubMed:38992439). Also regulates additional cellular pathways through ubiquitination of specific substrates. Acts as an E3 ubiquitin ligase for RNA demethylase FTO, promoting its ubiquitination and proteasomal degradation (PubMed:39661064). In turn, regulates antitumor immune responses (PubMed:39661064). Promotes 'Lys-27'-linked ubiquitination of TFRC, thereby modulating iron metabolism and inhibiting ferroptosis (PubMed:41772062). In addition, promotes transcription of telomerase reverse transcriptase by mediating 'Lys-63'-linked ubiquitination of nuclear factor 1 C-type (NFIC) that stabilizes its binding on hTERT promoter (PubMed:35198878). {ECO:0000269|PubMed:35198878, ECO:0000269|PubMed:38992439, ECO:0000269|PubMed:39661064, ECO:0000269|PubMed:40681873, ECO:0000269|PubMed:41772062}. This is the function of Ensembl gene identifier ENSG00000091073 (DTX2, deltex E3 ubiquitin ligase 2).