DTX2

E3 ubiquitin ligase that conjugates ubiquitin to ADP-ribosylated cysteine residues, independently of lysine side chains or free N-termini. 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. Functions in genome stability maintenance by acting as an ADP-ribosylation-dependent regulator of DNA double-strand break repair. Mechanistically, recognizes PARylated substrates generated in response to DNA damage and promotes their ubiquitination via its RING and DTC domains. 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. In turn, regulates antitumor immune responses. Promotes 'Lys-27'-linked ubiquitination of TFRC, thereby modulating iron metabolism and inhibiting ferroptosis. 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..

Function from UniProtKB (Q86UW9), read 2026-09-23. CC BY 4.0.