Ubiquitin-protein ligase which is a core component of severalcomplexes mainly involved pre-mRNA splicing and DNA repair. Requiredfor pre-mRNA splicing as component of the spliceosome. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex whichis part of the spliceosome and participates in its assembly, itsremodeling and is required for its activity. During assembly of thespliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows itsrecognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex. Recruited to RNApolymerase II C-terminal domain (CTD) and the pre-mRNA, it may alsocouple the transcriptional and spliceosomal machineries. The XAB2 complex, which contains PRPF19, is alsoinvolved in pre-mRNA splicing, transcription and transcription-coupledrepair. Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damageresponse/DDR. It is recruited to the sites of DNA damage by the RPAcomplex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment ofthe ATR-ATRIP complex and the activation of ATR, a master regulator ofthe DNA damage response. May also play a role in DNAdouble-strand break (DSB) repair by recruiting the repair factor SETMARto altered DNA. As part of the PSO4 complex may alsobe involved in the DNA interstrand cross-links/ICLs repair process. In addition, may also mediate 'Lys-48'-linkedpolyubiquitination of substrates and play a role in proteasomaldegradation. May play a role in the biogenesis oflipid droplets. May play a role in neuraldifferentiation possibly through its function as part of thespliceosome. [1-8]

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