| Primary Identifier | IPR038959 | Type | Family |
| Short Name | Prp19 |
| description | This family includes animal Pre-mRNA-processing factor 19 (Prp19) and its homologues.Prp19, also known as DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signalling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex [, , , , ].Prp19 is essential for spliceosome assembly and stability. It is a core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodelling and is required for its activity. During assembly of the spliceosome, it mediates Lys-63-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilises the U4/U5/U6 tri-snRNP spliceosomal complex [].Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerisation and is essential for its auto-ubiquitination activity in vitro or when overexpressed [], a coiled-coil Prp19 homology region that mediates its tetramerisation and interaction with CDC5L and SPF27 [, , ]and a C-terminal seven-bladed WD40 ��-propeller that forms an asymmetrical barrel-shaped structure important for substrate recognition and recruitment [, ]. |
