DET1- and DDB1-associated protein 1 (DDA1)

DET1- and DDB1-associated protein 1 (DDA1) is a highly conserved scaffolding protein that functions as a core component of various Cullin-RING E3 ubiquitin ligase complexes, particularly the CRL4 complex (comprised of CUL4, DDB1, and associated substrate receptors). DDA1 stabilizes and structurally integrates the assembly of the ligase complex, facilitating protein ubiquitination and subsequent proteasomal degradation of diverse targets, including those involved in DNA repair, cell cycle regulation, and transcription. DDA1 plays an important role in transcription-coupled nucleotide excision repair (TC-NER) by coordinating the dynamics of CRL4 ligase activity at sites of DNA damage-stalled RNA polymerase II, affecting complex assembly, substrate recognition, and turnover. Dysregulation or aberrant expression of DDA1 has been implicated in oncogenesis and rare developmental disorders. There are currently no approved therapies that directly target DDA1, but its function in the CRL4 complex highlights its importance in critical cellular processes and its relevance as a molecular node in protein homeostasis.

Other names

C19orf58PCIA1Placenta cross-immune reaction antigen 1MGC2594PCIA-1cross-immune reaction antigen PCIA1

Not directly targeted by drugs; functions as a regulatory/scaffold protein in E3 ubiquitin ligase complexes, which may be indirectly modulated by drugs that act on CRL4-associated pathways or neosubstrate recruitment.