DDB1- and CUL4-associated factor 12 (DCAF12)

DDB1- and CUL4-associated factor 12 (DCAF12) is a substrate receptor within the CRL4 (CUL4–DDB1) E3 ubiquitin ligase complexes, acting via the DesCEND (destruction via C-end degrons) pathway. DCAF12 specifically recognizes and binds proteins that have specific C-terminal degron motifs, most notably a diglutamate (Glu-Glu) sequence, and promotes their ubiquitination and proteasomal degradation. This pathway targets both full-length and cleaved forms of proteins, affecting protein quality control and cellular homeostasis. Well-characterized substrates include CCT5, MAGEA3/MAGEA6, and MOV10, with documented functional implications in autophagy, spermatogenesis, T cell function, and synaptic regulation. As a WD40 repeat-containing protein, DCAF12 forms a β-propeller structure critical for substrate interaction. It has been studied as a cancer/testis antigen and has roles in reproductive and neuronal tissues. No drugs directly targeting DCAF12 are currently known, but its molecular function is relevant for research into ubiquitin-mediated degradation, cellular stress responses, and cancer biology.

Other names

CT102KIAA1892TCC52WDR40AWD repeat-containing protein 40Acentrosome-related protein TCC52testis cancer centrosome-related proteincancer/testis antigen 102DKFZP434O125MGC1058

Promotes ubiquitination and subsequent proteasomal degradation of target proteins carrying specific C-terminal degron motifs (primarily di-glutamate but also glutamate-leucine)