DCAF12
Function
Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:16949367, PubMed:16964240, PubMed:29779948). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948). The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:31267705). Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12) complex is required for starvation-induced autophagy (PubMed:31267705). Also directly recognizes the C-terminal glutamate-leucine (Glu-Leu) degron as an alternative degron in proteins such as MOV10, leading to their ubiquitination and degradation. Controls the protein level of MOV10 during spermatogenesis and in T cells, especially after their activation (PubMed:34065512).
Pathway
Protein modification; protein ubiquitination.
Sequence Similarities
Belongs to the WD repeat DCAF12 family.
Tissue Specificity
Highly expressed in lung cancer tissues and some cancer cell lines (PubMed:18957058). Restricted expression in normal testis (PubMed:18957058).
Cellular localization
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Nucleus
Alternative names
KIAA1892, TCC52, WDR40A, DCAF12, DDB1- and CUL4-associated factor 12, Centrosome-related protein TCC52, Testis cancer centrosome-related protein, WD repeat-containing protein 40A