| Substrate | Recognition Motif/Mechanism | Post-translational Modification Requirement | Biological Context/Function | Citation |
|---|---|---|---|---|
| Lyn (Src family kinase) | Direct recognition by DCAF10 of an N-terminal acetylated glycine (Ac-Gly) degron in a DCAF10 β-propeller pocket; binding is favored by sequence features near positions 3-4 and weakened by acidic residues at positions 5-7; full-length Lyn interacts with DCAF10 and is directly ubiquitinated by reconstituted CUL4A-DDB1-DCAF10 | Requires initiator methionine removal and N-terminal acetylation of Gly2; becomes especially relevant when N-myristoylation is reduced or absent; Gly2 identity is critical, as G2A/G2P mutants strongly reduce DCAF10-dependent ubiquitination | Quality-control degradation of improperly N-myristoylated Src-family kinases; regulates Lyn abundance and links cotranslational N-terminal modification state to proteasomal turnover | (pqac-00000002, pqac-00000008, pqac-00000009, pqac-00000010) |
| Fyn (Src family kinase) | Direct DCAF10 binding to acetylated N-terminus, analogous to Lyn; robust pull-down with acetylated peptide and direct ubiquitination by reconstituted CUL4A-DDB1-DCAF10 | Requires an N-terminal acetylated Gly2; effect is enhanced under NMT1/2 depletion, consistent with competition between myristoylation and acetylation/failure states | Controls Fyn turnover when N-myristoylation fails, acting in an Ac-Gly/N-degron-like surveillance pathway parallel to ZYG11B/ZER1-mediated Gly/N-degron control | (pqac-00000000, pqac-00000008, pqac-00000009) |
| Src (Src family kinase) | DCAF10 recognizes acetylated Src N-terminus more weakly/shallowly than Lyn or Fyn, but still supports DCAF10-dependent ubiquitination in vitro and increased Src abundance after DCAF10 depletion | Requires N-terminal processing compatible with Ac-Gly recognition; dependence on the canonical Ac-Gly pocket appears weaker than for Lyn/Fyn, suggesting additional or shallower binding contacts | Extends DCAF10 surveillance to Src-family signaling proteins, potentially buffering aberrant non-myristoylated Src species | (pqac-00000000, pqac-00000008, pqac-00000009) |
| RUVBL1/2 | Identified in DCAF10 immunoprecipitates; adenoviral E1A promotes assembly of a DCAF10-containing CRL4 complex that targets RUVBL1/2 for proteasomal degradation | No specific substrate PTM requirement was defined for DCAF10 recognition in this context; degradation depends on Cullin-RING ligase activity and viral E1A-assisted CRL4 assembly | Loss of RUVBL1/2 suppresses IRF3 stabilization and interferon-stimulated gene activation, linking DCAF10 to innate immune control, multiprotein-machine assembly, and stress-response pathways | (pqac-00000003, pqac-00000005, pqac-00000006) |
| ALOX15B | DCAF10 binds depalmitoylated ALOX15B and promotes its association with DDB1/CUL4A; AlphaFold/co-IP mapping supports interaction between the ALOX15B N-terminal region and the DCAF10 WD40 region; DCAF10 promotes K48-linked ubiquitination and degradation | Requires prior ABHD17C-mediated depalmitoylation; mutation of ALOX15B C106 or blockade of depalmitoylation alters DCAF10 association; K175 in ALOX15B is implicated as a key ubiquitin-acceptor site | In KRAS-mutant pancreatic ductal adenocarcinoma, DCAF10-dependent ALOX15B degradation contributes to ferroptosis evasion and tumor progression | (pqac-00000011) |
| IRF3 (indirect) | DCAF10 depletion increases IRF3 protein without increasing IRF3 mRNA, but IRF3 was not detected as a direct DCAF10 interactor; current evidence supports indirect regulation, likely through DCAF10-dependent degradation of upstream factors such as RUVBL1/2 in the adenoviral system | No direct PTM-dependent recognition by DCAF10 has been demonstrated; effect depends on DCAF10 and Cullin-based ligase function in infected or uninfected epithelial cells | Negative regulation of innate immunity and interferon-stimulated gene expression; exploited by adenovirus to blunt antiviral responses | (pqac-00000004, pqac-00000005, pqac-00000006) |


*Table: This table summarizes the best-supported DCAF10 substrates and substrate-like targets, highlighting how DCAF10 recognizes them, what post-translational states are required, and the biological contexts in which these interactions matter. It is useful for separating direct DCAF10 substrates from cases, such as IRF3, where the evidence currently supports indirect regulation.*