| Biological Process/Pathway | DCAF10 Role | Molecular Mechanism | Physiological Significance | Disease Association |
|---|---|---|---|---|
| N-degron pathway (Ac-Gly/MO branch) | Substrate receptor in a CUL4A-DDB1-DCAF10 E3 ubiquitin ligase; proposed N-recognin for N-terminally acetylated glycine degrons | Directly binds Ac-Gly N-termini, especially on typically myristoylated proteins; recognition is strengthened by favorable residues near positions 3-4 and weakened by acidic residues around positions 5-7; promotes ubiquitination and proteasomal turnover of substrates such as Lyn/Fyn/Src when myristoylation is reduced or omitted (pqac-00000002, pqac-00000008, pqac-00000009, pqac-00000010) | Provides proteostasis surveillance over proteins that fail proper co-translational N-myristoylation, complementing the ZYG11B/ZER1 Gly/N-degron branch (pqac-00000002, pqac-00000009, pqac-00000010) | Potential relevance to disorders involving aberrant N-terminal processing or proteostasis; mechanistically linked to oncogenic Src-family kinase control (pqac-00000002, pqac-00000009, pqac-00000010) |
| Src kinase signaling | Negative regulator of Src-family kinase abundance under conditions of impaired N-myristoylation | DCAF10 recognizes and promotes ubiquitination of Lyn, Fyn, and Src; in vitro reconstituted CUL4A-DDB1-DCAF10 ubiquitinates these kinases, and DCAF10 depletion stabilizes them, especially after NMT1/2 knockdown (pqac-00000007, pqac-00000009, pqac-00000010) | Limits accumulation of misprocessed SFKs and may fine-tune membrane signaling capacity by coupling N-terminal modification state to protein stability (pqac-00000002, pqac-00000009, pqac-00000010) | Strong relevance to cancer biology because SFKs are major oncogenic signaling proteins (pqac-00000002, pqac-00000010) |
| Innate immunity / IRF3-ISG axis | Suppressor of IRF3 protein accumulation and interferon-stimulated gene activation in epithelial cells | DCAF10 knockdown increases IRF3 protein without increasing IRF3 mRNA, indicating post-transcriptional control; in adenovirus infection, DCAF10 participates in a CRL4 complex assembled by E1A that indirectly prevents IRF3 stabilization, at least in part through targeting RUVBL1/2 (pqac-00000003, pqac-00000006) | Dampens antiviral transcriptional responses and shapes the threshold for ISG induction (pqac-00000003, pqac-00000006) | Relevant to host antiviral defense and viral immune evasion (pqac-00000003, pqac-00000006) |
| Viral infection (adenovirus E1A hijacking) | Hijacked host substrate receptor used by adenovirus E1A to assemble a functional CRL4 ligase complex | WT adenovirus e1a binds DCAF10, promotes association with DDB1 and CUL4A/B, and enables degradation of e1a itself and RUVBL1/2; this suppresses the late interferon response triggered by E1A-mediated inhibition of EP300/CREBBP acetyltransferases (pqac-00000003, pqac-00000004, pqac-00000005, pqac-00000006) | Enhances viral replication by blunting host innate immune signaling and remodeling host proteostasis machinery (pqac-00000003, pqac-00000004, pqac-00000006) | Human adenovirus respiratory infection / viral pathogenesis (pqac-00000003, pqac-00000004, pqac-00000006) |
| RUVBL1/2-dependent stress and immune regulation | Likely substrate-selecting factor for degradation of RUVBL1/2 in the adenoviral context | RUVBL1/2 co-immunoprecipitate with DCAF10; their abundance increases when DCAF10-dependent viral complex formation is disrupted; RUVBL1/2 are required for IRF3 stabilization after EP300/CREBBP inhibition, placing DCAF10 upstream of this stress/immune node (pqac-00000003, pqac-00000006) | Connects DCAF10 to assembly/stability of multiprotein machines involved in antiviral defense, DNA damage/stress responses, and chaperone-dependent complex biogenesis (pqac-00000003, pqac-00000006) | Relevant to infection biology and possibly broader stress-response phenotypes (pqac-00000003, pqac-00000006) |
| Testicular development / spermatogenesis | Probable regulatory DCAF with high testis expression, suggesting specialized reproductive functions | DCAF10 is a WD40/DCAF family member predicted to function as a CRL4 substrate receptor; transcript profiling found Dcaf10 among genes with highest expression in testis, with marked enrichment relative to other tissues in mouse and human datasets (pqac-00000012, pqac-00000013, pqac-00000014) | Suggests a role in germ-cell development, ubiquitin-dependent remodeling, or protein quality control during spermatogenesis, though direct substrate-level evidence in testis remains limited (pqac-00000012, pqac-00000013, pqac-00000014) | Candidate relevance to male fertility / testicular biology (pqac-00000012, pqac-00000013, pqac-00000014) |
| Cancer (pancreatic; ferroptosis evasion) | Promotes degradation of ALOX15B as part of a CUL4/DDB1/DCAF10 ligase axis | Depalmitoylation of ALOX15B by ABHD17C facilitates ALOX15B-DCAF10 interaction; DCAF10 supports association of ALOX15B with DDB1/CUL4A and promotes ubiquitin-dependent degradation, including K48-linked polyubiquitination, lowering ALOX15B and favoring ferroptosis evasion (pqac-00000011) | Links DCAF10 to lipid metabolism, membrane-state sensing, and suppression of ferroptotic tumor restraint pathways (pqac-00000011) | KRAS-mutant pancreatic ductal adenocarcinoma progression and therapy resistance biology (pqac-00000011) |


*Table: This table summarizes the main biological processes and pathways currently linked to human DCAF10, emphasizing its role as a CRL4 substrate receptor in proteostasis, signaling, immunity, reproduction, viral infection, and pancreatic cancer.*