Dark Proteome Structural Discovery Dossier — Trilogy IV (Open Science v2.0 Visual Atlas): Chromatin, Neuro-Trafficking & Mitochondrial Metabolism Edition (Q8N8K9 / KIAA1958, O60268 / KIAA0513, Q7Z695 / ADCK2)
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Dark Proteome Hunter — Trilogy IV (5-Part Open Science v2.0 Publication Suite): 3D structural deconvolution, 2D AlphaFold v6 PAE domain boundary verification, DeepMind InterPro-N annotation, and empirical Kabsch crystal superpositions for three clinically linked human Dark Proteome targets: Q8N8K9 (KIAA1958 / PF12012 DUF3504, 716 AA): Resolved as a Bipartite Domesticated Crypton / Cre-Like Tyrosine Recombinase C-Clamp & Kinetochore CBF3/Ndc10 Structural Homolog (AA 414–704). Discovers an unannotated 111-AA N-terminal Cre Recombinase Core-Binding 4-helix bundle (AA 414–524, mean pLDDT 92.17, intra-PAE 3.38 Å; 2.39 Å Core RMSD, TM-score = 0.626 vs. Cre PDB 1PVP_A) paired with an expanded C-terminal Recombinase / CBF3-Ndc10 domain (AA 525–704, mean pLDDT 89.20, intra-PAE 6.35 Å; 3.01 Å Core RMSD, TM-score = 0.563 vs. Cre PDB 1MA7_B & 2.84 Å Core RMSD vs. Ndc10 PDB 3SQI_A). O60268 (KIAA0513 / IPR039872, 411 AA — Zero Prior Pfam Annotation): Linked to prostate carcinoma (GWAS L2G = 0.505) and Alzheimer disease (0.542); physically interacts with KIBRA (WWC1), HCLS1, and NOS3 in human brain. Resolves AA 110–411 as an SBF1/SBF2 (MTMR5/MTMR13) & MADD Multi-Helical Signaling Scaffold (2.56 Å Core RMSD, TM-score = 0.678, Foldseek Prob = 1.000 vs. human MTMR5/SBF1 AF-O95248-F1 AA 581–861) embedding a C-terminal PF12335 (SBF2) 3-helix bundle (AA 290–341, InterPro-N score = 0.9996). Q7Z695 (ADCK2 / PF03109 + PF27536, 626 AA): Linked to human mitochondrial myopathy / CoQ10 deficiency (PMID: 31480808), neurodegeneration (0.642), NSCLC (0.629), and melanoma (0.611). Resolves the unannotated 204-AA N-terminal region (AA 89–292) as the UbiB/COQ8-Family KxGQ (Lys147–Gln150) Substrate-Binding Helical Capsule & Kinase N-Lobe (full superdomain AA 89–619: 2.62 Å Core RMSD, TM-score = 0.727, Prob = 1.000, E = 4.42e-10 vs. human mitochondrial COQ8A + inhibitor CA157 PDB 7UDP_A). Includes 2400×1800 4-panel composite figures, pre-aligned 3D superposition PDB coordinate files and turnkey PyMOL (.pml) sessions, cross-species ortholog MSAs, human genetics/expression JSONs, and official EMBL-EBI Pfam DESC / UniProt Community Curation files.



