Mapping the interactome of recombinant human protein KIAA1143.

KIAA1143 is located within the 3p21.3 chromosomal region, which is frequently deleted in human cancers and enriched for tumor suppressor genes, and encodes an evolutionarily conserved protein; however, its biological functions and relevance to tumor biology remain largely uncharacterized. Here, we performed a comprehensive pan-cancer analysis of KIAA1143 through multi-omics data integration, optimized its prokaryotic expression and purification system, constructed its protein interactome by affinity purification coupled with mass spectrometry (AP-MS), and further predicted its three-dimensional structure by using AlphaFold 2. Our results demonstrate that KIAA1143 is widely expressed in multiple human tissues yet exhibits a marked discrepancy between mRNA and protein levels, suggesting stringent post-transcriptional regulation. Pan-cancer analysis further revealed that KIAA1143 is aberrantly expressed across diverse tumors and bears prominent cancer-specific prognostic relevance, exhibiting a bidirectional "prognostic paradox" in different tumor contexts. Interactome profiling identified 73 high-confidence interacting proteins, which were significantly enriched in key cancer-associated pathways, including oxidative phosphorylation, the ubiquitin-mediated proteolysis, mTOR, and MAPK signaling. Structural prediction indicated that KIAA1143 exhibits extensive intrinsic disorder throughout its full-length sequence. This study presents the first systematic multidimensional characterization of KIAA1143 by delineating its pan-cancer expression pattern, prognostic implication, interactome landscape and structural properties, and suggests that KIAA1143 acts as a novel context-dependent regulatory factor in cancer, providing a robust foundation for future mechanistic and functional investigations.