Evolutionary analysis through structural modeling of FAM222 proteins reveals a novel disordered conserved domain in vertebrates that interacts with NLK.

ABSTRACT: Intrinsically disordered regions (IDRs) play essential roles in signaling by mediating protein-protein interactions that are both dynamic and specific. Many IDRs have evolved as kinase-binding modules, particularly in mitogen-activated protein kinase (MAPK) networks, where they facilitate critical regulatory interactions for signaling specificity. However, the evolutionary constraints that shape IDRs and their role in MAPK regulation remain poorly understood. Here, we identify DCD222, a highly conserved IDR within the FAM222 protein family, which interacts with Nemo-like kinase (NLK), an atypical MAPK involved in WNT, NOTCH, VEGF, mTOR, and TGF-β signaling. Phylogenetic analysis reveals that DCD222 has been conserved from cyclostomes to humans, indicating strong evolutionary constraints on

SUBMITTER: Calvario E 

PROVIDER: S-EPMC12690120 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature