AXIN1

AXIN1 (Axis inhibition protein 1) is a cytosolic scaffold protein that serves as the core component of the beta-catenin destruction complex, which also includes APC, GSK3B, and CK1. AXIN1 coordinates the phosphorylation and subsequent ubiquitination of beta-catenin, thereby negatively regulating the canonical Wnt signaling pathway. Key functional domains include: an N-terminal tankyrase-binding motif, an RGS domain for APC binding, a GSK3B-binding helix (aa 383-400), a beta-catenin binding region, and a C-terminal DIX domain that mediates polymerization and formation of cytoplasmic condensates ("degradasomes"). AXIN1 is regulated by tankyrase-mediated ADP-ribosylation followed by RNF146-dependent ubiquitination and degradation. Loss-of-function mutations in AXIN1 are associated with hepatocellular carcinoma due to aberrant Wnt pathway activation. AXIN1 also has secondary roles in TGF-beta signaling (promoting Smad7 degradation via Arkadia) and JNK signaling, and participates in the AXIN1-HIPK2-TP53 complex upon UV irradiation.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.