AXIN

Axin is a family of cytoplasmic scaffold proteins that regulate the Wnt/β-catenin signaling pathway. In humans, two related genes, AXIN1 and AXIN2, encode the proteins Axin-1 and Axin-2, respectively. Both proteins participate in the β-catenin destruction complex, assembling with APC, GSK3, and CK1 to promote phosphorylation and degradation of β-catenin in the absence of Wnt signals. When Wnt ligands bind to their receptors, the destruction complex is inhibited, β-catenin accumulates and enters the nucleus to drive transcription of Wnt target genes.

AXIN2 is notable as a Wnt target gene, creating a negative feedback loop that helps moderate signaling by increasing Axin-2 levels when Wnt is active. This autoregulatory mechanism contributes to the fine-tuning of pathway output.

Structurally, Axin proteins contain an N-terminal regulatory region (including an RGS-like domain), a central β-catenin–binding region, and a C-terminal DIX domain that mediates self-assembly and interactions with Dishevelled, enabling coordinated assembly of the destruction complex.

Genetic and clinical relevance includes associations of AXIN1 mutations with several cancers, including hepatocellular carcinoma and desmoid-type fibromatosis. AXIN2 germline mutations are linked to tooth agenesis (such as hypodontia or oligodontia) and may confer an increased risk of colorectal neoplasia in some families.

Axin homologs are broadly conserved across metazoans, reflecting a fundamental role in Wnt signaling. In model organisms like Drosophila, a single axin gene performs a similar scaffolding function within the Wingless/Wnt pathway.