APC2

This gene encodes a strongly conserved protein that has an N-terminal coiled-coil domain followed by an armadillo domain, five 20-amino acid repeats, and two SAMP domains. This protein promotes the assembly of a multiprotein complex that recruits and phosphorylates the Wnt effector beta-catenin and targets beta-catenin for ubiquitylation and proteasomal degradation. This protein therefore plays a role in the reduction of cytoplasmic levels of beta-catenin which in turn reduces activation of Wnt target genes that play a pivotal role in the pathogenesis of various human cancers. The protein encoded by this gene is closely related to the adenomatous polyposis coli (APC) tumor-suppressor protein and has similar tumor-suppressor effects. This gene also plays a role in actin assembly, cell-cell adhesion, and microtubule network formation through its interaction with cytoskeletal proteins. This gene has its highest expression in the central nervous system and is involved in brain development through cytoskeletal regulation in neurons. Alternative splicing produces multiple transcript variants encoding distinct isoforms.

Full Name

APC regulator of WNT signaling pathway 2

Function

Stabilizes microtubules and may regulate actin fiber dynamics through the activation of Rho family GTPases (PubMed:25753423).
May also function in Wnt signaling by promoting the rapid degradation of CTNNB1 (PubMed:10021369, PubMed:11691822, PubMed:9823329).

Biological Process

Activation of GTPase activity
Cell fate specification
Cell migration
Microtubule cytoskeleton organization
Negative regulation of canonical Wnt signaling pathway
Negative regulation of microtubule depolymerization
Nervous system development
Pattern specification process
Proteasome-mediated ubiquitin-dependent protein catabolic process
Wnt signaling pathway

Cellular Location

Cytoplasm, cytoskeleton
Golgi apparatus
Cytoplasm
Cytoplasm, perinuclear region

Involvement in disease

Intellectual developmental disorder, autosomal recessive 74 (MRT74):
A disorder characterized by intellectual impairment, macrocephaly, and dysmorphic features. Epilepsy with eyelid myoclonus has also been reported.
Cortical dysplasia, complex, with other brain malformations 10 (CDCBM10):
An autosomal recessive disorder of aberrant neuronal migration during brain development. CDCBM10 is clinically characterized by onset in infancy of global developmental delay, impaired intellectual development, seizures, inability to ambulate, and absent language. Brain imaging shows lissencephaly, cortical dysplasia, subcortical heterotopia, and paucity of white matter.