AXIN1

Description

The AXIN1 (axin 1) is a protein-coding gene located on chromosome 16.

Axin-1 is a protein that in humans is encoded by the AXIN1 gene. This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometrioid adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene. The AXIN proteins attract substantial interest in cancer research as AXIN1 and AXIN2 work synergistically to control pro-oncogenic β-catenin signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers. Mutation in AXIN1 can provoke cancerous disease.

AXIN1, also known as Axis inhibition protein 1, is a key component of the beta-catenin destruction complex. It plays a critical role in regulating CTNNB1 levels by promoting its phosphorylation and ubiquitination, which in turn modulates Wnt signaling. AXIN1 exhibits dual effects on dorsoventral patterning: it downregulates CTNNB1 to suppress Wnt signaling and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. Within the Wnt signaling pathway, AXIN1 likely facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Furthermore, AXIN1 is believed to function as a tumor suppressor. It enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. AXIN1 is also a component of the AXIN1-HIPK2-TP53 complex, which regulates cell growth, apoptosis, and development. It facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation.

AXIN1 is also known as AXIN, CMDOH, PPP1R49.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing