Skip to main content

Domain

The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2.

Function

Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453, PubMed:28829046). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway (PubMed:12192039). In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (PubMed:16601693). Also a component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development (PubMed:17210684). Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation (PubMed:17210684).

Involvement in disease

Hepatocellular carcinoma

HCC

A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.

None

The gene represented in this entry is involved in disease pathogenesis.

Caudal duplication anomaly

CADUA

A condition characterized by the occurrence of duplications of different organs in the caudal region.

None

The disease is caused by variants affecting the gene represented in this entry. Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.

Craniometadiaphyseal osteosclerosis with hip dysplasia

CMDOH

An autosomal recessive skeletal dysplasia characterized by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings include hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. Bone biopsy shows evidence of increased osteoblast and reduced osteoclast function at the growth plate resorption zone, leading to coarse trabeculae.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1.

ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination at 'Lys-48' and subsequent activation of the Wnt signaling pathway.

Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Sumoylation at Lys-857 and Lys-860 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription. Ubiquitination by SIAH1 and SIAH2 induces its proteasomal degradation as part of the activation of the Wnt signaling pathway (PubMed:28546513).

Tissue specificity

Ubiquitously expressed.

Cellular localization

  • Cytoplasm
  • Nucleus
  • Membrane
  • Cell membrane
  • MACF1 is required for its translocation to cell membrane (By similarity). On UV irradiation, translocates to the nucleus and colocalizes with DAAX (PubMed:17210684).

Alternative names

AXIN, AXIN1, Axin-1, Axis inhibition protein 1, hAxin

Target type

Proteins

Primary research area

Oncology

Molecular weight

95635Da

We found 3 products in 2 categories

Primary Antibodies

Target

Application

Reactive species

Cell Lines & Lysates

Target

Cell type

Species or organism