Axin 1 consists of 11 exons (isoform a). Full gene transcript product length is 3675 bp. Isoform b lacks an in-frame exon in the 3 coding region and is shorter with sequence length of 3567 bp (Salahshor and Woodgett, 2005) (Figure 1).

There are two transcript variants. Variant 1 (encoding for isoform a) represents the longer transcript (NM 003502.3). Variant 2 (encoding for isoform b) is shorter compared to variant 1 (NM 181050.2). According to Ensembl there are six transcripts of AXIN1 of which first two are well known isoforms a and b and the remaining 4 are still in research.

Protein name: Axin 1, Axin, Axis inhibitor, Axis inhibitor protein 1.

At least two isoforms of protein axin are expressed. Longer isoform has all eleven exons translated and consists of 862 aminoacids while shorter has 826 aminoacids translated from ten exons. Axin 1 protein can be recognized primarily by two domains, the N-terminal RGS domain (regulators of G-protein signaling) and the C-terminal DIX domain (dishevelled and axin) (Luo et al., 2005; Shibata et al., 2007). RGS domain is needed for APC binding while DIX domain for homodimerization and heterodimerization (Ehebauer and Arias, 2009; Noutsou et al., 2011). There is also a central region of the protein that binds GSK3beta and beta-catenin. Axin protein has nuclear localization (NLS) and nuclear export (NES) sequences as well. It is well known that axin is a scaffold protein that can shuttle between the cytoplasm and the nucleus. Nucleo-cytoplasmatic shuttling under normal circumstances suggests existence of possible "salvage pathway" that would be activated by axin translocation to the nucleus in order to reduce beta-catenin oncogenic activity by exporting nuclear beta-catenin and degrading it in the cytoplasm (Wiechens et al., 2004). Axin can also undergo posttranslational modifications. Phosphorilation by casein kinase 1 (CK1) enhances binding of GSK3beta and AXIN1. For activation of JNK pathway axin needs to be SUMOylated (Kim et al., 2008) (Figure 2).

Axin is expressed ubiquitously.

Axin is predominantlly expressed in the cytoplasm, but periplasmic and nuclear localization are also observed depending on the stimulation of the cells (Cong and Varmus, 2004; Luo and Lin, 2004). In nonstimulated cells, axin colocalizes with Smad3. The subcellular location of axin is not well defined in the literature. It has been reported that physiological concentrations of axin is low in Xenopus egg cells. It has also been shown that it is located in cytoplasmic puncta in living mammalian cells. Wang et al. (2009) report that axin 1 is highly co-localized with beta-catenin in the cytoplasm of human cumulus cells and that this localization denotes intact wnt signaling. Pecina-Slaus et al. (2011) showed the subcellular location of axin in normal brain white matter and glioblastoma tissue. The majority of glioblastomas (69.04%) had axin localized in the cytoplasm. Nevertheless, 9.5% of glioblastomas samples had axin localized in the nucleus (Figure 3). Distribution of axin was reported previously by Anderson et al. (2002) in neoplastic colon. Altered nuclear expression of axin seen in colon polyps and carcinomas may be a consequence of the loss of full-length APC and the advent of nuclear beta-catenin.

Tumor suppressor protein Axin 1 is an inhibitor of the Wnt signaling pathway (Polakis, 2000; Salahshor and Woodgett, 2005). As a scaffold protein, its main role is binding multiple members of Wnt signaling and formation of the beta-catenin destruction complex. It down-regulates beta-catenin, wnt pathways main effector signaling molecule, by facilitating its phosphorylation by GSK3-beta (Hart et al., 1998). It binds directly to APC (adenomatous polyposis coli), beta-catenin, GSK3-beta and dishevelled forming a so called "beta-catenin destruction complex" in which phosphorylated beta-catenin is targeted for quick ubiquitinilation and degradation in the 26S proteosome (Yamamoto et al., 1999; Logan and Nusse, 2004). In response to wnt signaling, or under the circumstances of mutated axin or APC, beta-catenin is stabilized, accumulates in the cytoplasm and enters the nucleus, where it finds a partner, a member of the DNA binding protein family LEF/TCF. Together they stimulate the expression of target genes including c-myc, c-jun, fra-1 and cyclin D1. In developement Axin controls dorsoventral polarity axis formation (Zeng et al., 1997; Wodarz and Nusse, 1998) by two independent mechanisms: downregulation of beta-catenin, but also by activation of Wnt-independent JNK signaling activation. Axin has a role in determining cells fate upon damage, haematopoetic stem cells differentiation (Reya et al., 2003) and transforming growth factor beta signaling (Furuhashi et al., 2001). Reports indicate that beta-catenin and axin regulate critical developmental processes of normal CNS development (Pecina-Slaus, 2010).
Axin interacts with a number of proteins including: APC, Axam, Axin, beta-catenin, Ccd1, CKI, DAXX, DCAP, Diversin, Dvl, gamma-tubulin, GSK3beta, HIPK2, I-mfa, LRP5/LRP6, MDFIC, MEKK1, MEKK4, P53, PIAS, Pirh2, PP2A, Rnf11, Zbed3, Tip60, Smad3, Smad6, and Smad7 (Cliffe et al., 2003; Chen et al., 2009; Fumoto et al., 2009; Li et al., 2009; Choi et al., 2010; Kim and Jho, 2010).

Homologs are found in: Pan troglodytes, Canis lupus familiaris, Bos taurus, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio.

According to HGMD there are 3 missense mutations reported for AXIN 1 in colorectal carcinoma. Nikuseva Martic et al. (2010) identified gross deletions (Loss of Heterozygosity) of AXIN 1 in 6.3% of glioblastomas, in one neuroepithelial dysembrioplastic tumor and in one medulloblastoma. In a primary hepatocellular carcinoma 13 somatic events were reported by OMIM, a 33-bp deletion in exon 3 of the AXIN1 gene, and 12 missense mutations. OMIM also reports on hypermethylation of AXIN 1 promotor region in caudal duplication anomaly.