AXIN2

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Axin 2
Identifiers
Symbols AXIN2 ; AXIL; ODCRCS
External IDs OMIM604025 MGI1270862 HomoloGene3420 ChEMBL: 1255167 GeneCards: AXIN2 Gene
RNA expression pattern
PBB GE AXIN2 gnf1h00059 at tn.png
PBB GE AXIN2 gnf1h00060 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8313 12006
Ensembl ENSG00000168646 ENSMUSG00000000142
UniProt Q9Y2T1 O88566
RefSeq (mRNA) NM_004655 NM_015732
RefSeq (protein) NP_004646 NP_056547
Location (UCSC) Chr 17:
63.52 – 63.56 Mb
Chr 11:
108.92 – 108.95 Mb
PubMed search [1] [2]

Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the AXIN2 gene.[1][2]

Function[edit]

The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway, like its rodent homologs, mouse conductin/rat axil. In mouse, conductin organizes a multiprotein complex of APC (adenomatous polyposis of the colon), beta-catenin, glycogen synthase kinase 3-beta, and conductin, which leads to the degradation of beta-catenin.[2]

Clinical significance[edit]

The deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Mutations in this gene have been associated with colorectal cancer with defective mismatch repair.[2]

The most critical events of teeth, lip and palate formation occur almost concurrently. Hypodontia, defined as the congenital lack of one or more permanent teeth, is the most common dental abnormality found in humans and affects approximately 20% of the population worldwide.[3] AXIS inhibition protein 2 (AXIN2) gene polymorphic variants may be associated with both hypodontia and oligodontia (characterized by the lack of six or more permanent teeth).[4][5] Mutations of this gene have been found in individuals with colorectal carcinomas and liver tumors.[6]

An AXIN2 mutation (1966C>T) detected in a Finnish family was associated with both tooth agenesis and colon neoplasia. In essence, the mutation seems to disrupt tooth development early in life and later contributes to the emergence of polyps and eventually colon cancer, an observation that suggests that the lack of permanent teeth may be an indicator of colon cancer susceptibility.[4] Dentists may at the very least need to remain aware of the possible association, to be able to detect such cases of tooth agenesis and forward the patient to more complete genetic diagnostic examinations. This is a simple example of how molecular genetic discoveries today interact with traditional disciplines (Longtin, 2004).

Interactions[edit]

AXIN2 has been shown to interact with GSK3B.[7][8]

References[edit]

  1. ^ Mai M, Qian C, Yokomizo A, Smith DI, Liu W (May 1999). "Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24". Genomics 55 (3): 341–4. doi:10.1006/geno.1998.5650. PMID 10049590. 
  2. ^ a b c "Entrez Gene: AXIN2 axin 2 (conductin, axil)". 
  3. ^ Vastardis H (June 2000). "The genetics of human tooth agenesis: new discoveries for understanding dental anomalies". Am J Orthod Dentofacial Orthop 117 (6): 650–6. PMID 10842107. 
  4. ^ a b Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P (May 2004). "Mutations in AXIN2 Cause Familial Tooth Agenesis and Predispose to Colorectal Cancer". Am. J. Hum. Genet. 74 (5): 1043–50. doi:10.1086/386293. PMC 1181967. PMID 15042511. 
  5. ^ Mostowska A, Biedziak B, Jagodzinski PP (2006). "Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis". J. Hum. Genet. 51 (3): 262–6. doi:10.1007/s10038-005-0353-6. PMID 16432638. 
  6. ^ Salahshor S, Woodgett JR (March 2005). "The links between axin and carcinogenesis". J. Clin. Pathol. 58 (3): 225–36. doi:10.1136/jcp.2003.009506. PMC 1770611. PMID 15735151. 
  7. ^ von Kries JP, Winbeck G, Asbrand C, Schwarz-Romond T, Sochnikova N, Dell'Oro A, Behrens J, Birchmeier W (September 2000). "Hot spots in beta-catenin for interactions with LEF-1, conductin and APC". Nat. Struct. Biol. 7 (9): 800–7. doi:10.1038/79039. PMID 10966653. 
  8. ^ Schwarz-Romond T, Asbrand C, Bakkers J, Kühl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W (August 2002). "The ankyrin repeat protein Diversin recruits Casein kinase Iε to the β-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling". Genes Dev. 16 (16): 2073–84. doi:10.1101/gad.230402. PMC 186448. PMID 12183362. 

Further reading[edit]

External links[edit]