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FLASH GENE
Symbol AXIN2 contributors: mct/shn - updated : 07-11-2023
HGNC name axin 2
HGNC id 904
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinesmall intestine  highly Homo sapiens
 intestinelarge intestinecolon lowly Homo sapiens
Endocrineadrenal gland   moderately
 parathyroid   moderately
Lymphoid/Immunethymus   highly Homo sapiens
Nervousnerve   highly
Reproductivefemale systemovary  highly Homo sapiens
 male systemtestis  highly Homo sapiens
 male systemprostate  highly Homo sapiens
Respiratorylung   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral   
cell lineage immature oligodendrocyte progenitor cells in white matter lesions of human newborns with neonatal hypoxic-ischemic and gliotic brain damage (
cell lines
fluid/secretion blood
at STAGE
physiological period embryo
Text embryonic tissue
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal regulation of G protein signaling (RGS)
  • the GSK and the beta catenin binding domains
  • a dishevelled (DSH/DIX) homology domain
  • conjugated PhosphoP
    mono polymer homomer , heteromer , oligo
    HOMOLOGY
    interspecies ortholog to axin2, Danio rerio
    ortholog to Axin2, Rattus norvegicus
    ortholog to Axin2, Mus musculus
    intraspecies homolog to AXIN1
    Homologene
    FAMILY
    CATEGORY chaperone/stress , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • located to centrosome by binding to CEP250 (Hadjihannas 2010)
  • also present in the nucleus
  • basic FUNCTION
  • promoting the GSK3B dependent phosphorylation of beta catenin (CTNNB1)
  • negatively regulates both expansion of osteoprogenitors and maturation of osteoblasts through its modulation on Wnt/beta-catenin signaling
  • promotes centrosome cohesion by phosphorylating CTNNB1 at centrosomes (Hadjihannas 2010)
  • negative regulator of beta-catenin, localizes at the centrosomes by binding to the centriole-associated component CEP250
  • essential for normal kinetics of remyelination (
  • serves as a negative regulator of canonical WNT signaling in normal cells
  • tumor suppressor function of AXIN2 in normal cells is most likely coopted by cancer cells to promote, rather than suppress, key aspects of the cancer progression program
  • RUNX2 and AXIN2 regulate craniofacial development and skeletal maintenance
  • nuclear AXIN2 functions likely as a rheostat to control MYC expression in response to WNT/CTNNB1 signaling
  • AXIN1 and AXIN2 do not have equivalent functions in satellite cells, but are both involved in repression of WNT/CTNNB1 signalling to maintain proliferation and contribute to controlling timely myogenic differentiation
  • critical role for AXIN2 during ocular development, likely by restricting the activity of the WNT/CTNNB1 pathway
  • AXIN2-expressing cells produce a source of WNT that acts in an autocrine manner to modulate reparative dentinogenesis
  • AXIN2 gene plays a crucial role in morphogenesis of craniofacial area and is essential for tooth development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    negative regulator of the signaling Wnt pathway through interaction with GSK3B and beta catenin
    a component
  • complex of APC, beta catenin, GSK3B
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • glycogen synthase kinase 3beta and beta-catenin (
  • adenomatous polyposis coli and Smad3 (
  • acts as a potent promoter of carcinoma behavior by up-regulating the activity of the transcriptional repressor, SNAI1, inducing a functional epithelial-mesenchymal transition (EMT) program and driving metastatic activity
  • FOXM1 directly bound to and increased transcriptional activity of the AXIN2 promoter region
  • RUNX2 binds several regions of the AXIN2 promoter and RUNX2-mediated repression of AXIN2 transcription depends on HDAC3
  • cell & other
    REGULATION
    repressed by RUNX2, HDAC3, that repress AXIN2 transcription in osteoblasts
    Other phosphorylated by GSK3B and dephosphorylated by PP2A
    ASSOCIATED DISORDERS
    corresponding disease(s) FTACC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in breast cancer, neuroblastoma and others tumors
    tumoral   amplification    
    colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling (
    tumoral   LOH    
    in hepatocellular, colorectal and ovarian carcinoma
    tumoral somatic mutation      
    in hepatocellular carcinoma and hepatoblastoma
    tumoral       loss of function
    in colon cancer
    tumoral        
    frameshift mutations are common in gastric carcinoma with high microsatellite instability (MSI) and may contribute to development of gastric cancers with high MSI by deregulating the Wnt signaling in the affected cancer cells (
    constitutional       loss of function
    leads to supraphysiological WNT levels that disrupt hematopoietic stem cells differentiation and thymocyte development
    tumoral     --low  
    independently associated with more aggressive prostate cancer (PCa), biochemical recurrence, and metastasis-free survival after Radical prostatectomy (RP)
    constitutional germinal mutation      
    could be a potential cause in human calvarial malformations, especially for the sagittal synostosis
    Susceptibility
  • to carcinogenesis in microsatellite instability + colorectal carcinomas
  • to CRC (colorectal cancer)
  • Variant & Polymorphism SNP
  • two SNPs might be related to Hirschsprung disease (Zhonghua 2008)
  • epigenetic silencing of AXIN2 is specifically associated with carcinogenesis in microsatellite instability + colorectal carcinomas (
  • loss-of-function AXIN2 variants were strongly associated with genetic predisposition to CRC
  • Candidate gene strong candidate in multiple tumor types
    Marker
  • AXIN2, a classical WNT reporter gene, is a marker for endometrial stem cells that also serve as the cells of origin for endometrial cancer
  • Therapy target
    SystemTypeDisorderPubmed
    neurology  
    an essential regulator of remyelination and that it might serve as a pharmacological checkpoint in this process
    ANIMAL & CELL MODELS
    disruption of Axin2 in mice induces skeletal defects, a phenotype resembling craniosynostosis in humans