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FLASH GENE
Symbol AXIN1 contributors: mct/pgu - updated : 07-11-2023
HGNC name axin 1
HGNC id 903
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal regulation of G protein signaling (RGS), a domain, which is similar to that of proteins that accelerate the GTPase activity of heterotrimeric Galpha/Gna proteins and thereby limit the duration of active G-protein signaling
  • a central region, implicated in binding GSK3B and CTNNB1, is natively unfolded , a large intrinsically disordered region (IDR)
  • a bipartite nuclear localization signal (NLS)
  • and a C-terminal Dvl-Axin-interacting (DIX) domain , C-terminal region (aa 597-832)is responsible for its interaction with PML
  • mono polymer homomer , heteromer , oligo
    HOMOLOGY
    interspecies homolog to murine Axin
    homolog to C.elegans c34f11.5
    Homologene
    FAMILY
    CATEGORY chaperone/stress , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleolus
    text
  • localizes to the centrosome and along mitotic spindles
  • localization to centrosomes and mitotic spindles, requires Aurora kinase activity
  • AXIN1, TNKS2 and KIF3A are co-localized with SLC2A4 on the trans-Golgi network
  • basic FUNCTION
  • promoting the GSK3B dependent phosphorylation of beta catenin CTNNB1
  • regulation of the embryonic axis formation
  • modulates distribution of Axin-associated proteins such as PLK1 and GSK3B in an expression level-dependent manner and these interactions affect the mitotic process, including cytokinesis under certain conditions, such as in the presence of Aurora kinase inhibitor
  • may be an important molecular target in hepatocellular carcinomas as well as other cancers with compromised Axin1 function
  • key regulator of multiple signalling pathways
  • is involved in microtubule nucleation by forming a complex with gamma-tubulin at the centrosome
  • PML and the key Wnt signaling regulator AXIN1 regulate TP53-dependent apoptosis in response to DNA damage
  • promotes PML sumoylation, a modification necessary for PML functions
  • its expression facilitates cell death induced by aurora kinase inhibition through PARP activation
  • negative regulator of Wnt/beta-catenin signaling via regulating the level of beta-catenin
  • 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
  • AXIN1 has redundant function with AXIN2 for WNT down-regulation and infers a new role for AXIN1
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    negative regulator of the signaling Wnt pathway through interaction with GSK3B and beta catenin
    a component
  • regulatory subunit
  • AXIN1, PML and TP53 form a ternary complex
  • STRAP, GSK3B and Axin form a ternary complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Gsk-3b
  • regulating CTNNB1 mediated response through oligomerization of its C terminus
  • Lrp5
  • .gamma-catenin
  • APC
  • DVL
  • PP2A
  • activates TGF-beta signaling by forming a multimeric complex consisting of SMAD7 and ubiquitin E3 ligase RNF111
  • CDH2-axin1-LRP5 interaction negatively regulates Wnt/beta-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass
  • interacting with ZBED3 through the "PPPPSPT" motif
  • associates with the transactivation domain of MYC- dependent on S62 phosphorylation
  • interacting with DAB2 (could attenuate Wnt/beta-catenin signaling by stabilizing AXIN1 and preventing its translocation to the membrane
  • SMURF2 is an E3 ubiquitin ligase for AXIN1
  • PRMT1 directly interacts with and methylates the 378th arginine residue of AXIN1 (methylation of AXIN1 by PRMT1 may serve as a finely tuned regulation mechanism for Wnt/CTNNB signaling)
  • functions downstream of the CTNNB1 destruction complex to control the stability of AXIN1 and opposes its TNKS-dependent ubiquitination
  • bivalent binding of AXIN1 to TNKS is required for AXIN1 turnover, since mutations in either gate-binding glycine residue in AXIN1 lead to its stabilization in the cell
  • interacts with TNKS2 and the kinesin motor protein KIF3A, forming a ternary complex crucial for SLC2A4 translocation in response to insulin
  • degradation of cytosolic CTNNB1 by the APC/AXIN1 destruction complex represents the key regulated step of the WNT pathway
  • involved in protein modification, ubiquitin cycle
  • HECTD1 promotes the APC-AXIN1 interaction to negatively regulate WNT signaling
  • MDM2 can inhibit AXIN1-stimulated TP53-dependent apoptosis by suppressing TP53 phosphorylation at Ser 46 and apoptosis-related TP53 transactivational activity
  • APC2 functions at the embryonic cortex with several protein partners, including AXIN1, to promote mitotic fidelity
  • AXIN1 and NFE2L2 physically associated in a protein complex that was regulated by WNT3A, involving the central region of AXIN1 and the Neh4/Neh5 domains of NFE2L2
  • AXIN1 is a VDR target gene provides novel and fundamental insights into the interactions between the VDR and CTNNB1 signaling pathways
  • TRIM65 exerted oncogenic activities via ubiquitylation of AXIN1 to activate the CTNNB1 signaling pathway
  • SAPCD2, a tumor-specific protein, is a novel AXIN1-interacting protein
  • UCHL5 is required for both the stabilization and the polymerization of AXIN1 proteins
  • UCHL5 controls CTNNB1 destruction complex function through AXIN1 regulation
  • is the principal coordinator of the CTNNB1 destruction complex, bringing all its major components in close proximity and thereby vastly accelerating CTNNB1 phosphorylation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CMDOH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in hepatocellular (late event for malignant progression), colorectal, ovarian carcinoma, hepatoblastoma and medulloblastoma
    tumoral     --low  
    hypermethylated AXIN1 gene significantly correlates with the progression of lung cancer
    constitutional     --low  
    during influenza virus infection
    constitutional       loss of function
    Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation
    Susceptibility
    Variant & Polymorphism
    Candidate gene candidate in multiple tumor types; for caudal duplication (murine model)
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    AXIN1 may be a potential target for gene therapy of primary hepatocellular carcinoma (HCC) (PMID: 23879168)
    cancerdigestivecolon
    colonic AXIN1 signature offers therapeutic perspectives for Colorectal cancer
    immunologyinfectious 
    potential therapeutic of targeting Axin1 against influenza virus infection
    cancerreproductivebreast
    AXIN1 is a potential target for the management of ER(+) breast cancer
    ANIMAL & CELL MODELS
  • AxinFu mice
  • Axin1 deficiency in intestinal epithelial cells rendered mice more susceptible to chemically induced colon carcinogenesis, but reduced dextran sulfate sodium-induced colitis by attenuating the induction of a proinflammatory program