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Symbol AXIN1 contributors: mct/pgu - updated : 28-08-2016
HGNC name axin 1
HGNC id 903
  • 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 bipartite nuclear localization signal (NLS)
  • a C terminal dishevelled (DSH/DIX) homology domains, C-terminal region (aa 597-832)is responsible for its interaction with PML
  • mono polymer homomer , heteromer , oligo
    interspecies homolog to murine Axin
    homolog to C.elegans c34f11.5
    CATEGORY chaperone/stress , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
  • 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
    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
    small molecule
  • 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
  • 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
  • cell & other
    corresponding disease(s)
    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
    Variant & Polymorphism
    Candidate gene candidate in multiple tumor types; for caudal duplication (murine model)
    Therapy target
    AXIN1 may be a potential target for gene therapy of primary hepatocellular carcinoma (HCC) (PMID: 23879168)
    AxinFu mice