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FLASH GENE
Symbol AXIN1 contributors: mct/pgu - updated : 28-08-2015
HGNC name axin 1
HGNC id 903
Location 16p13.3      Physical location : 337.439 - 402.464
Synonym name
  • axis inhibitor 1
  • fused, mouse, homolog of
  • axis inhibition protein 1
  • Synonym symbol(s) AXIN, MGC52315
    DNA
    TYPE functioning gene
    STRUCTURE 65.03 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC390662 16 similar to DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11; DEAD/H box-11 (CHL1-related helicase gene-1); yeast CHL1 homolog CXYorf1P 16p13.3 pseudogene of CXYorf1 POLR3K 16p13.3 polymerase (RNA) III (DNA directed) polypeptide K, 12.3 kDa C16orf33 16p13.3 chromosome 16 open reading frame 33 RHBDF1 16p13.3 rhomboid family 1 (Drosophila) MPG 16p13.3 N-methylpurine-DNA glycosylase C16orf35 16p13.3 chromosome 16 open reading frame 35 HBZ 16p13.3 hemoglobin, zeta HBZP 16p13.3 hemoglobin, zeta pseudogene HBAP2 16p13.3 hemoglobin, alpha pseudogene 2 HBAP1 16p13.3 hemoglobin, alpha pseudogene 1 HBA2 16p13.3 hemoglobin, alpha 2 HBA1 16p13.3 hemoglobin, alpha 1 HBQ1 16p13.3 hemoglobin, theta 1 LUC7L 16p13.3 LUC7-like (S. cerevisiae) DKFZP761D0211 16p13.3 hypothetical protein DKFZp761D0211 PDIP 16p13.3 protein disulfide isomerase, pancreatic RGS11 16p13.3 regulator of G-protein signalling 11 ARHGDIG 16p13.3 Rho GDP dissociation inhibitor (GDI) gamma AXIN1 16p13.3 axin 1 MRPL28 16p13.3 mitochondrial ribosomal protein L28 TMEM8 16p13.3 transmembrane protein 8 (five membrane-spanning domains) LOC388197 16 hypothetical gene supported by BC028568 NME4 16p13 non-metastatic cells 4, protein expressed in DECR2 16p13.3 2,4-dienoyl CoA reductase 2, peroxisomal
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3477 95.5 862 - 2009 19331826
    10 - 3369 91.5 826 - 2009 19331826
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Lymphoid/Immunetonsils   highly
    Reproductivefemale systemuteruscervix highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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 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
    HOMOLOGY
    interspecies homolog to murine Axin
    homolog to C.elegans c34f11.5
    Homologene
    FAMILY
    CATEGORY chaperone/stress , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    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
  • 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
  • TRIM65 exerted oncogenic activities via ubiquitylation of AXIN1 to activate the CTNNB1 signaling pathway
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    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
    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)
    ANIMAL & CELL MODELS
    AxinFu mice