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FLASH GENE

Symbol

AXIN1

contributors: mct/pgu - updated : 07-11-2023

HGNC name	axin 1
HGNC id	903

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive stomach       highly Lymphoid/Immune tonsils       highly Reproductive female system uterus cervix   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 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer digestive liver AXIN1 may be a potential target for gene therapy of primary hepatocellular carcinoma (HCC) (PMID: 23879168) cancer digestive colon colonic AXIN1 signature offers therapeutic perspectives for Colorectal cancer immunology infectious   potential therapeutic of targeting Axin1 against influenza virus infection cancer reproductive breast 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