AXIN1

AXIN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1DK8, 1EMU, 1O9U, 3ZDI, 4B7T, 4NM0, 4NM3, 4NM5, 4NM7, 4NU1
Identifiers
Aliases	AXIN1, AXIN, PPP1R49, axin 1
External IDs	MGI: 1096327 HomoloGene: 2614 GeneCards: AXIN1
Gene ontology Molecular function • beta-catenin binding • protein homodimerization activity • I-SMAD binding • GTPase activator activity • signal transducer activity • protein binding • identical protein binding • enzyme binding • receptor signaling complex scaffold activity • SMAD binding • ubiquitin protein ligase binding • protein complex scaffold • armadillo repeat domain binding • protein kinase binding Cellular component • cytoplasm • cytosol • lateral plasma membrane • membrane • postsynaptic density • plasma membrane • cytoplasmic, membrane-bounded vesicle • cell cortex • perinuclear region of cytoplasm • cytoplasmic microtubule • cytoplasmic vesicle • nucleus • beta-catenin destruction complex • cell periphery Biological process • regulation of catenin import into nucleus • Wnt signaling pathway involved in somitogenesis • forebrain anterior/posterior pattern specification • negative regulation of fat cell differentiation • positive regulation of protein phosphorylation • olfactory placode formation • positive regulation of protein catabolic process • activation of JUN kinase activity • positive regulation of canonical Wnt signaling pathway • embryonic eye morphogenesis • negative regulation of Wnt signaling pathway • cellular response to organic cyclic compound • cell death • cellular protein complex assembly • positive regulation of JNK cascade • negative regulation of transcription elongation from RNA polymerase II promoter • positive regulation of peptidyl-serine phosphorylation • dorsal/ventral axis specification • positive regulation of transcription, DNA-templated • multicellular organism development • optic placode formation • determination of left/right symmetry • canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation • positive regulation of ubiquitin-protein transferase activity • positive regulation of peptidyl-threonine phosphorylation • positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process • cytoplasmic microtubule organization • canonical Wnt signaling pathway • embryonic skeletal joint morphogenesis • axial mesoderm formation • positive regulation of protein ubiquitination • activation of protein kinase activity • muscle cell development • Wnt-activated signaling pathway involved in forebrain neuron fate commitment • negative regulation of canonical Wnt signaling pathway • signal transduction • apoptotic process • beta-catenin destruction complex disassembly • positive regulation of GTPase activity • proteasome-mediated ubiquitin-dependent protein catabolic process • Wnt signaling pathway • beta-catenin destruction complex assembly Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8312	12005
Ensembl	ENSG00000103126	ENSMUSG00000024182
UniProt	O15169	O35625
RefSeq (mRNA)	NM_003502 NM_181050	NM_001159598 NM_009733
RefSeq (protein)	NP_003493.1 NP_851393.1	NP_033863.2
Location (UCSC)	Chr 16: 0.29 – 0.35 Mb	Chr 17: 26.14 – 26.2 Mb
PubMed search	[1]	[2]
Wikidata

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.^[3]

Function

This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.^[4]

Structure

The full-length human protein comprises 862 amino acids with a (predicted) molecular mass of 96 kDa. The N-terminal RGS domain, a GSK3 kinase interacting peptide of Axin1 and homologs of the C-terminal DIX domains have been solved at atomic resolution. Large WNT-downregulating central regions have been characterized as intrinsically disordered by biophysical experiments and bioinformatic analysis.^[5] Biophysical destabilization of the folded RGS domain induces formation of nanoaggregates that expose and locally concentrate intrinsically disordered regions, which in turn misregulate Wnt signalling. Many other large IDPs are affected by missense mutations, such as BRCA1, Adenomatous polyposis coli(APC), CREB-binding protein/(CBP) and might be affected in similar ways by missense mutations of their folded domains.^[6]

Interactions

AXIN1 has been shown to interact with:

References

Further reading

PDB gallery
1dk8: CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN  1emu: STRUCTURE OF THE AXIN RGS-HOMOLOGOUS DOMAIN IN COMPLEX WITH A SAMP REPEAT FROM APC  1wsp: Crystal structure of axin dix domain  2d5g: Structure of ubiquitin fold protein R767E mutant