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axin-1; axis inhibition protein 1; hAxin (AXIN1, AXIN)
Function:
- controls dorsoventral patterning via two opposing effects
a) down-regulates beta-catenin to inhibit the Wnt signaling pathway & ventralize embryos
b) dorsalizes embryos by activating a Wnt-independent JNK signaling pathway
- in Wnt signaling, probably facilitates phosphorylation of beta-catenin & APC by GSK3B
- likely to function as a tumor suppressor
- facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation
- wild-type axin1 can induce apoptosis in hepatocellular carcinoma & colorectal cancer cells
- enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase & promoting degradation of inhibitory SMAD7
- probably phosphorylated by GSK3B & dephosphorylated by PP2A
- interacts with TP53 & HIPK2
- probably part of a complex consisting of TP53, HIPK2 & AXIN1
- interacts with glycogen synthase kinase-3 beta (GSK3B) & beta-catenin
- reduces levels of beta-catenin by targeting for proteasomal degradation
- interaction between axin & beta-catenin occurs via the armadillo repeats contained in beta-catenin
- ternary complex also binds to plakoglobin (gamma-catenin), APC, DVL & PP2A
- interacts with SMAD6, SMAD7 & RNF111. interacts with DIXDC1
- prevents interaction with MAP3K1
- interacts with MAP3K4, MDFI & MDFIC
- interacts with ANKRD6
- interacts with AIDA
Structure:
- homodimer (putative)
- contains 1 DIX domain
- contains 1 RGS domain
Compartment: cytoplasm
Alternative splicing:
- named isoforms=2
Expression:
- ubiquitously expressed
Pathology:
- mutations in AXIN1 found in hepatocellular carcinomas [2]
- hypermethylation of the AXIN1 promoter may be associated with caudal duplication anomaly
General
axin
Properties
SIZE: entity length = 862 aa
MW = 96 kD
COMPARTMENT: cytoplasm
MOTIF: RGS {88-211}
TP53 interaction {209-338}
GSK3B interaction {348-433}
beta-catenin interaction {434-502}
MOTIF: Ser phosphorylation site {S493}
RNF111 interaction {507-757}
MOTIF: HIPK2 interaction {677-752}
DIX {780-862}
References
- Clevers H
Axin and hepatocellular carcinomas.
Nature Genetics 24:206-8, 2000
PMID: 10700164
- Satoh S et al
AXIN1 mutations in hepatocellular carcinomas, and growth
suppression in cancer cells by virus-mediated transfer of AXIN1.
Nature genetics 24:245-50, 2000
PMID: 10700176
- Entrez Gene :accession 8312
- UniProt :accession O15169
Databases & Figures
OMIM correlations
UniProt O15169
PFAM correlations
Entrez Gene 8312
Kegg hsa:8312
Wnt1 signalling pathway