Tbio AXIN1 Axin-1

Protein Summary

Description

Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (PubMed:12192039, PubMed:27098453). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway (PubMed:12192039). In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B (PubMed:12192039). Likely to function as a tumor suppressor. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (PubMed:16601693). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development (PubMed:17210684). Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation (PubMed:17210684). 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 beta-1, glycogen synthase kinase 3 beta, protein phosphate 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 medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Uniprot Accession IDs

• O15169
• Q4TT26
• Q4TT27
• Q86YA7
• Q8WVW6
• Q96S28

Gene Name

• AXIN1

Ensembl ID

• ENST00000262320
• ENSP00000262320
• ENSG00000103126
• ENST00000354866
• ENSP00000346935

Symbol

• AXIN
• AXIN
• PPP1R49

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	0.95
hub protein	0.92
phosphatase	0.9
protein domain	0.85

Protein Classes

DTO Classes

Syntaxin-12 / Syntaxin-18 / Syntaxin-16 / Syntaxin-11 / Syntaxin-17 / Syntaxin-10 / Syntaxin-1a / Syntaxin-19 / Syntaxin-1b

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 467.96   (req: < 5)

Gene RIFs: 103   (req: <= 3)

Antibodies: 477   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 467.96   (req: >= 5)

Gene RIFs: 103   (req: > 3)

Antibodies: 477   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 32

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (344)

Explore Interacting Targets

1 – 10 of 344

• See Interactions on String-DB

GSK3A

Tclin

Family:  Kinase

Novelty:  0.00925708

p_int:  1

Score:  0.994

Data Source:  BioPlex,STRINGDB

WDYHV1

Tbio

Family:  Enzyme

Novelty:  0.1844203

p_int:  0.774650241

p_ni:  0.000001701

p_wrong:  0.225348058

Score:  0.224

Data Source:  BioPlex,STRINGDB

CTNNB1

Tchem

Novelty:  0.0000744

Score:  0.999

Data Source:  STRINGDB

GSK3B

Tclin

Family:  Kinase

Novelty:  0.00095115

Score:  0.999

Data Source:  Reactome,STRINGDB

APC

Tchem

Novelty:  0.00168376

Score:  0.999

Data Source:  STRINGDB

LRP5

Tbio

Novelty:  0.00089807

Score:  0.997

Data Source:  STRINGDB

SIAH1

Tbio

Family:  Enzyme

Novelty:  0.00831224

Score:  0.997

Data Source:  STRINGDB

LRP6

Tbio

Novelty:  0.00305615

Score:  0.996

Data Source:  Reactome,STRINGDB

DVL1

Tchem

Novelty:  0.00356876

Score:  0.996

Data Source:  Reactome,STRINGDB

TNKS

Tchem

Family:  Enzyme

Novelty:  0.00404545

Score:  0.992

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets (2)

Explore Nearest Tclin Targets

Upstream (1)

Downstream (1)

1 – 1 of 1

GSK3B

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  12

1: Gastric cancer

2: Cushing syndrome

3: Breast cancer

4: Signaling pathways regulating pluripotency of stem cells

more:  8 more common pathways

Pathways (87)

Reactome (36)

KEGG (12)

PathwayCommons (22)

WikiPathways (17)

AMER1 mutants destabilize the destruction complex (R-HSA-4839748)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	AMER1 mutants destabilize the destruction complex	14 targets	R-HSA-4839748
Reactome	APC truncation mutants have impaired AXIN binding	14 targets	R-HSA-5467337
Reactome	AXIN missense mutants destabilize the destruction complex	14 targets	R-HSA-5467340
Reactome	AXIN mutants destabilize the destruction complex, activating WNT signaling	14 targets	R-HSA-4839735
Reactome	Beta-catenin phosphorylation cascade	17 targets	R-HSA-196299

Name	Explore in Pharos	Explore in Source
AMER1 mutants destabilize the destruction complex	14 targets	R-HSA-4839748
APC truncation mutants have impaired AXIN binding	14 targets	R-HSA-5467337
AXIN missense mutants destabilize the destruction complex	14 targets	R-HSA-5467340
AXIN mutants destabilize the destruction complex, activating WNT signaling	14 targets	R-HSA-4839735
Beta-catenin phosphorylation cascade	17 targets	R-HSA-196299

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (40)

Functions (12)

Components (8)

Processes (20)

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GO Term	Evidence	Assigned by
beta-catenin binding	Inferred from Direct Assay (IDA)	BHF-UCL
protein-containing complex scaffold activity	Inferred from Direct Assay (IDA)	BHF-UCL
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
I-SMAD binding	Inferred from Physical Interaction (IPI)	BHF-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
SMAD binding	Inferred from Physical Interaction (IPI)	BHF-UCL
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
armadillo repeat domain binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
protein homodimerization activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
protein kinase binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL

Disease Associations ()

No disease associations found

GWAS Traits (31)

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1 – 5 of 31

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular hemoglobin concentration	EFO_0004528	10	14	20		99.7
heel bone mineral density	EFO_0009270	3	8	15		98.9
erythrocyte count	EFO_0004305	6	8	12		98.1
red blood cell distribution width	EFO_0005192	7	5	9		97.4
mean corpuscular hemoglobin	EFO_0004527	3	5	5		97

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular hemoglobin concentration	EFO_0004528	20		99.7
heel bone mineral density	EFO_0009270	15		98.9
erythrocyte count	EFO_0004305	12		98.1
red blood cell distribution width	EFO_0005192	9		97.4
mean corpuscular hemoglobin	EFO_0004527	5		97

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
ADP-ribosylation
Alternative splicing
Apoptosis
Cell membrane
Complete proteome
Cytoplasm
Developmental protein
Disease mutation
Isopeptide bond

GWAS Trait Find Similar Targets

No Header	No Header
analgesia requirement measurement
balding measurement
bilirubin measurement
body height
body mass index
bone density
erythrocyte count
femoral neck bone mineral density
ferritin measurement
glucose measurement

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
limbs/digits/tail phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	axin 1	VGNC:5679	453789
Mouse	axin 1	MGI:1096327	12005
Dog	axin 1	VGNC:38324	490099
Horse	axin 1	VGNC:15716	100065116
Cow	axin 1	VGNC:26364	504357

Species	Name	OMA	EggNOG	Inparanoid
Chimp	axin 1
Mouse	axin 1
Dog	axin 1
Horse	axin 1
Cow	axin 1

Publication Statistics

PubMed Score 467.96

PubMed score by year

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PubTator Score 290.74

PubTator score by year

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Related Publications

Text Mined References (188)

GeneRif Annotations (103)

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PMID	Year	Title