Tbio ZNRF3 E3 ubiquitin-protein ligase ZNRF3

Protein Summary

Description

E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone (PubMed:22575959). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (By similarity).

Uniprot Accession IDs

• Q9ULT6
• B3KU18
• Q6ICH1
• Q6NTF8
• Q8WU18

Gene Name

• ZNRF3

Ensembl ID

• ENST00000402174
• ENSP00000384456
• ENSG00000183579
• ENST00000406323
• ENSP00000384553
• ENST00000544604
• ENSP00000443824

Symbol

• KIAA1133
• RNF203
• RNF203
• BK747E2.3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
cell type or tissue	0.76
histone modification site profile	0.74
transcription factor	0.71
tissue sample	0.63
cell line	0.62

IDG Partner Tools

GlyGen

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: 32.43   (req: < 5)

Gene RIFs: 19   (req: <= 3)

Antibodies: 80   (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: 32.43   (req: >= 5)

Gene RIFs: 19   (req: > 3)

Antibodies: 80   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13

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

GWAS Traits (15)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	8	2	15		99
waist-hip ratio	EFO_0004343	5	3	6		98.9
heel bone mineral density	EFO_0009270	2	4	4		95.7
balding measurement	EFO_0007825	1	1	1		90
type II diabetes mellitus	EFO_0001360	2	2	1	1	78.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	15		99
waist-hip ratio	EFO_0004343	6		98.9
heel bone mineral density	EFO_0009270	4		95.7
balding measurement	EFO_0007825	1		90
type II diabetes mellitus	EFO_0001360	1	1	78.7

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Pathways (6)

Reactome (4)

KEGG (1)

UniProt (1)

Regulation of FZD by ubiquitination (R-HSA-4641263)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Regulation of FZD by ubiquitination	21 targets	R-HSA-4641263
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by WNT	299 targets	R-HSA-195721
Reactome	TCF dependent signaling in response to WNT	204 targets	R-HSA-201681

Name	Explore in Pharos	Explore in Source
Regulation of FZD by ubiquitination	21 targets	R-HSA-4641263
Signal Transduction	2704 targets	R-HSA-162582
Signaling by WNT	299 targets	R-HSA-195721
TCF dependent signaling in response to WNT	204 targets	R-HSA-201681

Gene Ontology Terms (15)

Functions (4)

Components (2)

Processes (9)

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GO Term	Evidence	Assigned by
ubiquitin-protein transferase activity	Inferred from Direct Assay (IDA)	UniProtKB
frizzled binding	Inferred from Physical Interaction (IPI)	UniProtKB
ubiquitin protein ligase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (43)

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1 – 10 of 43

• See Interactions on String-DB

UBE2W

Tbio

Novelty: 0.07255713

p_int: 0.998487338

p_ni: 0.000012133

p_wrong: 0.001500529

Score: 0.22

Data Source: BioPlex,STRINGDB

RSPO2

Tbio

Novelty: 0.0188211

Score: 0.996

Data Source: Reactome,STRINGDB

RSPO1

Tbio

Novelty: 0.00365075

Score: 0.994

Data Source: Reactome,STRINGDB

LGR4

Tbio

Family: GPCR

Novelty: 0.01180123

Score: 0.992

Data Source: Reactome,STRINGDB

LGR5

Tbio

Family: GPCR

Novelty: 0.00105035

Score: 0.987

Data Source: Reactome,STRINGDB

RSPO3

Tbio

Novelty: 0.02321039

Score: 0.984

Data Source: Reactome,STRINGDB

RSPO4

Tbio

Novelty: 0.05670413

Score: 0.982

Data Source: Reactome,STRINGDB

LRP6

Tbio

Novelty: 0.00305615

Score: 0.97

Data Source: Reactome,STRINGDB

LRP5

Tbio

Novelty: 0.00089807

Score: 0.962

Data Source: STRINGDB

LGR6

Tbio

Family: GPCR

Novelty: 0.02186397

Score: 0.96

Data Source: Reactome,STRINGDB

Publication Statistics

PubMed Score  32.43

PubMed score by year

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PubTator Score  21.11

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

Alternative splicing
Cell membrane
Complete proteome
Developmental protein
Membrane
Metal-binding
Reference proteome
Signal
Transferase
Transmembrane

GWAS Trait Find Similar Targets

balding measurement
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
heel bone mineral density
hematocrit
high density lipoprotein cholesterol measurement
intraocular pressure measurement
leukocyte count
lymphocyte percentage of leukocytes
neutrophil percentage of leukocytes

MGI Phenotype Find Similar Targets

embryo phenotype
mortality/aging
nervous system phenotype
vision/eye phenotype