Tchem FZD4 Frizzled-4

Protein Summary

Description

Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9ULV1
• A8K9Q3
• Q14C97
• Q6S9E4
• Fz-4

Gene Name

• FZD4

Ensembl ID

• ENST00000531380
• ENSP00000434034
• ENSG00000174804

Symbol

• Fz4
• EVR1
• FEVR
• Fz-4
• FzE4
• GPCR
• hFz4
• CD344
• FZD4S

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.96
histone modification site profile	0.79
transcription factor perturbation	0.74
molecular function	0.73
protein domain	0.73

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Frizzled-4

Protein / Receptor / G-protein Coupled Receptor / Frizzled-4

Protein / ... / Protease Inhibitor / Frizzled-4

DTO Classes

Protein / G-protein Coupled Receptor / Class F Frizzled-type / Frizzled Receptor / Frizzled-4

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: 178.05   (req: < 5)

Gene RIFs: 55   (req: <= 3)

Antibodies: 465   (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: 178.05   (req: >= 5)

Gene RIFs: 55   (req: > 3)

Antibodies: 465   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 35

Tchem

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

Active Ligands: 2

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

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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 (2)

Explore Active Ligands

1 – 2 of 2

FzM1

FZD4Tchem GPCR

-log(-) : 6.2

FzM1.8

FZD4Tchem GPCR

pEC50 : 6.4

Protein-Protein Interactions (249)

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1 – 10 of 249

• See Interactions on String-DB

TSPAN15

Tbio

Novelty:  0.16947672

p_int:  0.9990887

p_ni:  0.000911039

p_wrong:  2.61e-7

Data Source:  BioPlex

CD47

Tchem

Novelty:  0.00129086

p_int:  0.94978833

p_ni:  0.047096797

p_wrong:  0.003114873

Data Source:  BioPlex

MPZL1

Tbio

Novelty:  0.03292508

p_int:  0.88257275

p_ni:  0.115654736

p_wrong:  0.001772514

Data Source:  BioPlex

CERS6

Tbio

Family:  TF

Novelty:  0.01956925

p_int:  0.83434176

p_ni:  0.161825612

p_wrong:  0.003832628

Data Source:  BioPlex

YIPF3

Tbio

Novelty:  0.12021667

p_int:  0.777086619

p_ni:  0.222912919

p_wrong:  4.62e-7

Data Source:  BioPlex

NDP

Tbio

Novelty:  0.01020963

Score:  0.997

Data Source:  STRINGDB

WNT5A

Tbio

Novelty:  0.00125563

Score:  0.988

Data Source:  Reactome,STRINGDB

LRP5

Tbio

Novelty:  0.00089807

Score:  0.988

Data Source:  STRINGDB

DVL2

Tbio

Novelty:  0.00833084

Score:  0.986

Data Source:  Reactome,STRINGDB

WNT2

Tbio

Novelty:  0.00313614

Score:  0.986

Data Source:  STRINGDB

Nearest Tclin Targets (9)

Explore Nearest Tclin Targets

Upstream (7)

Downstream (2)

1 – 5 of 7

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  10

1: Gastric cancer

2: mTOR signaling pathway

3: Cushing syndrome

4: Breast cancer

more:  6 more common pathways

BRAF

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  7

1: Gastric cancer

2: mTOR signaling pathway

3: Cushing syndrome

4: Breast cancer

more:  3 more common pathways

MAP2K2

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  10

1: Gastric cancer

2: mTOR signaling pathway

3: Cushing syndrome

4: Breast cancer

more:  6 more common pathways

RAF1

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  9

1: Gastric cancer

2: mTOR signaling pathway

3: Breast cancer

4: Signaling pathways regulating pluripotency of stem cells

more:  5 more common pathways

EGFR

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  7

1: Gastric cancer

2: Cushing syndrome

3: Breast cancer

4: Hepatocellular carcinoma

more:  3 more common pathways

Pathways (70)

Reactome (20)

KEGG (13)

PathwayCommons (30)

WikiPathways (7)

Asymmetric localization of PCP proteins (R-HSA-4608870)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Asymmetric localization of PCP proteins	65 targets	R-HSA-4608870
Reactome	Beta-catenin independent WNT signaling	146 targets	R-HSA-3858494
Reactome	Ca2+ pathway	61 targets	R-HSA-4086398
Reactome	Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Reactome	Class B/2 (Secretin family receptors)	97 targets	R-HSA-373080

Name	Explore in Pharos	Explore in Source
Asymmetric localization of PCP proteins	65 targets	R-HSA-4608870
Beta-catenin independent WNT signaling	146 targets	R-HSA-3858494
Ca2+ pathway	61 targets	R-HSA-4086398
Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Class B/2 (Secretin family receptors)	97 targets	R-HSA-373080

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (43)

Functions (11)

Components (8)

Processes (24)

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Items per page:

10

1 – 10 of 11

GO Term	Evidence	Assigned by
PDZ domain binding	Inferred from Direct Assay (IDA)	UniProtKB
Wnt-activated receptor activity	Inferred from Direct Assay (IDA)	BHF-UCL
amyloid-beta binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
cytokine binding	Inferred from Physical Interaction (IPI)	BHF-UCL
protein heterodimerization activity	Inferred from Physical Interaction (IPI)	BHF-UCL
protein homodimerization activity	Inferred from Physical Interaction (IPI)	BHF-UCL
protein-containing complex binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
Wnt-protein binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
signaling receptor activity	Inferred from Sequence or structural Similarity (ISS)	ARUK-UCL

Disease Associations ()

No disease associations found

GWAS Traits (6)

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1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	3	2	4		93.7
blood urea nitrogen measurement	EFO_0004741	1	1	1		56.6
cup-to-disc ratio measurement	EFO_0006939	2	2	2		54.3
serum urea measurement	EFO_0009795	1	1	1		36.9
bone density	EFO_0003923	1	1	1		15.8

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	4		93.7
blood urea nitrogen measurement	EFO_0004741	1		56.6
cup-to-disc ratio measurement	EFO_0006939	2		54.3
serum urea measurement	EFO_0009795	1		36.9
bone density	EFO_0003923	1		15.8

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UniProt Keyword Find Similar Targets

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3D-structure
Cell membrane
Complete proteome
Developmental protein
Disease mutation
Disulfide bond
G-protein coupled receptor
Glycoprotein
Membrane
Polymorphism

GWAS Trait Find Similar Targets

No Header	No Header
blood urea nitrogen measurement
bone density
calcaneal bone quantitative ultrasound measurement
cup-to-disc ratio measurement
heel bone mineral density
serum urea measurement

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
homeostasis/metabolism phenotype
integument phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	frizzled class receptor 4	VGNC:11783	466732
Macaque	frizzled class receptor 4		704754
Mouse	frizzled class receptor 4	MGI:108520	14366
Rat	frizzled class receptor 4	RGD:71017	64558
Dog	frizzled class receptor 4	VGNC:41032	485149

Species	Name	OMA	EggNOG	Inparanoid
Chimp	frizzled class receptor 4
Macaque	frizzled class receptor 4
Mouse	frizzled class receptor 4
Rat	frizzled class receptor 4
Dog	frizzled class receptor 4

Publication Statistics

PubMed Score 178.05

PubMed score by year

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PubTator Score 93.95

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Patents

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Related Publications

Text Mined References (80)

GeneRif Annotations (55)

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PMID	Year	Title