Tchem FZD4 Frizzled-4

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

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

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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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

Active Ligands (2)

Explore Active Ligands

1 – 2 of 2

FzM1

FZD4Tchem GPCR

- : 6.19999981

FzM1.8

FZD4Tchem GPCR

EC50 : 6.4000001

GWAS Traits (6)

• Explore on Target Illumination GWAS Analytics (TIGA)

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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)

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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

Reset Zoom  Beta Count   Odds Ratio

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

Protein Structure (7 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q9ULV1-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 7

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (70)

Reactome (20)

KEGG (13)

PathwayCommons (30)

WikiPathways (7)

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

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Find Similar Targets

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5

1 – 5 of 20

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

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

Protein-Protein Interactions (249)

Explore Interacting Targets

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

Publication Statistics

PubMed Score  178.05

PubMed score by year

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PubTator Score  93.95

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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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