Tbio FZD3 Frizzled-3

Protein Summary

Description

Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. 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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner (By similarity). 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. The function of this protein is unknown, although it may play a role in mammalian hair follicle development. Alternative splicing results in multiple transcript variants. This gene is a susceptibility locus for schizophrenia. [provided by RefSeq, Dec 2010]

Uniprot Accession IDs

• Q9NPG1
• A8K615
• Fz-3

Gene Name

• FZD3

Ensembl ID

• ENST00000240093
• ENSP00000240093
• ENSG00000104290
• ENST00000537916
• ENSP00000437489

Symbol

• Fz-3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.88
PubMedID	0.78
protein domain	0.73
pathway	0.68
biological process	0.67

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Frizzled-3

Protein / Receptor / G-protein Coupled Receptor / Frizzled-3

Protein / ... / Protease Inhibitor / Frizzled-3

DTO Classes

Protein / G-protein Coupled Receptor / Class F Frizzled-type / Frizzled Receptor / Frizzled-3

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: 120.73   (req: < 5)

Gene RIFs: 22   (req: <= 3)

Antibodies: 420   (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: 120.73   (req: >= 5)

Gene RIFs: 22   (req: > 3)

Antibodies: 420   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 27

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

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

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 (129)

Explore Interacting Targets

1 – 10 of 129

• See Interactions on String-DB

VNN2

Tbio

Novelty:  0.02286648

p_int:  0.999883026

p_ni:  0.000116955

p_wrong:  1.9e-8

Data Source:  BioPlex

XAGE1A

Tbio

Novelty:  0.04421526

p_int:  0.999789754

p_ni:  0.000210203

p_wrong:  4.4e-8

Data Source:  BioPlex

UPK1A

Tbio

Novelty:  0.01748122

p_int:  0.999788027

p_ni:  0.000055802

p_wrong:  0.000156171

Data Source:  BioPlex

GPR21

Tdark

Family:  GPCR

Novelty:  0.90865557

p_int:  0.999513608

p_ni:  0.000398671

p_wrong:  0.000087721

Data Source:  BioPlex

SYNE4

Tbio

Novelty:  0.0739848

p_int:  0.999377269

p_ni:  0.000353119

p_wrong:  0.000269612

Score:  0.198

Data Source:  BioPlex,STRINGDB

ADGRG5

Tdark

Family:  GPCR

Novelty:  0.26575982

p_int:  0.999086792

p_ni:  0.000906767

p_wrong:  0.000006442

Data Source:  BioPlex

ZBBX

Tdark

Novelty:  1.66474399

p_int:  0.874832977

p_ni:  0.012378008

p_wrong:  0.112789015

Score:  0.215

Data Source:  BioPlex,STRINGDB

VANGL2

Tbio

Novelty:  0.00529796

Score:  0.989

Data Source:  Reactome,STRINGDB

WNT5A

Tbio

Novelty:  0.00125563

Score:  0.985

Data Source:  STRINGDB

DVL2

Tbio

Novelty:  0.00833084

Score:  0.984

Data Source:  STRINGDB

Nearest Tclin Targets (9)

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Upstream (7)

Downstream (2)

1 – 5 of 7

RAF1

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  11

1: Axon guidance

2: Gastric cancer

3: mTOR signaling pathway

4: Breast cancer

more:  7 more common pathways

MAP2K2

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  11

1: Gastric cancer

2: mTOR signaling pathway

3: Cushing syndrome

4: Breast cancer

more:  7 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

MAP2K1

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  11

1: Gastric cancer

2: mTOR signaling pathway

3: Cushing syndrome

4: Breast cancer

more:  7 more common pathways

EGFR

Tclin

Family:  Kinase

KEGG Distance:  5

Common Pathways:  8

1: Gastric cancer

2: Cushing syndrome

3: Breast cancer

4: Hepatocellular carcinoma

more:  4 more common pathways

Pathways (64)

Reactome (9)

KEGG (15)

PathwayCommons (30)

WikiPathways (10)

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

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Find Similar Targets

Items per page:

5

1 – 5 of 9

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	Class B/2 (Secretin family receptors)	97 targets	R-HSA-373080
Reactome	GPCR ligand binding	460 targets	R-HSA-500792

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
Class B/2 (Secretin family receptors)	97 targets	R-HSA-373080
GPCR ligand binding	460 targets	R-HSA-500792

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (38)

Functions (4)

Components (11)

Processes (23)

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Items per page:

10

1 – 4 of 4

GO Term	Evidence	Assigned by
PDZ domain binding	Inferred from Physical Interaction (IPI)	UniProtKB
Wnt-protein binding	Inferred from Physical Interaction (IPI)	UniProtKB
Wnt-activated receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
G protein-coupled receptor activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (3)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
brain measurement	EFO_0004464	1	1	0	8.7	59.8
cortical thickness	EFO_0004840	1	1	0	6.6	36.4
cortical surface area measurement	EFO_0010736	1	1	0	6.6	6.7

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 3 of 3

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
brain measurement	EFO_0004464	0	8.7	59.8
cortical thickness	EFO_0004840	0	6.6	36.4
cortical surface area measurement	EFO_0010736	0	6.6	6.7

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
Alternative splicing
Cell membrane
Complete proteome
Developmental protein
Direct protein sequencing
Disulfide bond
G-protein coupled receptor
Glycoprotein
Membrane
Neurogenesis

GWAS Trait Find Similar Targets

No Header	No Header
brain measurement
cortical surface area measurement
cortical thickness

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
embryo phenotype
homeostasis/metabolism phenotype
limbs/digits/tail phenotype
mortality/aging
nervous system phenotype
respiratory system phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	frizzled class receptor 3	VGNC:868	472726
Macaque	frizzled class receptor 3		713839
Mouse	frizzled class receptor 3	MGI:108476	14365
Rat	frizzled class receptor 3	RGD:628814	266715
Dog	frizzled class receptor 3	VGNC:41031	486093

Species	Name	OMA	EggNOG	Inparanoid
Chimp	frizzled class receptor 3
Macaque	frizzled class receptor 3
Mouse	frizzled class receptor 3
Rat	frizzled class receptor 3
Dog	frizzled class receptor 3

Publication Statistics

PubMed Score 120.73

PubMed score by year

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PubTator Score 45.70

PubTator score by year

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Patents

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Related Publications

Text Mined References (41)

GeneRif Annotations (22)

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10

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PMID	Year	Title