InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Fzd4

Summary

InnateDB Protein

IDBP-198318.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Fzd4

Protein Name

frizzled homolog 4 (Drosophila)

Synonyms

Fz4;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000049852

InnateDB Gene

IDBG-198316 (Fzd4)

Protein Structure

UniProt Annotation

Function

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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. {ECO:0000269PubMed:10097073, ECO:0000269PubMed:19837033}.

Subcellular Localization

Membrane {ECO:0000269PubMed:10097073}; Multi-pass membrane protein {ECO:0000269PubMed:10097073}. Cell membrane {ECO:0000269PubMed:10097073}; Multi-pass membrane protein {ECO:0000269PubMed:10097073}.

Disease Associations

Tissue Specificity

Expressed in chondrocytes.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	11 [view]
Protein-Protein	10 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004888	transmembrane signaling receptor activity
GO:0004930	G-protein coupled receptor activity
GO:0005515	protein binding
GO:0017147	Wnt-protein binding
GO:0019955	cytokine binding
GO:0030165	PDZ domain binding
GO:0031625	ubiquitin protein ligase binding
GO:0042803	protein homodimerization activity
GO:0042813	Wnt-activated receptor activity
GO:0046982	protein heterodimerization activity

Biological Process

GO:0001553	luteinization
GO:0001568	blood vessel development
GO:0001570	vasculogenesis
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0007166	cell surface receptor signaling pathway
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007223	Wnt receptor signaling pathway, calcium modulating pathway
GO:0007605	sensory perception of sound
GO:0010812	negative regulation of cell-substrate adhesion
GO:0016055	Wnt signaling pathway
GO:0030947	regulation of vascular endothelial growth factor receptor signaling pathway
GO:0031987	locomotion involved in locomotory behavior
GO:0034446	substrate adhesion-dependent cell spreading
GO:0035426	extracellular matrix-cell signaling
GO:0042701	progesterone secretion
GO:0043507	positive regulation of JUN kinase activity
GO:0045893	positive regulation of transcription, DNA-templated
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0060070	canonical Wnt signaling pathway
GO:0061299	retina vasculature morphogenesis in camera-type eye
GO:0061301	cerebellum vasculature morphogenesis
GO:0061304	retinal blood vessel morphogenesis

Cellular Component

GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0042995	cell projection
GO:0070062	extracellular vesicular exosome