CD344 FZD4 (frizzled homolog 4), Frizzled-4, Fz-4, hFz-4, FzE4
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Lung
Brain
Kidney
Liver
60 / 60

Expression
CD344 is largely expressed in kidney, lung, brain and liver.  There is moderate expression in pancreas, and spleen with lowl expression in placenta, prostate, testis and colon.  Expression is also by fetal neuronal progentior cells and neuronal intestinal cells.

Structure
MOLECULAR FAMILY NAME: Belongs to the G-protein coupled receptor, Frizzled family.

CD344 is a multi-pass type-3 501 aa glycoprotein.  It contains an 186 aa extracellular N-terminus domain which contains a cysteine-rich ligand binding domain with 2 cysteine residues in the second and third extracellular loops and 2 N-linked glycosylation sites, 7 transmembrane-spanning domains and 39 aa cytoplasmic C-terminal domain that contains a Lys-Thr-X-X-X-Trp motif.  This motif is the binding site for PDZ-domain containing proteins and is essential for activation of the Wnt/β-catenin pathway.  Most frizzled receptors are coupled to the β-catenin canonical signaling pathway, which leads to the activation of dishevelled proteins, inhibition of GSK-3 kinase, nuclear accumulation of β-catenin and activation of Wnt target genes.  A second 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 pathways, as PKC seem to be required for Wnt-mediated inactivation of GSK-3 kinase.  Both pathways seem to involved interactions with G-proteins.  This protein may play a role as a positive regulator of Wnt integration site signaling pathway.  Studies suggest that CD344 may form heterodimers.  

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD344 has 2 N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD344

The CD344 domain is involved with Wnt proteins and norrin (Norrie disease pseudoglioma homolog).

Function

CD344 is a marker for neuronal stem cells.  CD344 is essential for the regulation of tissue and cell polarity, embryonic development, regulation of proliferation and many other processes in developing and adult organisms.  CD344 is a receptor for Wnt proteins and norrie and participates in the activation of the Wnt/β-catenin pathway (canonical Wnt signaling) and is involved in coupling to members of the G proteins.  These interactions with G-proteins may be involved in transduction and intercellular transmission of information during tissue morphogenesis and/or in differentiated tissues.  

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD344 IN INTACT ANIMAL
 
Defects in CD344 are a cause of familial exudative vitreoretinopathy 1 (FEVR), a retinal disease which is characterized by a failure of peripheral retinal vasculatization leading to retinal degeneration and associated progressive hearing loss indicating that CD344 plays a role retinal angiogenesis.  Patients with FEVR carry mutations in CD344.  Defects also cause Criswick-Schepens syndrome, a retinal neovascularization disease.  CD344 mice are infertile due to impaired corpora lutea formation and function.  They exhibit vascular defects in the retina, cochlea, cerebullum and defects in cell survival in the cerebullum as well as progressive dysfunction and distention of the esophagus. 



Comments
MOLECULAR INTERACTION-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD344: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD344: No information.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8322Q9ULV1
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University