frizzled-4; Fz-4; hFz4; FzE4; CD344 (FZD4)

Function

• 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 & activation of Wnt target genes
• a second signaling pathway involving PKC & Ca+2 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 & intercellular transmission of polarity information during tissue morphogenesis &/or in differentiated tissues
• interacts with MAGI3 & norrin (NDP)
• component of a complex, at least composed of TSPAN12, FZD4 & norrin (NDP)

Structure

• Lys-Thr-X-X-X-Trp motif is involved in the activation of the Wnt/beta-catenin signaling pathway (putative)
• FZ domain is involved in binding with Wnt ligands
• belongs to the G-protein coupled receptor Fz/smo family
• contains 1 FZ (frizzled) domain

Compartment

membrane

Expression

• almost ubiquitous
• largely expressed in adult heart, skeletal muscle, ovary, & fetal kidney
• moderate amounts in adult liver, kidney, pancreas, spleen, & fetal lung
• small amounts in placenta, adult lung, prostate, testis, colon, fetal brain & liver

Pathology

• defects in FZD4 are the cause of vitreoretinopathy exudative type 1

More general terms

• frizzled homolog protein
• glycoprotein
• CD antigen

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8322
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8322
• OMIM: https://mirror.omim.org/entry/133780
• OMIM: https://mirror.omim.org/entry/604579
• UniProt: http://www.uniprot.org/uniprot/Q9ULV1.html