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

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen frizzled homolog protein glycoprotein

Properties

SIZE: entity length = 537 aa MW = 60 kD COMPARTMENT: plasma membrane MOTIF: exoplasmic domain {1-222} MOTIF: signal sequence {1-36} frizzled domain {40-161} cysteine residue {C45} MODIFICATION: cysteine residue {C106} cysteine residue {C53} MODIFICATION: cysteine residue {C99} N-glycosylation site {N59} cysteine residue {C90} MODIFICATION: cysteine residue {C128} cysteine residue {C99} MODIFICATION: cysteine residue {C53} cysteine residue {C106} MODIFICATION: cysteine residue {C45} cysteine residue {C117} MODIFICATION: cysteine residue {C158} cysteine residue {C121} MODIFICATION: cysteine residue {C145} cysteine residue {C128} MODIFICATION: cysteine residue {C90} N-glycosylation site {N144} cysteine residue {C145} MODIFICATION: cysteine residue {C121} cysteine residue {C158} MODIFICATION: cysteine residue {C117} transmembrane domain {223-243} cytoplasmic loop {244-254} transmembrane domain {255-275} exoplasmic loop {276-302} transmembrane domain {303-323} cytoplasmic loop {324-344} transmembrane domain {345-365} exoplasmic loop {366-389} transmembrane domain {390-410} cytoplasmic loop {411-436} transmembrane domain {437-457} exoplasmic loop {458-477} transmembrane domain {478-498} cytoplasmic domain {499-537} MOTIF: Lys-Thr-X-X-X-Trp {499-504} PDZ recognition motif NAME: PDZ recognition motif SITE: 535-537 FOR-BINDING-VIA: PDZ domain

Database Correlations

OMIM correlations MORBIDMAP 604579 UniProt Q9ULV1 PFAM correlations Entrez Gene 8322 Kegg hsa:8322