FZD6

This gene represents a member of the 'frizzled' gene family, which encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The protein encoded by this family member contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, and seven transmembrane domains, but unlike other family members, this protein does not contain a C-terminal PDZ domain-binding motif. This protein functions as a negative regulator of the canonical Wnt/beta-catenin signaling cascade, thereby inhibiting the processes that trigger oncogenic transformation, cell proliferation, and inhibition of apoptosis. Alternative splicing results in multiple transcript variants, some of which do not encode a protein with a predicted signal peptide.[provided by RefSeq, Aug 2011]

Frizzled Class Receptor 6

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. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, 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 (By similarity).

Canonical Wnt signaling pathway Source: GO_Central
Cell proliferation in midbrain Source: Ensembl
Embryonic nail plate morphogenesis Source: Ensembl
Establishment of body hair planar orientation Source: Ensembl
Hair follicle development Source: Ensembl
Inner ear morphogenesis Source: Ensembl
Midbrain morphogenesis Source: ParkinsonsUK-UCL
Negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
Negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
Neural tube closure Source: Ensembl
Non-canonical Wnt signaling pathway Source: BHF-UCL
Platelet activation Source: Ensembl
Wnt signaling pathway, planar cell polarity pathway Source: ParkinsonsUK-UCL

Endoplasmic reticulum membrane; Cell membrane; Apical cell membrane; Membrane; Cell surface; Cytoplasmic vesicle membrane. Colocalizes with FZD3 at the apical face of cells (By similarity). Localizes to the endoplasmic reticulum membrane in the presence of LMBR1L (By similarity).

Nail disorder, non-syndromic congenital, 1 (NDNC1):
An autosomal recessive nail disorder characterized by a variable degree of onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals. No other anomalies of ectodermal tissues, including hair, teeth, sweat glands, or skin, are noted, and individuals with dysplastic nails have normal hearing and normal psychomotor development. Rare non-synonymous variants in FZD6 may contribute to neural tube defects, congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy.

Extracellular: 19-201
Helical: 202-222
Cytoplasmic: 223-233
Helical: 234-254
Extracellular: 255-284
Helical: 285-305
Cytoplasmic: 306-324
Helical: 325-345
Extracellular: 346-370
Helical: 371-391
Cytoplasmic: 392-416
Helical: 417-437
Extracellular: 438-473
Helical: 474-494
Cytoplasmic: 495-706

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.