Recombinant Human Frizzled-3 (FZD3) Protein

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 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. Activation by Wnt5A stimulates PKC activity via a G protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, 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. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner (By similarity)

Subcellular Location

Membrane (Multi-pass membrane protein); Cell membrane (Multi-pass membrane protein); Cell surface; Apical cell membrane (Multi-pass membrane protein)

Tissue Specificity

Widely expressed. Relatively high expression in the CNS, including regions of the limbic system, in kidney, pancreas, skeletal muscle, uterus and testis

Subunit

Interacts with VANGL2

• Kirikoshi H. et al. Molecular cloning and genomic structure of human frizzled-3 at chromosome 8p21. — Biochem. Biophys. Res. Commun. (2000)
• Sala C.F. et al. Identification, gene structure and expression of human frizzled-3 (FZD3). — Biochem. Biophys. Res. Commun. (2000)
• Hung B.S. et al. Characterization of mouse frizzled-3 expression in hair follicle development and identification of the human homolog in keratinocytes. — J. Invest. Dermatol. (2001)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Zhang Z. et al. Signal peptide prediction based on analysis of experimentally verified cleavage sites. — Protein Sci. (2004)
• De Marco P. et al. FZD6 is a novel gene for human neural tube defects. — Hum. Mutat. (2012)