Alternative titles; symbols
HGNC Approved Gene Symbol: FZD3
Cytogenetic location: 8p21.1 Genomic coordinates (GRCh38): 8:28,494,212-28,574,258 (from NCBI)
Drosophila cuticle hairs are arranged in a defined polarity that is genetically controlled by 'frizzled,' a 7-transmembrane receptor with a large extracellular N-terminal cysteine-rich domain (CRD). Members of the FZD family are receptors for secreted WNT glycoproteins (see 602863), which are involved in developmental control. FZD proteins transmit signals through the beta-catenin (CTNNB1; 116806) or JNK (e.g., JNK3; 602897) pathways. The selection of intracellular signaling cascade may be determined by different C-terminal motifs in FZD proteins.
By PCR on a gastric cancer cDNA library with degenerate primers based on mouse Fzd3, followed by screening a fetal brain cDNA library, Kirikoshi et al. (2000) isolated a cDNA encoding human FZD3. Sequence analysis predicted that the 666-amino acid FZD3 protein, which is 98% identical to mouse Fzd3, contains an N-terminal CRD, 7 transmembrane domains, 2 cys residues in the second and third extracellular loops, and 3 N-linked glycosylation sites. Northern blot analysis revealed expression of 14.0-, 9.0-, 4.0-, and 1.8-kb FZD3 transcripts mostly in central nervous system (CNS) tissue. The largest transcript predominated in fetal brain and adult cerebellum, and the 1.8-kb transcript predominated in adult pancreas and in many cancer cell lines. Kirikoshi et al. (2000) proposed that FZD3 may play a role in neurogenesis during embryogenesis.
By in silico and PCR analyses, Sala et al. (2000) cloned FZD3. RT-PCR and quantitative TaqMan analysis detected wide expression of FZD3, with highest levels in the limbic areas of the CNS and significant levels in testis, kidney, and uterus, as well as in a neuroblastoma cell line.
By genomic sequence analysis, Kirikoshi et al. (2000) determined that the FZD3 gene contains 8 exons. Sala et al. (2000) estimated that the FZD3 gene spans 48 kb and has 6 exons.
By FISH, Kirikoshi et al. (2000) mapped the FZD3 gene to 8p21, a region associated with loss of heterozygosity in human tumors.
Sala et al. (2000) determined that the FZD3 gene maps distal to the NFL gene (162280) on 8p21. They mapped the mouse gene to chromosome 14, between the Gja3 and Nfl genes in a region showing homology of synteny to human 8p21. Sala et al. (2000) noted that the human FZD3 gene is in close proximity to a putative schizophrenia susceptibility locus (SCZD6; 603013) and that WNT signaling is abnormal in some schizophrenic patients.
Kirikoshi, H., Koike, J., Sagara, N., Saitoh, T., Tokuhara, M., Tanaka, K., Sekihara, H., Hirai, M., Katoh, M. Molecular cloning and genomic structure of human Frizzled-3 at chromosome 8p21. Biochem. Biophys. Res. Commun. 271: 8-14, 2000. [PubMed: 10777673] [Full Text: https://doi.org/10.1006/bbrc.2000.2578]
Sala, C. F., Formenti, E., Terstappen, G. C., Caricasole, A. Identification, gene structure, and expression of human frizzled-3 (FZD3). Biochem. Biophys. Res. Commun. 273: 27-34, 2000. [PubMed: 10873558] [Full Text: https://doi.org/10.1006/bbrc.2000.2882]