WNT5A: Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression. Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells. Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes. Interacts with PORCN. Interacts with WLS. Expression is increased in differentiated thyroid carcinomas compared to normal thyroid tissue and anaplastic thyroid tumors where expression is low or undetectable. Expression is found in thyrocytes but not in stromal cells. Belongs to the Wnt family. 2 isoforms of the human protein are produced by alternative splicing.
Protein type: Secreted; Secreted, signal peptide
Chromosomal Location of Human Ortholog: 3p14.3
Cellular Component: cell surface; clathrin-coated vesicle membrane; endoplasmic reticulum lumen; extracellular region; extracellular space; Golgi lumen; plasma membrane; proteinaceous extracellular matrix
Molecular Function: cytokine activity; DNA binding transcription factor activity; frizzled binding; frizzled-2 binding; protein binding; protein domain specific binding; receptor ligand activity; receptor tyrosine kinase-like orphan receptor binding
Biological Process: activation of JNK activity; activation of MAPK activity; activation of protein kinase B activity; anterior/posterior axis specification, embryo; axon guidance; cartilage development; cell fate commitment; cervix development; convergent extension involved in axis elongation; convergent extension involved in organogenesis; embryonic digit morphogenesis; embryonic skeletal system development; epithelial to mesenchymal transition; establishment of epithelial cell apical/basal polarity; establishment of planar polarity; genitalia development; heart looping; hindgut morphogenesis; hypophysis morphogenesis; keratinocyte differentiation; lens development in camera-type eye; lung development; male gonad development; midgut development; negative regulation of apoptosis; negative regulation of axon extension involved in axon guidance; negative regulation of BMP signaling pathway; negative regulation of epithelial cell proliferation; negative regulation of fat cell differentiation; negative regulation of fibroblast growth factor receptor signaling pathway; negative regulation of melanin biosynthetic process; negative regulation of synaptogenesis; negative regulation of transcription, DNA-dependent; neuron differentiation; notochord morphogenesis; olfactory bulb interneuron development; palate development; paraxial mesoderm formation; positive regulation of angiogenesis; positive regulation of cGMP metabolic process; positive regulation of chemokine biosynthetic process; positive regulation of cytokine secretion involved in immune response; positive regulation of endocytosis; positive regulation of endothelial cell proliferation; positive regulation of fibroblast proliferation; positive regulation of inflammatory response; positive regulation of interferon-gamma production; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-6 production; positive regulation of macrophage activation; positive regulation of meiosis; positive regulation of mesenchymal cell proliferation; positive regulation of NF-kappaB transcription factor activity; positive regulation of ossification; positive regulation of peptidyl-serine phosphorylation; positive regulation of protein binding; positive regulation of protein catabolic process; positive regulation of timing of anagen; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; response to organic substance; somitogenesis; urinary bladder development; uterus development; vagina development; Wnt receptor signaling pathway through beta-catenin; Wnt receptor signaling pathway, calcium modulating pathway; Wnt receptor signaling pathway, planar cell polarity pathway; Wnt signaling pathway; wound healing
Disease: Robinow Syndrome, Autosomal Dominant
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