Function: May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In response to WNT3 stimulation, receptor C-terminal cleavage occurs in its transmembrane region and allows the C-terminal intracellular product to translocate from the cytoplasm to the nucleus where it plays a crucial role in neuronal development. Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure: Interacts with DVL1 (via PDZ domain). Ref.7
Subcellular location: Membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm. Note: In cells that have undergone neuronal differentiation, the C-terminal cleaved part is translocated from the cytoplasm to the nucleus. Ref.10
Tissue specificity: Is detected in all the tissues. Highest levels are seen in the ovary, lung and placenta.
Developmental stage: Highest expression at E16 when callosal axons are beginning to cross the midline. At E17-E18, when the majority of axons are projecting away from the midline, expression is observed but at a lower level. Present on the cell bodies of neurons in cortical layers at E18. Ref.9 Ref.10
Domain: The extracellular WIF domain is responsible for Wnt binding. Ref.7
Post-translational modification: Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Ref.10
Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family.Contains 1 protein kinase domain.Contains 1 WIF domain.
Sequence caution: The sequence AAA40079.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.The sequence AAA40079.1 differs from that shown. Reason: Frameshift at positions 17 and 28.
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