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VILIP-1 (Visinin-Like Protein 1, Hippocalcin-like protein 3, HLP3, VILIP, VLP-1, VSNL1, VISL1)

Visinin like protein 1 (VILIP-1, VLP-1 or VSNL-1) is a cytoplasmic protein of low molecular weight (approximately 22 kDa) consisting of 191 amino acid residues. It belongs to the visinin/recoverin subfamily of neuronal calcium sensor proteins involved in calcium-dependent signal transduction mechanisms in neurons. It is found primarily in the brain, in nerve cells, but it also has a peripheral distribution in liver, lung, kidney, spleen, pancreas and colon. When localized at the membrane, it modulates various cellular signal transduction pathways, including cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-signaling in neural cells, human embryonic kidney cells, the pancreatic β cell line MIN6, and various skin tumor cell lines. It contains four internal repeats of 36–38 amino-acids, each containing a potential EF-hand domain. Two of the four EF-hand Ca2+-binding motifs of VILIP-1 are able to bind either Ca2+ or Mg2+in a non-cooperative manner. Binding of Ca2+ leads to specific conformational changes in the protein and this may regulate the interaction of VILIP with intracellular target molecules. VILIP-1 has been identified as a potential biomarker for brain injury and several neurodegenerative diseases. VILIP-1-expressing cells appear to be vulnerable to neurotoxic insults. As a result, the protein is released into the cerebrospinal fluid (CSF), and can be used as a biomarker for stroke and Alzheimer’s di­sease. The intracellular protein was detected in cerebrospinal fluid (CSF) of a rat model of stroke and in plasma of patients after stroke. VILIP-1 was detected in 44% of subjects with stroke, in samples taken 24 hours after onset of stroke, and in 8% of controls with no stroke. In Alzheimer’s di­sease, CSF levels of VILIP-1 were significantly higher than in healthy individuals. Post mortem studies in the hippocampus of schizophrenia patients revealed increased expression of VILIP-1 in interneurons, while its expression in pyramidal neurons was downregulated. Expressions of VILIP-1 were also found in different types of cancer and in pancreatic α- and β-cells, being involved in the regulation of insulin secretion and insulin gene expression.

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