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Contactin4 (CNTN4), also known as BIG2 (Brainderived Immunoglobulin Superfamily molecule 2), is an axonal cell adhesion molecule that belongs to the contactin family, a subfamily of the Ig superfamily (1 3). The contactin family comprises six members (CNTN1/F3, CNTN2/TAG1, CNTN3/BIG1, CNTN4/BIG2, CNTN5/NB2 and CNTN6/NB3) and are characterized by the presence of six Ig like domains, four fibronectin type III like repeats, and a glycosylphosphatidylinositol (GPI) anchoring domain. Contactin family proteins exist as membranebound proteins, but can also be released as soluble proteins by GPIspecific phospholipase D. Soluble Contactins are functionsl proteins that are able to promote neurite outgrowth.
Image: Rat hippocampal neurons grown on microplates pre-coated with human Contactin-4
Human CNTN4 has been mapped to chromosome 3p26 p25. Three alternative transcripts of CNTN4, encoding isoforms a, b, and c precursor proteins containing 1026, 282, and 698 amino acid (aa) residues, respectively, have been described. Human CNTN4 isoform a shares 94% aa sequence identity with its rat homolog. It also shares from 44 66% aa sequence identity with other CNTN family members. CNTN family members display overlapping but distinct expression patterns. CNTN4 expression is detected in multiple organs including brains, pancreas, kidney, aorta, small intestine, thyroid, uterus and testis. However, expression of the 282 aa isoform b is primarily restricted to the brain. CNTN4 has been suggested to play important roles in the formation of neuronal networks during nervous sytems development. Disruption of CNTN4 has been implicated in the 3p deletion syndrome characterized by growth failure, developmental delay, and mental retardation. CNTN4 expression is induced in human neuroblastoma tumor cells treated with retinoic acid and may be responsible for the the neuritogenic response of tumor cells to retinoids. Recombinant CNTN4 shows in vitro neurite outgrowth promoting activity.