Nicalin (NICAstrin-Like proteIN) is a 60-62kD member of the nicastrin family of proteins. It is an ER-embedded transmembrane protein that is found in skeletal and cardiac muscle, hepatocytes and neurons. Nicalin interacts with 22kD TMEM147 and 130kD NOMO1 to form a 200-220kD complex that antagonizes Nodal signaling. Mature human nicalin is a 521 amino acid (aa) type I transmembrane glycoprotein. It contains a 480aa luminal/extracellular region (aa 43-522) plus a 20aa cytoplasmic domain (aa544-563). The luminal region possesses one likely inactive M28 Zn-peptidase-like domain (aa130-429). Four potential isoform variants are reported. One shows an alternative start site at Met75, a second contains a seven aa insertion after Gln543, a third contains a 102aa substitution for aa162-563, and a fourth shows a deletion of Gln446. Over aa1-522, human nicalin shares 95% aa sequence identity with mouse nicalin.
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