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Lefty Proteins

Lefty proteins are novel TGF-beta ligands that function as antagonists of Nodal signaling. The expression of Lefty proteins on the left side of the developing mouse embryo earned this protein family its name. Two genes exist in mouse (Lefty-1 and Lefty-2) and two in humans (Lefty-A and Lefty-B). By amino acid sequence, human Lefty-A and Lefty-B are more similar to each other (96%) than to either Lefty-1 or Lefty-2 in the mouse (81-82%). The Leftys contains some of the features of the cysteine-knot structure conserved among TGF-beta-related proteins, but also some structural differences. Specifically, they lack the alpha-helical segment important for ligand dimerization as well as the cysteine residue involved in stabilization of dimers.