ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecules. Accumulation of misfolded proteins in the Endoplasmic Reticulum results in the proteolytic cleavage of ATF6. The cytosolic portion of ATF6 will move to the nucleus and act as a transcription factor to cause the transcription of ER chaperones.Sequence analysis predicted that the 670-amino acid protein contains an N-terminal serine-rich domain and a central DNA-binding domain followed by a leucine zipper sequence. Northern blot analysis revealed expression of a 2.5-kb transcript in HeLa cells and 4.5- and 8.0-kb transcripts in all mouse tissues tested, with the exception of spleen. Immunoblot analysis detected expression of a 90-kD protein in HeLa and COS cell lysates.