Identification and Characterization of Novel Members of the CREG Family, Putative Secreted Glycoproteins Expressed Specifically in Brain

The cellular repressor of E1A-stimulated genes, CREG, is a secreted glycoprotein that enhances differentiation of pluripotent stem cells. Here we report two novel members of the CREG family, human CREG2 and mouse Creg2 cDNAs. The predicted human and mouse protein sequences exhibit 35% identity with CREG protein. Northern blot analyses demonstrate specific CREG2 and Creg2 transcription in brain—in the case of CREG2, mainly in the limbic system of the brain. Both mouse and human CREG2 fused to the carboxy terminus of EGFP in NIH3T3 cells localize to the perinuclear region, which demonstrates implicit endoplasmic reticulum and Golgi localization. Human and mouse CREG2 are N-glycosylated in HeLa cells and deletion of amino-terminal sequences completely abolishes N-glycosylation, indicating that the N termini of both proteins may function as signal sequences. Thus, human and mouse CREG2 are putative secreted glycoproteins and may be novel neuronal extracellular molecules.