ZNF649 encodes a deduced 505-amino acid protein that contains an N-terminal Kruppel-associated box (KRAB) belonging to the classic KRAB-AB box, and 10 C2H2 zinc finger motifs that extend to the end of the protein sequence. Northern blot analysis of multiple human tissues detected expression of a 3.2-kb ZNF649 transcript in fetal heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas; in adult tissues, the transcript was detected predominantly in heart, skeletal muscle, and brain, and at lower levels in other tissues. A GFP-ZNF649 fusion protein localized primarily in the nucleus of COS-7 cells.ZNF649 can suppress the transcriptional activities of SRE and AP1 transcription factors. Deletion analysis with truncated proteins indicated that the KRAB domain is required for the repressive activity of ZNF649.