ABSTRACT
Chordin-like cysteine-rich repeats (CRs) are conserved domains present in an expanding family of secreted proteins that associate with members of the TGF beta superfamily. In this study, we report the molecular cloning and characterization of CHL2 (chordin-like 2), a novel protein closely related to CHL (chordin-like). Both are members of the chordin family of proteins, and contain a signal peptide and three CR domains. We found that recombinant human CHL2 (hCHL2) protein is secreted and binds activin A, but not BMP-2, -4, or -6. Expression of hCHL2 mRNA and protein was detected in a variety of human tissues and is particularly abundant in the uterus. Extensive and complex alternative splicing of hCHL2 was observed in different tissues, resulting in several distinct protein isoforms that vary substantially in the presence of a signal peptide and their content of CR domains. Differential expression of CHL2 variants was observed during myoblast and osteoblast differentiation, implying a role for this gene in these physiological processes.
