Identification and Characterization of K12 (SECTM1), a Novel Human Gene That Encodes a Golgi-Associated Protein with Transmembrane and Secreted Isoforms

The investigation of a DNase-hypersensitive site upstream of the CD7 gene on chromosome 17q25 has led to the discovery of a novel human gene designated K12 (SECTM1, the HGMW assignment). This gene spans approximately 14 kb and encodes a 1.8-kb mRNA detected at the highest levels in peripheral blood leukocytes and breast cancer cell lines. The open reading frame predicts a 248-amino-acid protein with the hydropathic characteristics of a type 1a membrane protein. Western blots show that the K12 protein exists as a cluster of bands around 27 kDa, and extractions using nonionic detergents or high pH conditions demonstrate that it behaves as an integral membrane protein. Immunofluorescence localization studies reveal that K12 is not detectable on the cell surface, but instead is found in a perinuclear Golgi-like pattern and colocalizes with a well-known Golgi marker. In addition, an approximately 20-kDa soluble form of the K12 protein derived from the N-terminal domain is specifically secreted by cells into the culture medium. Immunohistochemical analysis of peripheral blood cells shows that K12 is found in leukocytes of the myeloid lineage, with the strongest staining observed in granulocytes and no detectable expression in lymphocytes. Based on its range of expression, its broad structural characteristics that resemble cytokines and growth factors, and the chromosomal location of the gene in an area already associated with myelogenous leukemias and other malignant neoplasms, this study concludes that K12 is a novel molecule with potential importance in hematopoietic and/or immune system processes.