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Primate Epididymis-Specific Proteins: Characterization of ESC42, a Novel Protein Containing a Trefoil-Like Motif in Monkey and Human

Departments of Pediatrics (Q.L., K.G.H., F.S.F., S.H.H.) and Cell and Developmental Biology (P.S., G.G., R.T.R., M.G.O., P.P.) and Laboratories for Reproductive Biology (Q.L., K.G.H., P.S., G.G., R.S., R.T.R., M.G.O., P.P., F.S.F., S.H.H.), University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599; State Key Laboratory of Molecular Biology (Q.L.,Y.-L.Z.), Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Sinica Academia, Shanghai 200031, China; and Department of Biochemistry (A.J.R.), Indian Institute of Science, Bangalore, India 560012

Address all correspondence and requests for reprints to: Susan H. Hall, Laboratories for Reproductive Biology, CB 7500, University of North Carolina, Chapel Hill, North Carolina 27599. E-mail: shh{at}med.unc.edu

Epididymal secreted proteins promote sperm maturation and fertilizing capacity by interacting with sperm during passage through the epididymis. Here we investigate the molecular basis of sperm maturation by isolating cDNA clones for novel epididymis-specific expressed sequences. Thirty-six novel cDNAs were isolated and sequenced from a subtracted Macaca mulatta epididymis library. The clones encode proteins with a range of motifs characteristic of protein-modifying enzymes, protease inhibitors, hydrophobic ligand-binding and transport proteins, extracellular matrix-interacting proteins, and transcription regulatory factors. The full length coding sequences were obtained for 11 clones representing a range of abundance levels. Expression of each is regionally localized and androgen regulated. The most abundant, ESC42, contains a cysteine-rich region similar to the signature binding domain of the trefoil family of motogenic wound repair proteins. The monkey and human proteins are nearly 90% identical. Immunohistochemical staining revealed that the protein is most abundant in the epithelium of the caput and is also present in the lumen and bound to sperm. The ESC42 gene, located on chromosome 20q11, contains two exons encoding two nearly identical predicted signal peptides and a third exon encoding the rest of the protein.

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