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A novel recently evolved gene C19orf24 encodes a non-classical secreted protein


Secreted proteins play important roles in many crucial biological processes, and can be new agents or targets for drug therapies. Here, we report on the isolation and characterization of a novel human non-classical secreted protein which is encoded by the hypothetical gene C19orf24 (chromosome 19 open reading frame 24). It has no signal peptide, but can still secrete extracellularly despite the presence of the inhibitor brefeldin A (BFA), proving its non-classical secreted protein status. Via subcellular localization using C19orf24 in vivo and transfected pEYFP-Golgi plasmid in Hela cells, C19orf24 was shown not to co-localize in the Golgi apparatus, which suggested that it secretes via a new and unknown pathway. Deglycosylation analysis with PNGase F verified that it has no N-glycosylation modification sites. Via the reverse transcription-PCR method, it was found to be expressed only in the human liver, and preferentially in normal tissue. In addition, C19orf24 was shown to be a recently evolved gene, found only in Homo sapiens and Pan troglodytes. By calculating its synonymous and non-synonymous substitution rate (d S/d N), we found that it experienced a purifying selection, which suggests that C19orf24 may have a special, irreplaceable biological function in the human organism.



brefeldin A


chromosome 19 open reading frame 24


cell lysate


culture media

d S/d N :

synonymous and non-synonymous substitution rate


growth hormone




  1. Ladunga, I. Large-scale predictions of secretory proteins from mammalian genomic and EST sequences. Curr. Opin. Biotechnol. 11 (2000) 13–18.

    Article  PubMed  CAS  Google Scholar 

  2. Fukuda, M.E., Iwadate, Y., Machida, T., Hiwasa, T., Nimura, Y., Nagai, Y., Takiguchi, M., Tanzawa, H., Yamaura, A. and Seki, N. Cathepsin D is a potential serum marker for poor prognosis in glioma patients. Cancer Res. 65 (2005) 5190–5194.

    Article  PubMed  CAS  Google Scholar 

  3. Wu, C.C., Chien, K.Y., Tsang, N.M., Chang, K.P., Hao, S.P., Tsao, C.H., Chang, Y.S. and Yu, J.S. Cancer cell-secreted proteomes as a basis for searching potential tumor markers: nasopharyngeal carcinoma as a model. Proteomics 5 (2005) 3173–3182.

    Article  PubMed  CAS  Google Scholar 

  4. Mignatti, P., Morimoto, T. and Rifkin, D.B. Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J. Cell. Physiol. 151 (1992) 81–93.

    Article  PubMed  CAS  Google Scholar 

  5. Rubartelli, A., Cozzolino, F., Talio, M. and Sitia, R. A novel secretory pathway for interleukin-1, a protein lacking a signal sequence. EMBO J. 9 (1990) 1503–1510.

    PubMed  CAS  Google Scholar 

  6. Marcel, T., Sarah, H. and Steven, L.C. The nonclassic secretion of thioredoxin is not sensitive to redox state. Am. J. Physiol. Cell Physiol. 284 (2003) 1272–1279.

    Google Scholar 

  7. Walter, N. The mystery of nonclassical protein secretion: A current view on cargo proteins and potential export routes. Eur. J. Biochem. 270 (2003) 2109–2119.

    Article  Google Scholar 

  8. Cleves, A.E. Protein transport: The nonclassical ins and outs. Curr. Biol. 7 (1997) 318–320.

    Article  Google Scholar 

  9. Wang, W., Brunet, F.G., Nevo, E. and Long, M. Origin of Sphinx, a young chimeric RNA gene in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 99 (2002) 4448–4453.

    Article  PubMed  CAS  Google Scholar 

  10. Wang, W., Zhang, J., Alvarez, C., Llopart, A. and Long, M. The origin of the jingwei gene and the complex modular structure of its parental gene, yellow emperor, in D. melanogaster. Mol Biol. Evol. 17 (2000) 1294–1301.

    PubMed  CAS  Google Scholar 

  11. Bendtsen, J.D., Kiemer, L., Fausbøll, A. and Brunak S. Non-classical protein secretion in bacteria. BMC Microbiology 5 (2005) 58.

    Article  PubMed  Google Scholar 

  12. Bendtsen, J.D., Jensen, L. J., Blom, N., Heijne, G.V. and Brunak S. Feature based prediction of non-classical and leaderless protein secretion. Protein Eng. Des. Sel. 17 (2004) 349–356.

    Article  PubMed  CAS  Google Scholar 

  13. Gomi, M., Sonoyama, M. and Mitaku S. High performance system for signal peptide prediction: SOSUI signal. Chem. Bio Info. J. 4 (2004) 142–147.

    Article  CAS  Google Scholar 

  14. Lu, Z., Szafron, D., Greiner, R., Lu, P., Wishart, D.S., Poulin, B., Anvik, J., Macdonell, C. and Eisner, R. Predicting subcellular localization of proteins using machine-learned classifiers. Bioinformatics 4 (2004) 547–556.

    Article  Google Scholar 

  15. Higgins, D., Thompson, J., Gibson, T., Thompson, J.D., Higgins, D.G. and Gibson, T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22 (1994) 4673–4680.

    PubMed  Google Scholar 

  16. Korber, B. HIV signature and sequence variation analysis. In: Computational Analysis of HIV Molecular Sequences (Rodrigo, A.G. and Learn, G.H., Eds.) Kluwer Academic Publishers, Dordrecht, Netherlands (2000) 55–72.

    Google Scholar 

  17. Blom, N., Gammeltoft, S. and Brunak S. Sequence-and structure-based prediction of eukaryotic protein phosphorylation sites. J. Mol. Biol. 294 (1999) 1351–1362.

    Article  PubMed  CAS  Google Scholar 

  18. Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S., Wilkins, M.R., Appel, R.D. and Bairoch, A. Protein identification and analysis tools on the ExPASy server. In: The Proteomics Protocols Handbook (Walker, J.M. Ed.) Humana Press, Totowa, New York (2005) 571–607.

    Google Scholar 

  19. Zhang, J.Z. Evolution of the human ASPM gene, a major determinant of brain size. Genetics 165 (2003) 2063–2070.

    PubMed  CAS  Google Scholar 

  20. Philippe, D., Will, H., Guy B. and Denis L.B. Brefeldin A-induced prosomatostatin N-glycosylation in AtT20 cells. Biochem. Biophys. Res. Commun. 296 (2002) 618–624.

    Article  Google Scholar 

  21. Klausner, R.D., Donaldson, J.G. and Lippincott-Schwartz J. Brefeldin A: insights into the control of membrane traffic and organelle structure. J. Cell Biol. 116 (1992) 1071–1080.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ze-Guang Han.

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Wang, XR., Zhou, YB., Liu, F. et al. A novel recently evolved gene C19orf24 encodes a non-classical secreted protein. Cell. Mol. Biol. Lett. 11, 161–170 (2006).

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