Skip to main content
Cellular & Molecular Biology Letters logoLink to Cellular & Molecular Biology Letters
. 2006 Jun 1;11(2):161–170. doi: 10.2478/s11658-006-0014-6

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

Xin-Rong Wang 1,2, Yu-Bo Zhou 2, Feng Liu 2, Ke-Sheng Wang 2, Yan Shen 2, Jian-Hua Liu 1, Ze-Guang Han 2,
PMCID: PMC6275723  PMID: 16847563

Abstract

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.

Key words: C19orf24, Late evolution, Non-classical secreted protein, BFA

Full Text

The Full Text of this article is available as a PDF (527.2 KB).

Abbreviations used

BFA

brefeldin A

C19orf24

chromosome 19 open reading frame 24

CL

cell lysate

CM

culture media

dS/dN

synonymous and non-synonymous substitution rate

GH

growth hormone

TRX

theoredoxin

References

  • 1.Ladunga I. Large-scale predictions of secretory proteins from mammalian genomic and EST sequences. Curr. Opin. Biotechnol. 2000;11:13–18. doi: 10.1016/S0958-1669(99)00048-8. [DOI] [PubMed] [Google Scholar]
  • 2.Fukuda M.E., Iwadate Y., Machida T., Hiwasa T., Nimura Y., Nagai Y., Takiguchi M., Tanzawa H., Yamaura A., Seki N. Cathepsin D is a potential serum marker for poor prognosis in glioma patients. Cancer Res. 2005;65:5190–5194. doi: 10.1158/0008-5472.CAN-04-4134. [DOI] [PubMed] [Google Scholar]
  • 3.Wu C.C., Chien K.Y., Tsang N.M., Chang K.P., Hao S.P., Tsao C.H., Chang Y.S., Yu J.S. Cancer cell-secreted proteomes as a basis for searching potential tumor markers: nasopharyngeal carcinoma as a model. Proteomics. 2005;5:3173–3182. doi: 10.1002/pmic.200401133. [DOI] [PubMed] [Google Scholar]
  • 4.Mignatti P., Morimoto T., 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. 1992;151:81–93. doi: 10.1002/jcp.1041510113. [DOI] [PubMed] [Google Scholar]
  • 5.Rubartelli A., Cozzolino F., Talio M., Sitia R. A novel secretory pathway for interleukin-1, a protein lacking a signal sequence. EMBO J. 1990;9:1503–1510. doi: 10.1002/j.1460-2075.1990.tb08268.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Marcel T., Sarah H., Steven L.C. The nonclassic secretion of thioredoxin is not sensitive to redox state. Am. J. Physiol. Cell Physiol. 2003;284:1272–1279. doi: 10.1152/ajpcell.00521.2002. [DOI] [PubMed] [Google Scholar]
  • 7.Walter N. The mystery of nonclassical protein secretion: A current view on cargo proteins and potential export routes. Eur. J. Biochem. 2003;270:2109–2119. doi: 10.1046/j.1432-1033.2003.03577.x. [DOI] [PubMed] [Google Scholar]
  • 8.Cleves A.E. Protein transport: The nonclassical ins and outs. Curr. Biol. 1997;7:318–320. doi: 10.1016/S0960-9822(06)00148-5. [DOI] [PubMed] [Google Scholar]
  • 9.Wang W., Brunet F.G., Nevo E., Long M. Origin of Sphinx, a young chimeric RNA gene in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 2002;99:4448–4453. doi: 10.1073/pnas.072066399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Wang W., Zhang J., Alvarez C., Llopart A., 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. 2000;17:1294–1301. doi: 10.1093/oxfordjournals.molbev.a026413. [DOI] [PubMed] [Google Scholar]
  • 11.Bendtsen J.D., Kiemer L., Fausbøll A., Brunak S. Non-classical protein secretion in bacteria. BMC Microbiology. 2005;5:58. doi: 10.1186/1471-2180-5-58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Bendtsen J.D., Jensen L. J., Blom N., Heijne G.V., Brunak S. Feature based prediction of non-classical and leaderless protein secretion. Protein Eng. Des. Sel. 2004;17:349–356. doi: 10.1093/protein/gzh037. [DOI] [PubMed] [Google Scholar]
  • 13.Gomi M., Sonoyama M., Mitaku S. High performance system for signal peptide prediction: SOSUI signal. Chem. Bio Info. J. 2004;4:142–147. doi: 10.1273/cbij.4.142. [DOI] [Google Scholar]
  • 14.Lu Z., Szafron D., Greiner R., Lu P., Wishart D.S., Poulin B., Anvik J., Macdonell C., Eisner R. Predicting subcellular localization of proteins using machine-learned classifiers. Bioinformatics. 2004;4:547–556. doi: 10.1093/bioinformatics/btg447. [DOI] [PubMed] [Google Scholar]
  • 15.Higgins D., Thompson J., Gibson T., Thompson J.D., Higgins D.G., 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. 1994;22:4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Korber B. HIV signature and sequence variation analysis. In: Rodrigo A.G., Learn G.H., editors. Computational Analysis of HIV Molecular Sequences. Dordrecht, Netherlands: Kluwer Academic Publishers; 2000. pp. 55–72. [Google Scholar]
  • 17.Blom N., Gammeltoft S., Brunak S. Sequence-and structure-based prediction of eukaryotic protein phosphorylation sites. J. Mol. Biol. 1999;294:1351–1362. doi: 10.1006/jmbi.1999.3310. [DOI] [PubMed] [Google Scholar]
  • 18.Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D., Bairoch A. Protein identification and analysis tools on the ExPASy server. In: Walker J.M., editor. The Proteomics Protocols Handbook. Totowa, New York: Humana Press; 2005. pp. 571–607. [Google Scholar]
  • 19.Zhang J.Z. Evolution of the human ASPM gene, a major determinant of brain size. Genetics. 2003;165:2063–2070. doi: 10.1093/genetics/165.4.2063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Philippe D., Will H., Guy B., Denis L.B. Brefeldin A-induced prosomatostatin N-glycosylation in AtT20 cells. Biochem. Biophys. Res. Commun. 2002;296:618–624. doi: 10.1016/S0006-291X(02)00904-X. [DOI] [PubMed] [Google Scholar]
  • 21.Klausner R.D., Donaldson J.G., Lippincott-Schwartz J. Brefeldin A: insights into the control of membrane traffic and organelle structure. J. Cell Biol. 1992;116:1071–1080. doi: 10.1083/jcb.116.5.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Cellular & Molecular Biology Letters are provided here courtesy of BMC

RESOURCES