Influenza C virus CM2 integral membrane glycoprotein is produced from a polypeptide precursor by cleavage of an internal signal sequence

Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13233-8. doi: 10.1073/pnas.95.22.13233.


The influenza C virus CM2 protein is a small glycosylated integral membrane protein (115 residues) that spans the membrane once and contains a cleavable signal sequence at its N terminus. The coding region for CM2 (CM2 ORF) is located at the C terminus of the 342-amino acid (aa) ORF of a colinear mRNA transcript derived from influenza C virus RNA segment 6. Splicing of the colinear transcript introduces a translational stop codon into the ORF and the spliced mRNA encodes the viral matrix protein (CM1) (242 aa). The mechanism of CM2 translation was investigated by using in vitro and in vivo translation of RNA transcripts. It was found that the colinear mRNA derived from influenza C virus RNA segment 6 serves as the mRNA for CM2. Furthermore, CM2 translation does not depend on any of the three in-frame methionine residues located at the beginning of CM2 ORF. Rather, CM2 is a proteolytic cleavage product of the p42 protein product encoded by the colinear mRNA: a cleavage event that involves the recognition and cleavage of an internal signal peptide presumably by signal peptidase resident in the endoplasmic reticulum. Alteration of the predicted signal peptidase cleavage site by mutagenesis blocked generation of CM2. The other polypeptide species resulting from the cleavage of p42, designated p31, contains the CM1 coding region and an additional C-terminal 17 aa (formerly the CM2 signal peptide). Protein p31, in comparison to CM1, displays characteristics of an integral membrane protein.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Codon, Terminator
  • HeLa Cells
  • Humans
  • Influenzavirus C / genetics*
  • Influenzavirus C / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Open Reading Frames
  • Protein Biosynthesis
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational*
  • RNA Splicing
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Transcription, Genetic
  • Transfection
  • Viral Matrix Proteins / biosynthesis*
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics


  • CM2 protein, Influenza C virus
  • Codon, Terminator
  • Protein Precursors
  • RNA, Messenger
  • Recombinant Proteins
  • Viral Matrix Proteins