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Gene Review

HN  -  hemagglutinin-neuraminidase protein

Parainfluenza virus 5

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Disease relevance of HN


High impact information on HN

  • The effects of monospecific antibodies to the viral glycoprotein with hemagglutinating and neuraminidase activity (HN) and the viral glycoprotein with membrane-fusing activity (F) of the paramyxovirus simian virus 5 (SV5) on the spread of infection in two cell types have been investigated [6].
  • In these cells, antibodies specific for the HN glycoprotein prevented the dissemination of infection by released infectious virus, but spread by cell fusion was not inhibited [6].
  • The temperature dependence of fusion by F suggests that thermal energy, destabilizing proline residues and receptor binding by the hemagglutinin-neuraminidase (HN) protein collectively contribute to F activation from a metastable native state [7].
  • The characteristic cleavage of SV5 HN in the late endosome distinguishes internalization from transport to later stages of the endocytic pathway [8].
  • The intracellular assembly and transport of HN in CV1 cells was examined using conformation-specific HN mAbs and sucrose density sedimentation analysis [4].

Chemical compound and disease context of HN


Biological context of HN

  • The paramyxovirus hemagglutinin-neuraminidase (HN) functions in virus attachment to cells, cleavage of sialic acid from oligosaccharides, and stimulating membrane fusion during virus entry into cells [3].
  • The F and HN proteins synthesized in recombinant infected cells are indistinguishable in terms of electrophoretic mobility and glycosylation from the proteins synthesized in simian virus 5-infected cells [13].
  • cDNAs encoding the mRNAs for the fusion protein (F) and the hemagglutinin/neuraminidase protein (HN) of the paramyxovirus simian virus 5 have been inserted into a eukaryotic expression vector under the control of the simian virus 40 late promoter [13].
  • In addition, the expressed F and HN proteins have been shown to be anchored in the plasma membrane in a biologically active form by indirect live cell immunofluorescence, the F-mediated formation of syncytia, and the ability of HN to cause the hemadsorption of erythrocytes to the infected cell surface [13].
  • The F and HN proteins of all these viruses, including SV5 and NDV, however, were shown to have protein-specific structures as well as short but well-conserved amino acid sequences, suggesting that these structures and sequences are related to the activities of these glycoproteins [14].

Anatomical context of HN


Associations of HN with chemical compounds

  • A truncated form of HN, HNT (molecular weight, 63,000), was synthesized in the presence of tunicamycin and was also recognized only by group I antibodies [20].
  • In contrast, group II antibodies, which preferentially recognized native virus in the enzyme-linked immunosorbent assay, reacted with native HN but failed to bind HN after sodium dodecyl sulfate denaturation [20].
  • Deletion of groups of four of aa 478-485, single alanine, or other amino acid substitutions among aa 478-485 had minimal or limited effects on HPIV2 F/HN-induced cell fusion [21].
  • A cell-surface-expressed chimeric protein (APK), consisting of the cytoplasmic tail, transmembrane (TM) domain, and 12 residues of the ectodomain of HN joined to the cytoplasmic protein pyruvate kinase is internalized, indicating that the N-terminal region of HN contains an internalization signal [22].
  • A glutamic acid residue (E37) that abuts this presumptive HN TM domain/ectodomain boundary is important for SV5 HN internalization [22].

Other interactions of HN

  • Chimeric SV5 minigenomes were constructed to contain exchanges of a 10 base gene end sequence and the U tract from the M-F (approximately 40% readthrough) and SH-HN (approximately 15% readthrough) junctions [23].

Analytical, diagnostic and therapeutic context of HN


  1. Sequence comparison between the haemagglutinin-neuraminidase genes of simian, canine and human isolates of simian virus 5. Baty, D.U., Southern, J.A., Randall, R.E. J. Gen. Virol. (1991) [Pubmed]
  2. Hemagglutinin-neuraminidase protein of the paramyxovirus simian virus 5: nucleotide sequence of the mRNA predicts an N-terminal membrane anchor. Hiebert, S.W., Paterson, R.G., Lamb, R.A. J. Virol. (1985) [Pubmed]
  3. Structural studies of the parainfluenza virus 5 hemagglutinin-neuraminidase tetramer in complex with its receptor, sialyllactose. Yuan, P., Thompson, T.B., Wurzburg, B.A., Paterson, R.G., Lamb, R.A., Jardetzky, T.S. Structure (Camb.) (2005) [Pubmed]
  4. Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface. Ng, D.T., Randall, R.E., Lamb, R.A. J. Cell Biol. (1989) [Pubmed]
  5. Determination of the complete nucleotide sequence of the Sendai virus genome RNA and the predicted amino acid sequences of the F, HN and L proteins. Shioda, T., Iwasaki, K., Shibuta, H. Nucleic Acids Res. (1986) [Pubmed]
  6. Importance of antibodies to the fusion glycoprotein of paramyxoviruses in the prevention of spread of infection. Merz, D.C., Scheid, A., Choppin, P.W. J. Exp. Med. (1980) [Pubmed]
  7. Membrane fusion machines of paramyxoviruses: capture of intermediates of fusion. Russell, C.J., Jardetzky, T.S., Lamb, R.A. EMBO J. (2001) [Pubmed]
  8. Rab 7: an important regulator of late endocytic membrane traffic. Feng, Y., Press, B., Wandinger-Ness, A. J. Cell Biol. (1995) [Pubmed]
  9. Mumps virus infection of the developing mouse brain--appearance of structural virus proteins demonstrated with monoclonal antibodies. Kristensson, K., Orvell, C., Malm, G., Norrby, E. J. Neuropathol. Exp. Neurol. (1984) [Pubmed]
  10. Complete nucleotide sequence of the hemagglutinin-neuraminidase (HN) mRNA of mumps virus and comparison of paramyxovirus HN proteins. Kövamees, J., Norrby, E., Elango, N. Virus Res. (1989) [Pubmed]
  11. Purification and characterization of the hemagglutinin-neuraminidase of Porcine rubulavirus LPMV. Reyes-Leyva, J., Espinosa, B., Santos, G., Zenteno, R., Hernández, J., Vallejo, V., Zenteno, E. Glycoconj. J. (1999) [Pubmed]
  12. Secondary structure prediction of the hemagglutinin-neuraminidase from a porcine rubulavirus. Zenteno-Cuevas, R., Hernández, J., Espinosa, B., Reyes, J., Zenteno, E. Arch. Virol. (1998) [Pubmed]
  13. Expression at the cell surface of biologically active fusion and hemagglutinin/neuraminidase proteins of the paramyxovirus simian virus 5 from cloned cDNA. Paterson, R.G., Hiebert, S.W., Lamb, R.A. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  14. Nucleotide sequence of the bovine parainfluenza 3 virus genome: the genes of the F and HN glycoproteins. Suzu, S., Sakai, Y., Shioda, T., Shibuta, H. Nucleic Acids Res. (1987) [Pubmed]
  15. Different roles of individual N-linked oligosaccharide chains in folding, assembly, and transport of the simian virus 5 hemagglutinin-neuraminidase. Ng, D.T., Hiebert, S.W., Lamb, R.A. Mol. Cell. Biol. (1990) [Pubmed]
  16. The paramyxovirus simian virus 5 hemagglutinin-neuraminidase glycoprotein, but not the fusion glycoprotein, is internalized via coated pits and enters the endocytic pathway. Leser, G.P., Ector, K.J., Lamb, R.A. Mol. Biol. Cell (1996) [Pubmed]
  17. Mutations in the cytoplasmic domain of a paramyxovirus fusion glycoprotein rescue syncytium formation and eliminate the hemagglutinin-neuraminidase protein requirement for membrane fusion. Seth, S., Vincent, A., Compans, R.W. J. Virol. (2003) [Pubmed]
  18. Differentiation of mumps virus strains with monoclonal antibody to the HN glycoprotein. Server, A.C., Merz, D.C., Waxham, M.N., Wolinsky, J.S. Infect. Immun. (1982) [Pubmed]
  19. Expression of mumps virus glycoproteins in mammalian cells from cloned cDNAs: both F and HN proteins are required for cell fusion. Tanabayashi, K., Takeuchi, K., Okazaki, K., Hishiyama, M., Yamada, A. Virology (1992) [Pubmed]
  20. Intracellular maturation of mumps virus hemagglutinin-neuraminidase glycoprotein: conformational changes detected with monoclonal antibodies. Waxham, M.N., Merz, D.C., Wolinsky, J.S. J. Virol. (1986) [Pubmed]
  21. Three membrane-proximal amino acids in the human parainfluenza type 2 (HPIV 2) F protein are critical for fusogenic activity. Tong, S., Yi, F., Martin, A., Yao, Q., Li, M., Compans, R.W. Virology (2001) [Pubmed]
  22. The signal for clathrin-mediated endocytosis of the paramyxovirus SV5 HN protein resides at the transmembrane domain-ectodomain boundary region. Leser, G.P., Ector, K.J., Ng, D.T., Shaughnessy, M.A., Lamb, R.A. Virology (1999) [Pubmed]
  23. Molecular basis for naturally occurring elevated readthrough transcription across the M-F junction of the paramyxovirus SV5. Rassa, J.C., Parks, G.D. Virology (1998) [Pubmed]
  24. Human parainfluenza type 3 virus hemagglutinin-neuraminidase glycoprotein: nucleotide sequence of mRNA and limited amino acid sequence of the purified protein. Elango, N., Coligan, J.E., Jambou, R.C., Venkatesan, S. J. Virol. (1986) [Pubmed]
  25. Functional interactions between the fusion protein and hemagglutinin-neuraminidase of human parainfluenza viruses. Hu, X.L., Ray, R., Compans, R.W. J. Virol. (1992) [Pubmed]
  26. Sequence determination of the mumps virus HN gene. Waxham, M.N., Aronowski, J., Server, A.C., Wolinsky, J.S., Smith, J.A., Goodman, H.M. Virology (1988) [Pubmed]
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