The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it

EMBO J. 1988 Jul;7(7):1947-55. doi: 10.1002/j.1460-2075.1988.tb03032.x.


Genomic clones for the largest human neurofilament protein (NF-H) were isolated, the intron/exon boundaries mapped and the entire protein-coding regions (exons) sequenced. The predicted protein contains a central region that obeys the structural criteria identified for alpha-helical 'rod' domains typically present in all IF protein components: it is approximately 310 amino acids long, shares amino acid sequence homology with other IF protein rod domains and displays the characteristic heptad repeats of apolar amino acids which facilitate coiled-coil interaction. Nevertheless, anomalies are noted in the structure of the NF-H rod which could explain observations of its poor homopolymeric assembly in vitro. The protein segment on the carboxy-terminal side of the human NF-H rod is uniquely long (greater than 600 amino acids) compared to other IF proteins and is highly charged (greater than 24% Glu, greater than 25% Lys), rich in proline (greater than 12%) and impoverished in cysteine, methionine and aromatic amino acids. Its most remarkable feature is a repetitive sequence that covers more than half its length and includes the sequence motif, Lys-Ser-Pro (KSP) greater than 40 times. Together with the recent identification of the serine in KSP as the main target for NF-directed protein kinases in vivo, this repetitive character explains the massive phosphorylation of the NF-H subunit that can occur in axons. The human NF-H gene has three introns, two of which interrupt the protein-coding sequence at identical points to introns in the genes for the two smaller NF proteins, NF-M and NF-L.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • DNA / isolation & purification
  • Exons
  • Genes*
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Introns
  • Macromolecular Substances
  • Molecular Sequence Data
  • Neurofilament Proteins
  • Protein Conformation
  • Sequence Homology, Nucleic Acid


  • Intermediate Filament Proteins
  • Macromolecular Substances
  • Neurofilament Proteins
  • DNA