An N-terminal hydrophobic peak is the sorting signal of regulated secretory proteins

Sven Ulrik Gorr, Douglas S. Darling

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Endocrine and exocrine cells each contain a regulated and constitutive secretory pathway. The presence of two distinct secretory pathways in the same cell type requires a sorting step to direct secretory proteins to the correct pathway. It is thought that regulated secretory proteins contain a specific sorting signal. However, this signal has not been identified. Amino acid sequence comparisons have not revealed any significant similarity between different regulated secretory proteins, suggesting that the sorting signal does not consist of a conserved primary sequence. In the present report, we have analyzed the predicted secondary structures of regulated secretory proteins and identified an N-terminal hydrophobic peak (NHP) which is located approximately from amino acids 9-26, overlaps with a predicted α-helix and contains charged amino acid residues. This signal is present in regulated secretory proteins that exhibit an N-terminal sorting sequence, but it is absent from constitutively secreted proteins and proteins where the sorting sequence is not located near the N-terminus. It appears that the NHP is both necessary and sufficient for sorting of many secretory proteins to the regulated secretory pathway.

Original languageEnglish (US)
Pages (from-to)8-12
Number of pages5
JournalFEBS Letters
Issue number1
StatePublished - Mar 13 1995

Bibliographical note

Funding Information:
Acknowledgements." Work in the authors' laboratories is supported by a grant-in-aid from the American Heart Association, Kentucky Affiliate and a grant from NIH, NIDDK (DSD). The authors thank Harpreet S. Dhaliwal for preliminary sequence analyses and Dr. Robert D. Gray for advice and critical reading of the manuscript.


  • Chromogranin
  • Prohormone
  • Proopiomelanocortin
  • Protein structure
  • Regulated secretion
  • Targeting


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