NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle

Tatsiana Kosciuk, Ian R. Price, Xiaoyu Zhang, Chengliang Zhu, Kayla N. Johnson, Shuai Zhang, Steve L. Halaby, Garrison P. Komaniecki, Min Yang, Caroline Jane DeHart, Paul Martin Thomas, Neil L. Kelleher, J. Christopher Fromme, Hening Lin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Lysine fatty acylation in mammalian cells was discovered nearly three decades ago, yet the enzymes catalyzing it remain unknown. Unexpectedly, we find that human N-terminal glycine myristoyltransferases (NMT) 1 and 2 can efficiently myristoylate specific lysine residues. They modify ADP-ribosylation factor 6 (ARF6) on lysine 3 allowing it to remain on membranes during the GTPase cycle. We demonstrate that the NAD+-dependent deacylase SIRT2 removes the myristoyl group, and our evidence suggests that NMT prefers the GTP-bound while SIRT2 prefers the GDP-bound ARF6. This allows the lysine myrisotylation-demyristoylation cycle to couple to and promote the GTPase cycle of ARF6. Our study provides an explanation for the puzzling dissimilarity of ARF6 to other ARFs and suggests the existence of other substrates regulated by this previously unknown function of NMT. Furthermore, we identified a NMT/SIRT2-ARF6 regulatory axis, which may offer new ways to treat human diseases.

Original languageEnglish (US)
Article number1067
JournalNature communications
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle'. Together they form a unique fingerprint.

Cite this