The HIV-1 transactivator protein Tat is a critical regulator of HIV transcription primarily enabling efficient elongation of viral transcripts. Its interactions with RNA and various host factors are regulated by ordered, transient post-translational modifications. Here, we report a novel Tat modification, monomethylation at lysine 71 (K71). We found that Lys-71 monomethylation (K71me) is catalyzed by KMT7, a methyltransferase that also targets lysine 51 (K51) in Tat. Using mass spectrometry, in vitro enzymology, and modification-specific antibodies, we found that KMT7 monomethylates both Lys-71 and Lys-51 in Tat. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity of wild type (WT) Tat but not a Tat K71R mutant. These findings underscore the role of KMT7 as an important monomethyltransferase regulating HIV transcription through Tat.

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Published in Journal of Biological Chemistry, v. 291, no. 31, p. 16240-16248.

This research was originally published in the Journal of Biological Chemistry. Ali, I., Ramage, H., Boehm, D., Dirk, L., Sakane, N., Hanada, K., Pagans, S., Kaehlcke, K., Aull, K., Weinberger, L., Trievel, R., Schnoelzer, M., Kamada, M., Houtz, R., and Ott, M. The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. J. Biol. Chem. 2016; 291:16240-16248. © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

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This work was supported by the University of California San Francisco, Gladstone Institute of Virology and Immunology Center for AIDS Research, a collaboration with JT Pharma, Gladstone Institutes, CA AIDS Research Program, and Grants R01AI083139, U19AI096113, T32IA7334-26, and P30AI027763 from the National Institutes of Health, and Grant ID F13-GI-316 from the California HIV/AIDS Research Program (CHRP).

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This article contains supplemental Tables S-1 and S-2.

jbc.M116.735415-1.pdf (27 kB)
Supplemental Tables - Mass Spectrometry ion annotation data for Figure 1 and Figure 3