# Determining the scope of prenylatable protein sequences

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $390,494

## Abstract

PROJECT SUMMARY
This study investigates the specificity of farnesyl transferase (FTase) that isoprenylates CaaX proteins.
Studies probing the in vivo activity of the FTase have historically used reporters (e.g. Ras GTPases) that
undergo complex multi-step post-translational modification (PTM), involving initial farnesylation followed by
CaaX proteolysis and carboxyl methylation. This study takes advantage of Hsp40 Ydj1, a farnesylation-only
reporter for which we have developed a range of methods to monitor its PTM status. Its use reveals that
farnesylation is not necessarily coupled to subsequent PTMs as has been generally accepted for CaaX
proteins, and that FTase specificity is significantly more promiscuous than anticipated. These findings
challenge the conventional paradigm for how farnesylated proteins are modified and which proteins are
targeted by FTase. We will extend our studies to fully resolve the specificity of FTase using a combination of
genetic, biochemical, bioinformatic, and biophysical studies. We bring to bear on our investigations an
exceptionally strong set of preliminary findings, the complementary expertise of several research groups, and a
comprehensive molecular toolbox for the study of farnesylated proteins and other enzymes associated with this
post-translational modification pathway.

## Key facts

- **NIH application ID:** 10019396
- **Project number:** 5R01GM132606-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Natarajan Kannan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,494
- **Award type:** 5
- **Project period:** 2019-09-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019396

## Citation

> US National Institutes of Health, RePORTER application 10019396, Determining the scope of prenylatable protein sequences (5R01GM132606-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019396. Licensed CC0.

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