CaltechAUTHORS
  A Caltech Library Service

PRMT7 Is a Member of the Protein Arginine Methyltransferase Family with a Distinct Substrate Specificity

Miranda, Tina Branscombe and Miranda, Mark and Frankel, Adam and Clarke, Steven (2004) PRMT7 Is a Member of the Protein Arginine Methyltransferase Family with a Distinct Substrate Specificity. Journal of Biological Chemistry, 279 (22). pp. 22902-22907. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:20110907-133655558

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:20110907-133655558

Abstract

We have identified a mammalian arginine N-methyltransferase, PRMT7, that can catalyze the formation of ω-N^G-monomethylarginine in peptides. This protein is encoded by a gene on human chromosome 16q22.1 (human locus AK001502). We expressed a full-length human cDNA construct in Escherichia coli as a glutathione S-transferase (GST) fusion protein. We found that GST-tagged PRMT7 catalyzes the S-adenosyl-[methyl-^3H]-L-methionine-dependent methylation of the synthetic peptide GGPGGRGGPGG-NH_2 (R1). The radiolabeled peptide was purified by high-pressure liquid chromatography and acid hydrolyzed to free amino acids. When the hydrolyzed products were separated by high-resolution cation-exchange chromatography, we were able to detect one tritiated species which co-migrated with an ω-N^G-monomethylarginine standard. Surprisingly, GST-PRMT7 was not able to catalyze the in vitro methylation of a GST-fibrillarin (amino acids 1–148) fusion protein (GST-GAR), a methyl-accepting substrate for the previously characterized PRMT1, PRMT3, PRMT4, PRMT5, and PRMT6 enzymes. Nor was it able to methylate myelin basic protein or histone H2A, in vitro substrates of PRMT5. This specificity distinguishes PRMT7 from all of the other known arginine methyltransferases. An additional unique feature of PRMT7 is that it seems to have arisen from a gene duplication event and contains two putative AdoMet-binding motifs. To see if both motifs were necessary for activity, each putative domain was expressed as a GST-fusion and tested for activity with peptides R1 and R2 (acetyl-GGRGG-NH_2). These truncated proteins were enzymatically inactive, suggesting that both domains are required for functionality.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1074/jbc.M312904200DOIUNSPECIFIED
http://dx.doi.org/10.1074/jbc.M312904200PublisherUNSPECIFIED
Additional Information:© 2004 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, November 26, 2003, and in revised form, March 10, 2004. First Published on March 24, 2004. This work was supported by National Institutes of Health Grant GM26020. Supported in part by United States Public Health Service Training Program Grant GM07185. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHGM26020
United States Public Health Service (USPHS) Training ProgramGM07185
Record Number:CaltechAUTHORS:20110907-133655558
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20110907-133655558
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25247
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 Sep 2011 15:24
Last Modified:08 Sep 2011 15:24

Repository Staff Only: item control page