Abstract
A previously uncharacterized member of the M1 family of zinc metallopeptidases, arginyl aminopeptidase-like 1 (RNPEPL1; EC 3.4.11.1), was cloned and expressed, and the recombinant enzyme characterized. RNPEPL1 was a broad specificity aminopeptidase with preference for a P1 methionine, glutamine, or citrulline residue, and exhibited a broad pH preference, with maximal activity observed between pH 6.6 and 8.0. The enzyme was inhibited by calcium ions but unaffected by chloride ions, and was insensitive to specific inhibitors of the closely-related arginyl aminopeptidase, indicating similarity to leukotriene A4 hydrolase. RT-PCR analysis of RNPEPL1 expression revealed a ubiquitous tissue distribution, consistent with a general housekeeping function, but also revealed alternative splicing of the mRNA in all tissues examined. The inclusion of intron 5 was predicted to result in a truncated protein product, while an alternative 3 ’ splice site of exon 9 of the reference sequence was predicted to result in the omission of a conserved eleven amino acid stretch from the C-terminal domain.
Keywords: alternative splicing, calcium, zinc, protease, metallopeptidase, Aminopeptidase
Protein & Peptide Letters
Title: Arginyl Aminopeptidase-Like 1 (RNPEPL1) Is an Alternatively Processed Aminopeptidase with Specificity for Methionine, Glutamine, and Citrulline Residues
Volume: 16 Issue: 10
Author(s): Michael W. Thompson, Karen A. Beasley, Matthew D. Schmidt and Rebecca L. Seipelt
Affiliation:
Keywords: alternative splicing, calcium, zinc, protease, metallopeptidase, Aminopeptidase
Abstract: A previously uncharacterized member of the M1 family of zinc metallopeptidases, arginyl aminopeptidase-like 1 (RNPEPL1; EC 3.4.11.1), was cloned and expressed, and the recombinant enzyme characterized. RNPEPL1 was a broad specificity aminopeptidase with preference for a P1 methionine, glutamine, or citrulline residue, and exhibited a broad pH preference, with maximal activity observed between pH 6.6 and 8.0. The enzyme was inhibited by calcium ions but unaffected by chloride ions, and was insensitive to specific inhibitors of the closely-related arginyl aminopeptidase, indicating similarity to leukotriene A4 hydrolase. RT-PCR analysis of RNPEPL1 expression revealed a ubiquitous tissue distribution, consistent with a general housekeeping function, but also revealed alternative splicing of the mRNA in all tissues examined. The inclusion of intron 5 was predicted to result in a truncated protein product, while an alternative 3 ’ splice site of exon 9 of the reference sequence was predicted to result in the omission of a conserved eleven amino acid stretch from the C-terminal domain.
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Cite this article as:
Thompson Michael W., Beasley Karen A., Schmidt Matthew D. and Seipelt Rebecca L., Arginyl Aminopeptidase-Like 1 (RNPEPL1) Is an Alternatively Processed Aminopeptidase with Specificity for Methionine, Glutamine, and Citrulline Residues, Protein & Peptide Letters 2009; 16 (10) . https://dx.doi.org/10.2174/092986609789071199
DOI https://dx.doi.org/10.2174/092986609789071199 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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