Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome
In 11 patients with a recessive congenital disorder, which we refer to as ¿the hypotonia-cystinuria syndrome,¿ microdeletion of part of the SLC3A1 and PREPL genes on chromosome 2p21 was found. Patients present with generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, and failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. Since loss-of-function mutations in SLC3A1 are known to cause isolated cystinuria type I, and since the expression of the flanking genes, C2orf34 and PPM1B, was normal, the extended phenotype can be attributed to the deletion of PREPL. PREPL is localized in the cytosol and shows homology with prolyl endopeptidase and oligopeptidase B. Substitution of the predicted catalytic residues (Ser470, Asp556, and His601) by alanines resulted in loss of reactivity with a serine hydrolase-specific probe. In sharp contrast to prolyl oligopeptidase and oligopeptidase B, which require both aminoterminal and carboxyterminal sequences for activity, PREPL activity appears to depend only on the carboxyterminal domain. Taken together, these results suggest that PREPL is a novel oligopeptidase, with unique structural and functional characteristics, involved in hypotonia-cystinuria syndrome.
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Format: | Article/Letter to editor biblioteca |
Language: | English |
Subjects: | active-site, alpha/beta-hydrolase fold, endopeptidase, host-cell invasion, mutations, peptide libraries, processing enzyme, prolyl oligopeptidase, substrate, trypanosoma-cruzi, |
Online Access: | https://research.wur.nl/en/publications/deletion-of-prepl-a-gene-encoding-a-putative-serine-oligopeptidas |
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dig-wur-nl-wurpubs-3643082024-08-16 Jaeken, J. Martens, K. Francois, I. Eyskens, F. Lecointre, C. Derua, R. Meulemans, S. Slootstra, J.W. Waelkens, E. de Zegher, F. Creemers, J.W.M. Matthijs, G. Article/Letter to editor American Journal of Human Genetics 78 (2006) 1 ISSN: 0002-9297 Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome 2006 In 11 patients with a recessive congenital disorder, which we refer to as ¿the hypotonia-cystinuria syndrome,¿ microdeletion of part of the SLC3A1 and PREPL genes on chromosome 2p21 was found. Patients present with generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, and failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. Since loss-of-function mutations in SLC3A1 are known to cause isolated cystinuria type I, and since the expression of the flanking genes, C2orf34 and PPM1B, was normal, the extended phenotype can be attributed to the deletion of PREPL. PREPL is localized in the cytosol and shows homology with prolyl endopeptidase and oligopeptidase B. Substitution of the predicted catalytic residues (Ser470, Asp556, and His601) by alanines resulted in loss of reactivity with a serine hydrolase-specific probe. In sharp contrast to prolyl oligopeptidase and oligopeptidase B, which require both aminoterminal and carboxyterminal sequences for activity, PREPL activity appears to depend only on the carboxyterminal domain. Taken together, these results suggest that PREPL is a novel oligopeptidase, with unique structural and functional characteristics, involved in hypotonia-cystinuria syndrome. en application/pdf https://research.wur.nl/en/publications/deletion-of-prepl-a-gene-encoding-a-putative-serine-oligopeptidas 10.1086/498852 https://edepot.wur.nl/35534 active-site alpha/beta-hydrolase fold endopeptidase host-cell invasion mutations peptide libraries processing enzyme prolyl oligopeptidase substrate trypanosoma-cruzi Wageningen University & Research |
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active-site alpha/beta-hydrolase fold endopeptidase host-cell invasion mutations peptide libraries processing enzyme prolyl oligopeptidase substrate trypanosoma-cruzi active-site alpha/beta-hydrolase fold endopeptidase host-cell invasion mutations peptide libraries processing enzyme prolyl oligopeptidase substrate trypanosoma-cruzi |
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active-site alpha/beta-hydrolase fold endopeptidase host-cell invasion mutations peptide libraries processing enzyme prolyl oligopeptidase substrate trypanosoma-cruzi active-site alpha/beta-hydrolase fold endopeptidase host-cell invasion mutations peptide libraries processing enzyme prolyl oligopeptidase substrate trypanosoma-cruzi Jaeken, J. Martens, K. Francois, I. Eyskens, F. Lecointre, C. Derua, R. Meulemans, S. Slootstra, J.W. Waelkens, E. de Zegher, F. Creemers, J.W.M. Matthijs, G. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
description |
In 11 patients with a recessive congenital disorder, which we refer to as ¿the hypotonia-cystinuria syndrome,¿ microdeletion of part of the SLC3A1 and PREPL genes on chromosome 2p21 was found. Patients present with generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, and failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. Since loss-of-function mutations in SLC3A1 are known to cause isolated cystinuria type I, and since the expression of the flanking genes, C2orf34 and PPM1B, was normal, the extended phenotype can be attributed to the deletion of PREPL. PREPL is localized in the cytosol and shows homology with prolyl endopeptidase and oligopeptidase B. Substitution of the predicted catalytic residues (Ser470, Asp556, and His601) by alanines resulted in loss of reactivity with a serine hydrolase-specific probe. In sharp contrast to prolyl oligopeptidase and oligopeptidase B, which require both aminoterminal and carboxyterminal sequences for activity, PREPL activity appears to depend only on the carboxyterminal domain. Taken together, these results suggest that PREPL is a novel oligopeptidase, with unique structural and functional characteristics, involved in hypotonia-cystinuria syndrome. |
format |
Article/Letter to editor |
topic_facet |
active-site alpha/beta-hydrolase fold endopeptidase host-cell invasion mutations peptide libraries processing enzyme prolyl oligopeptidase substrate trypanosoma-cruzi |
author |
Jaeken, J. Martens, K. Francois, I. Eyskens, F. Lecointre, C. Derua, R. Meulemans, S. Slootstra, J.W. Waelkens, E. de Zegher, F. Creemers, J.W.M. Matthijs, G. |
author_facet |
Jaeken, J. Martens, K. Francois, I. Eyskens, F. Lecointre, C. Derua, R. Meulemans, S. Slootstra, J.W. Waelkens, E. de Zegher, F. Creemers, J.W.M. Matthijs, G. |
author_sort |
Jaeken, J. |
title |
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
title_short |
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
title_full |
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
title_fullStr |
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
title_full_unstemmed |
Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
title_sort |
deletion of prepl, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome |
url |
https://research.wur.nl/en/publications/deletion-of-prepl-a-gene-encoding-a-putative-serine-oligopeptidas |
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