Localization of a Human Nucleoporin 155 Gene (NUP155) to the 5p13 Region and Cloning of Its cDNA

Zhang, Xiuqing; Yang, Huanming; Corydon, Morten J.; Zhang, Xiaoxiao; Pedersen, Søren; Korenberg, Julie R.; Chen, Xiao Ning; Laporte, Jocelyn; Gregersen, Niels; Niebuhr, Erik; Liu, Guoyang; Bolund, Lars

doi:10.1006/geno.1999.5741

Cited by 20 publications

(19 citation statements)

References 32 publications

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“…The O-GlcNAc-modified serine 96, which is located in the nucleoplasmic amino-terminal tail, may play a role in proteinprotein interactions and/or NPC assembly and function. Ser-525 was also found to be O-GlcNAc-modified on Nup155, a recently identified member of the mammalian NPC whose function remains to be elucidated (54). We are currently using the BEMAD method to perform a more global analysis of sites of O-GlcNAc modification on the NPC and other subproteomes.…”

Section: Discussionmentioning

confidence: 99%

Mapping Sites of O-GlcNAc Modification Using Affinity Tags for Serine and Threonine Post-translational Modifications

Wells

Vosseller

Cole

et al. 2002

Molecular & Cellular Proteomics

406

366

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Identifying sites of post-translational modifications on proteins is a major challenge in proteomics. O-Linked ␤-N-acetylglucosamine (O-GlcNAc) is a dynamic nucleocytoplasmic modification more analogous to phosphorylation than to classical complex O-glycosylation. We describe a mass spectrometry-based method for the identification of sites modified by O-GlcNAc that relies on mild ␤-elimination followed by Michael addition with dithiothreitol (BEMAD). Using synthetic peptides, we also show that biotin pentylamine can replace dithiothreitol as the nucleophile. The modified peptides can be efficiently enriched by affinity chromatography, and the sites can be mapped using tandem mass spectrometry. This same methodology can be applied to mapping sites of serine and threonine phosphorylation, and we provide a strategy that uses modification-specific antibodies and enzymes to discriminate between the two post-translational modifications. The BEMAD methodology was validated by mapping three previously identified O-GlcNAc sites, as well as three novel sites, on Synapsin I purified from rat brain. BEMAD was then used on a purified nuclear pore complex preparation to map novel sites of O-GlcNAc modification on the Lamin B receptor and the nucleoporin Nup155. This method is amenable for performing quantitative mass spectrometry and can also be adapted to quantify cysteine residues. In addition, our studies emphasize the importance of distinguishing between O-phosphate versus O-GlcNAc when mapping sites of serine and threonine post-translational modification using ␤-elimination/Michael addition methods. The rapid identification of proteins by mass spectrometry has become commonplace in the postgenomic era (1). However, one major challenge that remains is the identification of post-translational modifications on these proteins. More than 25 years ago, Finn Wold and colleagues (2) recognized the abundance of naturally occurring modified forms of the genetically encoded 21 amino acids. In addition to phosphorylation, a variety of post-translational modifications, including acetylation (3), methylation (4), and O-linked ␤-N-acetylglucosamine (OGlcNAc) 1 (5-7), are now recognized to regulate protein functions in cellular processes. Therefore, identification of proteins along with their post-translational modifications, which has been referred to as "functional proteomics," is an important step in the characterization of proteomes. O-GlcNAc is a dynamic post-translational modification occurring on a variety of nucleocytoplasmic proteins and, in several instances, O-GlcNAc maps to the same or adjacent sites as phosphorylation (8, 9). Diverse classes of proteins are modified including cytoskeletal proteins, transcription factors, signaling adapter molecules, hormone receptors, nuclear pore complex (NPC) proteins, and kinases (10). The nucleocytoplasmic enzymes for the addition (O-GlcNAc transferase) and removal (neutral ␤-N-acetylglucosaminidase, O-GlcNAcase) of this modification have been cloned and characterized (11-16) and may ac...

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Section: Discussionmentioning

confidence: 99%

Mapping Sites of O-GlcNAc Modification Using Affinity Tags for Serine and Threonine Post-translational Modifications

Wells

Vosseller

Cole

et al. 2002

Molecular & Cellular Proteomics

406

366

View full text Add to dashboard Cite

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“…The gene is located on chromosome 5q13. 76 Oberti et al 77 mapped an AF locus to chromosome 5q13 in a large AF family with an autosomal recessive inheritance pattern. Subsequently, Zhang et al 78 revealed that the above mentioned locus was NUP155 and identified a homozygous mutation in NUP155 in all the affected family members.…”

Section: Non-ion Channel Mutationsmentioning

confidence: 99%

Atrial fibrillation: the role of common and rare genetic variants

Olesen

Nielsen

Haunsø³

et al. 2013

Eur J Hum Genet

105

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Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1-2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized for many years. Presently, mutations in 25 genes have been associated with AF. However, the complexity of monogenic AF is illustrated by the recent finding that both gain-and loss-of-function mutations in the same gene can cause AF. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Following the first GWAS discovering the association between PITX2 and AF, several new GWAS reports have identified SNPs associated with susceptibility of AF. To date, nine SNPs have been associated with AF. The exact biological pathways involving these SNPs and the development of AF are now starting to be elucidated. Since the first GWAS, the number of papers concerning the genetic basis of AF has increased drastically and the majority of these papers are for the first time included in a review. In this review, we discuss the genetic basis of AF and the role of both common and rare genetic variants in the susceptibility of developing AF. Furthermore, all rare variants reported to be associated with AF were systematically searched for in the Exome Sequencing Project Exome Variant Server.

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“…One of the mutations was located in the nucleoporin gene (NUP155) [9]. NUP155 encodes a nucleoporin which is an important component of the nuclear pore complex (NPC) [35]. In a more recent study, a heterozygous frameshift mutation in NPPA, the gene encoding atrial naturetic peptide (ANP) has been reported.…”

Section: Linkage Analysismentioning

confidence: 98%

“…These effects may provide a proarrhythmogenic substrate. NUP155 encodes a nucleoporin which is one of the main components of the nuclear pore complex [35]. The link between nuclear pore complexes and AF is presently unclear.…”

Section: Candidate Gene Studiesmentioning

confidence: 99%