A novel family of transmembrane proteins interacting with β subunits of the Na,K-ATPase

Gorokhova, Svetlana; Bibert, Stéphanie; Geering, Käthi; Heintz, Nathaniel

doi:10.1093/hmg/ddm167

Cited by 47 publications

(50 citation statements)

References 62 publications

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“…The gene start is 24.6 kb downstream of the enhancer end (defined by FANTOM5). NKAIN is a member of the mammalian protein family with similarity to Drosophila Nkain and interacts with the beta subunit of Na, K-ATPase (77). NKAIN1 could be considered a ‘typical’ enhancer-neighboring gene of neuronal cells.…”

Section: Resultsmentioning

confidence: 99%

Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers

Kuznetsov

Bondarenko

Wongsurawat

et al. 2018

Nucleic Acids Research

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R-loops are three-stranded RNA:DNA hybrid structures essential for many normal and pathobiological processes. Previously, we generated a quantitative R-loop forming sequence (RLFS) model, quantitative model of R-loop-forming sequences (QmRLFS) and predicted ∼660 000 RLFSs; most of them located in genes and gene-flanking regions, G-rich regions and disease-associated genomic loci in the human genome. Here, we conducted a comprehensive comparative analysis of these RLFSs using experimental data and demonstrated the high performance of QmRLFS predictions on the nucleotide and genome scales. The preferential co-localization of RLFS with promoters, U1 splice sites, gene ends, enhancers and non-B DNA structures, such as G-quadruplexes, provides evidence for the mechanical linkage between DNA tertiary structures, transcription initiation and R-loops in critical regulatory genome regions. We introduced and characterized an abundant class of reverse-forward RLFS clusters highly enriched in non-B DNA structures, which localized to promoters, gene ends and enhancers. The RLFS co-localization with promoters and transcriptionally active enhancers suggested new models for in cis and in trans regulation by RNA:DNA hybrids of transcription initiation and formation of 3D-chromatin loops. Overall, this study provides a rationale for the discovery and characterization of the non-B DNA regulatory structures involved in the formation of the RNA:DNA interactome as the basis for an emerging quantitative R-loop biology and pathobiology.

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Section: Resultsmentioning

confidence: 99%

Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers

Kuznetsov

Bondarenko

Wongsurawat

et al. 2018

Nucleic Acids Research

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“…One possibility is that the β-subunits at the rhabdomere base are bound to proteins other than the Na,K-ATPase α-subunit. Notably, a transmembrane protein termed dNKAIN (Drosophila Na,KATPase interacting) has been demonstrated to interact with Na,K-ATPase β-subunits (Gorokhova et al 2007). dNKAIN is present at least in the brain, and its expression in Xenopus oocytes induces a voltage-independent Na + -specific conductance.…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in β-subunit composition of Na,K-ATPase in the Drosophila eye

Baumann

Salvaterra

2010

Cell Tissue Res

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The Drosophila genome contains at least three loci for the Na,K-ATPase beta-subunit; however, only the protein products of nrv1 and nrv2 have been characterized hitherto. Here, we provide evidence that nrv3 also encodes for a functional Na,K-ATPase beta-subunit, as its protein product co-precipitates with the Na,K-ATPase alpha-subunit. Nrv3 expression in adult flies is restricted to the nervous system in which Nrv3 is enriched in selective types of sensory cells. Because Nrv3 expression is especially prominent in the compound eye, we have analyzed the subcellular and developmental distribution of Nrv3 within the visual cells and related this distribution to those of the alpha-subunit and of the beta-subunits Nrv1 and Nrv2. Prospective visual cells express Nrv2 in the third larval instar stage and during the first half of pupal development. During the last third of pupal life, Nrv3 gradually replaces Nrv2 as the Na,K-ATPase beta-subunit in the photoreceptor cells. Adult photoreceptors express Nrv3 as their major beta-subunit; the visual cells R1-R6 co-express Nrv2 at a low level, whereas R7 and R8 co-express Nrv1. Notably, beta-subunits do not co-distribute exactly with the alpha-subunit at some developmental stages, supporting the concept that the alpha-subunit and beta-subunit can exist in the plasma membrane without being engaged in alpha/beta heterodimers. The non-visual cells within the compound eye express almost exclusively Nrv2, which segregates together with the alpha-subunit to septate junctions throughout development.

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“…This gene is highly conserved among species, transcribed in different splice variants, specific to the central nervous system [5], and critical for neuronal functions [6]. It has also been associated with neuroticism in a genome-wide associations study (GWAS) [7], a complex neurological phenotype [5], and a developmental delay with recurrent infections [8].…”

Section: Introductionmentioning

confidence: 99%

Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent

Zuo

Wang

Zhang

et al. 2013

Pharmacogenetics and Genomics

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Objectives We previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in the subjects of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency (MAF) < 0.05] in the NKAIN1-SERINC2 region, in order to confirm our previous finding. Methods A discovery sample (1,409 European-American cases with alcohol dependence and 1,518 European-American controls) and a replication sample (6,438 European-Australian family subjects with 1,645 alcohol dependent probands) underwent association analysis. A total of 39,903 subjects from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 SNPs in the subjects with European descent and about 450 SNPs in the subjects with African descent with 0

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A novel family of transmembrane proteins interacting with β subunits of the Na,K-ATPase

Cited by 47 publications

References 62 publications

Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers

Toward predictive R-loop computational biology: genome-scale prediction of R-loops reveals their association with complex promoter structures, G-quadruplexes and transcriptionally active enhancers

Developmental changes in β-subunit composition of Na,K-ATPase in the Drosophila eye

Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent

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