Topic
GNB4
About: GNB4 is a research topic. Over the lifetime, 8 publications have been published within this topic receiving 85 citations. The topic is also known as: CMTD1F & G protein subunit beta 4.
Papers
TL;DR: In this article, the upregulation of the GNB4 protein was associated with primary tumor, nodal metastasis, histological grade, vascular invasion and mitotic rate in UC patients.
Abstract: Data mining on a public domain detected eight potential transcripts which were upregulated in advanced UBUCs, suggesting that they may take part in UC development or/and progression. Retrospectively, immunohistochemistry along with H-score recording was carried out to evaluate the GNB4 protein levels on tissues from UC patients. Correlations between GNB4 H-score and imperative clinicopathological factors, as well as the implication of GNB4 protein level on disease-specific and metastasis-free survivals were assessed. In UTUCs (n = 340) and UBUCs (n = 295), 170 (50.0%) and 148 (50.0%) cases, respectively, were identified to be of high GNB4 expression. The GNB4 protein levels were correlated to numerous clinicopathological features and patients’ survivals. Upregulation of the GNB4 protein was significantly associated with primary tumor, nodal metastasis, histological grade, vascular invasion and mitotic rate. High GNB4 protein levels independently and significantly predicted poor disease-specific and metastasis-free in UTUC and UBUC, respectively. Ingenuity pathway analysis furthermore showed that multiple signaling pathways were enriched including ‘Communication between Innate and Adaptive Immune Cells’ and ‘NFκB Signaling’. Our findings demonstrated that the upregulation of the GNB4 protein is an independent unfavorable prognosticator in UC. High GNB4 gene expression plays an important role in UC progression.
5 citations
TL;DR: Caprine GNAI3 gene can be used as a possible biomarker for studying heat tolerance mechanism in goats and degree of hydrophobicity of the generated protein structures revealed the presence of alternate hydrophobic and hydrophilic regions.
Abstract: Goat is the most preferred domesticated animal in Indian subcontinent. However, the climatic change-induced heat stresscauses a formidable challenge for maintaining optimum productivity. G protein subunit alpha i3 (GNAI3) is one of the genes that may have significant role in heat tolerance mechanism in goats. The caprine GNAI3 gene was searched for homology analysis and its three dimensional protein structure was predicted followed by its validation through in silico approach. Nucleotide sequence-based phylogenetic tree analysis showed that the caprine GNAI3 gene has close evolutionary relationship with that of Ovis aries. Homology modelling of caprine GNAI3 protein was done in MODELLER 9.18 (P1), PHYRE2 (P2), GENO3D (P3) and SWISS MODEL (P4). The modelled structures were further validated after observing the Ramachandran and hydrophobicity plots. In the best of three dimensional protein structure (P4 as produced by SWISS MODEL), 330 (98.8%), three (0.9%) and one (0.3%) amino acid residues were found in favoured region, allowed region and outlier region, respectively. Degree of hydrophobicity of the generated protein structures revealed the presence of alternate hydrophobic and hydrophilic regions. The ligand receptor interaction site of the predicted 3D model was traced out using Discovery Studio 3.5. STRING database revealed protein interactions with Plcb1, Plcb2, Plcb3 and other proteins of G family such as Gnb1, Gnb2, Gnb3,Gnb4, Gng2, Gng4 and Gpsm1. KEGG pathway maps revealed interaction with eNOS, iNOS, VEGF and MAPK, which are reported to be transcribed in response to heat stress. Thus, caprine GNAI3 can be used as a possible biomarker for studying heattolerance mechanism in goats.
2 citations
TL;DR: The study identified a heterozygous mutation (G53D) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (Gb4), to cosegregate with the CMT phenotype in this family [Soong et al., 2013].
TL;DR: It is concluded that a novel heterozygous nonsynonymous GNB4 variant is causative for CMTDIF in these patients, who represent the first record of the disease in the Japanese population.
TL;DR: GNB4 mutations are identified as a cause ofarcot-Marie-Tooth disease and the importance of Gβ4-related GPCR signaling in peripheral-nerve function in humans is highlighted.
Abstract: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited neuropathies. Mutations in approximately 45 genes have been identified as being associated with CMT. Nevertheless, the genetic etiologies of at least 30% of CMTs have yet to be elucidated. Using a genome-wide linkage study, we previously mapped a dominant intermediate CMT to chromosomal region 3q28–q29. Subsequent exome sequencing of two affected first cousins revealed heterozygous mutation c.158G>A (p.Gly53Asp) in GNB4, encoding guanine-nucleotide-binding protein subunit beta-4 (Gβ4), to cosegregate with the CMT phenotype in the family. Further analysis of GNB4 in an additional 88 unrelated CMT individuals uncovered another de novo mutation, c.265A>G (p.Lys89Glu), in this gene in one individual. Immunohistochemistry studies revealed that Gβ4 was abundant in the axons and Schwann cells of peripheral nerves and that expression of Gβ4 was significantly reduced in the sural nerve of the two individuals carrying the c.158G>A (p.Gly53Asp) mutation. In vitro studies demonstrated that both the p.Gly53Asp and p.Lys89Glu altered proteins impaired bradykinin-induced G-protein-coupled-receptor (GPCR) signaling, which was facilitated by the wild-type Gβ4. This study identifies GNB4 mutations as a cause of CMT and highlights the importance of Gβ4-related GPCR signaling in peripheral-nerve function in humans.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 1 |
| 2020 | 2 |
| 2019 | 1 |
| 2018 | 1 |
| 2017 | 1 |
| 2013 | 1 |