Ask about this productRelated genes to: SHANK1 antibody
- Gene:
- SHANK1 NIH gene
- Name:
- SH3 and multiple ankyrin repeat domains 1
- Previous symbol:
- -
- Synonyms:
- SSTRIP, SPANK-1, synamon
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-22
- Date modifiied:
- 2016-10-05
Related products to: SHANK1 antibody
Related articles to: SHANK1 antibody
- The development of ligands that modulate protein-protein interactions (PPIs) remains an ongoing challenge in chemical biology and drug discovery. While several approaches have been elaborated to target α-helix-mediated PPIs, methods for β-strand-mediated PPIs are less well developed. In addition to the shallow and extended interfaces characteristic of PPIs, β-strand-mediated PPIs exhibit topographical complexity, with side chains oriented above and below the plane of the strand, alongside hydrogen-bond donor and acceptor groups oriented perpendicular to the side chains. One class of β-strand-mediated PPIs involves the structurally conserved PDZ domains, which recognize protein partners through a β-strand containing a short consensus motif; canonical PDZ binding motifs (PBMs) recognize their substrates through a C-terminal carboxylate, offering a particularly challenging motif to mimic. Peptides and peptidomimetics represent a promising template for the design of ligands that target β-strand-mediated PPIs. In this work, we replaced segments of a peptide-based template using target/structure-agnostic fragments to achieve β-strand mimicry. Using reversible hydrazone exchange reactions allowed us to identify fragments at both the C- and N-terminus of an internal PDZ recognition motif with affinity for the SHANK1-PDZ domain. When combined into ligands bearing two different fragments, negative co-operativity was observed. In addition to broadening the acylhydrazone-fragment approach to screen for PDZ-binding ligands, this workflow for successive screening and combination of fragments should have broader applicability to other targets in future. - Source: PubMed
Publication date: 2026/04/07
Li YueGimenez DianaWarriner Stuart LWilson Andrew J - Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological conditions. In this study, we investigated the role of HPCA in regulating NMDA receptor expression and function in mouse hippocampal neural precursor cells (mHNPCs). HPCA knockdown significantly reduced the expression of NMDA receptor-related genes, including , , , and selectively attenuated NMDA-induced calcium signaling. Transcriptomic analysis identified ELAV-like RNA-binding protein 3 (Elavl3), a neuron-enriched factor associated with neuronal activity, as a downstream candidate affected by HPCA knockdown. Consistently, Elavl3 suppression phenocopied HPCA deficiency, resulting in impaired NMDA receptor activity and reduced neuronal differentiation. Furthermore, hippocampal HPCA knockdown in vivo led to alterations in locomotor activity, contextual memory, and affective behaviors. Taken together, these findings demonstrate that HPCA supports NMDA receptor function and neuronal development, in part through Elavl3-associated pathways, and highlight HPCA as an important regulator of hippocampal function. - Source: PubMed
Publication date: 2026/03/06
Kang Min-JeongJung Sung JunSon HyeonHan Joong-SooPark Shin-Young - Despite the extensive agricultural utilization owing to distinctive physicochemical properties and robust broad-spectrum antimicrobial activity, Cu(OH) nanopesticide (NP) has raised escalating neurotoxic concerns due to its environmental persistence and bioaccumulation potential. Adolescence constitutes a pivotal window of postnatal neurodevelopment, characterized by maturation and refinement of synaptic architecture and neural circuitry, which critically determines cognitive ontogeny. In the present investigation, adolescent C57BL/6 mice were subjected to subchronic oral administration via gavage of Cu(OH)₂ NP or vehicle control over a 30-day exposure period. This exposure regimen was demonstrated to elicit neurodevelopmental perturbations, manifesting as pronounced impairments in social interaction and novelty-seeking behavior, phenotypes resembling depression and autism spectrum disorders, concurrent with dysregulated synaptic molecular signatures and compromised neurotransmission equilibrium. These observed aberrations were pathologically linked to aberrant copper homeostasis and induction of cuproptosis pathways in mitochondrion, identified as principal drivers of neurodevelopmental impairment. The Cu(OH) NP-mediated epigenetic reprogramming of the transcription factor (TF) Kdm1a, executed through the long noncoding RNAs (lncRNAs) Shank1-204 and Acsl1-206, delineated the core molecular pathogenesis underpinning this NP-evoked neurodevelopmental deficits. Collectively, these discoveries substantially advanced the current insights into the developmental neurotoxicity attributable to engineered NPs, providing an essential scientific foundation for establishing rigorous neurotoxicological risk assessment paradigms. - Source: PubMed
Publication date: 2026/01/29
Ren ZhihuaDuan YonghuiRen MengyaoCai YixueLiang JiefengWang XiaoSun JiafeiRen DanqinKu TingtingNing XiaSang Nan - Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors primarily involving the adrenal medulla and its associated paraganglia, with heterogeneous clinical behavior and complex molecular drivers. This study aimed to characterize DNA methylation and gene expression patterns in PPGLs to understand the molecular differences between tumor subtypes and malignancy. We performed an integrative analysis of DNA methylation (Illumina EPIC 850K) and gene expression profiles (Affymetrix microarrays) in 24 PPGLs, comparing these with The Cancer Genome Atlas (TCGA) data, to delineate cluster- and malignancy-specific epigenetic patterns. Comparison between pseudohypoxic Cluster I and kinase-signaling Cluster II tumors revealed 13 differentially methylated CpG sites, with a specific CpG within showing hypermethylation in Cluster II accompanied by increased expression, suggesting context-dependent gene body methylation effects. Benign versus malignant comparisons identified 101 differentially methylated CpGs, including hypermethylated CpG in and hypomethylated CpG in in malignant tumors. Pathway enrichment of differentially methylated genes revealed alterations in Notch signaling, adherens junctions, cytoskeletal regulation, and intracellular transport. Gene expression analysis demonstrated partial overlap between clusters, with malignant tumors exhibiting distinct transcriptional profiles involving RNA processing, metabolism, and adhesion pathways. Correlation between methylation and expression was generally limited, emphasizing that methylation-dependent gene regulation is a locus-specific and context-dependent regulation. These findings illustrate a complex interplay between epigenetic modifications and transcriptional programs in PPGLs, enhancing our understanding of molecular heterogeneity and tumor classification, and identifying candidate biomarkers and therapeutic targets for malignant progression. - Source: PubMed
Publication date: 2026/01/20
Tabebi MounaŁysiak MałgorzataGimm OliverSöderkvist Peter - Stress-induced mental disorders, including depression and anxiety disorders, constitute a global issue in contemporary society due to treatment complexity and the diversity of manifestations. Understanding the molecular mechanisms of these disorders presents a significant challenge for neurobiology. We investigated the effects of social defeat stress (SDS) of varying durations (10 and 30 days) on behavioral patterns and the H3K4me3 (trimethylation at the 4th lysine residue of histone H3) landscape in the prefrontal cortex of C57BL/6 mice. Furthermore, we compared these data with previously published H3K4me3 landscape data obtained after 15 days of SDS and transcriptomic data collected after 10, 15, and 30 days. We discovered that a 30-day period of stress results in more pronounced depressive-like behavior. SDS induces slight alterations in the H3K4me3 density across numerous nucleosomal peaks. The analysis of differential enrichment peaks of H3K4me3 in promoter regions following varying durations of SDS revealed that the aggregation of multiple H3K4me3 nucleosome peaks in the promoter region functions as a QR code, likely affecting the promoter's state regarding the accessibility of transcription factors. Furthermore, we identified a cluster of genes in the promoter regions exhibiting differential enrichment peaks of H3K4me3 following SDS of any duration. This cluster includes genes encoding transcription factors such as and , as well as postsynaptic density proteins (, , and ), which are associated with stress sensitivity and the onset of depression; their protein products are involved in synaptic transmission and signal transduction mechanisms. The comparison of ChIP-seq and RNA-seq data following varying durations of SDS enabled a deeper insight in to the dynamics of SDS-induced changes. Together, these findings provide a better understanding of the molecular mechanisms of SDS in the prefrontal cortex. - Source: PubMed
Publication date: 2025/12/19
Bondar NatalyaReshetnikov VasiliyRitter PolinaErshov NikitaZhukova NataliaKolmykov SemyonMerkulova Tatyana