Ask about this productRelated genes to: KCNIP2 Blocking Peptide
- Gene:
- KCNIP2 NIH gene
- Name:
- potassium voltage-gated channel interacting protein 2
- Previous symbol:
- -
- Synonyms:
- KCHIP2
- Chromosome:
- 10q24.32
- Locus Type:
- gene with protein product
- Date approved:
- 2001-05-23
- Date modifiied:
- 2016-02-04
Related products to: KCNIP2 Blocking Peptide
Related articles to: KCNIP2 Blocking Peptide
- Annexin A4 (A4) is a negative modulator of adenylyl cyclase type 5 (AC5) with increased expression in failing human hearts. Here, we investigated whether A4 deficiency contributes to cardiac electrical and structural remodeling induced by chronic stimulation of β-adrenergic receptors (βAR). A4-deficient mice (gene trapped, GT) and wild-type (WT) were infused for 7 days with isoprenaline (ISO) or NaCl as control. Myocytes of ISO-treated GT (GT) displayed more hypertrophy, increased action potential duration, reduced K-current I, preserved L-type Ca current I with a negative shift of voltage dependence of activation, in line with increased AC/cAMP/PKA signaling, and increased NCX1 versus WT. At the molecular level, mRNA levels for Kcnd3, Kcnip2, Cacna1c decreased at unchanged protein levels of Kv4.2, Kv4.3, KChIP2, α1C, independent of genotype, suggesting posttranslational modifications of the channels underlying I and I. Chronic ISO-induced βAR desensitization and redox stress were confirmed by decreased cAMP production and lower mRNA levels of Adrb1, Adcy5/6, and Sod2, and reduced response to acute ISO, with no additional genotype-dependent effects on calcium handling or contractility. Nevertheless, GT cardiomyocytes retained a greater cAMP response to acute ISO, in line with AC5 disinhibition and preserved β2AR and Gαs/i, suggesting genotype-dependent differences in β-adrenergic signaling under stress. mRNA levels of Anxa4 were increased in hypertrophied WT vs. normal WT hearts, supporting a protective role for A4. Overall, the advanced remodeling in A4-deficient myocytes detected in response to chronic βAR stimulation proposes using A4 peptide as a therapeutic tool to prevent the progression of cardiac electrical remodeling. - Source: PubMed
Pluteanu FlorentinaHeinick AlexanderDomnik-Lehnert ManuelMüller Frank UHermes Christina - Hypertension is highly prevalent in Asian populations and represents a major cardiovascular risk factor. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have focused primarily on Caucasian cohorts. This study aimed to identify genetic loci and gene expression signatures associated with hypertension in an Asian population. - Source: PubMed
Publication date: 2026/07/27
Chang Sheng-NanLee Guan-WeiChen Jien-JiunWang Chih-HsienChiu Fu-ChunHuang Pang-ShuoChuang Eric YTsai Chia-Ti - This study aims to explore the molecular association between di(2-ethylhexyl)phthalate (DEHP) and dilated cardiomyopathy (DCM) through interpretable machine learning and molecular docking techniques. DCM transcriptome datasets (GSE120895, GSE9800, GSE29819) are integrated. Disease-related genes are screened through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Potential targets of DEHP are predicted using CHEMBL, SwissTargetPrediction, and PharmMapper databases. The associated targets of DEHP and DCM are identified via intersection analysis, and a multi-algorithm machine learning framework is used to further screen core genes. Finally, molecular docking is performed to verify the binding affinity between DEHP and core targets. A total of 1364 potential targets of DEHP are identified. Intersection with 61 DCM-related genes yields 11 key targets. Functional enrichment analysis shows that these genes are involved in ion homeostasis, metabolic reprogramming, and regulation of inflammatory pathways. Machine learning further screens eight core genes: ABAT, ACE2, BLM, C3, IGFBP2, KCNIP2, NPPA, and TYMS. Molecular docking confirms that DEHP has strong binding specificity with all eight core proteins. - Source: PubMed
Publication date: 2026/01/22
Xia XiaoHu LanshuoTao ShiyiLi JunHuang Xuanchun - Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, including T-wave flattening, inversion, and biphasic T waves, which are also observed clinically. Loss of HDAC3 deacetylase activity, without affecting HDAC3 protein levels, was sufficient to induce QT prolongation. Disruption of HDAC3 function altered the expression of ion channel genes, including the downregulation of potassium channel genes such as , , and . Moreover, a single dose of HDAC inhibitors, romidepsin or mocetinostat, caused reversible QT prolongation in mice. Consistent with these findings, HDAC inhibitor treatment altered the expression of potassium channel genes, with a predominant downregulation of multiple Kcn family members, including , , and . These findings establish HDAC3 enzymatic activity as a key regulator of cardiac repolarization and provide mechanistic insight into HDAC inhibitor-associated cardiotoxicity. - Source: PubMed
Publication date: 2026/05/14
Lu JiaoWard ChristopherQian SichongZhang LileiChang JiangSun Zheng - The present study aimed to discover novel KChIP ligands as pharmacological tools for modulating the K4.3/KChIP channels. A multidisciplinary approach, combining medicinal chemistry and electrophysiology studies, led to the successfully identification of a novel K4.3/KChIP modulator (IQM-22110). Its design was guided by the previous knowledge of the (phenylacetamido)benzoic acid moiety as suitable scaffold, along with virtual screening of a focused chemical library that suggested improved KChIP3 binding upon incorporation of an additional aromatic ring. IQM-22110 was selected for synthesis and identified as a potent KChIP3 ligand. Its electrophysiological effects on K4.3/KChIP3 currents indicate that IQM-22110 binds to a high affinity site in K4.3/KChIP3 channels that it is not present in K4.3/KChIP2 or K4.3. To the best of our knowledge, here we describe the first KChIP3 ligand that selectively modulates K4.3/KChIP3 versus K4.3/KChIP2 and K4.3 channels at nanomolar concentration. Since KChIP2 is predominantly expressed in cardiac tissue, this selectivity may enable the development of K4.3/KChIP3-targeted therapeutics with reduced risk of cardiac side effects. Computational and site-directed mutagenesis studies allowed the identification of IQM-22110's binding site on KChIP3. Knowledge gained from structural and functional studies with this novel KChIP3 ligand could establish the basis for drug discovery programs fostering treatments for diseases in which K4.3/KChIPs channels are involved. - Source: PubMed
Publication date: 2026/03/21
Socuellamos Paula GViedma-Barba Carmende Benito-Bueno AngelaBonache Maria AngelesRopero MariaDiez SaraElizalde PabloMarín-Olivero IreneRedondo-Moya MariaNaranjo Jose RamonGonzalez-Vera Juan AOrte AngelPerez-Lara AngelMartin-Martinez MercedesValenzuela CarmenGutierrez-Rodriguez Marta