Ask about this productRelated genes to: SKAP2 antibody
- Gene:
- SKAP2 NIH gene
- Name:
- src kinase associated phosphoprotein 2
- Previous symbol:
- SCAP2
- Synonyms:
- RA70, SKAP-HOM, SKAP55R, SAPS
- Chromosome:
- 7p15.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-19
- Date modifiied:
- 2014-11-19
Related products to: SKAP2 antibody
Related articles to: SKAP2 antibody
- Many genetic variants associated with increased type 1 diabetes (T1D) risk are located within the gene; however, the mechanisms by which these variants confer disease risk remain unclear. encodes an adapter protein that functions within the integrin signaling pathway and is found at the highest levels in myeloid leukocytes. We recently identified a gain-of-function mutation in an individual with T1D, leading to hyperactive integrin signaling in myeloid cells. To dissect the mechanisms by which this mutation may lead to T1D, we generated a knock-in mouse line containing the orthologous p.G153R substitution in mouse SKAP2 on the diabetes-prone nonobese diabetic (NOD) genetic background. Both female and male SKAP2 mice developed accelerated T1D. The SKAP2 mice also exhibited a unique spectrum of autoantibodies, leading to immune-complex nephritis. Accelerated infiltration of pancreatic islets by myeloid cells, B lymphocytes, and activated T cells was observed in SKAP2 mice. Single-cell RNA sequencing demonstrated a type 1 IFNγ-driven inflammatory program within the pancreatic islets of SKAP2 mice. Dendritic cells from SKAP2 mice demonstrated increased antigen-presenting capacity, characterized by enhanced adhesion to T cells during immune synapse formation. Macrophages and neutrophils from SKAP2 mice also showed increased integrin signaling responses, with neutrophils expressing high levels of activated β2 integrins on the cell surface. When backcrossed onto the C57BL/6J genetic background, the SKAP2 mice developed spontaneous autoantibody formation and exhibited accelerated autoimmunity, including nephritis, in the pristane-induced model of autoimmune disease. These findings demonstrate that dysregulation of leukocyte integrin signaling, through alterations in may increase the genetic risk for autoimmunity and T1D. - Source: PubMed
Publication date: 2026/04/06
Tamaki Courtney MChamberlain Chester EAbram Clare LPoojary SumithBridge JenniferMatsuda Jennifer LTamaki WhitneyRutsch NiklasSpector LaurenDixon WesleyProekt IrinaLetourneau-Freiberg Lisa RPhilipson Louis HGerman Michael SAnderson Mark SLowell Clifford A - - Source: PubMed
Publication date: 2025/11/27
Zhang GuanghuiSun KuanZhou JiamingLin XianhuaWang LuluYang XiaotongZheng JiayunZhang YuRen JingchaoCao JiaHuang HefengZhang Chen - Sperm motility and morphology are indispensable for sperm-egg interaction and successful fertilization. However, the RNA splicing mechanisms in an m6A-dependent manner regulating spermiogenesis-related genes remain poorly defined, and targeted therapy strategies to restore impaired sperm motility and morphology are lacking. In this study, we identify heterogeneous nuclear ribonucleoprotein R (hnRNPR) as a critical m6A-dependent splicing mediator. Pathogenic mutations in HNRNPR cause sperm motility decline, morphological abnormality, and male infertility in both humans and mice. Mechanistically, Hnrnpr mutation disrupts m6A-dependent splicing of Skap2 pre-mRNA, thus impairing cytoskeletal structure and mitochondrial organization in sperm. Consistently, specific knockout of Skap2 in male germ cells displays sperm abnormalities, which phenocopy those observed in humans and mice with Hnrnpr mutants, unveiling a functional hnRNPR-SKAP2 axis. Leveraging these insights, we developed a therapeutic strategy to restore sperm motility and morphology, relying on extracellular vesicle-mediated SKAP2 delivery to enter the efferent ductules of the testicles, which could promote sperm cytoskeletal remodeling and mitochondrial organization. Notably, the co-culture of extracellular vesicle SKAP2 with human and mouse sperms also significantly enhanced the sperm motility. Altogether, these findings identify hnRNPR as a pivotal regulator of m6A-mediated Skap2 splicing during spermiogenesis and highlight extracellular vesicle SKAP2 as a promising therapeutic target for poor sperm quality and male infertility. - Source: PubMed
Publication date: 2025/12/24
Gan ShimingYin LinZhou JiamingLi SisiZhou ShuminYang XiaotongLiu RuiFan XuLi YangyangYao ZhendongChen JingshouHu PeiranXiong WenjingYuan YuanWen YujiaoLi YoujiangJin GeSheng JianzhongGao YuzhenHuang HefengZhang Chen - The regulation of gene expression through chromatin architecture plays a critical role in acute myeloid leukemia (AML). In this study, the influence of MAPK3 on CTCF-mediated chromatin interactions in AML was examined, focusing on gene regulation and chromatin architecture. Immunoprecipitation coupled with mass spectrometry (IP-MS) was conducted to identify CTCF-binding proteins in AML cell lines. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to assess the impact of MAPK3 modulation on CTCF DNA binding, following treatment with an MAPK3 activator or inhibitor. Additionally, chromatin interactions were evaluated using 3C-qPCR, and specific enhancer sites at the SKAP2 locus were deleted using CRISPR-Cas9. Results demonstrated that IP-MS identified MAPK3 as a key CTCF-binding protein, indicating its potential role in AML chromatin regulation. MAPK3 significantly influences CTCF binding at distal intergenic regions upstream of SKAP2, as confirmed by ChIP-seq. Chromatin interaction analyses revealed that CTCF-regulated enhancer-promoter interactions at SKAP2 are modulated by MAPK3 activity. Furthermore, deletion of enhancer regions E4 and E6 led to decreased SKAP2 expression. These findings highlight the critical role of MAPK3 in regulating CTCF-mediated chromatin interactions and suggest that targeting MAPK3-regulated chromatin remodeling could be a novel therapeutic strategy for AML. - Source: PubMed
Hu YanpingChen FangWang TingjieWang BoWang ZhizhongZheng JiawenShen YifenShen YihangMa JieGuo Yongjun - This study aims to identify and validate key genes associated with brucellosis. Due to diagnostic challenges, we focused on a bioinformatics-driven approach to construct a robust diagnostic model, providing a theoretical basis for clinical diagnosis. We specifically investigated Prosaposin-related genes (PRGs) due to their role in host-pathogen interactions. The brucellosis dataset GSE69597 was downloaded from the GEO database. After processing, differentially expressed genes were identified and intersected with PRGs to obtain Prosaposin-Related Differentially Expressed Genes (PRDEGs). We employed Random Forest and LASSO regression to screen for key genes and construct a multivariate logistic regression model. Model performance was evaluated using ROC curves. Finally, the expression of the key genes was validated by qPCR in an independent cohort of clinical peripheral blood samples (16 patients, 11 controls). A total of 19 PRDEGs were identified, from which 5 key genes (SKAP2, EIF2B1, PRKAB1, IRF8, RPN1) were selected. The logistic regression model based on these genes demonstrated good diagnostic performance with an Area Under the Curve (AUC) value of 0.844. Crucially, qPCR validation confirmed that the expression of all five genes was significantly different between patients and controls (all p < 0.05), consistent with the bioinformatic findings. Through comprehensive bioinformatic analysis and experimental validation, this study identified key genes closely associated with brucellosis and constructed an effective diagnostic model. This work provides new insights and a promising foundation for the early diagnosis and targeted therapy of brucellosis. - Source: PubMed
Publication date: 2025/10/06
Wang XiaFei Qing-CaoZhang LeMao Xiao-RongMa Zi-MinMa Li-NaDing Xiang-Chun