Ask about this productRelated genes to: RanGAP1 antibody
- Gene:
- RANGAP1 NIH gene
- Name:
- Ran GTPase activating protein 1
- Previous symbol:
- SD
- Synonyms:
- Fug1, KIAA1835
- Chromosome:
- 22q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-02-26
- Date modifiied:
- 2016-10-05
Related products to: RanGAP1 antibody
Related articles to: RanGAP1 antibody
- Castration-resistant prostate cancer (CRPC) represents an aggressive stage of prostate cancer that develops following resistance to androgen deprivation therapy. Although androgen receptor (AR) signaling remains a central driver of disease progression, additional adaptive molecular mechanisms contribute to therapeutic resistance. Understanding the transcriptional programs underlying CRPC may facilitate the identification of novel biomarkers and therapeutic targets. - Source: PubMed
Publication date: 2026/06/25
Naeem Abdulghani AAbdulsamad Saud AHayat AteequllahNaeem AyeshaAlhazmi NadaFallata GhaithBokhari AnasAlharbi Abdulmajeed HAlkinani Kinani AAlshehri Abdullah MAldabbagh Khadijah M - RanGAP1 promotes GTP hydrolysis of nuclear pore complex (NPC) transport complexes at the cytoplasmic face. A disordered linker connects its catalytic GAP domain to the C-terminal sumoylation domain, anchoring into NPC's cytoplasmic filaments. This arrangement raises the question of how these distinct functions are coordinated within a crowded cellular environment. Using atomistic molecular dynamics simulations, we show that RanGAP1 adopts an autoinhibited conformation, where the C-terminal domain masks the catalytic GAP domain. Sumoylation allosterically relieves this autoinhibition, enabling GTP-bound Ran access to the GAP domain. In the cytosol, Ran-GTP/RanBP1 can bind a less populated open conformation of RanGAP1, providing a backup mechanism for GTP hydrolysis in Ran. Importantly, we observe that Arg191 of human RanGAP1 inserts into the GTP-binding pocket of Ran and directly interacts with the γ-phosphate, consistent with a canonical arginine finger. This observation contrasts with earlier models derived from yeast RanGAP and suggests that human RanGAP1 may follow a catalytic mechanism similar to classical small GTPase regulators like NF1. Together, these findings provide a framework of RanGAP1, linking autoinhibition, sumoylation, spatial organization at the NPC, and the catalytic mechanism. They also highlight how conformational regulation and post-translational modification coordinate efficient GTP hydrolysis in Ran during nuclear transport. - Source: PubMed
Publication date: 2026/04/29
Xu LiangJang HyunbumNussinov Ruth - Mitophagy is essential for cancer formation and invasion, but its role in colorectal cancer (CRC) remains unclear. We obtained sequencing data and mitophagy-related genes (MP-RGs) from public databases. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) identified mitophagy-related differentially expressed genes (DE-MPGs). Mendelian randomization (MR) analysis identified candidate genes with genetically supported causal relevance to CRC. Biomarkers were identified using machine learning, receiver operating characteristic (ROC) analysis and expression studies. Single-cell RNA sequencing (scRNA-seq) analyzed biomarker expression profiles in various CRC cell types. Quantitative PCR (qPCR) validated biomarker expression in clinical CRC samples. 147 DE-MPGs were identified. MR analysis revealed seven genes with potential causal contributions to CRC susceptibility. Three genes, SGCE (IVW: OR = 1.00041, p = 0.011), ATP8B2 (IVW: OR = 0.99920, p = 0.042), and RANGAP1 (IVW: OR = 0.99861, p = 0.002), were selected as biomarkers. Immune microenvironment and checkpoint differences were observed between CRC and controls. Biomarker expression varied among cell types. qPCR showed decreased SGCE and ATP8B2 and increased RANGAP1 in CRC. SGCE, ATP8B2, and RANGAP1 can serve as mitophagy-related biomarkers with genetically supported causal relevance to CRC, providing new insights for CRC diagnosis and therapy. - Source: PubMed
Zhao JingyiKong MengWang SiningCao ZhixinTian Xiangguo - TMEM106B is a lysosomal membrane protein and major genetic modifier of multiple neurodegenerative diseases, including frontotemporal lobar degeneration, Alzheimer's disease, and amyotrophic lateral sclerosis. Proteolytically generated C-terminal fragments of TMEM106B assemble into amyloid fibrils that accumulate in the brains of individuals with neurodegenerative disease and in cognitively normal aged adults, yet how these fibrils produce neuronal dysfunction has remained unclear. Here, we show that cytosolic and lysosome-directed TMEM106B C-terminal fragments (CTF and gCTF) form detergent-insoluble amyloid aggregates, drive redistribution of endogenous TDP-43 from the nucleus to the cytoplasm, and accelerate neuronal death. Unbiased proximity proteomics identified the inner nuclear membrane LAP1-TorsinA axis as a fragment-specific interactome, and co-immunoprecipitation confirmed a direct physical interaction between gCTF and LAP1 that was not observed with full-length TMEM106B. Fragment expression disrupted Lamin B1 organization, mislocalized the nuclear import machinery KPNB1 and RanGAP1, and impaired importin-dependent nuclear transport in primary cortical neurons. Critically, neurons harboring endogenous TMEM106B fibrillar pathology in aged human frontal cortex exhibited the same phenotypes, namely disrupted Lamin B1 and LAP1 localization and cytoplasmic redistribution of TDP-43, whereas fibril-negative neurons from the same cases and younger control tissue retained intact nuclear envelope organization. These findings define TMEM106B proteinopathy as an upstream driver of nuclear envelope disruption and nucleocytoplasmic transport failure, linking a widespread feature of brain aging to a central mechanism of neurodegeneration. - Source: PubMed
Publication date: 2026/04/27
Tilahun KedamawitParameswaran JananiDudley MylesPun DanielMa FuyingZhang JesseeBold TatianaJiang Jie - Ran GTPase-activating protein 1 (RanGAP1) is a known regulator of nucleocytoplasmic transport; however, its specific function within innate immunity remains undefined. Here, we show that low RanGAP1 expression correlates with poor survival outcomes in septic patients and demonstrate that RanGAP1 expression and subcellular localization are dynamically regulated in macrophages following lipopolysaccharide (LPS) stimulation. We observed that deletion of RanGAP1 in macrophages exacerbates sepsis progression by using a cecal ligation and puncture (CLP) murine model. Mechanistically, RanGAP1 deficiency significantly impairs macrophage anti-infective functions, including inflammatory cytokine production, pathogen clearance, and antigen processing. These findings highlight RanGAP1 as a central regulator of macrophage immune responses, suggesting that its activity is a critical determinant of septic outcomes. - Source: PubMed
Publication date: 2026/04/27
Mao LinlinLiu GenmingZhang JiahuanZhao QiongzhiZhang XinyiZhang ShengZhang YueBai Xiaochun