更新于：2024-09-19

ATP8A1

更新于：2024-09-19

基本信息

别名

ATP8A1、ATPase class I type 8A member 1、ATPase phospholipid transporting 8A1

+ [5]

简介

Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:31416931). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. In vitro, its ATPase activity is selectively and stereospecifically stimulated by phosphatidylserine (PS) (PubMed:31416931). The flippase complex ATP8A1:TMEM30A seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the cell membrane (By similarity). Acts as aminophospholipid translocase at the cell membrane in neuronal cells (By similarity).

关联

100 项与 ATP8A1 相关的临床结果

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100 项与 ATP8A1 相关的转化医学

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0 项与 ATP8A1 相关的专利（医药）

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项与 ATP8A1 相关的文献（医药）

2024-08-01·Archives of Biochemistry and Biophysics

The lipid flippase ATP8A1 regulates the recruitment of ARF effectors to the trans-Golgi Network

Article

作者: Pocognoni, Cristian A ; Lee, Eunjoo ; Jian, Xiaoying ; Randazzo, Paul ; Nawara, Tomasz ; Sztul, Elizabeth ; Bhatt, Jay M

Formation of transport vesicles requires the coordinate activity of the coating machinery that selects cargo into the nascent vesicle and the membrane bending machinery that imparts curvature to the forming bud. Vesicle coating at the trans-Golgi Network (TGN) involves AP1, GGA2 and clathrin, which are recruited to membranes by activated ARF GTPases. The ARF activation at the TGN is mediated by the BIG1 and BIG2 guanine nucleotide exchange factors (GEFs). Membrane deformation at the TGN has been shown to be mediated by lipid flippases, including ATP8A1, that moves phospholipids from the inner to the outer leaflet of the TGN membrane. We probed a possible coupling between the coating and deformation machineries by testing for an interaction between BIG1, BIG2 and ATP8A1, and by assessing whether such an interaction may influence coating efficiency. Herein, we document that BIG1 and BIG2 co-localize with ATP8A1 in both, static and highly mobile TGN elements, and that BIG1 and BIG2 bind ATP8A1. We show that the interaction involves the catalytic Sec7 domain of the GEFs and the cytosolic C-terminal tail of ATP8A1. Moreover, we report that the expression of ATP8A1, but not ATP8A1 lacking the GEF-binding cytosolic tail, increases the generation of activated ARFs at the TGN and increases the selective recruitment of AP1, GGA2 and clathrin to TGN membranes. This occurs without increasing BIG1 or BIG2 levels at the TGN, suggesting that the binding of the ATP8A1 flippase tail to the Sec7 domain of BIG1/BIG2 increases their catalytic activity. Our results support a model in which a flippase component of the deformation machinery impacts the activity of the GEF component of the coating machinery.

2024-03-26·Journal of Chemical Theory and Computation

Switching Go̅-Martini for Investigating Protein Conformational Transitions and Associated Protein–Lipid Interactions

Article

作者: Yang, Song ; Song, Chen

Proteins are dynamic biomolecules that can transform between different conformational states when exerting physiological functions, which is difficult to simulate using all-atom methods. Coarse-grained (CG) Go̅-like models are widely used to investigate large-scale conformational transitions, which usually adopt implicit solvent models and therefore cannot explicitly capture the interaction between proteins and surrounding molecules, such as water and lipid molecules. Here, we present a new method, named Switching Go̅-Martini, to simulate large-scale protein conformational transitions between different states, based on the switching Go̅ method and the CG Martini 3 force field. The method is straightforward and efficient, as demonstrated by the benchmarking applications for multiple protein systems, including glutamine binding protein (GlnBP), adenylate kinase (AdK), and β₂-adrenergic receptor (β2AR). Moreover, by employing the Switching Go̅-Martini method, we can not only unveil the conformational transition from the E2Pi-PL state to E1 state of the type 4 P-type ATPase (P4-ATPase) flippase ATP8A1-CDC50 but also provide insights into the intricate details of lipid transport.

2023-12-01·Clinical Proteomics

Identification of potential molecular targets for the treatment of cluster 1 human pheochromocytoma and paraganglioma via comprehensive proteomic characterization

Article

作者: Talacko, Pavel ; Petrak, Jiri ; Pacak, Karel ; Vit, Ondrej ; Hartmann, Igor ; Musil, Zdenek

AbstractBackgroundPheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors. New drug targets and proteins that would assist sensitive PPGL imagining could improve therapy and quality of life of patients with PPGL, namely those with recurrent or metastatic disease. Using a combined proteomic strategy, we looked for such clinically relevant targets among integral membrane proteins (IMPs) upregulated on the surface of tumor cells and non-membrane druggable enzymes in PPGL.MethodsWe conducted a detailed proteomic analysis of 22 well-characterized human PPGL samples and normal chromaffin tissue from adrenal medulla. A standard quantitative proteomic analysis of tumor lysate, which provides information largely on non-membrane proteins, was accompanied by specific membrane proteome-aimed methods, namely glycopeptide enrichment using lectin-affinity, glycopeptide capture by hydrazide chemistry, and enrichment of membrane-embedded hydrophobic transmembrane segments.ResultsThe study identified 67 cell surface integral membrane proteins strongly upregulated in PPGL compared to control chromaffin tissue. We prioritized the proteins based on their already documented direct role in cancer cell growth or progression. Increased expression of the seven most promising drug targets (CD146, CD171, ANO1, CD39, ATP8A1, ACE and SLC7A1) were confirmed using specific antibodies. Our experimental strategy also provided expression data for soluble proteins. Among the druggable non-membrane enzymes upregulated in PPGL, we identified three potential drug targets (SHMT2, ARG2 and autotaxin) and verified their upregulated expression.ConclusionsApplication of a combined proteomic strategy recently presented as “Pitchfork” enabled quantitative analysis of both, membrane and non-membrane proteome, and resulted in identification of 10 potential drug targets in human PPGL. Seven membrane proteins localized on the cell surface and three non-membrane druggable enzymes proteins were identified and verified as significantly upregulated in PPGL. All the proteins have been previously shown to be upregulated in several human cancers, and play direct role in cancer progression. Marked upregulation of these proteins along with their localization and established direct roles in tumor progression make these molecules promising candidates as drug targets or proteins for sensitive PPGL imaging.

项与 ATP8A1 相关的新闻（医药）

2024-03-19

·生物谷

中山大学研究者们强调circATP8A1作为胃癌的潜在预后生物标志物和治疗靶点

该研究揭示了胃癌外泌体环状rna诱导肿瘤微环境内巨噬细胞极化的新机制。胃癌(GC)是世界上第五大常见癌症，也是全球癌症相关死亡的第三大原因。胃癌常表现不典型，甚至无明显症状。绝大多数胃癌患者诊断为晚期，此时淋巴结累及和远处脏器转移较为常见。因此，晚期胃癌患者的预后仍然很差，明确促进局部浸润和远处转移的机制对于早期诊断和治疗至关重要。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1186/s12943-024-01966-4 近日，来自中山大学的研究者们在Mol Cancer.杂志上发表了题为“Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression”的文章，该研究强调了circATP8A1作为胃癌的潜在预后生物标志物和治疗靶点。环状rna (circRNAs)在胃癌进展中发挥重要作用，但其在控制巨噬细胞功能中的调节作用尚不明确。外泌体作为circrna的货物，在促进癌细胞和肿瘤微环境之间的通信中起着至关重要的介质作用。在这项研究中，研究者发现circATP8A1，一种以前未报道的环状RNA，在胃癌组织和血浆来源的外泌体中都有高表达。circATP8A1的升高与胃癌患者TNM分期晚期和预后较差相关。研究发现circATP8A1敲低在体外和体内均能显著抑制胃癌的增殖和侵袭。功能上，外泌体circATP8A1通过STAT6途径而不是STAT3途径诱导巨噬细胞M2极化。在机制上，经荧光原位杂交(FISH)、RNA免疫沉淀、RNA下拉和荧光素酶报告基因检测证实，circATP8A1通过与miR-1-3p的竞争性结合激活STAT6通路。阻断miR-1-3p后，观察到circatp8a1诱导的STAT6通路激活和巨噬细胞极化的逆转。用过表达circATP8A1的胃癌细胞外泌体处理巨噬细胞能够促进胃癌迁移，而在体内敲低circATP8A1则逆转了这种作用。外泌体circatp8a1介导胃癌发生作用的模型图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1186/s12943-024-01966-4 总之，该研究揭示了胃癌外泌体环状rna诱导肿瘤微环境内巨噬细胞极化的新机制，该研究独特地表明，来自胃癌的外泌体circATP8A1通过与miR-1-3p的竞争性结合激活STAT6通路，从而促进M2巨噬细胞极化，放大胃癌的进展。此研究筛选并验证了一种新的致癌circRNA circATP8A1，该circRNA在胃癌中表达上调，与预后较差相关。（生物谷 Bioon.com）参考文献 Cuncan Deng et al. Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression. Mol Cancer. 2024 Mar 8;23(1):49. doi: 10.1186/s12943-024-01966-4.