SLC7A9

更新于：2025-05-07

基本信息

别名

b(0,+)-type amino acid transporter 1、b(0,+)AT1、BAT1

+ [5]

简介

Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1 (PubMed:16825196, PubMed:32494597, PubMed:32817565, PubMed:8663357). Has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids (PubMed:16825196, PubMed:32494597, PubMed:8663357). Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine (PubMed:8663357). Required for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in renal proximal tubules.

关联

项与 SLC7A9 相关的药物

Cystinuria (BridgeBio Pharma)

靶点

SLC3A1 x SLC7A9

作用机制

SLC3A1 modulators [+1]

在研机构-

原研机构

BridgeBio Pharma, Inc.

在研适应症-

非在研适应症

胱氨酸尿症

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SLC7A9 相关的临床结果

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100 项与 SLC7A9 相关的转化医学

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0 项与 SLC7A9 相关的专利（医药）

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282

项与 SLC7A9 相关的文献（医药）

2025-06-01·Poultry Science

Transport and expression of transporters for 3-O-methyl-D-glucose and L-methionine along the intestine of broiler chickens receiving different methionine supplements

Article

作者: Schermuly, Isabel I ; Riedel, Julia ; Saliu, Eva-Maria ; Romanet, Stella ; Lemme, Andreas ; Zentek, Jürgen ; Aschenbach, Jörg R

The present study hypothesized that supplementation of different methionine (Met) sources might influence the intestinal absorption of l-Met and 3-O-methyl-d-glucose (3-OMG) in broilers. In a completely randomized study, a total of 53 Cobb500 broilers (30 males and 23 females) received a grower-finisher diet that was either not supplemented with Met (Met + Cys, 0.49 %; control) or supplemented with either 0.27 % l-Met, 0.27 % DL-Met or 0.47 % DL-2‑hydroxy-4-(methylthio) butanoic acid (HMTBA). After ≥10 days on the diets, uptakes of 3-OMG and l-Met were measured in duodenum, mid-jejunum and caecum at 50 µM and 5 mM concentrations in Ussing chambers, each in the presence and absence of Na⁺. We also investigated the mRNA expression of apical glucose and Met transporters. Dietary supplements had no effect on 3-OMG and l-Met uptakes (P > 0.05), except for male broilers receiving DL-Met or DL-HMTBA, that showed higher jejunal uptakes of l-Met than control at 5 mM (P < 0.001). Except for l-Met uptakes at 5 mM, tissue × sodium interactions (P ≤ 0.05) for 3-OMG and l-Met uptakes verified higher uptakes in jejunum compared to duodenum and caecum; with higher uptakes in the presence vs. absence of Na⁺ in jejunum only. In duodenum, uptakes of l-Met and 3-OMG at 50 µM concentration were higher in males vs. females. Expression of SGLT1, B⁰AT1, ATB^0,+ and rBAT, but not ASCT1, were lowest in caecum (P ≤ 0.05). Expression of B⁰AT1 was higher in males vs. females (P ≤ 0.05). Expression of ASCT1 was higher with DL-Met and DL-HMTBA supplements compared to l-Met and control (P ≤ 0.05). These findings indicate that jejunum is the main intestinal segment for Na⁺-dependent l-Met and 3-OMG absorption in broilers with minor effects of dietary Met source. A sexual dimorphism for duodenal nutrient uptake and mRNA abundance of B⁰AT1 was congruent with the more efficient growth performance of male chickens known from the literature.

2025-04-01·Naunyn-Schmiedeberg's Archives of Pharmacology

Differential uptake of arginine derivatives by the human heteromeric amino acid transporter b0,+AT-rBAT (SLC7A9-SLC3A1)

Article

作者: Maas, Renke ; Banjarnahor, Sofna ; König, Jörg ; Keller, Max ; Scherpinski, Lorenz A ; Scherpinski, Lorenz A.

AbstractL-arginine and its (patho-)physiologically active derivatives, L-homoarginine and asymmetric dimethylarginine (ADMA), show significant differences in their renal clearance. The underlying molecular mechanisms remain to be elucidated, but selective tubular transport protein-mediated mechanisms likely play a role. In the present study, we investigate the human heteromeric transporter b0,+AT-rBAT (encoded by the SLC7A9 and SLC3A1 genes) as a potential candidate because it is localized in the luminal membrane of human proximal tubule cells and capable of mediating the cellular uptake of amino acids, including L-arginine. Double-transfected Madin-Darby canine kidney (MDCK) cells stably expressing human b0,+AT-rBAT exhibited significant uptake of L-arginine and L-homoarginine, with apparent Km values of 512.6 and 197.0 μM, respectively. On the contrary, ADMA uptake was not saturated up to 4000 μM, with a transport rate > 5 nmol × mg protein−1 × min−1. With an IC50 value of 115.8 μM, L-arginine inhibited L-homoarginine uptake. Conversely, L-arginine only exhibited a partial inhibitory effect on ADMA uptake. Taken together, our data indicate that b0,+AT-rBAT may contribute to the differential renal handling of L-arginine, L-homoarginine, and ADMA.

2025-03-03·Inorganic Chemistry

Structural Changes at the Zinc Active Site of ACE2 on Binding the SARS-CoV-2 Spike Protein Receptor Binding Domain

Article

作者: Cotelesage, Julien J. H. ; Latimer, Matthew ; Cygler, Miroslaw ; Kroll, Thomas ; Sokaras, Dimosthenis ; Grishin, Andrey ; Vogt, Linda I. ; George, Graham N. ; Dolgova, Natalia V. ; Pickering, Ingrid J. ; Qureshi, Muhammad

The causative agent of Covid-19 is the SARS-CoV-2 virus. Initiation of cell entry by SARS-CoV-2 is critically dependent upon binding of the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23). The mechanism of binding of the SARS-CoV-2 spike receptor binding domain to ACE2 is among the most intensively studied infection mechanisms of any pathogen, including a very large number of structural studies. ACE2 is a membrane-associated zinc carboxypeptidase, comprising three domains, the protease domain, a neck domain, and a membrane-spanning α-helical domain. In addition to its role as a carboxypeptidase, ACE2 is also a chaperone for a Na⁺-amino acid cotransporter called B⁰AT1, and in the presence of B⁰AT1, full-length ACE2 forms dimers. Most studies to date related to Covid-19 have employed just the ACE2 protease domain and have neglected any possible roles of the Zn²⁺-containing ACE2 active site. We show here that ACE2, including the neck domain in addition to the protease domain (and in the absence of B⁰AT1), is dimeric and shows distinctive allostery in its catalytic activity. In contrast, the intensively studied protease domain is monomeric and shows no allostery. Binding of the spike receptor binding domain (RBD) to dimeric ACE2 eliminates its allostery. X-ray absorption spectroscopy of Zn²⁺ ACE2 shows distinctive changes in the active site structure upon binding of spike RBD but only in the dimeric form. Taken together, our results indicate that the Zn²⁺-containing active site exhibits a notable level of flexibility and that the dimeric form of ACE2, including both protease and neck domains, likely presents a superior model for the study of ACE2-spike interactions than the monomeric ACE2.

项与 SLC7A9 相关的新闻（医药）

2024-10-23

·今日头条

【Lancet子刊】瑞金医院刘炳亚团队发现SLC7A9抑制剂如何精准打击胃癌，开辟化疗新天地

【导读】 SLC7A9负责二元氨基酸和胱氨酸（内流）与中性氨基酸（外排）的交换。胱氨酸/半胱氨酸转运与铁死亡有关。 2024年10月21日，上海交通大学医学院附属瑞金医院刘炳亚团队在期刊《eBioMedicine》上发表了题为“SLC7A9 suppression increases chemosensitivity by inducing ferroptosis via the inhibition of cystine transport in gastric cancer”的研究论文。研究结果表明， SLC7A9作为铁死亡抑制剂，独立于SLC7A11。因此，针对SLC7A9的治疗干预有望使胃癌细胞对铁死亡和化疗治疗敏感，并最终改善胃癌患者的预后。 https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00411-0/fulltext 铁死亡与癌症 01 SLC7A11在铁死亡和癌症发展中起着关键作用。许多研究都集中在SLC7A9与慢性肾病之间的关系上，已发现SLC7A9突变可导致各种类型的胱氨酸尿症。此外，研究人员已经确定了SLC7A9表达水平与细胞内GSH水平之间的关系。这些发现表明，SLC7A9可能在铁死亡的调节中发挥作用。在团队之前对胃癌的差异调节网络（DRN）分析中，SLC7A9被确定为胃癌与癌旁组织之间最重要的差异调节基因（DRG）。在这项研究中，团队证明SLC7A9表达在TP53缺陷型胃癌中上调，并且，SLC7A9的上调通过抑制铁死亡诱导化疗耐药，与SLC7A1无关，表明SLC7A9充当铁死亡抑制因子。 SLC7A9抑制铁死亡并在PDO和PDX模型中，抵抗erastin的作用 02 PDO模型是使用胃癌组织建立的。为了进一步证实SLC7A9在人胃癌中的致癌作用，团队用erastin处理细胞并评估类器官的生长。PDO的生长速率表明，erastin抑制P2类器官（低SLC7A9表达水平）的活力，比P5类器官（高SLC7A9表达水平）更有效；SLC7A9表达水平较高的PDO，显示出更高的IC50erastin的值。erastin比P5/shNC类器官更有效地抑制P5/shSLC7A9类器官的活力，而erastin的抗肿瘤作用在P2/oeSLC7A9类器官中减弱。团队发现，SLC7A9敲低或erastin治疗抑制肿瘤生长，双重治疗显示出最大的治疗效果。IHC分析显示，shSLC7A9和erastin治疗的肿瘤中ki67阳性细胞的数量少于对照肿瘤，ki67阳性细胞在shSLC7A9+erastin治疗的肿瘤中最少。GPX4阳性细胞，表现出与ki67阳性细胞相同的趋势。这些发现证实， SLC7A9驱动铁死亡耐药，SLC7A9敲除使胃癌细胞在体内对铁死亡敏感。 SLC7A9在PDO和PDX模型中逆转了erastin的肿瘤杀伤作用，shSLC7A9在体内使erastin致敏。总结 03 1. SLC7A9的作用： SLC7A9通过促进胱氨酸的转运，增加GSH的产生，并促进GPX4蛋白的合成，从而抑制脂质过氧化物的积累和铁死亡。 2. SLC7A9与胃癌： SLC7A9的表达水平在TP53突变的胃癌中升高，且p53可以转录抑制SLC7A9。SLC7A9在胃癌中的作用，可能比SLC7A11更重要。 3. 铁死亡与化疗耐药性：铁死亡有助于癌细胞克服对化疗的耐药性，并可能逆转对放疗、免疫疗法和靶向治疗的耐药性。 4. SLC7A9作为治疗靶点： SLC7A9的表达介导了细胞对化疗的耐药性，敲低SLC7A9可以使胃癌细胞对化疗药物敏感。 5. 研究的未来方向：未来的研究方向包括设计siRNA药物和探索靶向SLC7A9的化合物。参考资料： 1.Sung, H. ∙ Ferlay, J. ∙ Siegel, R.L. ∙ et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin. 2021; 71:209-249 2.Joshi, S.S. ∙ Badgwell, B.D. Current treatment and recent progress in gastric cancer CA A Cancer J Clin. 2021; 71:264-279 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门推荐活动点击免费报名 🕓 上海｜11月15日-16日 ▶ 2024第一届中国类器官转化医学大会 🕓 上海｜11月21日-24日 ▶ 第七届上海国际肿瘤内科学论坛 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会 🕓 上海｜2025年02月28日-03月01日 ▶ 第四届长三角单细胞组学技术应用论坛暨空间组学前沿论坛点击对应文字查看详情

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