更新于：2024-11-01

SLC20A1

更新于：2024-11-01

基本信息

别名

gibbon ape leukemia virus receptor 1、Glvr-1、GLVR1

+ [8]

简介

Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:7929240, PubMed:8041748, PubMed:19726692, PubMed:17494632, PubMed:16790504). May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification (PubMed:11009570). Essential for cell proliferation but this function is independent of its phosphate transporter activity (PubMed:19726692). (Microbial infection) May function as a retroviral receptor as it confers human cells susceptibility to infection to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine leukemia virus (10A1 MLV).

关联

项与 SLC20A1 相关的药物

AP-306

靶点

NaPi-2b x P-gp x SLC20A1 x SLC20A2

作用机制

NaPi-2b抑制剂 [+3]

在研机构

上海礼邦医药科技有限公司

原研机构

上海礼邦医药科技有限公司

在研适应症

慢性肾病 [+1]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 SLC20A1 相关的临床试验

NCT05764590 / Completed临床2期

A Phase 2, Randomized, Open-Label, Active-Controlled, Multicenter Study to Evaluate the Safety and Serum Phosphorus Lowering Effect of AP-306 in Chronic Kidney Disease Patients Receiving Maintenance Hemodialysis With Hyperphosphatemia

The goal of this clinical trial is to learn about the following questions in the patients receiving maintenance hemodialysis with elevated blood phosphorus:
How much effect AP-306 has assessed by blood phosphorus lowering;
How safe and tolerable AP-306 is.
Participants will receive either following treatments:
AP-306, and
Sevelamer carbonate.

开始日期2023-02-20

申办/合作机构

上海礼邦医药科技有限公司

CTR20230189 / Completed临床2期

一项在接受维持性血液透析的慢性肾脏病高磷血症患者中评价AP-306安全性和血清磷降低作用的II期、随机、开放、阳性药物对照、多中心研究

本研究的主要疗效目的是根据以下终点评价 AP-306 的有效性：在接受维持性血液透析的高磷血症患者中探索 AP-306 降低血清磷水平的能力；安全性目的是评价AP-306的总体安全性和耐受性。

开始日期2023-02-20

申办/合作机构

上海礼邦医药科技有限公司

NCT02965053 / Completed临床1期

A Single-center, Randomized, 2-Period, Crossover, Study to Explore The Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis

This study is a randomized study designed as a 2x2 cross-over in two periods (Period 1 and Period 2) to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of EOS789 in patients with chronic kidney disease (CKD) and hyperphosphatemia receiving hemodialysis. Period 1 is double-blind and Period 2 is open-label. Period 1 and Period 2 are identical with regard to the design, inclusion/exclusion criteria, and assessments. EOS789 and its combination with sevelamer carbonate are tested in Period 1 and Period 2 respectively.

开始日期2016-12-01

申办/合作机构

Chugai Pharmaceutical Co., Ltd.

100 项与 SLC20A1 相关的临床结果

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100 项与 SLC20A1 相关的转化医学

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0 项与 SLC20A1 相关的专利（医药）

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172

项与 SLC20A1 相关的文献（医药）

2024-10-22·Journal of Virology

Sodium-dependent phosphate transporter PiT1/SLC20A1 as the receptor for the endogenous retroviral envelope syncytin-B involved in mouse placenta formation

Article

作者: Bireau, Caroline ; Pierron, Gérard ; Heidmann, Thierry ; Souquere, Sylvie ; Préault, Noémie ; Dupressoir, Anne ; Jacob, Yves ; Bacquin, Agathe ; Cassonnet, Patricia ; Beck, Laurent ; Mousseau, Guillaume

ABSTRACTSyncytins are envelope genes of retroviral origin that play a critical role in the formation of a syncytial structure at the fetomaternal interface via their fusogenic activity. The mouse placenta is unique among placental mammals since the fetomaternal interface comprises two syncytiotrophoblast layers (ST-I and ST-II) instead of one observed in all other hemochorial placentae. Each layer specifically expresses a distinct mouse syncytin, namely syncytin-A (SynA) for ST-I and syncytin-B (SynB) for ST-II, which have been shown to be essential to placentogenesis and embryonic development. The cellular receptor for SynA has been identified as the membrane protein LY6E and is not the receptor for SynB. Here, by combining a cell–cell fusion assay with the screening of a human ORFeome-derived expression library, we identified the transmembrane multipass sodium-dependent phosphate transporter 1 PiT1/SLC20A1 as the receptor for SynB. Transfection of cells with the cloned receptor, but not the closely related PiT2/SLC20A2, leads to their fusion with cells expressing SynB, with no cross-reactive fusion activity with SynA. The interaction between the two partners was further demonstrated by immunoprecipitation. PiT1/PiT2 chimera and truncation experiments identified the PiT1 N-terminus as the major determinant for SynB-mediated fusion. RT-qPCR analysis of PiT1 expression on a panel of mouse adult and fetal tissues revealed a concomitant increase of PiT1 and SynB specifically in the developing placenta. Finally, electron microscopy analysis of the placenta of PiT1 null embryo before they die (E11.5) disclosed default of ST-II formation with lack of syncytialization, as previously observed in cognate SynB null placenta, and consistent with the present identification of PiT1 as the SynB partner. IMPORTANCE Syncytins are envelope genes of endogenous retroviruses, coopted for a physiological function in placentation. They are fusogenic proteins that mediate cell–cell fusion by interacting with receptors present on the partner cells. Here, by devising an in vitro fusion assay that enables the screening of an ORFeome-derived expression library, we identified the long-sought receptor for syncytin-B (SynB), a mouse syncytin responsible for syncytiotrophoblast formation at the fetomaternal interface of the mouse placenta. This protein – PiT1/SLC20A1 – is a multipass transmembrane protein, also known as the receptor for a series of infectious retroviruses. Its profile of expression is consistent with a role in both ancestral endogenization of a SynB founder retrovirus and present-day mouse placenta formation, with evidence—in PiT1 knockout mice—of unfused cells at the level of the cognate placental syncytiotrophoblast layer.

2024-07-01·Current Opinion in Nephrology & Hypertension

Phosphate sensing in health and disease

Review

作者: Rhee, Eugene P. ; Zechner, Christoph

Purpose of reviewDisruptions of phosphate homeostasis are associated with a multitude of diseases with insufficient treatments. Our knowledge regarding the mechanisms underlying metazoan phosphate homeostasis and sensing is limited. Here, we highlight four major advancements in this field during the last 12–18 months.Recent findingsFirst, kidney glycolysis senses filtered phosphate, which results in the release of glycerol 3-phosphate (G-3-P). Circulating G-3-P then stimulates synthesis of the phosphaturic hormone fibroblast growth factor 23 in bone. Second, the liver serves as a postprandial phosphate reservoir to limit serum phosphate excursions. It senses phosphate ingestion and triggers renal excretion of excess phosphate through a nerve-dependent mechanism. Third, phosphate-starvation in cells massively induces the phosphate transporters SLC20A1/PiT1 and SLC20A2/PiT2, implying direct involvement of cellular phosphate sensing. Under basal phosphate-replete conditions, PiT1 is produced but immediately destroyed, which suggests a novel mechanism for the regulation of PiT1 abundance. Fourth, Drosophila melanogaster intestinal cells contain novel organelles called PXo bodies that limit intracellular phosphate excursions. Phosphate starvation leads to PXo body dissolution, which triggers midgut proliferation.SummaryThese studies have opened novel avenues to dissect the mechanisms that govern metazoan phosphate sensing and homeostasis with the potential to identify urgently needed therapeutic targets.

2024-05-23·Journal of Biomolecular Structure and Dynamics

Computational analysis of sodium-dependent phosphate transporter SLC20A1/PiT1 gene identifies missense variations C573F, and T58A as high-risk deleterious SNPs

Article

作者: Santhy, K S ; Vineeth Kumar, T V ; Payva, Febby ; James, Remya ; Kanchi, Subbarao ; Siva Sankari, G ; Sivaramakrishnan, Venketesh

SLC20A1/PiT1 is a sodium-dependent inorganic phosphate transporter, initially recognized as the retroviral receptor for Gibbon Ape Leukemia Virus in humans. SNPs in SLC20A1 is associated with Combined Pituitary Hormone Deficiency and Sodium Lithium Counter transport. Using in silico techniques, we have screened the nsSNPs for their deleterious effect on the structure and function of SLC20A1. Screening with sequence and structure-based tools on 430 nsSNPs, filtered 17 nsSNPs which are deleterious. To evaluate the role of these SNPs, protein modeling and MD simulations were performed. A comparative analysis of model generated with SWISS-MODEL and AlphaFold shows that many residues are in the disallowed region of Ramachandran plot. Since SWISS-MODEL structure has a 25-residue deletion, the AlphaFold structure was used to perform MD simulation for equilibration and structure refinement. Further, to understand perturbation of energetics, we performed in silico mutagenesis and ΔΔG calculation using FoldX on MD refined structures, which yielded SNPs that are neutral (3), destabilizing (12) and stabilizing (2) on protein structure. Furthermore, to elucidate the impact of SNPs on structure, we performed MD simulations to discern the changes in RMSD, Rg, RMSF and LigPlot of interacting residues. RMSF profiles of representative SNPs revealed that A114V (neutral) and T58A (positive) were more flexible & C573F (negative) was more rigid compared to wild type, which is also reflected in the changes in number of local interacting residues in LigPlot and ΔΔG. Taken together, our results show that SNPs can lead to structural perturbations and impact the function of SLC20A1 with potential implications for disease.Communicated by Ramaswamy H. Sarma.