1D-myo-inositol 1,3,4-trisphosphate(6-)

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1D-myo-inositol 1,3,4-trisphosphate(6-)
• 英文别名: [(1S,2R,3R,4S,5S,6S)-2,3,5-trihydroxy-4,6-diphosphonatooxycyclohexyl] phosphate
• 化学式: C6H9O15P3-6
• 分子量: 414.05
• InChiKey: MMWCIQZXVOZEGG-MLQGYMEPSA-H

计算性质

• 辛醇/水分配系数(LogP)：
  -7.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  278
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  1D-myo-inositol 1,3,4-trisphosphate(6-) 、 水 生成 1D-myo-inositol 1,3-bisphosphate 、 H3PO4
  参考文献：
  名称：

  The Isolation and Characterization of cDNA Encoding Human and Rat Brain Inositol Polyphosphate 4-Phosphatase

  摘要：

  Inositol polyphosphate 4-phosphatase, an enzyme of the inositol phosphate signaling pathway, catalyzes the hydrolysis of the 4-position phosphate of inositol 3,4-bisphosphate. inositol 1,3,4-trisphosphate, and phosphatidylinositol 3,4-bisphosphate. The amino acid sequences of tryptic and CNBr peptides of the enzyme isolated from rat brain were determined. Degenerate oligonucleotide primers based on this sequence were used to amplify a 74-base pair polymerase chain reaction product, This product was used to isolate a 5607-base pair composite cDNA, which had an open reading frame encoding a protein with 939 amino acids with a predicted molecular mass of 105,588 Da. The rat brain polymerase chain reaction product was used as a probe to isolate a human brain cDNA that predicts a protein with 938 amino acids and a molecular mass of 105,710 Da. Remarkably, the human and rat proteins were 97% identical, Recombinant rat protein expressed in Escherichia coli catalyzed the hydrolysis of all three substrates of the 4-phosphatase. Northern blot hybridization indicates that the 4-phosphatase is widely expressed in rat tissues with the highest levels of expression occurring in brain, heart, and skeletal muscle. Polyclonal antiserum directed against the carboxyl terminus of the 4-phosphatase immunoprecipitated >95% of the 4 phosphatase activity in crude homogenates of rat brain, heart, skeletal muscle, and spleen, suggesting that this enzyme accounts for the 4-phosphate activity present in rat tissues. This antiserum also immuno-precipitated the 4-phosphatase from human platelet sonicates.

  DOI：

  10.1074/jbc.270.27.16128
• 作为产物：
  描述：

  1D-myo-inositol 1,3,4,5-tetrakisphosphate 、 水 生成 1D-myo-inositol 1,3,4-trisphosphate(6-) 、 H3PO4
  参考文献：
  名称：

  新型肌醇多磷酸5-磷酸酶定位在膜褶皱处。

  摘要：

  我们已经从大鼠脑cDNA文库中克隆了一种新型的肌醇多磷酸5-磷酸酶。它包含两个高度保守的5-磷酸酶基序，这两个基序对其酶活性都是必不可少的。有趣的是，该蛋白质的脯氨酸含量很高，并且集中在其N和C末端区域。在氨基酸序列中发现了一个推定的SH3结合基序和六个14-3-3 Zeta结合基序。该酶在肌醇1,4,5-三磷酸，肌醇1,3,4、5-四磷酸和磷脂酰肌醇4,5-二磷酸的D-5位置水解磷酸，与II型5-磷酸酶的底物特异性一致，OCRL，突触动蛋白和突触动蛋白2已经表征了5-磷酸酶。当Myc表位标记的酶在COS-7细胞中表达并用抗Myc多克隆抗体染色时，在波纹膜和细胞质中观察到信号。我们准备了几个缺失突变体，并证明了其123个N端氨基酸（311-433）和一个C端富含脯氨酸的区域，其中包含277个氨基酸（725-1001）对于其定位到波纹膜至关重要。该酶可能调节膜皱褶处的肌醇和磷脂酰肌醇多磷酸盐的水平。

  DOI：

  10.1074/jbc.274.51.36790

文献信息

• Regulation of ins(3456)p4 signalling by a reversible kinase phosphatase and methods and compositions related thereto
  申请人：Shears B Stephen

  公开号：US20060035810A1

  公开（公告）日：2006-02-16

  Provided is a method of increasing 3,4,5,6-tetrakisphosphate by increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase, and a method of decreasing 3,4,5,6-tetrakisphosphate by decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase. A method of reducing salt, fluid or mucous secretion in a subject, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject is provided. A method of treating a disease that is exacerbated by salt, fluid or mucous secretion is also provided, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate phosphatase in a subject having a disease that is exacerbated by mucous, whereby mucous secretion is reduced and the disease is treated. Also provided is method of increasing salt and fluid secretion in a subject, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject. A method of treating a disease that is treated by increased salt and fluid secretion is provided, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is treated by increased salt and fluid secretion, whereby salt and fluid secretion is increased and the disease is treated.

  提供了一种通过增加肌醇1,3,4,5,6五磷酸1-磷酸酶的活性来增加3,4,5,6四磷酸盐的方法，以及通过降低肌醇1,3,4,5,6五磷酸1-磷酸酶的活性来减少3,4,5,6四磷酸盐的方法。提供了一种在受试对象中减少盐、液体或黏液分泌的方法，包括增加受试对象中肌醇1,3,4,5,6五磷酸1-磷酸酶的活性。还提供了一种治疗因盐、液体或黏液分泌加重的疾病的方法，包括增加患有因黏液分泌加重的疾病的受试对象中肌醇1,3,4,5,6五磷酸磷酸酶的活性，从而减少黏液分泌并治疗疾病。还提供了一种在受试对象中增加盐和液体分泌的方法，包括降低受试对象中肌醇1,3,4,5,6五磷酸1-磷酸酶的活性。提供了一种治疗因增加盐和液体分泌而治疗的疾病的方法，包括降低因增加盐和液体分泌而治疗的疾病的受试对象中肌醇1,3,4,5,6五磷酸1-磷酸酶的活性，从而增加盐和液体分泌并治疗疾病。
• <i>Arabidopsis thaliana</i>inositol 1,3,4-trisphosphate 5/6-kinase 4 (AtITPK4) is an outlier to a family of ATP-grasp fold proteins from Arabidopsis
  作者：Dylan Sweetman、Ioanna Stavridou、Sue Johnson、Porntip Green、Samuel E.K. Caddick、Charles A. Brearley

  DOI：10.1016/j.febslet.2007.07.046

  日期：2007.9.4

  The Arabidopsis genome encodes a family of inositol 1,3,4‐trisphosphate 5/6‐kinases which form a subgroup of a larger group of ATP‐grasp fold proteins. An analysis of the inositol 1,3,4‐trisphosphate 5/6‐kinase family might, ultimately, be best rewarded by detailed comparison of related enzymes in a single genome. The enzyme encoded by At2G43980, AtITPK4; is an outlier to its family. At2G43980 is expressed

  拟南芥基因组编码一个肌醇 1,3,4-三磷酸 5/6-激酶家族，它们形成了一个更大的 ATP 抓握折叠蛋白组的一个亚组。对肌醇 1,3,4-三磷酸 5/6-激酶家族的分析可能最终通过对单个基因组中相关酶的详细比较得到最好的回报。At2G43980，AtITPK4编码的酶；是其家族的异类。At2G43980 在幼花和成熟花的雄性和雌性器官中表达。AtITPK4 与其他家族成员的不同之处在于它不显示肌醇 3,4,5,6-四磷酸 1-激酶活性；相反，它显示出肌醇 1,4,5,6-四磷酸和肌醇 1,3,4,5-四磷酸异构酶活性。
• Isolation of Inositol 1,3,4-Trisphosphate 5/6-Kinase, cDNA Cloning, and Expression of the Recombinant Enzyme
  作者：Monita P. Wilson、Philip W. Majerus

  DOI：10.1074/jbc.271.20.11904

  日期：1996.5

  the enzyme for inositol 1,3,4-trisphosphate was 80 nM with a Vmax of 60 nmol of product/min/mg of protein. The amino acid sequence of the tryptic peptide HSKLLARPAGGLVGERTCNAXP matched the protein sequence encoded by a human expressed sequence tag clone (GB T09063) at 16 of 22 residues. The expressed sequence tag clone was used to screen a human fetal brain cDNA library to obtain a cDNA clone of 1991

  使用肝素-琼脂糖层析并用肌醇六磷酸酯亲和洗脱，从小腿大脑中纯化肌醇1,3,4-三磷酸5 / 6-激酶12900倍。最终的制剂包含48和36-38kDa的蛋白质。所有这些蛋白质都具有相同的氨基末端序列，并且具有酶活性。较小的物种代表具有羧基末端截短的蛋白水解产物。肌醇1,3,4-三磷酸酯的酶Km为80 nM，Vmax为60 nmol产品/ min / mg蛋白质。胰蛋白酶肽HSKLLARPAGGLVGERTCNAXP的氨基酸序列与人类表达的序列标签克隆（GB T09063）编码的22个残基中的16个氨基酸序列匹配。表达的序列标签克隆用于筛选人胎儿脑cDNA文库，以获得1991个碱基对（bp）的cDNA克隆，该蛋白预测46 kDa的蛋白质。该克隆编码得自纯化小牛脑制备物的氨基末端氨基酸序列，表明它代表其人同源物。该cDNA在大肠杆菌中表达为融合蛋白，并发现具有肌醇1,3,4-三磷酸5 / 6-
• Characterization of a cDNA EncodingArabidopsis thalianaInositol 1,3,4-trisphosphate 5/6-kinase
  作者：Monita P. Wilson、Philip W. Majerus

  DOI：10.1006/bbrc.1997.6355

  日期：1997.3

  protein in Escherichia coli, with a carboxyl terminal deletion removing one region of high identity between the two proteins. The protein product of this construct was found to have inositol 1,3,4-trisphosphate 5/6-kinase activity. The Arabidopsis enzyme produced both inositol 1,3,4,6-tetrakisphosphate and inositol 1,3,4,5-tetrakisphosphate as products in a ratio of 1:3, in contrast with the human enzyme

  我们已经测序并重组表达了来自拟南芥的表达序列标签克隆（GB Z25963），作为融合蛋白，其代表人肌醇1、3、4三磷酸5 / 6-激酶的植物同源物。1365个碱基对的克隆具有960个碱基对的开放阅读框，预测其蛋白质产物为36.2 kDa，pI为6.1。没有聚腺苷酸化信号或聚（A）尾巴，表明还有待鉴定的其他3'序列。氨基酸序列与人蛋白质的同源性为30％。人和拟南芥蛋白序列之间有几个具有高度同一性的短区，这些短区可能有助于鉴定酶的活性位点。表达的序列标签在大肠杆菌中表达为融合蛋白，带有羧基末端的缺失，去除了两种蛋白质之间的高度同一性区域。发现该构建体的蛋白质产物具有肌醇1,3,4-三磷酸5/6激酶活性。拟南芥酶以1：3的比例生产肌醇1,3,4,6-四磷酸和肌醇1,3,4,5-四磷酸作为人的酶，而人酶的产物比例为3： 1。
• Molecular Characterization of At5PTase1, an Inositol Phosphatase Capable of Terminating Inositol Trisphosphate Signaling,
  作者：Sara E. Berdy、Joerg Kudla、Wilhelm Gruissem、Glenda E. Gillaspy

  DOI：10.1104/pp.126.2.801

  日期：2001.6.1

  The inositol triphosphate (IP3)-signaling pathway has been associated with several developmental and physiological processes in plants, but we currently know little about the regulation of this pathway. Inositol 5′ phosphatases (5PTases) are enzymes that remove a 5′ phosphate from several potential second messengers, including IP3. In catalyzing the removal of a 5′ phosphate from second messenger substrates, 5PTases can act to terminate signal transduction events. We describe the molecular analysis of At5PTase1, a 5PTase gene from Arabidopsis. When expressed transiently in Arabidopsis leaf tissue or ectopically in transgenic plants, At5PTase1 allowed for the increased hydrolysis of I(1,4,5)P3 and I(1,3,4,5)P4 substrates. At5PTase1 did not hydrolyze I(1)P, I(1,4)P2, or PI(4,5)P2 substrates. This substrate specificity was similar to that of the human Type I 5PTase. We identified 14 other potential At5PTase genes and constructed an unrooted phylogenetic tree containing putative Arabidopsis, human, and yeast 5PTase proteins. This analysis indicated that the Arabidopsis 5PTases were grouped in two separate branches of the tree. The multiplicity of At5PTases indicates that these enzymes may have different substrate specificities and play different roles in signal termination in Arabidopsis.

  肌醇三磷酸（IP3）信号通路与植物中的几个发育和生理过程有关，但我们目前对该通路的调控知之甚少。肌醇5'-磷酸酶（5PTases）是一种酶，可从多种潜在的第二信使中去除5'-磷酸，包括IP3。通过催化第二信使底物中的5'-磷酸的去除，5PTases可以终止信号转导事件。我们描述了来自拟南芥的5PTase基因At5PTase1的分子分析。当在拟南芥叶组织中短暂表达或在转基因植物中异位表达时，At5PTase1允许增加I（1,4,5）P3和I（1,3,4,5）P4底物的水解。At5PTase1不水解I（1）P，I（1,4）P2或PI（4,5）P2底物。这种底物特异性类似于人类I型5PTase。我们鉴定了其他14个潜在的At5PTase基因，并构建了一个包含拟南芥、人类和酵母5PTase蛋白的未根的系统发育树。该分析表明，拟南芥5PTases被分成树的两个分支。At5PTases的多样性表明这些酶可能具有不同的底物特异性，并在拟南芥的信号终止中发挥不同的作用。