IRA2, a second gene of Saccharomyces cerevisiae that encodes a protein with a domain homologous to mammalian ras GTPase-activating protein.
IRA2, a second gene of Saccharomyces cerevisiae that encodes a protein with a domain homologous to mammalian ras GTPase-activating protein.
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IRA2 是酿酒酵母的第二个基因，编码的蛋白质具有与哺乳动物 ras GTP 酶激活蛋白同源的结构域。
DOI：
10.1128/mcb.10.8.4303-4313.1990
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发表时间：
1990
影响因子：
5.3
通讯作者：
Toh-e,A
中科院分区：
文献类型：
--
作者：
Tanaka,K;Nakafuku,M;Tamanoi,F;Kaziro,Y;Matsumoto,K;Toh-e,A
IRA 1基因是酿酒酵母中RAS-环AMP途径的负调控因子。为了鉴定参与这一途径的其他基因，我们在酵母基因组DNA文库中筛选了能够抑制多拷贝载体上theira 1突变的热休克敏感性的基因。我们鉴定了IRA 2，它编码一个3,079个氨基酸的蛋白质，与IRA 1蛋白质有45%的相同性。IRA 1蛋白和rasGTP酶激活蛋白之间的同源区域在IRA 2中也是保守的。IRA 2定位于第XV号染色体左臂上的arg 1位点的远端11厘摩处，并被发现与glc 4等位。IRA 2基因的破坏导致（i）对热激和氮饥饿的敏感性增加，（ii）孢子形成缺陷，和（iii）dc 25突变体的致死性抑制。对IRA 1和IRA 2的破坏突变体的分析表明，IRA 1和IRA 2蛋白以负向方式叠加调节RAS-环AMP途径。与GAP同源的IRA 2结构域的表达足以补充IRA 2的热休克敏感性，表明IRA通过刺激RAS蛋白的GT酶活性来下调RAS活性。
TheIRA1gene is a negative regulator of theRAS-cyclic AMP pathway inSaccharomyces cerevisiae. To identify other genes involved in this pathway, we screened yeast genomic DNA libraries for genes that can suppress the heat shock sensitivity of theira1mutation on a multicopy vector. We identifiedIRA2,encoding a protein of 3,079 amino acids, that is 45% identical to theIRA1protein. The region homologous between theIRA1protein andrasGTPase-activating protein is also conserved inIRA2. IRA2maps 11 centimorgans distal to thearg1locus on the left arm of chromosome XV and was found to be allelic toglc4.Disruption of theIRA2gene resulted in (i) increased sensitivity to heat shock and nitrogen starvation, (ii) sporulation defects, and (iii) suppression of the lethality of thecdc25mutant. Analysis of disruption mutants ofIRA1andIRA2indicated thatIRA1andIRA2proteins additively regulate theRAS-cyclic AMP pathway in a negative fashion. Expression of theIRA2domain homologous with GAP is sufficient for complementation of the heat shock sensitivity ofira2, suggesting thatIRAdown regulatesRASactivity by stimulating the GTPase activity ofRASproteins.