Mycobacterium tuberculosis Rv2140c is a function unknown conserved phosphatidylethanolamine-binding protein (PEBP), homologous to Raf kinase inhibitor protein (RKIP) in human beings. To delineate its function, we heterologously expressed Rv2140c in a non-pathogenic M. smegmatis. Quantitative phosphoproteomic analysis between two recombinant strains Ms_Rv2140c and Ms_vec revealed that Rv2140c differentially regulate 425 phosphorylated sites representing 282 proteins. Gene ontology GO, and a cluster of orthologous groups COG analyses showed that regulated phosphoproteins by Rv2140c were mainly associated with metabolism and cellular processes. Rv2140c significantly repressed phosphoproteins involved in signaling, including serine/threonine-protein kinases and two-component system, and the arabinogalactan biosynthesis pathway phosphoproteins were markedly up-regulated, suggesting a role of Rv2140c in modulating cell wall. Consistent with phosphoproteomic data, Rv2140c altered some phenotypic properties of M. smegmatis such as colony morphology, cell wall permeability, survival in acidic conditions, and active lactose transport. In summary, we firstly demonstrated the role of PEBP protein Rv2140c, especially in phosphorylation of mycobacterial arabinogalactan biosynthesis proteins.

结核分枝杆菌Rv2140c是一种功能未知的保守磷脂酰乙醇胺结合蛋白（PEBP），与人类Raf激酶抑制剂蛋白（RKIP）同源。为了描述其功能，我们在非致病性耻垢分枝杆菌中异源表达了Rv2140c。在两个重组菌株Ms_Rv2140c和Ms_vec之间进行的磷酸化蛋白质组学定量分析显示，Rv2140c差异调节了282个蛋白的425个磷酸化位点。基因本体论GO和一组直系同源基因COG分析表明，Rv2140c调控的磷蛋白主要与代谢和细胞过程有关。Rv2140c显着抑制了参与信号转导的磷蛋白，包括丝氨酸/苏氨酸蛋白激酶和两组分系统，阿拉伯半乳聚糖的生物合成途径磷酸蛋白明显上调，提示Rv2140c在调节细胞壁中的作用。与磷酸蛋白质组学数据一致，Rv2140c改变了耻垢分枝杆菌的某些表型特性，例如菌落形态，细胞壁通透性，在酸性条件下的存活率以及活性乳糖转运。总而言之，我们首先证明了PEBP蛋白Rv2140c的作用，特别是在分枝杆菌阿拉伯半乳聚糖生物合成蛋白的磷酸化中。