Popeye domain-containing proteins 1 and 2 (POPDC1 and POPDC2) are transmembrane proteins involved in cyclic AMP-mediated signalling processes and are required for normal cardiac pacemaking and conduction. In order to identify novel protein interaction partners, POPDC1 and 2 proteins were attached to beads and compared by proteomic analysis with control beads in the pull-down of proteins from cultured human skeletal myotubes. There were highly-significant interactions of both POPDC1 and POPDC2 with XIRP1 (Xin actin binding repeat-containing protein 1), actin and, to a lesser degree, annexin A5. In adult human skeletal muscle, both XIRP1 and POPDC1/2 were present at the sarcolemma and in T-tubules. The interaction of POPDC1 with XIRP1 was confirmed in adult rat heart extracts. Using new monoclonal antibodies specific for POPDC1 and POPDC2, both proteins, together with XIRP1, were found mainly at intercalated discs but also at T-tubules in adult rat and human heart. Mutations in human POPDC1, POPDC2 and in human XIRP1, all cause pathological cardiac arrhythmias, suggesting a possible role for POPDC1/2 and XIRP1 interaction in normal cardiac conduction.

中文翻译：

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心脏病相关蛋白POPDC1 / 2与XIRP1在横管和插层椎间盘中的相互作用

含有Popeye域的蛋白1和2（POPDC1和POPDC2）是参与环AMP介导的信号传导过程的跨膜蛋白，是正常心脏起搏和传导所必需的。为了鉴定新的蛋白质相互作用伴侣，将POPDC1和2个蛋白质附着在珠子上，并通过蛋白质组学分析与对照珠子进行比较，从培养的人骨骼肌管中提取蛋白质。POPDC1和POPDC2与XIRP1（含Xin肌动蛋白结合重复序列的蛋白1），肌动蛋白以及较小程度的膜联蛋白A5之间都存在高度重要的相互作用。在成人骨骼肌中，XIRP1和POPDC1 / 2均存在于肌膜和T管中。在成年大鼠心脏提取物中证实了POPDC1与XIRP1的相互作用。使用针对POPDC1和POPDC2的新型单克隆抗体，这两种蛋白与XIRP1一起主要在成年大鼠和人心脏的插入盘中发现，也发现在T管中。人POPDC1，POPDC2和人XIRP1中的突变均会引起病理性心律失常，提示POPDC1 / 2和XIRP1相互作用可能在正常心脏传导中发挥作用。