The FAM83 family of proteins: from pseudo-PLDs to anchors for CK1 isoforms.
The FAM83 family of proteins: from pseudo-PLDs to anchors for CK1 isoforms.
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DOI：
10.1042/bst20160277
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发表时间：
2018-06-19
影响因子：
3.9
通讯作者：
Sapkota GP
中科院分区：
文献类型：
--
作者：
Bozatzi P;Sapkota GP
FAM 83（具有序列相似性83的FAMily）家族的八个成员仅存在于脊椎动物中，并且通过在其N-末端存在未知功能的保守DUF 1669结构域来定义。DUF 1669结构域由保守的磷脂酶D（PLD）样催化基序组成。然而，FAM 83蛋白不显示PLD催化（PLDc）活性，并且每个FAM 83成员中存在的假PLDc基序缺乏天然PLDc基序的关键元件。在缺乏催化活性的情况下，DUF 1669结构域可能已经进化为支持生物学中的新功能。最近的研究表明DUF 1669结构域介导与丝氨酸/苏氨酸蛋白激酶CK 1（酪蛋白激酶1）家族的不同亚型的相互作用。反过来，不同的FAM 83蛋白，其中显示独特的氨基酸序列以外的DUF 1669域，提供CK 1亚型独特的亚细胞区室。作为最早被发现的蛋白激酶之一，CK 1亚型被认为是组成型活性的，并且已知控制过多的生物过程。然而，它们对激酶活性、底物选择性和亚细胞定位的调节仍然是一个谜。新出现的证据现在支持DUF 1669结构域和FAM 83蛋白在CK 1生物学调节中的核心作用。
The eight members of the FAM83 (FAMily with sequence similarity 83) family of poorly characterised proteins are only present in vertebrates and are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini. The DUF1669 domain consists of a conserved phospholipase D (PLD)-like catalytic motif. However, the FAM83 proteins display no PLD catalytic (PLDc) activity, and the pseudo-PLDc motif present in each FAM83 member lacks the crucial elements of the native PLDc motif. In the absence of catalytic activity, it is likely that the DUF1669 domain has evolved to espouse novel function(s) in biology. Recent studies have indicated that the DUF1669 domain mediates the interaction with different isoforms of the CK1 (casein kinase 1) family of Ser/Thr protein kinases. In turn, different FAM83 proteins, which exhibit unique amino acid sequences outside the DUF1669 domain, deliver CK1 isoforms to unique subcellular compartments. One of the first protein kinases to be discovered, the CK1 isoforms are thought to be constitutively active and are known to control a plethora of biological processes. Yet, their regulation of kinase activity, substrate selectivity and subcellular localisation has remained a mystery. The emerging evidence now supports a central role for the DUF1669 domain, and the FAM83 proteins, in the regulation of CK1 biology.