Diella Francesca, Chabanis Sophie, Luck Katja, Chica Claudia, Ramu Chenna, Nerlov Claus, Gibson Toby J
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Bioinformatics. 2009 Jan 1;25(1):1-5. doi: 10.1093/bioinformatics/btn594. Epub 2008 Nov 24.
We noted that the sumoylation site in C/EBP homologues is conserved beyond the canonical consensus sequence for sumoylation. Therefore, we investigated whether this pattern might define a more general protein motif.
We undertook a survey of the human proteome using a regular expression based on the C/EBP motif. This revealed significant enrichment of the motif using different Gene Ontology terms (e.g. 'transcription') that pertain to the nucleus. When considering requirements for the motif to be functional (evolutionary conservation, structural accessibility of the motif and proper cell localization of the protein), more than 130 human proteins were retrieved from the UniProt/Swiss-Prot database. These candidates were particularly enriched in transcription factors, including FOS, JUN, Hif-1alpha, MLL2 and members of the KLF, MAF and NFATC families; chromatin modifiers like CHD-8, HDAC4 and DNA Top1; and the transcriptional regulatory kinases HIPK1 and HIPK2. The KEPEmotif appears to be restricted to the metazoan lineage and has three length variants-short, medium and long-which do not appear to interchange.
我们注意到C/EBP同源物中的SUMO化位点在SUMO化的典型共有序列之外是保守的。因此,我们研究了这种模式是否可能定义一种更普遍的蛋白质基序。
我们使用基于C/EBP基序的正则表达式对人类蛋白质组进行了调查。这揭示了使用与细胞核相关的不同基因本体术语(如“转录”)时该基序的显著富集。在考虑该基序发挥功能的要求(进化保守性、基序的结构可及性以及蛋白质在细胞中的正确定位)时,从UniProt/Swiss-Prot数据库中检索到了130多种人类蛋白质。这些候选蛋白在转录因子中特别富集,包括FOS、JUN、Hif-1α、MLL2以及KLF、MAF和NFATC家族的成员;染色质修饰因子如CHD-8、HDAC4和DNA Top1;以及转录调节激酶HIPK1和HIPK2。KEP基序似乎仅限于后生动物谱系,并且有三种长度变体——短、中、长——它们似乎不会相互转换。