Abstract
The ATPase cation transporting 13A2 protein (ATP13A2), which maintains the homeostasis of mitochondria and lysosomes, plays a significant role in human neurodegenerative diseases and cancer. Through constructing a lamprey proteome database, employing multiple sequence alignment and phylogenetic analysis, 5 ATP13A2 proteins from Petromyzon marinus (Pm-ATP13A2) were identified based on the evolutionary perspective. The motif and domain analysis showed that the ATP13A2 protein was conserved. The multiple phosphorylation sites and transmembrane structures highlighted the characteristics of ATP13A2 as the P-ATPase-V cation transporting protein. Based on the information provided by the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, this study was conducted as a preliminary investigation of the carcinogenic effects of the ATP13A2 gene in a variety of tumors. The ATP13A2 was strongly expressed in most tumors, except in two types of nervous system tumors glioblastoma multiforme (GBM) and brain lower grade glioma (LGG). Moreover, the expression of ATP13A2 was strongly correlated with the prognosis of tumor patients. The high expression of ATP13A2 was obviously related to the poor prognosis of LGG. The poor prognosis of LGG patients may affect the ATP13A2 expression through the immune cells and radiotherapy. Also, cancer-related fibroblast infiltration was observed. All in all, this work offers more insights into the molecular evolution of the ATP13A2 protein and facilitates the understanding of the carcinogenic effects of the ATP13A2 in different tumors. Our discussion also promotes the study into the successful evolution of the vertebrate brain and the mechanism of clinical brain-related diseases.
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Code availability
JDK software (version 8.0.1310.11) was used for analysis, and some software needed its help for normal operation.
Availability of data and material
Information from TCGA, CPTAC, and GEO databases is used for pan-cancer analysis. A series of protein information from NCBI and Ensemble is used to identify and predict ATP13A2. These databases are open access.
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This study was supported by grants from National Natural Science Foundation (No. 31501907), Scientific and Technological Research Projects of Liaoning Provincial Department of Education (No. L2015287). The funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation.
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Kaifeng Zheng conceived and operated all the experiments and analyzed all the data. Tiesong Li oversaw the preparation of the final version of the manuscript.
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Zheng, K., Li, T. Prediction of ATPase cation transporting 13A2 molecule in Petromyzon marinus and pan-cancer analysis into human tumors from an evolutionary perspective. Immunogenetics 73, 277–289 (2021). https://doi.org/10.1007/s00251-021-01216-7
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DOI: https://doi.org/10.1007/s00251-021-01216-7