CERK - Gene

Gene

CERK is encoded by the CERK gene. The CERK gene is located on human chromosome 22q13, contains 13 exons, and is approximately 4.5kb in length. CERK shares sequence homology with sphingosine kinase type I, including an N-terminal pleckstrin homology (PH) domain and a diacylglycerol kinase domain. BLAST searches of expressed sequence tag (ESTs) by Sugiura and colleagues have yielded results showing orthologous CERK genes in other eukaryotes including Drosophila melanogaster, Caenorhabditis elegans, and Oryza sativa. A mouse homolog has been cloned as well.

The complete gene of human CERK contains 4459bp, which consists of a 123bp-5’-untranslated region, a 2772bp 3’-non-coding, and a 1611bp open reading frame. Sequence analysis of CERK putatively suggests that the following post-translational modification sites exist: 4 N-glycosylation sites, 15 phosphorylation sites, 5 prenylation sites, and 2 amidation sites. The complete gene of mouse CERK differed slightly, containing a 1593bp open reading frame. The decreased length of the open reading frame results in the loss of 2 prenylation sites and 1 amidation site.

In human CERK, a retinoic acid response element (RARE)-like exists between -40bp and -28bp and contains the sequence: TCCCCG C CGCCCG. RARE-like plays a role in transcription regulation of CERK. It is suspected that in the presence of all-trans retinoic acid (ATRA), chicken ovalbumin upstream promoter transcription factor I (COUP-TFI), retinoic acid receptor (RARα), retinoid X receptor (RXRα) bind the RARE-like of CERK in 5H-SY5Y cells. However, CERK expression varies per cell line. In contrast to SH-SY5Y neuroblastoma cells, HL60 leukemia cells demonstrated no binding of CERK even in the presence of ATRA. This suggests that differential expression of RARα, RXRα, and COUP-PTI may determine transcription levels in various cell lines.

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