Characterization of an intronless human calmodulin‐like pseudogene

Abstract

We report the isolation and characterization of a human genomic clone encoding a calmodulin-like psbudogene. It contains an open reading frame of 444 nucleotides, not interrupted by introns. The nucleotide sequence of the open reading frame shows 80%, 71% and 69% identity to the previously reported human calmodulin cDNAs kht6 [17], hCWP [22], and lhCE1 [23], respectively. The derived amino acid sequence has only 85% identity to vertebrate calmodulin, but shows four potentially functional Caz+-binding loops. In the human tissues tested, this pseudogene is not expressed, though gene structure including promoter elements and a putative polyadenylation site seems to be intact.

Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells.

“…Considering that the three calmodulin genes in humans diverge as much as is theoretically possible, while still encoding identical proteins (17), it is clear that the entire protein is stringently conserved to preserve proper function. The sequence of the NB-1 transcript is identical to that of a previously reported intronless calmodulin-like gene originally described as an unexpressed pseudogene (25). Although genomic sequences specifying calmodulin-like coding sequences that differ by more than three amino acids from the authentic protein have also been described in other vertebrates (26,27), the NB-1 gene is the only one to our knowledge that has been shown to be expressed at the mRNA level.…”

Emanuel Strehler’s work on calcium pumps and calcium signaling

“…This finding has introduced the unusual concept of multiple genes -one protein, and has raised interesting questions concerning the evolution and functional significance of the CALM gene family. In subsequent work, the Strehler group has characterized all three human CALM genes [24,25] (before the advent of the human genome sequence), and in the process, has discovered multiple CALM pseudogenes [26] , as well as an intriguing intronless calmodulin-like gene [27] (see below). Dr. Strehler's group also has provided the first analysis of all three CALM gene promoters and a direct comparison of their relative transcriptional strengths [25] .…”

“…The serendipitous discovery of an intronless gene for a human calmodulin-like protein [27] gained interest when it became clear that calmodulin-like protein (CLP) (human genome nomenclature CALML3) is a tumor-sensitive protein specifically expressed in normal epithelial cells but downregulated in tumorigenesis [29] . Dr. Strehler's group has characterized the biochemical properties of CLP [30,31] , provided the first description of the gene and its regulation [32] , and has shown that downregulation of the protein is an early event in breast cancer development [33] .…”

An in vitro Human Mammary Epithelial Model System for Studies of Differentiation and Carcinogenesis

“…The initial characterization of genomic DNA corresponding to the NB-1 transcript indicated the unexpected absence of introns. A literature search revealed the existence of a previously reported human calmodulin "pseudogene" hOH6, which shared identity with NB-1 cDNA (20). This gene was designated a pseudogene since the authors were unable to demonstrate the existence of a corresponding mRNA.…”