Alternative titles; symbols
HGNC Approved Gene Symbol: TEP1
Cytogenetic location: 14q11.2 Genomic coordinates (GRCh38): 14:20,365,667-20,413,501 (from NCBI)
Telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex, which catalyzes the addition of new telomeres on the chromosome ends. This activity is mediated by the catalytic telomerase reverse transcriptase (TERT; 187270) and telomerase RNA component template (TERC; 602322). The ribonucleoprotein complex responsible for telomerase activity had been purified only in ciliates. Purified tetrahymena telomerase contains an RNA and 2 protein components, p80 and p95. The p80 component can be specifically cross linked to telomerase RNA, whereas the p95 component binds and cross links to single-stranded, telomeric DNA (Harrington et al., 1997).
Harrington et al. (1997) identified a cDNA encoding a tetrahymena p80 homolog from a murine colonic crypt expressed sequence tag (EST) database. The mouse sequence was used as a probe to identify contiguous human cDNA clones from a library prepared from a human colon carcinoma cell line. The mouse and human open reading frames were found to be 75% identical at the amino acid level. The predicted human polypeptide contains 2,627 amino acids, 2 fewer than the predicted mouse polypeptide. Northern blot analysis of both mouse and human tissues showed widespread expression of the gene, which they symbolized TP1. The studies indicated that telomerase-associated proteins are conserved from ciliates to humans.
Vaults are large cytoplasmic ribonucleoprotein organelles made up of the 100-kD subunit MVP (605088), minor vault proteins of 193 kD (PARP4; 607519) and 240 kD, and vault RNA (VTRNA1-1; 612695). By peptide sequencing of the 240-kD component of purified monkey vaults, followed by database analysis, Kickhoefer et al. (1999) identified human TEP1. The TEP1 protein contains an N-terminal repeat domain, an RNA-binding domain, an ATP/GTP-binding motif, and 16 C-terminal WD40 repeats.
Using coimmunoprecipitation and fractionation analyses, Kickhoefer et al. (1999) found that TEP1 was associated with vaults in HeLa cell microsomal pellets. Yeast 3-hybrid screens detected an interaction between mouse Tep1 and human VTRNA1-1.
Saito et al. (1997) mapped the human TEP1 gene and mouse Tep1 gene by fluorescence in situ hybridization to human chromosome 14q11.2 and to the C2-D1 band of mouse chromosome 14, respectively. By means of genetic linkage mapping, the mouse gene was further localized to a position 2.7 cM distal to D14Mit18 and D14Mit134, and 2.0 cM proximal to D14Mit5 on mouse chromosome 14, where conserved linkage homology with human chromosome 14q11-q12 had been identified.
Harrington, L., McPhail, T., Mar, V., Zhou, W., Oulton, R., Bass, M. B., Arruda, I., Robinson, M. O. A mammalian telomerase-associated protein. Science 275: 973-976, 1997. [PubMed: 9020079] [Full Text: https://doi.org/10.1126/science.275.5302.973]
Kickhoefer, V. A., Stephen, A. G., Harrington, L., Robinson, M. O., Rome, L. H. Vaults and telomerase share a common subunit, TEP1. J. Biol. Chem. 274: 32712-32717, 1999. [PubMed: 10551828] [Full Text: https://doi.org/10.1074/jbc.274.46.32712]
Saito, T., Matsuda, Y., Suzuki, T., Hayashi, A., Yuan, X., Saito, M., Nakayama, J., Hori, T., Ishikawa, F. Comparative gene mapping of the human and mouse TEP1 genes, which encode one protein component of telomerases. Genomics 46: 46-50, 1997. [PubMed: 9403057] [Full Text: https://doi.org/10.1006/geno.1997.5005]