Telomerase has reverse transcriptase motifs

The human telomerase (hTERT) sequence identified by all three groups has an open reading frame of 1132 amino acids predicted to encode a 127 kDa protein.  The identification of hTERT as a member of the telomerase family was based on the presence of motifs characteristic of the telomerase and reverse transcriptase (RT) family of enzymes.  In particular, hTERT contains six conserved motif sequences, shown below aligned to homologous motifs in other telomerase sequences and to RT motifs in HIV-1 RT (because the boundaries of these motifs are based on similarity and identity with other telomerase sequences, the functional boundary of each motif may be different.).  Consensus telomerase motif sequence is shown above and consensus RT motif sequence is shown below the alignments.  Notably, the invariant aspartic acid residues implicated in RT catalysis are conserved in the hTERT sequence.

Fig. 2. Alignment of RT sequence motifs of telomerase proteins.

For historical reasons, the motifs are called “1”, “2”, “A’”, “B”, “C”, and “D”.

Although the overall homology among the telomerase proteins is relatively low (approximately 40% similarity in all pair-wise combinations), the overall structure of the protein seems to be well conserved.  Four major domains: N-terminal, basic, reverse transcriptase (RT) and C-terminal are present in all telomerase proteins.  The regions of most sequence similarity are within the RT domain and in a motif located N-terminal to motif 1 (Nakamura et al. 1997; Meyerson et al. 1997b).  This first motif, called motif T, is not found in RTs or other proteins, suggesting that it may be specific to the telomerase family.