Gambusia_affinisFamily: TPP1 Number of Genes: 1
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Introduction

Pfam

TPP1 is a component of the telomerase holoenzyme, involved in telomere replication. It has been demonstrated that TPP1 dimerises and binds to DNA and RNA. Furthermore, TPP1 stimulates the dissociation of RNA/DNA hetero-duplexes [1,2]. Yeast telomerase protein TPP1 (Est3 in yeast) is a novel type of GTPase [3]. The key residues in Q03096 are an Asp at residue 86 and the Arg at residue 110. The Asp is totally conserved in the family, whereas the Arg is not so well conserved. The N-terminal of TPP1 is likely to be the binding surface for TINF2, whereas the C-terminus probably binds to POT1, thereby tethering POT1 to the shelterin complex [4]. The complex bound to telomeric DNA increases the activity and processivity of the human telomerase core enzyme, thus helping to maintain the length of the telomeres [5,6]. This domain is conserved from fungi to mammals, hence family Telomere_Pot1 has been merged into the family [7]. The human shelterin complex includes six proteins: telomere repeat binding factor 1 (TRF1), TRF2, repressor/activator protein 1 (RAP1), TRF1-interacting nuclear protein 2 (TIN2), TIN2-interacting protein 1 (TPP1) and protection of telomeres 1 (POT1) [8].

InterPro

No InterPro abstract

Reference

  1. Yang CP, Chen YB, Meng FL, Zhou JQ; , Nucleic Acids Res. 2006;34:407-416.: Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization contributes to efficient telomere replication in vivo. PUBMED:16418502 EPMC:16418502 .

  2. Sharanov YS, Zvereva MI, Dontsova OA; , FEBS Lett. 2006;580:4683-4690.: Saccharomyces cerevisiae telomerase subunit Est3p binds DNA and RNA and stimulates unwinding of RNA/DNA heteroduplexes. PUBMED:16884717 EPMC:16884717 .

  3. Shubernetskaya O, Logvina N, Sharanov Y, Zvereva M;, Biochimie. 2010; [Epub ahead of print]: Yeast telomerase protein Est3 is a novel type of GTPase. PUBMED:20884318 EPMC:20884318 .

  4. Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T;, Genes Dev. 2004;18:1649-1654.: POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. PUBMED:15231715 EPMC:15231715 .

  5. Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M; , Nature. 2007;445:506-510.: The POT1-TPP1 telomere complex is a telomerase processivity factor. PUBMED:17237768 EPMC:17237768 .

  6. Zaug AJ, Podell ER, Nandakumar J, Cech TR;, Genes Dev. 2010;24:613-622.: Functional interaction between telomere protein TPP1 and telomerase. PUBMED:20231318 EPMC:20231318 .

  7. Miyoshi T, Kanoh J, Saito M, Ishikawa F;, Science. 2008;320:1341-1344.: Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. PUBMED:18535244 EPMC:18535244 .

  8. Armanios M, Blackburn EH;, Nat Rev Genet. 2012;13:693-704.: The telomere syndromes. PUBMED:22965356 EPMC:22965356.