PF10341

Shelterin complex subunit, TPP1/ACD

Pfam entry
Member databasePfam
Pfam typefamily
Short nameTPP1
ClanOB
Author Wood V;0000-0001-6330-7526 Finn RD;0000-0001-8626-2148
Sequence Ontology0100021

Description

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
[6, 4]
. Yeast telomerase protein TPP1 (Est3 in yeast) is a novel type of GTPase
[5]
. The key residues in Swiss: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
[7]
. 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
[2, 8]
. This domain is conserved from fungi to mammals, hence family Telomere_Pot1 has been merged into the family
[1]
. 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)
[3]
.

References

1.Fission yeast Pot1-Tpp1 protects telomeres and regulates telomere length. Miyoshi T, Kanoh J, Saito M, Ishikawa F. Science 320, 1341-4, (2008). View articlePMID: 18535244

2.The POT1-TPP1 telomere complex is a telomerase processivity factor. Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M. Nature 445, 506-10, (2007). View articlePMID: 17237768

3.The telomere syndromes. Armanios M, Blackburn EH. Nat. Rev. Genet. 13, 693-704, (2012). View articlePMID: 22965356

4.Saccharomyces cerevisiae telomerase subunit Est3p binds DNA and RNA and stimulates unwinding of RNA/DNA heteroduplexes. Sharanov YS, Zvereva MI, Dontsova OA. FEBS Lett. 580, 4683-90, (2006). View articlePMID: 16884717

5.Yeast telomerase protein Est3 is a novel type of GTPase. Shubernetskaya O, Logvina N, Sharanov Y, Zvereva M. Biochimie 93, 202-6, (2011). View articlePMID: 20884318

6.Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization contributes to efficient telomere replication in vivo. Yang CP, Chen YB, Meng FL, Zhou JQ. Nucleic Acids Res. 34, 407-16, (2006). View articlePMID: 16418502

7.POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T. Genes Dev. 18, 1649-54, (2004). View articlePMID: 15231715

8.Functional interaction between telomere protein TPP1 and telomerase. Zaug AJ, Podell ER, Nandakumar J, Cech TR. Genes Dev. 24, 613-22, (2010). View articlePMID: 20231318

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