Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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TAN Telomere-length maintenance and DNA damage repair

SMART accession number:	SM01342
Description:	ATM is a large protein kinase, in humans, critical for responding to DNA double-strand breaks (DSBs). Tel1, the orthologue from budding yeast, also regulates responses to DSBs. Tel1 is important for maintaining viability and for phosphorylation of the DNA damage signal transducer kinase Rad53 (an orthologue of mammalian CHK2). In addition to functioning in the response to DSBs, numerous findings indicate that Tel1/ATM regulates telomeres. The overall domain structure of Tel1/ATM is shared by proteins of the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family, but this family carries a unique and functionally important TAN sequence motif, near its N-terminal, LxxxKxxE/DRxxxL. which is conserved specifically in the Tel1/ATM subclass of the PIKKs. The TAN motif is essential for both telomere length maintenance and Tel1 action in response to DNA damage (PMID:18625723). It is classified as an EC:2.7.11.1.
Interpro abstract (IPR021668):	ATM is a large protein kinase, in humans, critical for responding to DNA double-strand breaks (DSBs). Tel1, the orthologue from budding yeast, also regulates responses to DSBs. Tel1 is important for maintaining viability and for phosphorylation of the DNA damage signal transducer kinase Rad53 (an orthologue of mammalian CHK2). In addition to functioning in the response to DSBs, numerous findings indicate that Tel1/ATM regulates telomeres. The overall domain structure of Tel1/ATM is shared by proteins of the phosphatidylinositol 3-kinase (PI3K)-related kinase (PIKK) family, but this family carries a unique and functionally important TAN sequence motif, near its N-terminal, LxxxKxxE/DRxxxL. which is conserved specifically in the Tel1/ATM subclass of the PIKKs. The TAN motif is essential for both telomere length maintenance and Tel1 action in response to DNA damage [ (PUBMED:18625723) ]. It is classified as an EC 2.7.11.1 .
GO function:	protein serine/threonine kinase activity (GO:0004674)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 994 TAN domains in 994 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing TAN domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with TAN domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing TAN domain in the selected taxonomic class.

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Seidel JJ, Anderson CM, Blackburn EH
  • A novel Tel1/ATM N-terminal motif, TAN, is essential for telomere lengthmaintenance and a DNA damage response.
  • Mol Cell Biol. 2008; 28: 5736-46
  • Display abstract

  • Tel1/ATM, a conserved phosphatidylinositol 3-kinase-related kinase (PIKK), actsin the response to DNA damage and regulates telomere maintenance. PIKK familymembers share an extended N-terminal region of low sequence homology. Sequencealignment of the N terminus of Tel1/ATM orthologs revealed a conserved, novelmotif we term TAN (for Tel1/ATM N-terminal motif). Point mutations in conservedresidues of the TAN motif resulted in telomere shortening, and its deletioncaused the same short telomere phenotype as complete deletion of Tel1 did.Overexpressing Tel1 TAN mutants did not rescue telomere shortening. The TAN motifwas also essential for the function of Tel1 in the response to DNA damage, asTAN-deleted Tel1 was indistinguishable from the complete lack of Tel1 in causing reduced viability and signaling through Rad53 upon DNA damage. Strikingly, TANdeletion reduced recruitment of Tel1 to a double-strand DNA break. Together,these results define a conserved sequence motif within an otherwise poorlydefined region of the Tel1/ATM kinase family proteins that is essential fornormal Tel1 function in Saccharomyces cerevisiae.

• Links (links to other resources describing this domain)

• PFAM	TAN
  INTERPRO	IPR021668

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