Phosphatase Subfamily RTR1

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Phosphatase Classification: Fold RTR1: Superfamily RTR1: Family RTR1: Subfamily RTR1

RTR1 is a phosphatase conserved in eukaryotes that regulates the phosphorylation states of C-terminal domain (CTD) of RNA polymerase II.


RTR1 is found in most of eukaryotes. It is absent from Monosiga and sponge genome, though it is perhaps due to the quality of genome assembly. It is single copy in human, sea urchin, fruit fly, C elegans. However, two copies are found in yeast.


RTR1 has a conserved domain that carries out the phosphatase activity. Yeast RTR1 has a C-terminal region (CTR) that auto-inhibits the catalytic domain [1]. Human RTR1 encoded by gene RPAP2 has a longer tail, but whether its function is unclear given the limited sequence similarity with CTR in yeast RTR1.


Yeast RTR1 encodes the phosphatase that dephosphorylates serine-5 of CTD repeats of RNA pol II [2, 3]. These findings were challenged by later studies [4], but more recent study supports its activity towards serine-5 [1]. Moreover, it has been shown that Rtr1 dephosphorylates not only serine-5 but also the newly described anti-termination tyrosine 1 marker on CTD repeats [1].


  1. Hsu PL, Yang F, Smith-Kinnaman W, Yang W, Song JE, Mosley AL, and Varani G. Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD. J Mol Biol. 2014 Aug 12;426(16):2970-81. DOI:10.1016/j.jmb.2014.06.010 | PubMed ID:24951832 | HubMed [hsu14]
  2. Mosley AL, Pattenden SG, Carey M, Venkatesh S, Gilmore JM, Florens L, Workman JL, and Washburn MP. Rtr1 is a CTD phosphatase that regulates RNA polymerase II during the transition from serine 5 to serine 2 phosphorylation. Mol Cell. 2009 Apr 24;34(2):168-78. DOI:10.1016/j.molcel.2009.02.025 | PubMed ID:19394294 | HubMed [Mosley09]
  3. Xiang K, Manley JL, and Tong L. The yeast regulator of transcription protein Rtr1 lacks an active site and phosphatase activity. Nat Commun. 2012 Jul 10;3:946. DOI:10.1038/ncomms1947 | PubMed ID:22781759 | HubMed [xiang12]
  4. Kim M, Suh H, Cho EJ, and Buratowski S. Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2, 5, and 7. J Biol Chem. 2009 Sep 25;284(39):26421-6. DOI:10.1074/jbc.M109.028993 | PubMed ID:19679665 | HubMed [Kim09]
All Medline abstracts: PubMed | HubMed