Phosphatase Family RTR1
Phosphatase Classification: Fold RTR1: Superfamily RTR1: Family RTR1
RTR1 is a phosphatase conserved in eukaryotes that regulates the phosphorylation state of C-terminal domain (CTD) of RNA polymerase II.
Evolution
RTR1 is found in most eukaryotes. It is absent from the sponge genome, possibly due to incomplete genome assembly. It is single copy in most species including human (RPAP2). However, two copies are found in yeast (RTR1 and RTR2).
Domain
RTR1 proteins share a conserved catalytic domain. Yeast RTR1 has a C-terminal region that auto-inhibits the catalytic domain [1]. Human RPAP2 has a far longer tail of unknown function, though it is well conserved in most animals, and weakly conserved in plants. Nematode and Drosophila members lack this extended tail.
Function
Yeast RTR1 was shown to dephosphorylate serine-5 of CTD repeats of RNA pol II [2, 3], and similar activity was reported for human RPAP2 [4]. These findings were challenged by a later study [5] of RTR1 from K. lactis, but more recent reports supports its activity towards serine-5 [1], as well as the newly described anti-termination tyrosine 1 residue of CTD repeats [1].
References
- 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 |
- 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 |
- Egloff S, Zaborowska J, Laitem C, Kiss T, and Murphy S. Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes. Mol Cell. 2012 Jan 13;45(1):111-22. DOI:10.1016/j.molcel.2011.11.006 |
- 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 |
- 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 |