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Hydrolase PDB id
1t9z
Jmol
Contents
Protein chain
181 a.a. *
Ligands
CIT
Metals
_MG
Waters ×131
* Residue conservation analysis
PDB id:
1t9z
Name: Hydrolase
Title: Three-dimensional structure of a RNA-polymerase ii binding protein.
Structure: Carboxy-terminal domain RNA polymerase ii polypeptide a small phosphatase 1. Chain: a. Synonym: nuclear lim interactor-interacting factor 3, nli- interacting factor 3, nli-if, scp1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ctdsp1, nif3, nliif. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.187     R-free:   0.234
Authors: T.Kamenski,S.Heilmeier,A.Meinhart,P.Cramer
Key ref:
T.Kamenski et al. (2004). Structure and mechanism of RNA polymerase II CTD phosphatases. Mol Cell, 15, 399-407. PubMed id: 15304220 DOI: 10.1016/j.molcel.2004.06.035
Date:
19-May-04     Release date:   31-Aug-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9GZU7  (CTDS1_HUMAN) -  Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1
Seq:
Struc: 		261 a.a.
181 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.16  - Phosphoprotein phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A phosphoprotein + H2O = a protein + phosphate
phosphoprotein
 + H(2)O
 = protein
 + phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     phosphatase activity     1 term  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.molcel.2004.06.035 Mol Cell 15:399-407 (2004)
PubMed id: 15304220  
 
 
Structure and mechanism of RNA polymerase II CTD phosphatases.
T.Kamenski, S.Heilmeier, A.Meinhart, P.Cramer.
 
  ABSTRACT  
 
Recycling of RNA polymerase II (Pol II) after transcription requires dephosphorylation of the polymerase C-terminal domain (CTD) by the phosphatase Fcp1. We report the X-ray structure of the small CTD phosphatase Scp1, which is homologous to the Fcp1 catalytic domain. The structure shows a core fold and an active center similar to those of phosphotransferases and phosphohydrolases that solely share a DXDX(V/T) signature motif with Fcp1/Scp1. We demonstrate that the first aspartate in the signature motif undergoes metal-assisted phosphorylation during catalysis, resulting in a phosphoaspartate intermediate that was structurally mimicked with the inhibitor beryllofluoride. Specificity may result from CTD binding to a conserved hydrophobic pocket between the active site and an insertion domain that is unique to Fcp1/Scp1. Fcp1 specificity may additionally arise from phosphatase recruitment near the CTD via the Pol II subcomplex Rpb4/7, which is shown to be required for binding of Fcp1 to the polymerase in vitro.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Active Site and Mimicry of the Phosphoaspartate Intermediate 		Figure 6.
Figure 6. Protein-Protein Interaction Network in a Pol II-TFIIF-Fcp1 Complex
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 15, 399-407) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21288162 S.R.Pereira, V.T.Vasconcelos, and A.Antunes (2011).
The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins.
  Crit Rev Toxicol, 41, 83.  
20594956 B.Szöör (2010).
Trypanosomatid protein phosphatases.
  Mol Biochem Parasitol, 173, 53-63.  
20551176 B.Szöor, I.Ruberto, R.Burchmore, and K.R.Matthews (2010).
A novel phosphatase cascade regulates differentiation in Trypanosoma brucei via a glycosomal signaling pathway.
  Genes Dev, 24, 1306-1316.  
19807881 H.Ji, S.R.Kim, Y.H.Kim, H.Kim, M.Y.Eun, I.D.Jin, Y.S.Cha, D.W.Yun, B.O.Ahn, M.C.Lee, G.S.Lee, U.H.Yoon, J.S.Lee, Y.H.Lee, S.C.Suh, W.Jiang, J.I.Yang, P.Jin, S.R.McCouch, G.An, and H.J.Koh (2010).
Inactivation of the CTD phosphatase-like gene OsCPL1 enhances the development of the abscission layer and seed shattering in rice.
  Plant J, 61, 96.  
19299564 J.L.McConnell, and B.E.Wadzinski (2009).
Targeting protein serine/threonine phosphatases for drug development.
  Mol Pharmacol, 75, 1249-1261.  
19879837 Y.Shi (2009).
Serine/threonine phosphatases: mechanism through structure.
  Cell, 139, 468-484.  
19026779 A.Ghosh, S.Shuman, and C.D.Lima (2008).
The structure of Fcp1, an essential RNA polymerase II CTD phosphatase.
  Mol Cell, 32, 478-490.
PDB code: 3ef0
18337465 H.Qadota, L.A.McGaha, K.B.Mercer, T.J.Stark, T.M.Ferrara, and G.M.Benian (2008).
A novel protein phosphatase is a binding partner for the protein kinase domains of UNC-89 (Obscurin) in Caenorhabditis elegans.
  Mol Biol Cell, 19, 2424-2432.  
18441121 J.Verma-Gaur, S.N.Rao, T.Taya, and P.Sadhale (2008).
Genomewide recruitment analysis of Rpb4, a subunit of polymerase II in Saccharomyces cerevisiae, reveals its involvement in transcription elongation.
  Eukaryot Cell, 7, 1009-1018.  
18195044 V.M.Runner, V.Podolny, and S.Buratowski (2008).
The Rpb4 subunit of RNA polymerase II contributes to cotranscriptional recruitment of 3' processing factors.
  Mol Cell Biol, 28, 1883-1891.  
17487459 H.Qian, C.Ji, S.Zhao, J.Chen, M.Jiang, Y.Zhang, M.Yan, D.Zheng, Y.Sun, Y.Xie, and Y.Mao (2007).
Expression and characterization of HSPC129, a RNA polymerase II C-terminal domain phosphatase.
  Mol Cell Biochem, 303, 183-188.  
17493655 H.Zhu, P.Smith, L.K.Wang, and S.Shuman (2007).
Structure-function analysis of the 3' phosphatase component of T4 polynucleotide kinase/phosphatase.
  Virology, 366, 126-136.
PDB code: 2ia5
18039372 R.Brenchley, H.Tariq, H.McElhinney, B.Szöor, J.Huxley-Jones, R.Stevens, K.Matthews, and L.Tabernero (2007).
The TriTryp phosphatome: analysis of the protein phosphatase catalytic domains.
  BMC Genomics, 8, 434.  
18058037 S.C.Almo, J.B.Bonanno, J.M.Sauder, S.Emtage, T.P.Dilorenzo, V.Malashkevich, S.R.Wasserman, S.Swaminathan, S.Eswaramoorthy, R.Agarwal, D.Kumaran, M.Madegowda, S.Ragumani, Y.Patskovsky, J.Alvarado, U.A.Ramagopal, J.Faber-Barata, M.R.Chance, A.Sali, A.Fiser, Z.Y.Zhang, D.S.Lawrence, and S.K.Burley (2007).
Structural genomics of protein phosphatases.
  J Struct Funct Genomics, 8, 121-140.
PDB codes: 1rxd 2fh7 2g59 2hcm 2hhl 2hxp 2hy3 2i0o 2i1y 2i44 2iq1 2irm 2isn 2nv5 2oyc 2p27 2p4u 2p69 2p8e 2pbn 2q5e 2qjc 2r0b
17420445 Y.Kim, M.S.Gentry, T.E.Harris, S.E.Wiley, J.C.Lawrence, and J.E.Dixon (2007).
A conserved phosphatase cascade that regulates nuclear membrane biogenesis.
  Proc Natl Acad Sci U S A, 104, 6596-6601.  
16735508 A.Moisan, and L.Gaudreau (2006).
The BRCA1 COOH-terminal region acts as an RNA polymerase II carboxyl-terminal domain kinase inhibitor that modulates p21WAF1/CIP1 expression.
  J Biol Chem, 281, 21119-21130.  
16327806 A.Ujvári, and D.S.Luse (2006).
RNA emerging from the active site of RNA polymerase II interacts with the Rpb7 subunit.
  Nat Struct Mol Biol, 13, 49-54.  
17087928 C.A.Byrum, K.D.Walton, A.J.Robertson, S.Carbonneau, R.T.Thomason, J.A.Coffman, and D.R.McClay (2006).
Protein tyrosine and serine-threonine phosphatases in the sea urchin, Strongylocentrotus purpuratus: identification and potential functions.
  Dev Biol, 300, 194-218.  
16362371 C.Ganem, C.Miled, C.Facca, J.G.Valay, G.Labesse, S.Ben Hassine, C.Mann, and G.Faye (2006).
Kinase Cak1 functionally interacts with the PAF1 complex and phosphatase Ssu72 via kinases Ctk1 and Bur1.
  Mol Genet Genomics, 275, 136-147.  
16724108 J.Thompson, T.Lepikhova, N.Teixido-Travesa, M.A.Whitehead, J.J.Palvimo, and O.A.Jänne (2006).
Small carboxyl-terminal domain phosphatase 2 attenuates androgen-dependent transcription.
  EMBO J, 25, 2757-2767.  
17035229 K.H.Wrighton, D.Willis, J.Long, F.Liu, X.Lin, and X.H.Feng (2006).
Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling.
  J Biol Chem, 281, 38365-38375.  
16882717 M.Knockaert, G.Sapkota, C.Alarcón, J.Massagué, and A.H.Brivanlou (2006).
Unique players in the BMP pathway: small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling.
  Proc Natl Acad Sci U S A, 103, 11940-11945.  
16301539 M.H.Suh, P.Ye, M.Zhang, S.Hausmann, S.Shuman, A.L.Gnatt, and J.Fu (2005).
Fcp1 directly recognizes the C-terminal domain (CTD) and interacts with a site on RNA polymerase II distinct from the CTD.
  Proc Natl Acad Sci U S A, 102, 17314-17319.  
15681389 M.Yeo, S.K.Lee, B.Lee, E.C.Ruiz, S.L.Pfaff, and G.N.Gill (2005).
Small CTD phosphatases function in silencing neuronal gene expression.
  Science, 307, 596-600.  
15563457 S.E.Kong, M.S.Kobor, N.J.Krogan, B.P.Somesh, T.M.Søgaard, J.F.Greenblatt, and J.Q.Svejstrup (2005).
Interaction of Fcp1 phosphatase with elongating RNA polymerase II holoenzyme, enzymatic mechanism of action, and genetic interaction with elongator.
  J Biol Chem, 280, 4299-4306.  
16148005 S.Hausmann, H.Koiwa, S.Krishnamurthy, M.Hampsey, and S.Shuman (2005).
Different strategies for carboxyl-terminal domain (CTD) recognition by serine 5-specific CTD phosphatases.
  J Biol Chem, 280, 37681-37688.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.