PDBsum entry 1r6h

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protein links
Hydrolase PDB id
Protein chain
172 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Solution structure of human prl-3
Structure: Protein tyrosine phosphatase type iva, member 3 isoform 1. Chain: a. Synonym: prl-3 phosphatase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: G.Kozlov,K.Gehring,I.Ekiel
Key ref:
G.Kozlov et al. (2004). Structural insights into molecular function of the metastasis-associated phosphatase PRL-3. J Biol Chem, 279, 11882-11889. PubMed id: 14704153 DOI: 10.1074/jbc.M312905200
15-Oct-03     Release date:   13-Jan-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O75365  (TP4A3_HUMAN) -  Protein tyrosine phosphatase type IVA 3
173 a.a.
172 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     peptidyl-tyrosine dephosphorylation   3 terms 
  Biochemical function     hydrolase activity     6 terms  


DOI no: 10.1074/jbc.M312905200 J Biol Chem 279:11882-11889 (2004)
PubMed id: 14704153  
Structural insights into molecular function of the metastasis-associated phosphatase PRL-3.
G.Kozlov, J.Cheng, E.Ziomek, D.Banville, K.Gehring, I.Ekiel.
Phosphatases and kinases are the cellular signal transduction enzymes that control protein phosphorylation. PRL phosphatases constitute a novel class of small (20 kDa), prenylated phosphatases with oncogenic activity. In particular, PRL-3 is consistently overexpressed in liver metastasis in colorectal cancer cells and represents a new therapeutic target. Here, we present the solution structure of PRL-3, the first structure of a PRL phosphatase. The structure places PRL phosphatases in the class of dual specificity phosphatases with closest structural homology to the VHR phosphatase. The structure, coupled with kinetic studies of site-directed mutants, identifies functionally important residues and reveals unique features, differentiating PRLs from other phosphatases. These differences include an unusually hydrophobic active site without the catalytically important serine/threonine found in most other phosphatases. The position of the general acid loop indicates the presence of conformational change upon catalysis. The studies also identify a potential regulatory role of Cys(49) that forms an intramolecular disulfide bond with the catalytic Cys(104) even under mildly reducing conditions. Molecular modeling of the highly homologous PRL-1 and PRL-2 phosphatases revealed unique surface elements that are potentially important for specificity.
  Selected figure(s)  
Figure 1.
FIG. 1. Structure of PRL-3. A, stereo view of the backbone superposition of the 20 lowest energy structures for residues Ala^8-Gln156. The unstructured N and C termini are not shown. B, ribbon representation of the average PRL-3 structure generated with MOLSCRIPT (41) and Raster3D (42). The secondary structure elements and N and C termini are labeled.
Figure 2.
FIG. 2. PRL phosphatases are highly homologous within their family but show low sequence similarity to the catalytic domains of other dual specificity phosphatases. The aligned phosphatases include human PRL-3 (gi:14589856), PRL-1 (gi:4506283), PRL-2 (gi:4506285), Drosophila PRL-1 (gi:3135665), worm PaRaLysed_cae (gi:17569857), human VHR (gi:181840), CDC14 (gi:34811075), PTEN (gi:1916328), and KAP (gi:443669). The secondary structural elements refer to PRL-3. The catalytic residues are shown in bold type.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 11882-11889) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21053359 A.Q.Al-Aidaroos, and Q.Zeng (2010).
PRL-3 phosphatase and cancer metastasis.
  J Cell Biochem, 111, 1087-1098.  
20140626 R.T.Hao, X.H.Zhang, Y.F.Pan, H.G.Liu, Y.Q.Xiang, L.Wan, and X.L.Wu (2010).
Prognostic and metastatic value of phosphatase of regenerating liver-3 in invasive breast cancer.
  J Cancer Res Clin Oncol, 136, 1349-1357.  
19636948 A.L.Skinner, and J.S.Laurence (2009).
1H, 15N, 13C resonance assignments of the reduced and active form of human Protein Tyrosine Phosphatase, PRL-1.
  Biomol NMR Assign, 3, 61-65.  
19115206 E.Mizuuchi, S.Semba, Y.Kodama, and H.Yokozaki (2009).
Down-modulation of keratin 8 phosphorylation levels by PRL-3 contributes to colorectal carcinoma progression.
  Int J Cancer, 124, 1802-1810.  
19639556 L.Orsatti, F.Innocenti, P.Lo Surdo, F.Talamo, and G.Barbato (2009).
Mass spectrometry study of PRL-3 phosphatase inactivation by disulfide bond formation and cysteine into glycine conversion.
  Rapid Commun Mass Spectrom, 23, 2733-2740.  
19040419 M.Pascaru, C.Tanase, A.M.Vacaru, P.Boeti, E.Neagu, I.Popescu, and S.E.Szedlacsek (2009).
Analysis of molecular determinants of PRL-3.
  J Cell Mol Med, 13, 3141-3150.  
19322925 N.Dai, A.P.Lu, C.C.Shou, and J.Y.Li (2009).
Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer.
  World J Gastroenterol, 15, 1499-1505.  
19214221 R.Song, F.Qian, Y.P.Li, X.Sheng, S.X.Cao, and Q.Xu (2009).
Phosphatase of regenerating liver-3 localizes to cyto-membrane and is required for B16F1 melanoma cell metastasis in vitro and in vivo.
  PLoS ONE, 4, e4450.  
19371084 S.J.Tsai, U.Sen, L.Zhao, W.B.Greenleaf, J.Dasgupta, E.Fiorillo, V.Orrú, N.Bottini, and X.S.Chen (2009).
Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation .
  Biochemistry, 48, 4838-4845.
PDB code: 3h2x
18224294 D.C.Bessette, D.Qiu, and C.J.Pallen (2008).
PRL PTPs: mediators and markers of cancer progression.
  Cancer Metastasis Rev, 27, 231-252.  
18298792 R.Pulido, and R.Hooft van Huijsduijnen (2008).
Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease.
  FEBS J, 275, 848-866.  
17934070 U.M.Fagerli, R.U.Holt, T.Holien, T.K.Vaatsveen, F.Zhan, K.W.Egeberg, B.Barlogie, A.Waage, H.Aarset, H.Y.Dai, J.D.Shaughnessy, A.Sundan, and M.Børset (2008).
Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.
  Blood, 111, 806-815.  
17505108 J.Phan, J.E.Tropea, and D.S.Waugh (2007).
Structure-assisted discovery of Variola major H1 phosphatase inhibitors.
  Acta Crystallogr D Biol Crystallogr, 63, 698-704.
PDB code: 2p4d
17673310 L.Yu, U.Kelly, J.N.Ebright, G.Malek, P.Saloupis, D.W.Rickman, B.S.McKay, V.Y.Arshavsky, and C.Bowes Rickman (2007).
Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina.
  Biochim Biophys Acta, 1773, 1473-1482.  
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.  
16195543 C.L.Gustafson, C.V.Stauffacher, K.Hallenga, and R.L.Van Etten (2005).
Solution structure of the low-molecular-weight protein tyrosine phosphatase from Tritrichomonas foetus reveals a flexible phosphate binding loop.
  Protein Sci, 14, 2515-2525.
PDB code: 1p8a
16151248 I.C.Cuevas, P.Rohloff, D.O.Sánchez, and R.Docampo (2005).
Characterization of farnesylated protein tyrosine phosphatase TcPRL-1 from Trypanosoma cruzi.
  Eukaryot Cell, 4, 1550-1561.  
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.