PDBsum entry 1lar

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Hydrolase PDB id
Protein chains
566 a.a. *
533 a.a. *
Waters ×473
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the tandem phosphatase domains of rptp lar
Structure: Protein (lar). Chain: a, b. Fragment: phosphatase. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: de3
2.00Å     R-factor:   0.222     R-free:   0.274
Authors: H.-J.Nam,F.Poy,N.Krueger,H.Saito,C.A.Frederick
Key ref:
H.J.Nam et al. (1999). Crystal structure of the tandem phosphatase domains of RPTP LAR. Cell, 97, 449-457. PubMed id: 10338209 DOI: 10.1016/S0092-8674(00)80755-2
20-Apr-99     Release date:   25-Apr-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P10586  (PTPRF_HUMAN) -  Receptor-type tyrosine-protein phosphatase F
1907 a.a.
566 a.a.*
Protein chain
Pfam   ArchSchema ?
P10586  (PTPRF_HUMAN) -  Receptor-type tyrosine-protein phosphatase F
1907 a.a.
533 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B: 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!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  


DOI no: 10.1016/S0092-8674(00)80755-2 Cell 97:449-457 (1999)
PubMed id: 10338209  
Crystal structure of the tandem phosphatase domains of RPTP LAR.
H.J.Nam, F.Poy, N.X.Krueger, H.Saito, C.A.Frederick.
Most receptor-like protein tyrosine phosphatases (RPTPs) contain two conserved phosphatase domains (D1 and D2) in their intracellular region. The carboxy-terminal D2 domain has little or no catalytic activity. The crystal structure of the tandem D1 and D2 domains of the human RPTP LAR revealed that the tertiary structures of the LAR D1 and D2 domains are very similar to each other, with the exception of conformational differences at two amino acid positions in the D2 domain. Site-directed mutational changes at these positions (Leu-1644-to-Tyr and Glu-1779-to-Asp) conferred a robust PTPase activity to the D2 domain. The catalytic sites of both domains are accessible, in contrast to the dimeric blocked orientation model previously suggested. The relative orientation of the LAR D1 and D2 domains, constrained by a short linker, is stabilized by extensive interdomain interactions, suggesting that this orientation might be favored in solution.
  Selected figure(s)  
Figure 1.
Figure 1. Ribbon Diagrams of Two Views of the LAR D1D2 MoleculeD1 and D2 domains are shown in pink and cyan, respectively. On the left, the active site of D1 is facing the viewer and that of D2 is facing upward. On the right, the same molecule is rotated along the horizontal axis approximately 90°. (The relative positions of the two active sites approach a 4-fold screw rotation.) Side chains of residues at the active sites are shown. The loops connecting β1 and β2 of D2 are shown in magenta to indicate the location for the acidic 19-residue insertion in CD45. The boxed region is the interface between the D1 and D2 domains; a detailed view of this area is shown in Figure 5B. The figure was produced using the program SETOR ( [7]).
Figure 3.
Figure 3. Comparisons between the LAR D1 and D2 Domains(A) A superposition of main-chain atoms of the LAR D1 (pink) and D2 (cyan) domains. Disordered residues 1624–1627 of D2 are shown in blue. The loop between the two N-terminal helices (α1′ and α2′) of D2 is marked with an arrow. The side chains of the active site Cys are shown in yellow.(B) A stereo view of the superimposed active sites of the D1 and D2 domains. Side chains of residues involved in catalysis are shown in pink (D1) and cyan (D2). For emphasis, key residues used for comparison between D1 and D2 are colored individually.(C) Surface representation of the active sites of D1 (left) and D2 (right). Residues involved in catalysis are shown in the color scheme following that of the side chains in (B).
  The above figures are reprinted by permission from Cell Press: Cell (1999, 97, 449-457) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20230004 E.M.Flynn, J.A.Hanson, T.Alber, and H.Yang (2010).
Dynamic active-site protection by the M. tuberculosis protein tyrosine phosphatase PtpB lid domain.
  J Am Chem Soc, 132, 4772-4780.  
20180778 S.D.Hinton, M.P.Myers, V.R.Roggero, L.A.Allison, and N.K.Tonks (2010).
The pseudophosphatase MK-STYX interacts with G3BP and decreases stress granule formation.
  Biochem J, 427, 349-357.  
19573017 A.E.Hower, P.J.Beltran, and J.L.Bixby (2009).
Dimerization of tyrosine phosphatase PTPRO decreases its activity and ability to inactivate TrkC.
  J Neurochem, 110, 1635-1647.  
19167335 A.J.Barr, E.Ugochukwu, W.H.Lee, O.N.King, P.Filippakopoulos, I.Alfano, P.Savitsky, N.A.Burgess-Brown, S.Müller, and S.Knapp (2009).
Large-scale structural analysis of the classical human protein tyrosine phosphatome.
  Cell, 136, 352-363.
PDB codes: 2ahs 2b49 2cfv 2cjz 2gjt 2h4v 2i75 2jjd 2nlk 2nz6 2oc3 2ooq 2p6x 2pa5 2qep 3b7o
19252495 J.Woo, S.K.Kwon, S.Choi, S.Kim, J.R.Lee, A.W.Dunah, M.Sheng, and E.Kim (2009).
Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses.
  Nat Neurosci, 12, 428-437.  
19889974 K.Hofmeyer, and J.E.Treisman (2009).
The receptor protein tyrosine phosphatase LAR promotes R7 photoreceptor axon targeting by a phosphatase-independent signaling mechanism.
  Proc Natl Acad Sci U S A, 106, 19399-19404.  
19424502 M.C.Balasu, L.N.Spiridon, S.Miron, C.T.Craescu, A.J.Scheidig, A.J.Petrescu, and S.E.Szedlacsek (2009).
Interface analysis of the complex between ERK2 and PTP-SL.
  PLoS ONE, 4, e5432.  
19816407 S.H.Lim, S.K.Kwon, M.K.Lee, J.Moon, D.G.Jeong, E.Park, S.J.Kim, B.C.Park, S.C.Lee, S.E.Ryu, D.Y.Yu, B.H.Chung, E.Kim, P.K.Myung, and J.R.Lee (2009).
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
  EMBO J, 28, 3564-3578.  
18422654 A.Groen, J.Overvoorde, T.van der Wijk, and J.den Hertog (2008).
Redox regulation of dimerization of the receptor protein-tyrosine phosphatases RPTPalpha, LAR, RPTPmu and CD45.
  FEBS J, 275, 2597-2604.  
18298791 J.den Hertog, A.Ostman, and F.D.Böhmer (2008).
Protein tyrosine phosphatases: regulatory mechanisms.
  FEBS J, 275, 831-847.  
18298793 L.Tabernero, A.R.Aricescu, E.Y.Jones, and S.E.Szedlacsek (2008).
Protein tyrosine phosphatases: structure-function relationships.
  FEBS J, 275, 867-882.  
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
16557282 A.Ostman, C.Hellberg, and F.D.Böhmer (2006).
Protein-tyrosine phosphatases and cancer.
  Nat Rev Cancer, 6, 307-320.  
16497667 J.L.Sallee, E.S.Wittchen, and K.Burridge (2006).
Regulation of cell adhesion by protein-tyrosine phosphatases: II. Cell-cell adhesion.
  J Biol Chem, 281, 16189-16192.  
16864797 K.Hofmeyer, C.Maurel-Zaffran, H.Sink, and J.E.Treisman (2006).
Liprin-alpha has LAR-independent functions in R7 photoreceptor axon targeting.
  Proc Natl Acad Sci U S A, 103, 11595-11600.  
16423050 N.Holmes (2006).
CD45: all is not yet crystal clear.
  Immunology, 117, 145-155.  
17057753 N.K.Tonks (2006).
Protein tyrosine phosphatases: from genes, to function, to disease.
  Nat Rev Mol Cell Biol, 7, 833-846.  
16597593 T.Takahashi, K.Takahashi, R.L.Mernaugh, N.Tsuboi, H.Liu, and T.O.Daniel (2006).
A monoclonal antibody against CD148, a receptor-like tyrosine phosphatase, inhibits endothelial-cell growth and angiogenesis.
  Blood, 108, 1234-1242.  
16613844 Y.Xie, S.M.Massa, S.E.Ensslen-Craig, D.L.Major, T.Yang, M.A.Tisi, V.D.Derevyanny, W.O.Runge, B.P.Mehta, L.A.Moore, S.M.Brady-Kalnay, and F.M.Longo (2006).
Protein-tyrosine phosphatase (PTP) wedge domain peptides: a novel approach for inhibition of PTP function and augmentation of protein-tyrosine kinase function.
  J Biol Chem, 281, 16482-16492.  
15623519 A.Groen, S.Lemeer, T.van der Wijk, J.Overvoorde, A.J.Heck, A.Ostman, D.Barford, M.Slijper, and J.den Hertog (2005).
Differential oxidation of protein-tyrosine phosphatases.
  J Biol Chem, 280, 10298-10304.  
15890001 A.Salmeen, and D.Barford (2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
  Antioxid Redox Signal, 7, 560-577.  
15611135 F.Villa, M.Deak, G.B.Bloomberg, D.R.Alessi, and D.M.van Aalten (2005).
Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket.
  J Biol Chem, 280, 8180-8187.
PDB code: 1wch
15491993 R.L.Del Vecchio, and N.K.Tonks (2005).
The conserved immunoglobulin domain controls the subcellular localization of the homophilic adhesion receptor protein-tyrosine phosphatase mu.
  J Biol Chem, 280, 1603-1612.  
16078081 T.Uinuk-Ool, N.Nikolaidis, A.Sato, W.E.Mayer, and J.Klein (2005).
Organization, alternative splicing, polymorphism, and phylogenetic position of lamprey CD45 gene.
  Immunogenetics, 57, 607-617.  
15333922 A.K.Pedersen, G.H.Peters G, K.B.Møller, L.F.Iversen, and J.S.Kastrup (2004).
Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B.
  Acta Crystallogr D Biol Crystallogr, 60, 1527-1534.
PDB code: 1sug
15258570 C.Wiesmann, K.J.Barr, J.Kung, J.Zhu, D.A.Erlanson, W.Shen, B.J.Fahr, M.Zhong, L.Taylor, M.Randal, R.S.McDowell, and S.K.Hansen (2004).
Allosteric inhibition of protein tyrosine phosphatase 1B.
  Nat Struct Mol Biol, 11, 730-737.
PDB codes: 1t48 1t49 1t4j
14734566 D.F.McCain, L.Wu, P.Nickel, M.U.Kassack, A.Kreimeyer, A.Gagliardi, D.C.Collins, and Z.Y.Zhang (2004).
Suramin derivatives as inhibitors and activators of protein-tyrosine phosphatases.
  J Biol Chem, 279, 14713-14725.  
14625311 J.Felberg, D.C.Lefebvre, M.Lam, Y.Wang, D.H.Ng, D.Birkenhead, J.L.Cross, and P.Johnson (2004).
Subdomain X of the kinase domain of Lck binds CD45 and facilitates dephosphorylation.
  J Biol Chem, 279, 3455-3462.  
15674434 M.J.Chagnon, N.Uetani, and M.L.Tremblay (2004).
Functional significance of the LAR receptor protein tyrosine phosphatase family in development and diseases.
  Biochem Cell Biol, 82, 664-675.  
15390114 N.Muja, G.Lovas, E.Romm, D.Machleder, M.Ranjan, V.Gallo, and L.D.Hudson (2004).
Expression of a catalytically inactive transmembrane protein tyrosine phosphatase epsilon (tm-PTP epsilon) delays optic nerve myelination.
  Glia, 48, 278-297.  
15084579 V.B.Cismasiu, S.A.Denes, H.Reiländer, H.Michel, and S.E.Szedlacsek (2004).
The MAM (meprin/A5-protein/PTPmu) domain is a homophilic binding site promoting the lateral dimerization of receptor-like protein-tyrosine phosphatase mu.
  J Biol Chem, 279, 26922-26931.  
12677003 A.B.Huber, A.L.Kolodkin, D.D.Ginty, and J.F.Cloutier (2003).
Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance.
  Annu Rev Neurosci, 26, 509-563.  
12853468 C.H.Gray, V.M.Good, N.K.Tonks, and D.Barford (2003).
The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase.
  EMBO J, 22, 3524-3535.
PDB codes: 1ohc 1ohd 1ohe
12861030 H.Toledano-Katchalski, Z.Tiran, T.Sines, G.Shani, S.Granot-Attas, J.den Hertog, and A.Elson (2003).
Dimerization in vivo and inhibition of the nonreceptor form of protein tyrosine phosphatase epsilon.
  Mol Cell Biol, 23, 5460-5471.  
12698188 N.Konishi, K.Tsujikawa, H.Yamamoto, E.Ishida, M.Nakamura, K.Shimada, K.Yane, H.Yamashita, and S.Noguchi (2003).
Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas.
  Br J Cancer, 88, 1223-1228.  
12972609 N.X.Krueger, R.S.Reddy, K.Johnson, J.Bateman, N.Kaufmann, D.Scalice, D.Van Vactor, and H.Saito (2003).
Functions of the ectodomain and cytoplasmic tyrosine phosphatase domains of receptor protein tyrosine phosphatase Dlar in vivo.
  Mol Cell Biol, 23, 6909-6921.  
12377129 A.E.Todd, C.A.Orengo, and J.M.Thornton (2002).
Sequence and structural differences between enzyme and nonenzyme homologs.
  Structure, 10, 1435-1451.  
12376545 C.Blanchetot, L.G.Tertoolen, J.Overvoorde, and J.den Hertog (2002).
Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases.
  J Biol Chem, 277, 47263-47269.  
11847098 C.Blanchetot, L.G.Tertoolen, and J.den Hertog (2002).
Regulation of receptor protein-tyrosine phosphatase alpha by oxidative stress.
  EMBO J, 21, 493-503.  
12364328 S.Gross, C.Blanchetot, J.Schepens, S.Albet, R.Lammers, J.den Hertog, and W.Hendriks (2002).
Multimerization of the protein-tyrosine phosphatase (PTP)-like insulin-dependent diabetes mellitus autoantigens IA-2 and IA-2beta with receptor PTPs (RPTPs). Inhibition of RPTPalpha enzymatic activity.
  J Biol Chem, 277, 48139-48145.  
11350947 A.Changela, C.K.Ho, A.Martins, S.Shuman, and A.Mondragón (2001).
Structure and mechanism of the RNA triphosphatase component of mammalian mRNA capping enzyme.
  EMBO J, 20, 2575-2586.
PDB codes: 1i9s 1i9t
11241288 G.Terszowski, A.Jankowski, W.J.Hendriks, A.G.Rolink, and P.Kisielow (2001).
Within the hemopoietic system, LAR phosphatase is a T cell lineage-specific adhesion receptor-like protein whose phosphatase activity appears dispensable for T cell development, repertoire selection and function.
  Eur J Immunol, 31, 832-840.  
11585896 J.N.Andersen, O.H.Mortensen, G.H.Peters, P.G.Drake, L.F.Iversen, O.H.Olsen, P.G.Jansen, H.S.Andersen, N.K.Tonks, and N.P.Møller (2001).
Structural and evolutionary relationships among protein tyrosine phosphatase domains.
  Mol Cell Biol, 21, 7117-7136.  
11401727 L.G.Tertoolen, C.Blanchetot, G.Jiang, J.Overvoorde, T.W.Gadella, T.Hunter, and J.den Hertog (2001).
Dimerization of receptor protein-tyrosine phosphatase alpha in living cells.
  BMC Cell Biol, 2, 8.  
11170399 M.V.Chengalvala, A.R.Bapat, W.W.Hurlburt, B.Kostek, D.S.Gonder, R.A.Mastroeni, and D.E.Frail (2001).
Biochemical characterization of osteo-testicular protein tyrosine phosphatase and its functional significance in rat primary osteoblasts.
  Biochemistry, 40, 814-821.  
11248552 N.K.Tonks, and B.G.Neel (2001).
Combinatorial control of the specificity of protein tyrosine phosphatases.
  Curr Opin Cell Biol, 13, 182-195.  
10934323 B.K.Mueller, M.M.Ledig, and S.Wahl (2000).
The receptor tyrosine phosphatase CRYPalpha affects growth cone morphology.
  J Neurobiol, 44, 204-218.  
10777529 C.Blanchetot, and J.den Hertog (2000).
Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine phosphatase domains of various RPTPs.
  J Biol Chem, 275, 12446-12452.  
10809770 E.Feiken, I.van Etten, M.F.Gebbink, W.H.Moolenaar, and G.C.Zondag (2000).
Intramolecular interactions between the juxtamembrane domain and phosphatase domains of receptor protein-tyrosine phosphatase RPTPmu. Regulation of catalytic activity.
  J Biol Chem, 275, 15350-15356.  
10913175 G.Jiang, J.den Hertog, and T.Hunter (2000).
Receptor-like protein tyrosine phosphatase alpha homodimerizes on the cell surface.
  Mol Cell Biol, 20, 5917-5929.  
10982240 H.Avraham, S.Avraham, and Y.Taniguchi (2000).
Receptor protein tyrosine phosphatases in hematopoietic cells.
  J Hematother Stem Cell Res, 9, 425-432.  
10723800 L.Li, and J.E.Dixon (2000).
Form, function, and regulation of protein tyrosine phosphatases and their involvement in human diseases.
  Semin Immunol, 12, 75-84.  
10735562 N.R.Glover, and A.S.Tracey (2000).
The phosphatase domains of LAR, CD45, and PTP1B: structural correlations with peptide-based inhibitors.
  Biochem Cell Biol, 78, 39-50.  
10525146 K.L.Lim, C.H.Ng, and C.J.Pallen (1999).
Catalytic activation of the membrane distal domain of protein tyrosine phosphatase epsilon, but not CD45, by two point mutations.
  Biochim Biophys Acta, 1434, 275-283.  
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 codes are shown on the right.