PDBsum entry 1ygr

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protein ligands links
Hydrolase PDB id
Protein chains
574 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the tandem phosphatase domain of rptp cd45
Structure: Cd45 protein tyrosine phosphatase. Chain: a, b. Fragment: cytoplasmic domain. Engineered: yes. Mutation: yes. T-cell receptor cd3 zeta itam-1. Chain: c, d. Fragment: itam-1 (residues 80-85. Sws:p20963). Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans.
Biol. unit: Dimer (from PQS)
2.90Å     R-factor:   0.255     R-free:   0.312
Authors: H.J.Nam,F.Poy,H.Saito,C.A.Frederick
Key ref: H.J.Nam et al. (2005). Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45. J Exp Med, 201, 441-452. PubMed id: 15684325
05-Jan-05     Release date:   22-Feb-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P08575  (PTPRC_HUMAN) -  Receptor-type tyrosine-protein phosphatase C
1304 a.a.
574 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.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
Bound ligand (Het Group name = PTR)
matches with 76.00% similarity
+ 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  


J Exp Med 201:441-452 (2005)
PubMed id: 15684325  
Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45.
H.J.Nam, F.Poy, H.Saito, C.A.Frederick.
CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3zeta immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 "active site" deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen-related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20164196 C.W.Cairo, R.Das, A.Albohy, Q.J.Baca, D.Pradhan, J.S.Morrow, D.Coombs, and D.E.Golan (2010).
Dynamic regulation of CD45 lateral mobility by the spectrin-ankyrin cytoskeleton of T cells.
  J Biol Chem, 285, 11392-11401.  
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
19129486 M.L.Hermiston, J.Zikherman, A.L.Tan, V.C.Lam, N.M.Cresalia, N.Oksenberg, N.Goren, D.Brassat, J.R.Oksenberg, and A.Weiss (2009).
Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses.
  Proc Natl Acad Sci U S A, 106, 546-551.  
19290935 M.L.Hermiston, J.Zikherman, and J.W.Zhu (2009).
CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells.
  Immunol Rev, 228, 288-311.  
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.  
18220476 H.P.Monteiro, R.J.Arai, and L.R.Travassos (2008).
Protein tyrosine phosphorylation and protein tyrosine nitration in redox signaling.
  Antioxid Redox Signal, 10, 843-889.  
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.  
18448457 R.J.Salmond, L.McNeill, N.Holmes, and D.R.Alexander (2008).
CD4+ T cell hyper-responsiveness in CD45 transgenic mice is independent of isoform.
  Int Immunol, 20, 819-827.  
18511809 S.Kirchberger, O.Majdic, S.Blüml, C.Schrauf, J.Leitner, C.Gerner, W.Paster, N.Gundacker, M.Sibilia, and J.Stöckl (2008).
The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells.
  Blood, 112, 1240-1248.  
18303998 T.Vang, A.V.Miletic, Y.Arimura, L.Tautz, R.C.Rickert, and T.Mustelin (2008).
Protein tyrosine phosphatases in autoimmunity.
  Annu Rev Immunol, 26, 29-55.  
17935964 A.R.Aricescu, and E.Y.Jones (2007).
Immunoglobulin superfamily cell adhesion molecules: zippers and signals.
  Curr Opin Cell Biol, 19, 543-550.  
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
17178832 S.Lee, C.Faux, J.Nixon, D.Alete, J.Chilton, M.Hawadle, and A.W.Stoker (2007).
Dimerization of protein tyrosine phosphatase sigma governs both ligand binding and isoform specificity.
  Mol Cell Biol, 27, 1795-1808.  
16534812 A.J.Barr, J.E.Debreczeni, J.Eswaran, and S.Knapp (2006).
Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution.
  Proteins, 63, 1132-1136.
PDB code: 2bzl
16557282 A.Ostman, C.Hellberg, and F.D.Böhmer (2006).
Protein-tyrosine phosphatases and cancer.
  Nat Rev Cancer, 6, 307-320.  
16423560 E.Z.Tchilian, and P.C.Beverley (2006).
Altered CD45 expression and disease.
  Trends Immunol, 27, 146-153.  
16672235 J.Eswaran, J.E.Debreczeni, E.Longman, A.J.Barr, and S.Knapp (2006).
The crystal structure of human receptor protein tyrosine phosphatase kappa phosphatase domain 1.
  Protein Sci, 15, 1500-1505.
PDB codes: 2a3k 2c7s
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.  
  16517710 R.Dawes, S.Petrova, Z.Liu, D.Wraith, P.C.Beverley, and E.Z.Tchilian (2006).
Combinations of CD45 isoforms are crucial for immune function and disease.
  J Immunol, 176, 3417-3425.  
16998493 S.J.van Vliet, S.I.Gringhuis, T.B.Geijtenbeek, and Y.van Kooyk (2006).
Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45.
  Nat Immunol, 7, 1200-1208.  
16356861 M.L.Hermiston, A.L.Tan, V.A.Gupta, R.Majeti, and A.Weiss (2005).
The juxtamembrane wedge negatively regulates CD45 function in B cells.
  Immunity, 23, 635-647.  
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.  
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.