PDBsum entry 2gph

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
345 a.a. *
16 a.a. *
Waters ×290
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Docking motif interactions in the map kinase erk2
Structure: Mitogen-activated protein kinase 1. Chain: a. Synonym: extracellular signal-regulated kinase 2, erk-2, mitogen-activated protein kinase 2, map kinase 2, mapk 2, p42-mapk, ert1. Engineered: yes. Mutation: yes. Tyrosine-protein phosphatase non-receptor type 7. Chain: b.
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: erk2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans.
Biol. unit: Dimer (from PQS)
1.90Å     R-factor:   0.216     R-free:   0.263
Authors: T.Zhou,L.Sun,J.Humphreys,E.J.Goldsmith
Key ref:
T.Zhou et al. (2006). Docking interactions induce exposure of activation loop in the MAP kinase ERK2. Structure, 14, 1011-1019. PubMed id: 16765894 DOI: 10.1016/j.str.2006.04.006
17-Apr-06     Release date:   04-Jul-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P63086  (MK01_RAT) -  Mitogen-activated protein kinase 1
358 a.a.
345 a.a.*
Protein chain
Pfam   ArchSchema ?
P35236  (PTN7_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 7
360 a.a.
16 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: Chain A: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
   Enzyme class 2: Chain 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
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitotic spindle   21 terms 
  Biological process     intracellular signal transduction   40 terms 
  Biochemical function     nucleotide binding     15 terms  


DOI no: 10.1016/j.str.2006.04.006 Structure 14:1011-1019 (2006)
PubMed id: 16765894  
Docking interactions induce exposure of activation loop in the MAP kinase ERK2.
T.Zhou, L.Sun, J.Humphreys, E.J.Goldsmith.
MAP kinases bind activating kinases, phosphatases, and substrates through docking interactions. Here, we report a 1.9 A crystallographic analysis of inactive ERK2 bound to a "D motif" docking peptide (pepHePTP) derived from hematopoietic tyrosine phosphatase, a negative regulator of ERK2. In this complex, the complete D motif interaction defined by mutagenic analysis is observed, including extensive electrostatic interactions with the "CD" site of the kinase. Large conformational changes occur in the activation loop where the dual phosphorylation sites, which are buried in the inactive form of ERK2, become exposed to solvent in the complex. Similar conformational changes occur in a complex between ERK2 and a MEK2 (MAP/ERK kinase-2)-derived D motif peptide (pepMEK2). D motif peptides are known to bind homologous loci in the MAP kinases p38alpha and JNK1, also inducing conformational changes in these enzymes. However, the binding interactions and conformational changes are unique to each, thus contributing to specificity among MAP kinases.
  Selected figure(s)  
Figure 6.
Figure 6. Comparison of Docking Peptide-Induced Conformational Changes in ERK2, p38a, and JNK1
Superpositions are based on inactive ERK2 (blue) (PDB code 1ERK) and ERK2-pepHePTPm (salmon) (this study), inactive p38a (blue) (1P38) and p38a-pepMEF2A (salmon) (1LEW), and inactive JNK3 (blue) (1JNK) and JNK1-pepJIP1 (salmon) (1UKH). Bound peptides are shown in yellow. In ERK2 and p38a, global superpositions are made, whereas in JNK3/JNK1-pepJIP1, superposition is made against the C-terminal domain of the two kinases. "A-loop" denotes activation loop. Note the disorder in the activation loops of p38a-pepMEF2A and JNK1-pepJIP1.
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 1011-1019) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22307056 M.O.Kim, S.H.Kim, Y.Y.Cho, J.Nadas, C.H.Jeong, K.Yao, D.J.Kim, D.H.Yu, Y.S.Keum, K.Y.Lee, Z.Huang, A.M.Bode, and Z.Dong (2012).
ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4.
  Nat Struct Mol Biol, 19, 283-290.  
21509657 H.Liang, T.Liu, F.Chen, Z.Liu, and S.Liu (2011).
A full-length 3D structure for MAPK/ERK kinase 2 (MEK2).
  Sci China Life Sci, 54, 336-341.  
21219631 S.R.Boston, R.Deshmukh, S.Strome, U.D.Priyakumar, A.D.MacKerell, and P.Shapiro (2011).
Characterization of ERK docking domain inhibitors that induce apoptosis by targeting Rsk-1 and caspase-9.
  BMC Cancer, 11, 7.  
20574990 K.Hong Lim, C.K.Hsu, and S.Park (2010).
Flow cytometric analysis of genetic FRET detectors containing variable substrate sequences.
  Biotechnol Prog, 26, 1765-1771.  
20622900 K.Nagasaka, D.Pim, P.Massimi, M.Thomas, V.Tomaić, V.K.Subbaiah, C.Kranjec, S.Nakagawa, T.Yano, Y.Taketani, M.Myers, and L.Banks (2010).
The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction.
  Oncogene, 29, 5311-5321.  
21134636 R.Akella, X.Min, Q.Wu, K.H.Gardner, and E.J.Goldsmith (2010).
The third conformation of p38α MAP kinase observed in phosphorylated p38α and in solution.
  Structure, 18, 1571-1578.
PDB code: 3p4k
21070949 W.Ma, Y.Shang, Z.Wei, W.Wen, W.Wang, and M.Zhang (2010).
Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase.
  Structure, 18, 1502-1511.
PDB code: 3o71
20579376 Y.Liu, and A.Tozeren (2010).
Modular composition predicts kinase/substrate interactions.
  BMC Bioinformatics, 11, 349.  
19805511 A.W.Truman, K.Y.Kim, and D.E.Levin (2009).
Mechanism of Mpk1 mitogen-activated protein kinase binding to the Swi4 transcription factor and its regulation by a novel caffeine-induced phosphorylation.
  Mol Cell Biol, 29, 6449-6461.  
19494114 F.Sacco, M.Tinti, A.Palma, E.Ferrari, A.P.Nardozza, R.Hooft van Huijsduijnen, T.Takahashi, L.Castagnoli, and G.Cesareni (2009).
Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases.
  J Biol Chem, 284, 22048-22058.  
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.  
19383128 P.Durek, C.Schudoma, W.Weckwerth, J.Selbig, and D.Walther (2009).
Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction.
  BMC Bioinformatics, 10, 117.  
19847302 S.Galli, O.Jahn, R.Hitt, D.Hesse, L.Opitz, U.Plessmann, H.Urlaub, J.J.Poderoso, E.A.Jares-Erijman, and T.M.Jovin (2009).
a new paradigm for mapk: structural interactions of herk1 with mitochondria in HeLa cells.
  PLoS One, 4, e7541.  
19364808 S.J.Deminoff, V.Ramachandran, and P.K.Herman (2009).
Distal recognition sites in substrates are required for efficient phosphorylation by the cAMP-dependent protein kinase.
  Genetics, 182, 529-539.  
19177573 S.J.Lee, M.H.Cobb, and E.J.Goldsmith (2009).
Crystal structure of domain-swapped STE20 OSR1 kinase domain.
  Protein Sci, 18, 304-313.
PDB code: 3dak
19243309 T.Chen, N.Kablaoui, J.Little, S.Timofeevski, W.R.Tschantz, P.Chen, J.Feng, M.Charlton, R.Stanton, and P.Bauer (2009).
Identification of small-molecule inhibitors of the JIP-JNK interaction.
  Biochem J, 420, 283-294.  
19141286 X.Min, R.Akella, H.He, J.M.Humphreys, S.E.Tsutakawa, S.J.Lee, J.A.Tainer, M.H.Cobb, and E.J.Goldsmith (2009).
The structure of the MAP2K MEK6 reveals an autoinhibitory dimer.
  Structure, 17, 96.
PDB code: 3enm
18197253 C.Poderoso, D.P.Converso, P.Maloberti, A.Duarte, I.Neuman, S.Galli, F.C.Maciel, C.Paz, M.C.Carreras, J.J.Poderoso, and E.J.Podestá (2008).
A Mitochondrial Kinase Complex Is Essential to Mediate an ERK1/2-Dependent Phosphorylation of a Key Regulatory Protein in Steroid Biosynthesis.
  PLoS ONE, 3, e1443.  
19053285 D.A.Critton, A.Tortajada, G.Stetson, W.Peti, and R.Page (2008).
Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.
  Biochemistry, 47, 13336-13345.
PDB codes: 2hvl 2qdc 2qdm 2qdp 3d42 3d44
18482985 D.L.Sheridan, Y.Kong, S.A.Parker, K.N.Dalby, and B.E.Turk (2008).
Substrate discrimination among mitogen-activated protein kinases through distinct docking sequence motifs.
  J Biol Chem, 283, 19511-19520.  
18347614 M.C.Lawrence, A.Jivan, C.Shao, L.Duan, D.Goad, E.Zaganjor, J.Osborne, K.McGlynn, S.Stippec, S.Earnest, W.Chen, and M.H.Cobb (2008).
The roles of MAPKs in disease.
  Cell Res, 18, 436-442.  
18068683 R.Akella, T.M.Moon, and E.J.Goldsmith (2008).
Unique MAP Kinase binding sites.
  Biochim Biophys Acta, 1784, 48-55.  
17967895 R.Lefloch, J.Pouysségur, and P.Lenormand (2008).
Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels.
  Mol Cell Biol, 28, 511-527.  
18545666 S.Galli, V.G.Antico Arciuch, C.Poderoso, D.P.Converso, Q.Zhou, E.Bal de Kier Joffé, E.Cadenas, J.Boczkowski, M.C.Carreras, and J.J.Poderoso (2008).
Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria.
  PLoS ONE, 3, e2379.  
18794356 T.Vomastek, M.P.Iwanicki, W.R.Burack, D.Tiwari, D.Kumar, J.T.Parsons, M.J.Weber, and V.K.Nandicoori (2008).
Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction.
  Mol Cell Biol, 28, 6954-6966.  
18212044 Y.Murakami, K.Tatebayashi, and H.Saito (2008).
Two adjacent docking sites in the yeast Hog1 mitogen-activated protein (MAP) kinase differentially interact with the Pbs2 MAP kinase kinase and the Ptp2 protein tyrosine phosphatase.
  Mol Cell Biol, 28, 2481-2494.  
17496919 A.G.Turjanski, J.P.Vaqué, and J.S.Gutkind (2007).
MAP kinases and the control of nuclear events.
  Oncogene, 26, 3240-3253.  
17937911 G.Bunkoczi, E.Salah, P.Filippakopoulos, O.Fedorov, S.Müller, F.Sobott, S.A.Parker, H.Zhang, W.Min, B.E.Turk, and S.Knapp (2007).
Structural and functional characterization of the human protein kinase ASK1.
  Structure, 15, 1215-1226.
PDB code: 2clq
17656361 M.N.Yazicioglu, D.L.Goad, A.Ranganathan, A.W.Whitehurst, E.J.Goldsmith, and M.H.Cobb (2007).
Mutations in ERK2 binding sites affect nuclear entry.
  J Biol Chem, 282, 28759-28767.  
17496909 M.Raman, W.Chen, and M.H.Cobb (2007).
Differential regulation and properties of MAPKs.
  Oncogene, 26, 3100-3112.  
  17918909 N.Fernandes, D.E.Bailey, D.L.Vanvranken, and N.L.Allbritton (2007).
Use of docking peptides to design modular substrates with high efficiency for mitogen-activated protein kinase extracellular signal-regulated kinase.
  ACS Chem Biol, 2, 665-673.  
17658891 O.Abramczyk, M.A.Rainey, R.Barnes, L.Martin, and K.N.Dalby (2007).
Expanding the repertoire of an ERK2 recruitment site: cysteine footprinting identifies the D-recruitment site as a mediator of Ets-1 binding.
  Biochemistry, 46, 9174-9186.  
17597065 S.Bendetz-Nezer, and R.Seger (2007).
Role of non-phosphorylated activation loop residues in determining ERK2 dephosphorylation, activity, and subcellular localization.
  J Biol Chem, 282, 25114-25122.  
18060821 Y.Zhu, H.Li, C.Long, L.Hu, H.Xu, L.Liu, S.Chen, D.C.Wang, and F.Shao (2007).
Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase.
  Mol Cell, 28, 899-913.
PDB codes: 2p1w 2q8y
17079133 A.Reményi, M.C.Good, and W.A.Lim (2006).
Docking interactions in protein kinase and phosphatase networks.
  Curr Opin Struct Biol, 16, 676-685.  
17085044 Z.Shi, K.A.Resing, and N.G.Ahn (2006).
Networks for the allosteric control of protein kinases.
  Curr Opin Struct Biol, 16, 686-692.  
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.