PDBsum entry 1zmu

Go to PDB code: 
protein Protein-protein interface(s) links
Signaling protein,transferase PDB id
Protein chains
293 a.a. *
* Residue conservation analysis
PDB id:
Name: Signaling protein,transferase
Title: Catalytic and ubiqutin-associated domains of mark2/par-1: wild type
Structure: Map/microtubule affinity regulating kinase 2. Chain: a, b. Fragment: catalytic and ubiquitin-associated domains. Synonym: par-1. Kin1. Serine/threonine kinase emk. Serine/threonine-protein kinase mark2. Elkl motif kinase. Emk1. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: mark2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.90Å     R-factor:   0.199     R-free:   0.270
Authors: S.Panneerselvam,A.Marx,E.-M.Mandelkow,E.Mandelkow
Key ref:
S.Panneerselvam et al. (2006). Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1. Structure, 14, 173-183. PubMed id: 16472737 DOI: 10.1016/j.str.2005.09.022
11-May-05     Release date:   14-Feb-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O08679  (MARK2_RAT) -  Serine/threonine-protein kinase MARK2
722 a.a.
293 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
   Enzyme class 3: E.C.  - [Tau protein] kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [tau protein] = ADP + [tau protein] phosphate
+ [tau protein]
+ [tau protein] 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!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     4 terms  


DOI no: 10.1016/j.str.2005.09.022 Structure 14:173-183 (2006)
PubMed id: 16472737  
Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1.
S.Panneerselvam, A.Marx, E.M.Mandelkow, E.Mandelkow.
The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause detachment from microtubules in Alzheimer neurofibrillary degeneration. Homologs of MARK2 include Par-1 in C. elegans and Drosophila, which generates embryonic polarity. We report the X-ray structure of the catalytic and ubiquitin-associated domains (UBA) of human MARK2. The activity was altered by mutations in the ATP binding site and/or activation loop. The catalytic domain shows the small and large lobes typical of kinases. The substrate cleft is in an inactive, open conformation in the inactivated and the wild-type structure. The UBA domain is attached via a taut linker to the large lobe of the kinase domain and leans against a hydrophobic patch on the small lobe. The UBA structure is unusual because the orientation of its third helix is inverted, relative to previous structures. Possible implications of the structure for the regulation of kinase activity are discussed.
  Selected figure(s)  
Figure 7.
Figure 7. Common Docking Domain and ED Site of MAP Kinases Compared to MARK2
The structures of (A) MARK2 and (B) ERK2 (PDB code 2ERK [Canagarajah et al., 1997]) are shown in the same orientations after least-squares superposition of 35 residues from helix E to the catalytic loop. The common docking domain (CD, in red) according to Tanoue and Nishida (2003) is C terminal to the kinase domain and corresponds in MARK to the first half of the tether connecting the kinase domain to the UBA domain (residues vert, similar 305-315). The C-terminal extensions following the CD domain (linker and UBA domain in MARK2) are shown in purple. Characteristic for the CD domain is a cluster of negatively charged residues exposed to the surface, located in a bulge at the end of the catalytic domain (stick model representation).
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 173-183) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19966800 D.Nesić, M.C.Miller, Z.T.Quinkert, M.Stein, B.T.Chait, and C.E.Stebbins (2010).
Helicobacter pylori CagA inhibits PAR1-MARK family kinases by mimicking host substrates.
  Nat Struct Mol Biol, 17, 130-132.
PDB code: 3iec
20336692 M.Rabiller, M.Getlik, S.Klüter, A.Richters, S.Tückmantel, J.R.Simard, and D.Rauh (2010).
Proteus in the world of proteins: conformational changes in protein kinases.
  Arch Pharm (Weinheim), 343, 193-206.  
  20951971 R.Tewari, U.Straschil, A.Bateman, U.Böhme, I.Cherevach, P.Gong, A.Pain, and O.Billker (2010).
The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission.
  Cell Host Microbe, 8, 377-387.  
21080395 S.Klüter, J.R.Simard, H.B.Rode, C.Grütter, V.Pawar, H.C.Raaijmakers, T.A.Barf, M.Rabiller, W.A.van Otterlo, and D.Rauh (2010).
Characterization of irreversible kinase inhibitors by directly detecting covalent bond formation: a tool for dissecting kinase drug resistance.
  Chembiochem, 11, 2557-2566.
PDB code: 3lok
19720857 A.C.Spilker, A.Rabilotta, C.Zbinden, J.C.Labbé, and M.Gotta (2009).
MAP kinase signaling antagonizes PAR-1 function during polarization of the early Caenorhabditis elegans embryo.
  Genetics, 183, 965-977.  
19559622 D.Matenia, and E.M.Mandelkow (2009).
The tau of MARK: a polarized view of the cytoskeleton.
  Trends Biochem Sci, 34, 332-342.  
19536824 G.Schmitt-Ulms, D.Matenia, G.Drewes, and E.M.Mandelkow (2009).
Interactions of MAP/microtubule affinity regulating kinases with the adaptor complex AP-2 of clathrin-coated vesicles.
  Cell Motil Cytoskeleton, 66, 661-672.  
19553659 H.Lu, N.Murata-Kamiya, Y.Saito, and M.Hatakeyama (2009).
Role of partitioning-defective 1/microtubule affinity-regulating kinases in the morphogenetic activity of Helicobacter pylori CagA.
  J Biol Chem, 284, 23024-23036.  
19245655 N.J.Bright, C.Thornton, and D.Carling (2009).
The regulation and function of mammalian AMPK-related kinases.
  Acta Physiol (Oxf), 196, 15-26.  
19029944 M.Hatakeyama (2008).
Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA.
  Oncogene, 27, 7047-7054.  
19090997 T.Timm, A.Marx, S.Panneerselvam, E.Mandelkow, and E.M.Mandelkow (2008).
Structure and regulation of MARK, a kinase involved in abnormal phosphorylation of Tau protein.
  BMC Neurosci, 9, S9.  
18424437 T.Timm, K.Balusamy, X.Li, J.Biernat, E.Mandelkow, and E.M.Mandelkow (2008).
Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2.
  J Biol Chem, 283, 18873-18882.  
18348280 Y.K.Hashimoto, T.Satoh, M.Okamoto, and H.Takemori (2008).
Importance of autophosphorylation at Ser186 in the A-loop of salt inducible kinase 1 for its sustained kinase activity.
  J Cell Biochem, 104, 1724-1739.  
17599067 F.Ikeda, C.M.Hecker, A.Rozenknop, R.D.Nordmeier, V.Rogov, K.Hofmann, S.Akira, V.Dötsch, and I.Dikic (2007).
Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes.
  EMBO J, 26, 3451-3462.  
17635922 G.Kozlov, P.Peschard, B.Zimmerman, T.Lin, T.Moldoveanu, N.Mansur-Azzam, K.Gehring, and M.Park (2007).
Structural basis for UBA-mediated dimerization of c-Cbl ubiquitin ligase.
  J Biol Chem, 282, 27547-27555.
PDB code: 2oo9
17507984 I.Saadat, H.Higashi, C.Obuse, M.Umeda, N.Murata-Kamiya, Y.Saito, H.Lu, N.Ohnishi, T.Azuma, A.Suzuki, S.Ohno, and M.Hatakeyama (2007).
Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity.
  Nature, 447, 330-333.  
17010524 P.Katajisto, T.Vallenius, K.Vaahtomeri, N.Ekman, L.Udd, M.Tiainen, and T.P.Mäkelä (2007).
The LKB1 tumor suppressor kinase in human disease.
  Biochim Biophys Acta, 1775, 63-75.  
17679095 P.Peschard, G.Kozlov, T.Lin, I.A.Mirza, A.M.Berghuis, S.Lipkowitz, M.Park, and K.Gehring (2007).
Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.
  Mol Cell, 27, 474-485.
PDB codes: 2ooa 2oob
17107637 S.Nikolaou, and R.B.Gasser (2007).
Extending from PARs in Caenorhabditis elegans to homologues in Haemonchus contortus and other parasitic nematodes.
  Parasitology, 134, 461-482.  
17088252 T.Pang, B.Xiong, J.Y.Li, B.Y.Qiu, G.Z.Jin, J.K.Shen, and J.Li (2007).
Conserved alpha-helix acts as autoinhibitory sequence in AMP-activated protein kinase alpha subunits.
  J Biol Chem, 282, 495-506.  
17573348 Y.Kojima, H.Miyoshi, H.C.Clevers, M.Oshima, M.Aoki, and M.M.Taketo (2007).
Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling.
  J Biol Chem, 282, 23532-23540.  
16803889 A.Marx, C.Nugoor, J.Müller, S.Panneerselvam, T.Timm, M.Bilang, E.Mylonas, D.I.Svergun, E.M.Mandelkow, and E.Mandelkow (2006).
Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2.
  J Biol Chem, 281, 27586-27599.
PDB code: 2hak
17075132 N.Tochio, S.Koshiba, N.Kobayashi, M.Inoue, T.Yabuki, M.Aoki, E.Seki, T.Matsuda, Y.Tomo, Y.Motoda, A.Kobayashi, A.Tanaka, Y.Hayashizaki, T.Terada, M.Shirouzu, T.Kigawa, and S.Yokoyama (2006).
Solution structure of the kinase-associated domain 1 of mouse microtubule-associated protein/microtubule affinity-regulating kinase 3.
  Protein Sci, 15, 2534-2543.
PDB code: 1ul7
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.