PDBsum entry 2rlo

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protein links
Signaling protein PDB id
Protein chain
128 a.a. *
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Split ph domain of pi3-kinase enhancer
Structure: Centaurin-gamma 1. Chain: a. Fragment: unp residues 674-752, 846-914, split_ph_domain. Synonym: arf-gap with gtp-binding protein-like, ankyrin repeat and pleckstrin homology domains 2, agap-2, phosphatidylinositol-3-kinase enhancer, pike, gtp-binding and gtpase-activating protein 2, ggap2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: centg1, agap2, kiaa0167. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: W.Wen,M.Zhang
Key ref:
J.Yan et al. (2008). Split pleckstrin homology domain-mediated cytoplasmic-nuclear localization of PI3-kinase enhancer GTPase. J Mol Biol, 378, 425-435. PubMed id: 18371979 DOI: 10.1016/j.jmb.2008.02.052
21-Jul-07     Release date:   29-Apr-08    
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Protein chain
Pfam   ArchSchema ?
Q99490  (AGAP2_HUMAN) -  Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2
1192 a.a.
128 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain


DOI no: 10.1016/j.jmb.2008.02.052 J Mol Biol 378:425-435 (2008)
PubMed id: 18371979  
Split pleckstrin homology domain-mediated cytoplasmic-nuclear localization of PI3-kinase enhancer GTPase.
J.Yan, W.Wen, L.N.Chan, M.Zhang.
Cytoplasm-nucleus shuttling of phosphoinositol 3-kinase enhancer (PIKE) is known to correlate directly with its cellular functions. However, the molecular mechanism governing this shuttling is not known. In this work, we demonstrate that PIKE is a new member of split pleckstrin homology (PH) domain-containing proteins. The structure solved in this work reveals that the PIKE PH domain is split into halves by a positively charged nuclear localization sequence. The PIKE PH domain binds to the head groups of di- and triphosphoinositides with similar affinities. Lipid membrane binding of the PIKE PH domain is further enhanced by the positively charged nuclear localization sequence, which is juxtaposed to the phosphoinositide head group-binding pocket of the domain. We demonstrate that the cytoplasmic-nuclear shuttling of PIKE is dynamically regulated by the balancing actions of the lipid-binding property of both the split PH domain and the nuclear targeting function of its nuclear localization sequence.
  Selected figure(s)  
Figure 1.
Fig. 1. Solution structure of the PIKE PH domain. (a) Stereo view showing the backbones of 20 superimposed NMR-derived structures of PIKE-A-PH[N]–PH[C]. In the drawing, the flexible β5/β6 loop is shown in gray. (b) Ribbon diagram of a representative structure of PIKE-A-PH[N]–PH[C]. (c) Amino acid sequence alignment of the PH domains of PIKE-L from different species. The absolutely conserved amino acids are highlighted in red, whereas the highly conserved residues are in green. The positively charged residues involved in binding to the head groups of PIPs are indicated with a purple star underneath the sequences. The polybasic clusters B6 and B3 in the putative NLS sequence are labeled with orange dots and cyan triangles, respectively. The 20 amino acid residues in the NLS region that are missing in the PIKE-A-PH domain are highlighted with a yellow dashed box.
Figure 5.
Fig. 5. Model depicting subcellular localization of PIKE by the balancing actions of its PH domain and NLS sequence. (a) A schematic model showing the association of the PIKE PH domain to the plasma membranes. (b) The cellular localization of PIKE can be regulated by the balancing actions between the plasma membrane-binding properties of the split PH domain and the NLS of the protein.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 378, 425-435) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18640982 W.Wen, W.Liu, J.Yan, and M.Zhang (2008).
Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases.
  J Biol Chem, 283, 26263-26273.  
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