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PIN4  -  protein (peptidylprolyl cis/trans...

Homo sapiens

Synonyms: EPVH, PAR14, PAR17, PPIase Pin4, Par14, ...
 
 
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Disease relevance of PIN4

  • To determine the solution structure of hPar14 the (1)H, (13)C, and (15)N chemical shifts of this protein have been assigned using heteronuclear two and three-dimensional NMR experiments on unlabeled and uniformly (15)N/(13)C-labeled recombinant protein isolated from Escherichia coli cells that overexpress the protein [1].
 

High impact information on PIN4

  • Human parvulin (hParvulin; Par14/EPVH) belongs to the third family of peptidylprolyl cis-trans isomerases that exhibit an enzymatic activity of interconverting the cis-trans conformation of the prolyl peptide bond, and shows sequence similarity to the regulator enzyme for cell cycle transitions, human Pin1 [2].
  • In contrast, the human parvulin hPar14 is not able to rescue the lethal phenotype of this yeast strain at nonpermissive temperatures [3].
  • Phosphorylation of hPar14 is inhibited both in vitro and in vivo by 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), a specific inhibitor of CK2 activity [4].
  • Immunostaining shows that a Glu19 mutant of hPar14, which mimics the phosphorylated state of Ser19, is localized around the nuclear envelope, but does not penetrate into the nucleoplasm [4].
  • Although hPar14 was nuclearly localized and bound to double-stranded DNA, the molecular basis of the subcellular localization and the functional regulation remained unknown.Here we show that subcellular localization and DNA-binding ability of hPar14 is regulated by posttranslational modification of its N-terminal domain [4].
 

Biological context of PIN4

  • Mutation of Ser19 to Ala abolishes phosphorylation and alters the subcellular localization of hPar14 from predominantly nuclear to significantly cytoplasmic [4].
  • Therefore, the mechanism determining the substrate specificity seems to be different between hPar14 and hPin1 [5].
  • The hPar14 folds into a betaalpha(3)betaalphabeta(2) structure, and contains an unstructured 35-amino acid basic tail N-terminal to the catalytic core that replaces the WW domain of hPin1 homologs [1].
  • Pin1 and Par14 peptidyl prolyl isomerase inhibitors block cell proliferation [6].
 

Anatomical context of PIN4

  • To determine the nuclear localization of hPar14 in vivo the molecule was fused to green fluorescent protein and expressed in human HeLa cells [7].
  • This showed hEPVH to be distributed throughout HEK 293 cells but in highest concentration within mitochondria [8].
  • The intracellular distribution of a novel human parvulin homologue (hEPVH) has been investigated in a human kidney cell line (HEK 293) by immunogold labeling transmission electron microscopy (TEM) [8].
  • The N-terminal elongation of Par17-QR and Par17-RS suggests these isoforms to perform divergent functions within the eukaryotic cell than the well characterized Par14 [9].
 

Other interactions of PIN4

  • Twelve of the 17 human cyclophilins and both human parvulins, but only one of the 13 human FKBPs, identified orthologues within these fungi. hPar14 orthologues were restricted to the Pezizomycotina fungi, and R. oryzae is unique in the known fungi in possessing an hCyp33 orthologue and a TPR-containing FKBP [10].
 

Analytical, diagnostic and therapeutic context of PIN4

References

  1. NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a different functionality of the protein. Sekerina, E., Rahfeld, J.U., Müller, J., Fanghänel, J., Rascher, C., Fischer, G., Bayer, P. J. Mol. Biol. (2000) [Pubmed]
  2. Isolation and proteomic characterization of human Parvulin-associating preribosomal ribonucleoprotein complexes. Fujiyama, S., Yanagida, M., Hayano, T., Miura, Y., Isobe, T., Fujimori, F., Uchida, T., Takahashi, N. J. Biol. Chem. (2002) [Pubmed]
  3. Functional replacement of the essential ESS1 in yeast by the plant parvulin DlPar13. Metzner, M., Stoller, G., Rücknagel, K.P., Lu, K.P., Fischer, G., Luckner, M., Küllertz, G. J. Biol. Chem. (2001) [Pubmed]
  4. Phosphorylation of the N-terminal domain regulates subcellular localization and DNA binding properties of the peptidyl-prolyl cis/trans isomerase hPar14. Reimer, T., Weiwad, M., Schierhorn, A., Ruecknagel, P.K., Rahfeld, J.U., Bayer, P., Fischer, G. J. Mol. Biol. (2003) [Pubmed]
  5. Solution structure of the human parvulin-like peptidyl prolyl cis/trans isomerase, hPar14. Terada, T., Shirouzu, M., Fukumori, Y., Fujimori, F., Ito, Y., Kigawa, T., Yokoyama, S., Uchida, T. J. Mol. Biol. (2001) [Pubmed]
  6. Pin1 and Par14 peptidyl prolyl isomerase inhibitors block cell proliferation. Uchida, T., Takamiya, M., Takahashi, M., Miyashita, H., Ikeda, H., Terada, T., Matsuo, Y., Shirouzu, M., Yokoyama, S., Fujimori, F., Hunter, T. Chem. Biol. (2003) [Pubmed]
  7. The N-terminal basic domain of human parvulin hPar14 is responsible for the entry to the nucleus and high-affinity DNA-binding. Surmacz, T.A., Bayer, E., Rahfeld, J.U., Fischer, G., Bayer, P. J. Mol. Biol. (2002) [Pubmed]
  8. Binding of a putative and a known chaperone protein revealed by immunogold labeling transmission electron microscopy: A suggested use of chaperones as probes for the distribution of their target proteins. Thorpe, J.R., Rulten, S.L., Kay, J.E. J. Histochem. Cytochem. (1999) [Pubmed]
  9. Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation. Mueller, J.W., Kessler, D., Neumann, D., Stratmann, T., Papatheodorou, P., Hartmann-Fatu, C., Bayer, P. BMC Mol. Biol. (2006) [Pubmed]
  10. Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires. Pemberton, T.J. BMC Genomics (2006) [Pubmed]
  11. Identification of eukaryotic parvulin homologues: a new subfamily of peptidylprolyl cis-trans isomerases. Rulten, S., Thorpe, J., Kay, J. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
 
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