Parvulin 14 Explained

See also: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4. Par14 (eukaryotic homolog of parvulin, EHPF) is a member of the parvulin family of peptidyl-prolyl-cis/trans-isomerases (PPIases) in humans, which possesses prolyl isomerase activity.[1]

History

In 1999, Par14 was identified by two groups independently.[2] [3] After the discovery of human Pin1 in 1996,[4] Par14 turned out to be the second member of the human parvulin family. In contrast to Pin1, Par14 exhibits minor catalytic activity, shows no preference for phosphorylated substrates[5] and fails to rescue the loss of the Pin1-related parvulin Ess1 in yeast.[6] Par14 orthologs are found in many unicellular eukaryotes and all multicellular organisms. In 2006, a Par14 isoform, denoted Par17, was described, which carries an N-terminal extension of 25 residues and is exclusively expressed in hominids.[7]

Expression and localization

Par14 originates from transcription of the PIN4 gene on chromosome Xq13.1. The promotor region is TATA-less and located within a CpG island. The protein is primarily active within the nucleus/nucleolus of the cell, but also found within the cytoplasm.[8]

Biological function

Cytoplasm:Par14 interacts with the insulin receptor substrate (IRS-1) and enhances insulin-induced tyrosine-phosphorylation of IRS-1.[9] During mitosis Par14 associates to the spindle apparatus. In vitro experiments demonstrated that Par14 may be involved in filament polymerization.[10] [11]

Nucleus/Nucleolus:Phosphorylation of Ser19 by casein kinase 2 translocates Par14 into the cellular nucleus.[12] After dephosphorylation the protein associates to chromatin,[13] with the N-terminus mainly responsible for high-affinity DNA binding.[14] Par14 is found in pre-ribosomal ribonuclear protein complexes, where it acts as an rRNA processing factor.[15] Photoaffinity labeling and Liquid chromatography–mass spectrometry analysis reveal the enzyme to be associated with proteins functioning in DNA replication, DNA repair and/or chromatin remodeling. Par14 requires phosphorylation of Ser7 and Ser9 by protein kinase B (Akt) (or protein kinase C) for nuclear export. This export is probably maintained by 14-3-3 protein in a Crm1 dependent way.

Structure

Par14’s catalytic domain exhibits the typical parvulin fold (order of secondary structure elements β1-α1-α2-h-β2-α3-β3-β4; α = α-helix, β = β-strand, h = helical turn) found in all members of this family, so far.[16] Its three-dimensional structure PDB-ID: 3UI4 PDB-ID: 1EQ3 is characterized by a ‘gripping hand’ topology with the central β-sheet core (consisting of four antiparallel strands) opposing α-helix 3. The catalytic center resides on the concave side of the β-sheet.[17] An N-terminal IDR-like stretch composed of mainly small or basic residues precedes this domain. The IDR element is prone to post-translational modifications.

Disease related function/clinical aspects

Par14 is involved in the upregulation of hepatitis B virus replication.[18] Expression of Par14 correlates to primary biliary cirrhosis, an autoimmune chronic cholestatic liver disease.[19] K-RAS exosomes of collateral cancer cells were found to carry Par14.[20]

Notes and References

  1. 10.1515/hsz-2017-0137 . Structure and function of the human parvulins Pin1 and Par14/17 . 2018 . Matena . Anja . Rehic . Edisa . Hönig . Dana . Kamba . Bianca . Bayer . Peter . Biological Chemistry . 399 . 2 . 101–125 . 29040060 . 46851627 . free .
  2. 10.1016/s0014-5793(99)00239-2 . Identification and characterization of a 14 k Da human protein as a novel parvulin-like peptidyl prolyl cis /Trans isomerase . 1999 . Uchida . Takafumi . Fujimori . Fumihiro . Tradler . Thomas . Fischer . Gunter . Rahfeld . Jens-U . FEBS Letters . 446 . 2–3 . 278–282 . 10100858 . 45172611 . free .
  3. 10.1177/002215549904701215 . 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 . 1999 . Thorpe . Julian R. . Rulten . Stuart L. . Kay . John E. . Journal of Histochemistry & Cytochemistry . 47 . 12 . 1633–1640 . 10567447 . 13140240 . free .
  4. 10.1038/380544a0 . A human peptidyl–prolyl isomerase essential for regulation of mitosis . 1996 . Ping Lu . Kun . Hanes . Steven D. . Hunter . Tony . Nature . 380 . 6574 . 544–547 . 8606777 . 1996Natur.380..544P . 4258406 .
  5. 10.1016/s0014-5793(99)00239-2 . Identification and characterization of a 14 k Da human protein as a novel parvulin-like peptidyl prolyl cis /Trans isomerase . 1999 . Uchida . Takafumi . Fujimori . Fumihiro . Tradler . Thomas . Fischer . Gunter . Rahfeld . Jens-U . FEBS Letters . 446 . 2–3 . 278–282 . 10100858 . 45172611 . free .
  6. 10.1074/jbc.M007005200 . Functional Replacement of the Essential ESS1 in Yeast by the Plant ParvulinDlPar13 . 2001 . Metzner . Martin . Stoller . Gerlind . Rücknagel . Karl P. . Lu . Kun Ping . Fischer . Gunter . Luckner . Martin . Küllertz . Gerhard . Journal of Biological Chemistry . 276 . 17 . 13524–13529 . 11118437 . 39847373 . free .
  7. 10.1186/1471-2199-7-9 . 2006 . Mueller . Jonathan . Kessler . Daniel . Neumann . Daniel . Stratmann . Tina . Papatheodorou . Panagiotis . Hartmann-Fatu . Cristina . Bayer . Peter . Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation . BMC Molecular Biology . 7 . 9 . 16522211 . 1420321 . free .
  8. 10.1074/mcp.M900147-MCP200 . Parvulin (Par14), a Peptidyl-Prolylcis-trans Isomerase, is a Novel rRNA Processing Factor That Evolved in the Metazoan Lineage . 2009 . Fujiyama-Nakamura . Sally . Yoshikawa . Harunori . Homma . Keiichi . Hayano . Toshiya . Tsujimura-Takahashi . Teruko . Izumikawa . Keiichi . Ishikawa . Hideaki . Miyazawa . Naoki . Yanagida . Mitsuaki . Miura . Yutaka . Shinkawa . Takashi . Yamauchi . Yoshio . Isobe . Toshiaki . Takahashi . Nobuhiro . Molecular & Cellular Proteomics . 8 . 7 . 1552–1565 . free . 19369196 . 2716718 .
  9. 10.1074/jbc.M113.485730 . Par14 Protein Associates with Insulin Receptor Substrate 1 (IRS-1), Thereby Enhancing Insulin-induced IRS-1 Phosphorylation and Metabolic Actions . 2013 . Zhang . Jun . Nakatsu . Yusuke . Shinjo . Takanori . Guo . Ying . Sakoda . Hideyuki . Yamamotoya . Takeshi . Otani . Yuichiro . Okubo . Hirofumi . Kushiyama . Akifumi . Fujishiro . Midori . Fukushima . Toshiaki . Tsuchiya . Yoshihiro . Kamata . Hideaki . Iwashita . Misaki . Nishimura . Fusanori . Katagiri . Hideki . Takahashi . Shin-Ichiro . Kurihara . Hiroki . Uchida . Takafumi . Asano . Tomoichiro . Journal of Biological Chemistry . 288 . 28 . 20692–20701 . 23720771 . 3711332 . free .
  10. 10.1016/j.jmb.2011.06.040 . Parvulin 17 Promotes Microtubule Assembly by Its Peptidyl-Prolyl Cis/Trans Isomerase Activity . 2011 . Thiele . Alexandra . Krentzlin . Karolin . Erdmann . Frank . Rauh . David . Hause . Gerd . Zerweck . Johannes . Kilka . Susann . Pösel . Stephanie . Fischer . Gunter . Schutkowski . Mike . Weiwad . Matthias . Journal of Molecular Biology . 411 . 4 . 896–909 . 21756916 .
  11. 10.1515/hsz-2019-0423 . Targeting of parvulin interactors by diazirine mediated cross-linking discloses a cellular role of human Par14/17 in actin polymerization . 2020 . Goehring . Anna . Michin . Irina . Gerdes . Tina . Schulze . Nina . Blueggel . Mike . Rehic . Edisa . Kaschani . Farnusch . Kaiser . Markus . Bayer . Peter . Biological Chemistry . 401 . 8 . 955–968 . 32142471 . 212621904 .
  12. 10.1016/s0022-2836(03)00713-7 . Phosphorylation of the N-terminal Domain Regulates Subcellular Localization and DNA Binding Properties of the Peptidyl-prolyl cis/Trans Isomerase hPar14 . 2003 . Reimer . Tatiana . Weiwad . Matthias . Schierhorn . Angelika . Ruecknagel . Peter-Karl . Rahfeld . Jens-Ulrich . Bayer . Peter . Fischer . Gunter . Journal of Molecular Biology . 330 . 5 . 955–966 . 12860119 .
  13. 10.1186/s12858-015-0033-x . Human DNA-binding peptidyl-prolyl cis/Trans isomerase Par14 is cell cycle dependently expressed and associates with chromatin in vivo . 2015 . Saningong . Akuma D. . Bayer . Peter . BMC Biochemistry . 16 . 4 . 25645591 . 4327958 . free .
  14. 10.1016/s0022-2836(02)00615-0 . The N-terminal Basic Domain of Human Parvulin hPar14 is Responsible for the Entry to the Nucleus and High-affinity DNA-binding . 2002 . Surmacz . Tatiana Anna . Bayer . Elena . Rahfeld . Jens-Ulrich . Fischer . Gunter . Bayer . Peter . Journal of Molecular Biology . 321 . 2 . 235–247 . 12144781 .
  15. 10.1074/jbc.M201181200 . Isolation and Proteomic Characterization of Human Parvulin-associating Preribosomal Ribonucleoprotein Complexes . 2002 . Fujiyama . Sally . Yanagida . Mitsuaki . Hayano . Toshiya . Miura . Yutaka . Isobe . Toshiaki . Takahashi . Nobuhiro . Uchida . T. . Takahashi . N. . Journal of Biological Chemistry . 277 . 26 . 23773–23780 . 11960984 . 43724722 . free .
  16. 10.1006/jmbi.2000.4013. NMR solution structure of h Par14 reveals similarity to the peptidyl prolyl cis/Trans isomerase domain of the mitotic regulator h Pin1 but indicates a different functionality of the protein 1 1Edited by A. Fersht. 2000. Sekerina. Elena. Rahfeld. Jens Ulrich. Müller. Jonathan. Fanghänel. Jörg. Rascher. Christine. Fischer. Gunter. Bayer. Peter. Journal of Molecular Biology. 301. 4. 1003–1017. 10966801.
  17. 10.1006/jmbi.2000.4293 . Solution structure of the human parvulin-like peptidyl prolyl cis/Trans isomerase, hPar14 . 2001 . Terada . Tohru . Shirouzu . Mikako . Fukumori . Yasuhiro . Fujimori . Fumihiro . Ito . Yutaka . Kigawa . Takanori . Yokoyama . Shigeyuki . Uchida . Takafumi . Journal of Molecular Biology . 305 . 4 . 917–926 . 11162102 .
  18. 10.1128/JVI.01840-18 . Parvulin 14 and Parvulin 17 Bind to HBX and cccDNA and Upregulate Hepatitis B Virus Replication from cccDNA to Virion in an HBX-Dependent Manner . 2018 . Saeed . Umar . Kim . Jumi . Piracha . Zahra Zahid . Kwon . Hyeonjoong . Jung . Jaesung . Chwae . Yong-Joon . Park . Sun . Shin . Ho-Joon . Kim . Kyongmin . Journal of Virology . 93 . 6 . 30567987 . 6401437 .
  19. 10.4161/epi.6.1.13405 . Epigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis . 2011 . Mitchell . Michelle M. . Lleo . Ana . Zammataro . Luca . Mayo . Marlyn J. . Invernizzi . Pietro . Bach . Nancy . Shimoda . Shinji . Gordon . Stuart . Podda . Mauro . Gershwin . M. Eric . Selmi . Carlo . Lasalle . Janine M. . Epigenetics . 6 . 1 . 95–102 . 20864813 . 3029486 .
  20. 10.1074/mcp.M112.022806. 3567858 . Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS . 2013 . Demory Beckler . Michelle . Higginbotham . James N. . Franklin . Jeffrey L. . Ham . Amy-Joan . Halvey . Patrick J. . Imasuen . Imade E. . Whitwell . Corbin . Li . Ming . Liebler . Daniel C. . Coffey . Robert J. . Molecular & Cellular Proteomics . 12 . 2 . 343–355 . 23161513 . 30398978 . free .

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