1urf is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
PKN1_HUMAN PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.[1][2][3][4][5][6][7][8][9]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
PRK1 is a serine/threonine kinase that belongs to the protein kinase C superfamily. It can be activated either by members of the Rho family of small G proteins, by proteolysis, or by interaction with lipids. Here we investigate the binding of PRK1 to RhoA and Rac1, two members of the Rho family. We demonstrate that PRK1 binds with a similar affinity to RhoA and Rac1. We present the solution structure of the second HR1 domain from the regulatory N-terminal region of PRK1, and we show that it forms an anti-parallel coiled-coil. In addition, we have used NMR to map the binding contacts of the HR1b domain with Rac1. These are compared with the contacts known to form between HR1a and RhoA. We have used mutagenesis to define the residues in Rac that are important for binding to HR1b. Surprisingly, as well as residues adjacent to Switch I, in Switch II, and in helix alpha5, it appears that the C-terminal stretch of basic amino acids in Rac is required for a high affinity interaction with HR1b.
Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1).,Owen D, Lowe PN, Nietlispach D, Brosnan CE, Chirgadze DY, Parker PJ, Blundell TL, Mott HR J Biol Chem. 2003 Dec 12;278(50):50578-87. Epub 2003 Sep 26. PMID:14514689[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Palmer RH, Schonwasser DC, Rahman D, Pappin DJ, Herget T, Parker PJ. PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163. FEBS Lett. 1996 Jan 15;378(3):281-5. PMID:8557118
↑Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y. PKN associates and phosphorylates the head-rod domain of neurofilament protein. J Biol Chem. 1996 Apr 19;271(16):9816-22. PMID:8621664
↑Matsuzawa K, Kosako H, Inagaki N, Shibata H, Mukai H, Ono Y, Amano M, Kaibuchi K, Matsuura Y, Azuma I, Inagaki M. Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN. Biochem Biophys Res Commun. 1997 May 29;234(3):621-5. PMID:9175763 doi:https://dx.doi.org/10.1006/bbrc.1997.6669
↑Taniguchi T, Kawamata T, Mukai H, Hasegawa H, Isagawa T, Yasuda M, Hashimoto T, Terashima A, Nakai M, Mori H, Ono Y, Tanaka C. Phosphorylation of tau is regulated by PKN. J Biol Chem. 2001 Mar 30;276(13):10025-31. Epub 2000 Dec 4. PMID:11104762 doi:https://dx.doi.org/10.1074/jbc.M007427200
↑Metzger E, Muller JM, Ferrari S, Buettner R, Schule R. A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer. EMBO J. 2003 Jan 15;22(2):270-80. PMID:12514133 doi:https://dx.doi.org/10.1093/emboj/cdg023
↑Schmidt A, Durgan J, Magalhaes A, Hall A. Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis. EMBO J. 2007 Mar 21;26(6):1624-36. Epub 2007 Mar 1. PMID:17332740 doi:https://dx.doi.org/10.1038/sj.emboj.7601637
↑Metzger E, Yin N, Wissmann M, Kunowska N, Fischer K, Friedrichs N, Patnaik D, Higgins JM, Potier N, Scheidtmann KH, Buettner R, Schule R. Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation. Nat Cell Biol. 2008 Jan;10(1):53-60. Epub 2007 Dec 9. PMID:18066052 doi:https://dx.doi.org/10.1038/ncb1668
↑Harrison BC, Huynh K, Lundgaard GL, Helmke SM, Perryman MB, McKinsey TA. Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. FEBS Lett. 2010 Mar 19;584(6):1103-10. doi: 10.1016/j.febslet.2010.02.057. Epub, 2010 Feb 24. PMID:20188095 doi:https://dx.doi.org/10.1016/j.febslet.2010.02.057
↑Lachmann S, Jevons A, De Rycker M, Casamassima A, Radtke S, Collazos A, Parker PJ. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration. PLoS One. 2011;6(7):e21732. doi: 10.1371/journal.pone.0021732. Epub 2011 Jul 6. PMID:21754995 doi:https://dx.doi.org/10.1371/journal.pone.0021732
↑Owen D, Lowe PN, Nietlispach D, Brosnan CE, Chirgadze DY, Parker PJ, Blundell TL, Mott HR. Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1). J Biol Chem. 2003 Dec 12;278(50):50578-87. Epub 2003 Sep 26. PMID:14514689 doi:10.1074/jbc.M304313200
