Serine/threonine-protein kinase PLK2

Details

Name
Serine/threonine-protein kinase PLK2
Synonyms
  • 2.7.11.21
  • hPlk2
  • hSNK
  • PLK-2
  • Polo-like kinase 2
  • Serine/threonine-protein kinase SNK
  • Serum-inducible kinase
  • SNK
Gene Name
PLK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051922|Serine/threonine-protein kinase PLK2
MELLRTITYQPAASTKMCEQALGKGCGADSKKKRPPQPPEESQPPQSQAQVPPAAPHHHH
HHSHSGPEISRIIVDPTTGKRYCRGKVLGKGGFAKCYEMTDLTNNKVYAAKIIPHSRVAK
PHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMAHILKARKVLTEP
EVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINEAMELKVGDFGLAARLEPLEHRRRTI
CGTPNYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYTMP
SSLLAPAKHLIASMLSKNPEDRPSLDDIIRHDFFLQGFTPDRLSSSCCHTVPDFHLSSPA
KNFFKKAAAALFGGKKDKARYIDTHNRVSKEDEDIYKLRHDLKKTSITQQPSKHRTDEEL
QPPTTTVARSGTPAVENKQQIGDAIRMIVRGTLGSCSSSSECLEDSTMGSVADTVARVLR
GCLENMPEADCIPKEQLSTSFQWVTKWVDYSNKYGFGYQLSDHTVGVLFNNGAHMSLLPD
KKTVHYYAELGQCSVFPATDAPEQFISQVTVLKYFSHYMEENLMDGGDLPSVTDIRRPRL
YLLQWLKSDKALMMLFNDGTFQVNFYHDHTKIIICSQNEEYLLTYINEDRISTTFRLTTL
LMSGCSSELKNRMEYALNMLLQRCN
Number of residues
685
Molecular Weight
78235.87
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / ATP-dependent protein binding / protein serine/threonine kinase activity / signal transducer activity
Processes
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / G1/S transition of mitotic cell cycle / long term synaptic depression / long-term synaptic potentiation / memory / mitotic cell cycle checkpoint / mitotic spindle organization / negative regulation of angiogenesis / negative regulation of apoptotic process / negative regulation of apoptotic process in bone marrow / negative regulation of cellular senescence / negative regulation of dendritic spine development / peptidyl-serine phosphorylation / positive regulation of autophagy / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of protein binding / positive regulation of protein catabolic process / protein phosphorylation / Rap protein signal transduction / Ras protein signal transduction / regulation of centriole replication / regulation of synaptic plasticity
Components
centriole / centrosome / chromatin / cytoplasm / cytosol / dendrite / intracellular
General Function
Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051923|Serine/threonine-protein kinase PLK2 (PLK2)
ATGGAGCTTTTGCGGACTATCACCTACCAGCCAGCCGCCAGCACCAAAATGTGCGAGCAG
GCGCTGGGCAAGGGTTGCGGAGCGGACTCGAAGAAGAAGCGGCCGCCGCAGCCCCCCGAG
GAATCGCAGCCACCTCAGTCCCAGGCGCAAGTGCCCCCGGCGGCCCCTCACCACCATCAC
CACCATTCGCACTCGGGGCCGGAGATCTCGCGGATTATCGTCGACCCCACGACTGGGAAG
CGCTACTGCCGGGGCAAAGTGCTGGGAAAGGGTGGCTTTGCAAAATGTTACGAGATGACA
GATTTGACAAATAACAAAGTCTACGCCGCAAAAATTATTCCTCACAGCAGAGTAGCTAAA
CCTCATCAAAGGGAAAAGATTGACAAAGAAATAGAGCTTCACAGAATTCTTCATCATAAG
CATGTAGTGCAGTTTTACCACTACTTCGAGGACAAAGAAAACATTTACATTCTCTTGGAA
TACTGCAGTAGAAGGTCAATGGCTCATATTTTGAAAGCAAGAAAGGTGTTGACAGAGCCA
GAAGTTCGATACTACCTCAGGCAGATTGTGTCTGGACTGAAATACCTTCATGAACAAGAA
ATCTTGCACAGAGATCTCAAACTAGGGAACTTTTTTATTAATGAAGCCATGGAACTAAAA
GTTGGGGACTTCGGTCTGGCAGCCAGGCTAGAACCCTTGGAACACAGAAGGAGAACGATA
TGTGGTACCCCAAATTATCTCTCTCCTGAAGTCCTCAACAAACAAGGACATGGCTGTGAA
TCAGACATTTGGGCCCTGGGCTGTGTAATGTATACAATGTTACTAGGGAGGCCCCCATTT
GAAACTACAAATCTCAAAGAAACTTATAGGTGCATAAGGGAAGCAAGGTATACAATGCCG
TCCTCATTGCTGGCTCCTGCCAAGCACTTAATTGCTAGTATGTTGTCCAAAAACCCAGAG
GATCGTCCCAGTTTGGATGACATCATTCGACATGACTTTTTTTTGCAGGGCTTCACTCCG
GACAGACTGTCTTCTAGCTGTTGTCATACAGTTCCAGATTTCCACTTATCAAGCCCAGCT
AAGAATTTCTTTAAGAAAGCAGCTGCTGCTCTTTTTGGTGGCAAAAAAGACAAAGCAAGA
TATATTGACACACATAATAGAGTGTCTAAAGAAGATGAAGACATCTACAAGCTTAGGCAT
GATTTGAAAAAGACTTCAATAACTCAGCAACCCAGCAAACACAGGACAGATGAGGAGCTC
CAGCCACCTACCACCACAGTTGCCAGGTCTGGAACACCCGCAGTAGAAAACAAGCAGCAG
ATTGGGGATGCTATTCGGATGATAGTCAGAGGGACTCTTGGCAGCTGTAGCAGCAGCAGT
GAATGCCTTGAAGACAGTACCATGGGAAGTGTTGCAGACACAGTGGCAAGGGTTCTTCGG
GGATGTCTGGAAAACATGCCGGAAGCTGATTGCATTCCCAAAGAGCAGCTGAGCACATCA
TTTCAGTGGGTCACCAAATGGGTTGATTACTCTAACAAATATGGCTTTGGGTACCAGCTC
TCAGACCACACCGTCGGTGTCCTTTTCAACAATGGTGCTCACATGAGCCTCCTTCCAGAC
AAAAAAACAGTTCACTATTACGCAGAGCTTGGCCAATGCTCAGTTTTCCCAGCAACAGAT
GCTCCTGAGCAATTTATTAGTCAAGTGACGGTGCTGAAATACTTTTCTCATTACATGGAG
GAGAACCTCATGGATGGTGGAGATCTGCCTAGTGTTACTGATATTCGAAGACCTCGGCTC
TACCTCCTTCAGTGGCTAAAATCTGATAAGGCCCTAATGATGCTCTTTAATGATGGCACC
TTTCAGGTGAATTTCTACCATGATCATACAAAAATCATCATCTGTAGCCAAAATGAAGAA
TACCTTCTCACCTACATCAATGAGGATAGGATATCTACAACTTTCAGGCTGACAACTCTG
CTGATGTCTGGCTGTTCATCAGAATTAAAAAATCGAATGGAATATGCCCTGAACATGCTC
TTACAAAGATGTAACTGA
Chromosome Location
5
Locus
5q11.2
External Identifiers
ResourceLink
UniProtKB IDQ9NYY3
UniProtKB Entry NamePLK2_HUMAN
HGNC IDHGNC:19699
General References
  1. Liby K, Wu H, Ouyang B, Wu S, Chen J, Dai W: Identification of the human homologue of the early-growth response gene Snk, encoding a serum-inducible kinase. DNA Seq. 2001;11(6):527-33. [Article]
  2. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Shimizu-Yoshida Y, Sugiyama K, Rogounovitch T, Ohtsuru A, Namba H, Saenko V, Yamashita S: Radiation-inducible hSNK gene is transcriptionally regulated by p53 binding homology element in human thyroid cells. Biochem Biophys Res Commun. 2001 Nov 30;289(2):491-8. [Article]
  5. Warnke S, Kemmler S, Hames RS, Tsai HL, Hoffmann-Rohrer U, Fry AM, Hoffmann I: Polo-like kinase-2 is required for centriole duplication in mammalian cells. Curr Biol. 2004 Jul 13;14(13):1200-7. [Article]
  6. Syed N, Smith P, Sullivan A, Spender LC, Dyer M, Karran L, O'Nions J, Allday M, Hoffmann I, Crawford D, Griffin B, Farrell PJ, Crook T: Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies. Blood. 2006 Jan 1;107(1):250-6. Epub 2005 Sep 13. [Article]
  7. Cizmecioglu O, Warnke S, Arnold M, Duensing S, Hoffmann I: Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain. Cell Cycle. 2008 Nov 15;7(22):3548-55. Epub 2008 Nov 26. [Article]
  8. Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, Chen P, Wang Y, Yan M, Qian Z, Neilly MB, Jin J, Zhang Y, Bohlander SK, Zhang DE, Larson RA, Le Beau MM, Thirman MJ, Golub TR, Rowley JD, Chen J: Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15535-40. doi: 10.1073/pnas.0808266105. Epub 2008 Oct 1. [Article]
  9. Chang J, Cizmecioglu O, Hoffmann I, Rhee K: PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J. 2010 Jul 21;29(14):2395-406. doi: 10.1038/emboj.2010.118. Epub 2010 Jun 8. [Article]
  10. Krause A, Hoffmann I: Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. PLoS One. 2010 Mar 24;5(3):e9849. doi: 10.1371/journal.pone.0009849. [Article]
  11. Benetatos L, Dasoula A, Hatzimichael E, Syed N, Voukelatou M, Dranitsaris G, Bourantas KL, Crook T: Polo-like kinase 2 (SNK/PLK2) is a novel epigenetically regulated gene in acute myeloid leukemia and myelodysplastic syndromes: genetic and epigenetic interactions. Ann Hematol. 2011 Sep;90(9):1037-45. doi: 10.1007/s00277-011-1193-4. Epub 2011 Feb 22. [Article]
  12. Strebhardt K: Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov. 2010 Aug;9(8):643-60. doi: 10.1038/nrd3184. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails