Serine/threonine-protein kinase PLK4
Details
- Name
- Serine/threonine-protein kinase PLK4
- Synonyms
- 2.7.11.21
- PLK-4
- Polo-like kinase 4
- SAK
- Serine/threonine-protein kinase 18
- Serine/threonine-protein kinase Sak
- STK18
- Gene Name
- PLK4
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0051926|Serine/threonine-protein kinase PLK4 MATCIGEKIEDFKVGNLLGKGSFAGVYRAESIHTGLEVAIKMIDKKAMYKAGMVQRVQNE VKIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEMNRYLKNRVKPFSENEARHFMHQI ITGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKMPHEKHYTLCGTPNYISP EIATRSAHGLESDVWSLGCMFYTLLIGRPPFDTDTVKNTLNKVVLADYEMPSFLSIEAKD LIHQLLRRNPADRLSLSSVLDHPFMSRNSSTKSKDLGTVEDSIDSGHATISTAITASSST SISGSLFDKRRLLIGQPLPNKMTVFPKNKSSTDFSSSGDGNSFYTQWGNQETSNSGRGRV IQDAEERPHSRYLRRAYSSDRSGTSNSQSQAKTYTMERCHSAEMLSVSKRSGGGENEERY SPTDNNANIFNFFKEKTSSSSGSFERPDNNQALSNHLCPGKTPFPFADPTPQTETVQQWF GNLQINAHLRKTTEYDSISPNRDFQGHPDLQKDTSKNAWTDTKVKKNSDASDNAHSVKQQ NTMKYMTALHSKPEIIQQECVFGSDPLSEQSKTRGMEPPWGYQNRTLRSITSPLVAHRLK PIRQKTKKAVVSILDSEEVCVELVKEYASQEYVKEVLQISSDGNTITIYYPNGGRGFPLA DRPPSPTDNISRYSFDNLPEKYWRKYQYASRFVQLVRSKSPKITYFTRYAKCILMENSPG ADFEVWFYDGVKIHKTEDFIQVIEKTGKSYTLKSESEVNSLKEEIKMYMDHANEGHRICL ALESIISEEERKTRSAPFFPIIIGRKPGSTSSPKALSPPPSVDSNYPTRERASFNRMVMH SAASPTQAPILNPSMVTNEGLGLTTTASGTDISSNSLKDCLPKSAQLLKSVFVKNVGWAT QLTSGAVWVQFNDGSQLVVQAGVSSISYTSPNGQTTRYGENEKLPDYIKQKLQCLSSILL MFSNPTPNFH
- Number of residues
- 970
- Molecular Weight
- 108971.055
- Theoretical pI
- Not Available
- GO Classification
- FunctionsATP binding / identical protein binding / protein serine/threonine kinase activityProcessescentriole replication / ciliary basal body-plasma membrane docking / de novo centriole assembly involved in multi-ciliated epithelial cell differentiation / G2/M transition of mitotic cell cycle / positive regulation of centriole replication / protein phosphorylation / regulation of G2/M transition of mitotic cell cycle / trophoblast giant cell differentiationComponentscentriole / centrosome / cleavage furrow / cytosol / deuterosome / nucleolus / XY body
- General Function
- Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124).
- Specific Function
- Atp binding
- Pfam Domain Function
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm
- Gene sequence
>lcl|BSEQ0051927|Serine/threonine-protein kinase PLK4 (PLK4) ATGGCGACCTGCATCGGGGAGAAGATCGAGGATTTTAAAGTTGGAAATCTGCTTGGTAAA GGATCATTTGCTGGTGTCTACAGAGCTGAGTCCATTCACACTGGTTTGGAAGTTGCAATC AAAATGATAGATAAGAAAGCCATGTACAAAGCAGGAATGGTACAGAGAGTCCAAAATGAG GTGAAAATACATTGCCAATTGAAACATCCTTCTATCTTGGAGCTTTATAACTATTTTGAA GATAGCAATTATGTGTATCTGGTATTAGAAATGTGCCATAATGGAGAAATGAACAGGTAT CTAAAGAATAGAGTGAAACCCTTCTCAGAAAATGAAGCTCGACACTTCATGCACCAGATC ATCACAGGGATGTTGTATCTTCATTCTCATGGTATACTACACCGGGACCTCACACTTTCT AACCTCCTACTGACTCGTAATATGAACATCAAGATTGCTGATTTTGGGCTGGCAACTCAA CTGAAAATGCCACATGAAAAGCACTATACATTATGTGGAACTCCTAACTACATTTCACCA GAAATTGCCACTCGAAGTGCACATGGCCTTGAATCTGATGTTTGGTCCCTGGGCTGTATG TTTTATACATTACTTATCGGGAGACCACCCTTCGACACTGACACAGTCAAGAACACATTA AATAAAGTAGTATTGGCAGATTATGAAATGCCATCTTTTTTGTCAATAGAGGCCAAGGAC CTTATTCACCAGTTACTTCGTAGAAATCCAGCAGATCGTTTAAGTCTGTCTTCAGTATTG GACCATCCTTTTATGTCCCGAAATTCTTCAACAAAAAGTAAAGATTTAGGAACTGTGGAA GACTCAATTGATAGTGGGCATGCCACAATTTCTACTGCAATTACAGCTTCTTCCAGTACC AGTATAAGTGGTAGTTTATTTGACAAAAGAAGACTTTTGATTGGTCAGCCACTCCCAAAT AAAATGACTGTATTTCCAAAGAATAAAAGTTCAACTGATTTTTCTTCTTCAGGAGATGGA AACAGTTTTTATACTCAGTGGGGAAATCAAGAAACCAGTAATAGTGGAAGGGGAAGAGTA ATTCAAGATGCAGAAGAAAGGCCACATTCTCGATACCTTCGTAGAGCTTATTCCTCTGAT AGATCTGGCACTTCTAATAGTCAGTCTCAAGCAAAAACATATACAATGGAACGATGTCAC TCAGCAGAAATGCTTTCAGTGTCCAAAAGATCAGGAGGAGGTGAAAATGAAGAGAGGTAC TCACCCACAGACAACAATGCCAACATTTTTAACTTCTTTAAAGAAAAGACATCCAGTAGT TCTGGATCTTTTGAAAGACCTGATAACAATCAAGCACTCTCCAATCATCTTTGTCCAGGA AAAACTCCTTTTCCATTTGCAGACCCGACACCTCAGACTGAAACCGTACAACAGTGGTTT GGGAATCTGCAAATAAATGCTCATTTAAGAAAAACTACTGAATATGACAGCATCAGCCCA AACCGGGACTTCCAGGGCCATCCAGATTTGCAGAAGGACACATCAAAAAATGCCTGGACT GATACAAAAGTCAAAAAGAACTCTGATGCTTCTGATAATGCACATTCTGTAAAACAGCAA AATACCATGAAATATATGACTGCACTTCACAGTAAACCTGAGATAATCCAACAAGAATGT GTTTTTGGCTCAGATCCTCTTTCTGAACAGAGCAAGACTAGGGGTATGGAGCCACCATGG GGTTATCAGAATCGTACATTAAGAAGCATTACATCTCCGTTGGTTGCTCACAGGTTAAAA CCAATCAGACAGAAAACCAAAAAGGCTGTGGTGAGCATACTTGATTCAGAGGAGGTGTGT GTGGAGCTTGTAAAGGAGTATGCATCTCAAGAATATGTGAAAGAAGTTCTTCAGATATCT AGTGATGGAAATACGATCACTATTTATTATCCAAATGGTGGTAGAGGTTTTCCTCTTGCT GATAGACCACCCTCACCTACTGACAACATCAGTAGGTACAGCTTTGACAATTTACCAGAA AAATACTGGCGAAAATATCAATATGCTTCCAGGTTTGTACAGCTTGTAAGATCTAAATCT CCCAAAATCACTTATTTTACAAGATATGCTAAATGCATTTTGATGGAGAATTCTCCTGGT GCTGATTTTGAGGTTTGGTTTTATGATGGGGTAAAAATACACAAAACAGAAGATTTCATT CAGGTGATTGAAAAGACAGGGAAGTCTTACACTTTAAAAAGTGAAAGTGAAGTTAATAGC TTGAAAGAGGAGATAAAAATGTATATGGACCATGCTAATGAGGGTCATCGTATTTGTTTA GCACTGGAATCCATAATTTCAGAAGAGGAAAGGAAAACTAGGAGTGCTCCCTTTTTCCCA ATAATCATAGGAAGAAAACCTGGTAGTACTAGTTCACCTAAGGCCTTATCACCTCCTCCT TCTGTGGATTCAAATTACCCAACGAGAGAGAGAGCATCTTTCAACAGAATGGTCATGCAT AGTGCTGCTTCTCCAACACAGGCACCAATCCTTAATCCCTCTATGGTTACAAATGAAGGA CTTGGTCTTACAACTACAGCTTCTGGAACAGACATCTCTTCTAATAGTCTAAAAGATTGT CTTCCTAAATCAGCACAACTTTTGAAATCTGTTTTTGTGAAAAATGTTGGTTGGGCTACA CAGTTAACTAGTGGAGCTGTGTGGGTTCAGTTTAATGATGGGTCCCAGTTGGTTGTGCAG GCAGGAGTGTCTTCTATCAGTTATACCTCACCAAATGGTCAAACAACTAGGTATGGAGAA AATGAAAAATTACCAGACTACATCAAACAGAAATTACAGTGTCTGTCTTCCATCCTTTTG ATGTTTTCTAATCCGACTCCTAATTTTCATTGA
- Chromosome Location
- 4
- Locus
- 4q28.1
- External Identifiers
Resource Link UniProtKB ID O00444 UniProtKB Entry Name PLK4_HUMAN HGNC ID HGNC:11397 - General References
- Yamashita Y, Kajigaya S, Yoshida K, Ueno S, Ota J, Ohmine K, Ueda M, Miyazato A, Ohya K, Kitamura T, Ozawa K, Mano H: Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase. J Biol Chem. 2001 Oct 19;276(42):39012-20. Epub 2001 Aug 6. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- 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]
- Mills GB, Schmandt R, Gibson S, Leung B, Hill M, May C, Shi YF, Branch DR, Radvanyi L, Truitt KE, et al.: Transmembrane signaling by the interleukin-2 receptor: progress and conundrums. Semin Immunol. 1993 Oct;5(5):345-64. [Article]
- Lehtola L, Partanen J, Sistonen L, Korhonen J, Warri A, Harkonen P, Clarke R, Alitalo K: Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF-7 breast-cancer cells. Int J Cancer. 1992 Feb 20;50(4):598-603. [Article]
- Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM: SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005 Dec 20;15(24):2199-207. Epub 2005 Dec 1. [Article]
- Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA: The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005 Nov;7(11):1140-6. [Article]
- Li J, Tan M, Li L, Pamarthy D, Lawrence TS, Sun Y: SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia. 2005 Apr;7(4):312-23. [Article]
- Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA: Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. [Article]
- Bonni S, Ganuelas ML, Petrinac S, Hudson JW: Human Plk4 phosphorylates Cdc25C. Cell Cycle. 2008 Feb 15;7(4):545-7. Epub 2007 Nov 25. [Article]
- Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
- Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
- Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW: Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009 Jan 15;8(2):327-9. [Article]
- Kuriyama R, Bettencourt-Dias M, Hoffmann I, Arnold M, Sandvig L: Gamma-tubulin-containing abnormal centrioles are induced by insufficient Plk4 in human HCT116 colorectal cancer cells. J Cell Sci. 2009 Jun 15;122(Pt 12):2014-23. doi: 10.1242/jcs.036715. Epub 2009 May 19. [Article]
- Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
- Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann-Weiss U, Antony C, Hoffmann I: Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol. 2010 Nov 15;191(4):731-9. doi: 10.1083/jcb.201007107. Epub 2010 Nov 8. [Article]
- Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G, Glover DM: Asterless is a scaffold for the onset of centriole assembly. Nature. 2010 Oct 7;467(7316):714-8. doi: 10.1038/nature09445. Epub 2010 Sep 19. [Article]
- Tang CJ, Lin SY, Hsu WB, Lin YN, Wu CT, Lin YC, Chang CW, Wu KS, Tang TK: The human microcephaly protein STIL interacts with CPAP and is required for procentriole formation. EMBO J. 2011 Oct 21;30(23):4790-804. doi: 10.1038/emboj.2011.378. [Article]
- Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, Grunwald V, Kubicka S, Pich A, Manns MP, Hoffmann I, Gonczy P, Malek NP: The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011 Jul 3;13(8):1004-9. doi: 10.1038/ncb2282. [Article]
- Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
- Martin CA, Ahmad I, Klingseisen A, Hussain MS, Bicknell LS, Leitch A, Nurnberg G, Toliat MR, Murray JE, Hunt D, Khan F, Ali Z, Tinschert S, Ding J, Keith C, Harley ME, Heyn P, Muller R, Hoffmann I, Daire VC, Dollfus H, Dupuis L, Bashamboo A, McElreavey K, Kariminejad A, Mendoza-Londono R, Moore AT, Saggar A, Schlechter C, Weleber R, Thiele H, Altmuller J, Hohne W, Hurles ME, Noegel AA, Baig SM, Nurnberg P, Jackson AP: Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet. 2014 Dec;46(12):1283-92. doi: 10.1038/ng.3122. Epub 2014 Oct 26. [Article]
- Brunk K, Zhu M, Barenz F, Kratz AS, Haselmann-Weiss U, Antony C, Hoffmann I: Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication. J Cell Sci. 2016 Jul 15;129(14):2713-8. doi: 10.1242/jcs.184093. Epub 2016 May 31. [Article]
- Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
- Fournier M, Orpinell M, Grauffel C, Scheer E, Garnier JM, Ye T, Chavant V, Joint M, Esashi F, Dejaegere A, Gonczy P, Tora L: KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in preventing centrosome amplification. Nat Commun. 2016 Oct 31;7:13227. doi: 10.1038/ncomms13227. [Article]