CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008684
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase PLK1 
Protein Synonyms/Alias
 Polo-like kinase 1; PLK-1; Serine/threonine-protein kinase 13; STPK13 
Gene Name
 PLK1 
Gene Synonyms/Alias
 PLK 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
9SAAVTAGKLARAPADubiquitination[1, 2]
19RAPADPGKAGVPGVAubiquitination[2]
38PAAAPPAKEIPEVLVubiquitination[2, 3]
61VRGRFLGKGGFAKCFubiquitination[2]
86FAGKIVPKSLLLKPHubiquitination[2]
91VPKSLLLKPHQREKMubiquitination[2]
143RSLLELHKRRKALTEubiquitination[2]
146LELHKRRKALTEPEAubiquitination[2]
178RVIHRDLKLGNLFLNubiquitination[2, 3]
200GDFGLATKVEYDGERubiquitination[3, 4]
209EYDGERKKTLCGTPNubiquitination[2]
226APEVLSKKGHSFEVDubiquitination[2]
272KNEYSIPKHINPVAAubiquitination[5, 6]
338SLDPSNRKPLTVLNKubiquitination[7]
358LPERPREKEEPVVREubiquitination[4]
388LHSVNASKPSERGLVubiquitination[2]
474SHPNSLMKKITLLKYacetylation[8]
474SHPNSLMKKITLLKYubiquitination[3]
475HPNSLMKKITLLKYFubiquitination[2]
480MKKITLLKYFRNYMSubiquitination[2, 5, 6]
492YMSEHLLKAGANITPubiquitination[3, 5, 6]
574LEEYGCCKELASRLRubiquitination[2, 4]
589YARTMVDKLLSSRSAubiquitination[2, 4, 5, 6]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional Description
 Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, MLF1IP, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, PLK1S1/KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGOL1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1 and WEE1. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating PLK1S1/KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, MLF1IP, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, MLF1IP, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGOL1: required for spindle pole localization of isoform 3 of SGOL1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73- mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning. 
Sequence Annotation
 DOMAIN 53 305 Protein kinase.
 DOMAIN 417 480 POLO box 1.
 DOMAIN 515 584 POLO box 2.
 NP_BIND 59 67 ATP.
 NP_BIND 178 181 ATP.
 REGION 194 221 Activation loop.
 REGION 493 507 Linker.
 REGION 538 540 Important for interaction with
 MOTIF 337 340 D-box that targets the protein for
 ACT_SITE 176 176 Proton acceptor.
 BINDING 82 82 ATP.
 BINDING 131 131 ATP; via carbonyl oxygen.
 BINDING 194 194 ATP.
 MOD_RES 6 6 Phosphothreonine.
 MOD_RES 103 103 Phosphoserine.
 MOD_RES 137 137 Phosphoserine (Probable).
 MOD_RES 210 210 Phosphothreonine; by AURKA.
 MOD_RES 214 214 Phosphothreonine.
 MOD_RES 269 269 Phosphoserine; by autocatalysis (By
 MOD_RES 335 335 Phosphoserine.
 MOD_RES 375 375 Phosphoserine.
 MOD_RES 450 450 Phosphoserine.
 MOD_RES 498 498 Phosphothreonine.
 CROSSLNK 19 19 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 492 492 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; ATP-binding; Cell cycle; Cell division; Centromere; Chromosome; Complete proteome; Cytoplasm; Cytoskeleton; Isopeptide bond; Kinase; Kinetochore; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 603 AA 
Protein Sequence
MSAAVTAGKL ARAPADPGKA GVPGVAAPGA PAAAPPAKEI PEVLVDPRSR RRYVRGRFLG 60
KGGFAKCFEI SDADTKEVFA GKIVPKSLLL KPHQREKMSM EISIHRSLAH QHVVGFHGFF 120
EDNDFVFVVL ELCRRRSLLE LHKRRKALTE PEARYYLRQI VLGCQYLHRN RVIHRDLKLG 180
NLFLNEDLEV KIGDFGLATK VEYDGERKKT LCGTPNYIAP EVLSKKGHSF EVDVWSIGCI 240
MYTLLVGKPP FETSCLKETY LRIKKNEYSI PKHINPVAAS LIQKMLQTDP TARPTINELL 300
NDEFFTSGYI PARLPITCLT IPPRFSIAPS SLDPSNRKPL TVLNKGLENP LPERPREKEE 360
PVVRETGEVV DCHLSDMLQQ LHSVNASKPS ERGLVRQEEA EDPACIPIFW VSKWVDYSDK 420
YGLGYQLCDN SVGVLFNDST RLILYNDGDS LQYIERDGTE SYLTVSSHPN SLMKKITLLK 480
YFRNYMSEHL LKAGANITPR EGDELARLPY LRTWFRTRSA IILHLSNGSV QINFFQDHTK 540
LILCPLMAAV TYIDEKRDFR TYRLSLLEEY GCCKELASRL RYARTMVDKL LSSRSASNRL 600
KAS 603 
Gene Ontology
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0000942; C:condensed nuclear chromosome outer kinetochore; IDA:BHF-UCL.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030496; C:midbody; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005876; C:spindle microtubule; IDA:BHF-UCL.
 GO:0051233; C:spindle midzone; IDA:UniProtKB.
 GO:0000922; C:spindle pole; IDA:BHF-UCL.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008017; F:microtubule binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0007092; P:activation of mitotic anaphase-promoting complex activity; IDA:UniProtKB.
 GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0051297; P:centrosome organization; IMP:UniProtKB.
 GO:0000910; P:cytokinesis; IDA:UniProtKB.
 GO:0031572; P:G2 DNA damage checkpoint; IDA:UniProtKB.
 GO:0000086; P:G2/M transition of mitotic cell cycle; IDA:UniProtKB.
 GO:0007091; P:metaphase/anaphase transition of mitotic cell cycle; TAS:Reactome.
 GO:0001578; P:microtubule bundle formation; IDA:UniProtKB.
 GO:0007077; P:mitotic nuclear envelope disassembly; TAS:Reactome.
 GO:0000070; P:mitotic sister chromatid segregation; IMP:UniProtKB.
 GO:0007094; P:mitotic spindle assembly checkpoint; IMP:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:BHF-UCL.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:BHF-UCL.
 GO:0031648; P:protein destabilization; IDA:UniProtKB.
 GO:0071168; P:protein localization to chromatin; IDA:UniProtKB.
 GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
 GO:0043393; P:regulation of protein binding; IMP:BHF-UCL. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000959; POLO_box_duplicated_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase
 PF00659; POLO_box 
SMART
 SM00220; S_TKc 
PROSITE
 PS50078; POLO_BOX
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS