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Protein

Serine/threonine-protein kinase PLK1

Gene

Plk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1 and WEE1. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating 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, CENPU, 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, CENPU, 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 SGO1: required for spindle pole localization of isoform 3 of SGO1 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. Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage. Phosphorylates CEP68 and is required for its degradation.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Enzyme regulationi

Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei82 – 821ATPPROSITE-ProRule annotation
Binding sitei131 – 1311ATP; via carbonyl oxygenPROSITE-ProRule annotation
Active sitei176 – 1761Proton acceptorPROSITE-ProRule annotation
Binding sitei194 – 1941ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi59 – 679ATPPROSITE-ProRule annotation
Nucleotide bindingi178 – 1814ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.21. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PLK1 (EC:2.7.11.21)
Alternative name(s):
Polo-like kinase 1
Short name:
PLK-1
Gene namesi
Name:Plk1
Synonyms:Plk
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3352. Plk1.

Subcellular locationi

  • Nucleus By similarity
  • Chromosomecentromerekinetochore By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
  • Cytoplasmcytoskeletonspindle By similarity
  • Midbody By similarity

  • Note: During early stages of mitosis, the phosphorylated form is detected on centrosomes and kinetochores. Localizes to the outer kinetochore. Presence of SGO1 and interaction with the phosphorylated form of BUB1 is required for the kinetochore localization. Localizes onto the central spindle by phosphorylating and docking at midzone proteins KIF20A/MKLP2 and PRC1 (By similarity). Colocalizes with FRY to separating centrosomes and spindle poles from prophase to metaphase in mitosis, but not in other stages of the cell cycle (By similarity).By similarity

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytoplasm Source: RGD
  • kinetochore Source: UniProtKB
  • midbody Source: UniProtKB
  • nucleus Source: UniProtKB
  • spindle Source: UniProtKB
  • spindle midzone Source: RGD
  • spindle pole Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 603602Serine/threonine-protein kinase PLK1PRO_0000086558Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki19 – 19Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei103 – 1031PhosphoserineBy similarity
Modified residuei210 – 2101Phosphothreonine; by AURKABy similarity
Modified residuei214 – 2141PhosphothreonineBy similarity
Modified residuei269 – 2691Phosphoserine; by autocatalysisBy similarity
Modified residuei335 – 3351Phosphoserine; by autocatalysisBy similarity
Modified residuei375 – 3751PhosphoserineBy similarity
Modified residuei450 – 4501PhosphoserineBy similarity
Cross-linki492 – 492Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei498 – 4981PhosphothreonineBy similarity

Post-translational modificationi

Catalytic activity is enhanced by phosphorylation of Thr-210. Phosphorylation at Thr-210 is first detected on centrosomes in the G2 phase of the cell cycle, peaks in prometaphase and gradually disappears from centrosomes during anaphase. Dephosphorylation at Thr-210 at centrosomes is probably mediated by protein phosphatase 1C (PP1C), via interaction with PPP1R12A/MYPT1. Autophosphorylation and phosphorylation of Ser-137 may not be significant for the activation of PLK1 during mitosis, but may enhance catalytic activity during recovery after DNA damage checkpoint. Phosphorylated in vitro by STK10 (By similarity).By similarity
Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase and following DNA damage, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Ubiquitination and subsequent degradation prevents entry into mitosis and is essential to maintain an efficient G2 DNA damage checkpoint. Monoubiquitination at Lys-492 by the BCR(KLHL22) ubiquitin ligase complex does not lead to degradation: it promotes PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62673.
PRIDEiQ62673.

PTM databases

iPTMnetiQ62673.
PhosphoSiteiQ62673.

Interactioni

Subunit structurei

Interacts with CEP170 and EVI5. Interacts and phosphorylates ERCC6L. Interacts with FAM29A. Interacts with SLX4/BTBD12 and TTDN1. Interacts with BUB1B. Interacts (via POLO-box domain) with the phosphorylated form of BUB1, CENPU and CDC25C. Interacts with isoform 3 of SGO1. Interacts with BORA, KIF2A and AURKA. Interacts with TOPORS and CYLD. Interacts with ECT2; the interaction is stimulated upon phosphorylation of ECT2 on 'Thr-444'. Interacts with PRC1. Interacts with KIF20A/MKLP2 (when phosphorylated), leading to the recruitment at the central spindle. Interacts (via POLO box domains) with PPP1R12A/MYPT1 (when previously phosphorylated by CDK1) (By similarity). Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with BIRC6/bruce. Interacts with CDK1-phosphorylated FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA-mediated PLK1 phosphorylation. Interacts with CDK1-phosphorylated DCTN6 during mitotic prometaphase; the interaction facilitates recruitment to kinetochores. Interacts with CEP68; the interaction phosphorylates CEP68.By similarity

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-4565080.
STRINGi10116.ENSRNOP00000025629.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 305253Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini417 – 48064POLO box 1PROSITE-ProRule annotationAdd
BLAST
Domaini515 – 58470POLO box 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni194 – 22128Activation loopBy similarityAdd
BLAST
Regioni493 – 50715LinkerBy similarityAdd
BLAST
Regioni538 – 5403Important for interaction with phosphorylated proteinsBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi337 – 3404D-box that targets the protein for proteasomal degradation in anaphaseBy similarity

Domaini

The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains (By similarity).By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.PROSITE-ProRule annotation
Contains 2 POLO box domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0575. Eukaryota.
ENOG410XQBP. LUCA.
HOGENOMiHOG000248546.
HOVERGENiHBG001843.
InParanoidiQ62673.
KOiK06631.
OrthoDBiEOG78M01K.

Family and domain databases

Gene3Di3.30.1120.30. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR000959. POLO_box_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00659. POLO_box. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50078. POLO_BOX. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62673-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNAAAKAGKL ARAPADLGKG GVPGDAAPGA PGAAPLAKEI PEVLMDPRSR
60 70 80 90 100
RQYVRGRFLG KGGFAKCFEI SDSDTKEVFP GKIVPKSLLL KPHQKEKMSM
110 120 130 140 150
EISIHRSLAH QHVVGFHGFF EDSDFVFVVL ELCRRRSLLE LHKRRKALTE
160 170 180 190 200
PEARYYLRQI VLGCQYLHRN QVIHRDLKLG NLFLNEDLEV KIGDFGLATK
210 220 230 240 250
VEYEGERKKT LCGTPNYIAP EVLSKKGHSF EVDVWSIGCI MYTLLVGKPP
260 270 280 290 300
FETSCLKETY LRIKKNEYSI PKHINPVAAS LIQKMLQTDP TARPTIHELL
310 320 330 340 350
NDEFFTSGYI PARLPITCLT IPPRFSIAPS SLDPSNRKPL TVLNKGVENP
360 370 380 390 400
LPDRPREKEE PVVRETNEAI ECHLSDLLQQ LTSVNASKPS ERGLVRQEEA
410 420 430 440 450
EDPACIPIFW VSKWVDYSDK YGLGYQLCDN SVGVLFNDST RLILYNDGDS
460 470 480 490 500
LQYIERDGTE SYLTVSSHPN SLMKKITLLN YFRNYMSEHL LKAGANITPR
510 520 530 540 550
EGDELARLPY LRTWFRTRSA IILHLSNGTV QINFFQDHTK LILCPLMAAV
560 570 580 590 600
TYINEKRDFR TYRLSLLEEY GCCKELASRL RYARTMVDKL LSSRSACNRL

KAS
Length:603
Mass (Da):68,291
Last modified:December 14, 2011 - v2
Checksum:iD756DD742CB14F6E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti27 – 271A → V in AAA18885 (Ref. 1) Curated
Sequence conflicti32 – 321G → V in AAA18885 (Ref. 1) Curated
Sequence conflicti45 – 451M → V in AAA18885 (Ref. 1) Curated
Sequence conflicti51 – 511R → Q in AAA18885 (Ref. 1) Curated
Sequence conflicti80 – 801P → A in AAH83926 (PubMed:15489334).Curated
Sequence conflicti102 – 1021I → T in AAA18885 (Ref. 1) Curated
Sequence conflicti109 – 1091A → E in AAA18885 (Ref. 1) Curated
Sequence conflicti291 – 2911T → A in AAA18885 (Ref. 1) Curated
Sequence conflicti543 – 5442LC → RG in AAA18885 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10188 mRNA. Translation: AAA18885.1.
BC083926 mRNA. Translation: AAH83926.1.
RefSeqiNP_058796.1. NM_017100.1.
UniGeneiRn.11034.

Genome annotation databases

GeneIDi25515.
KEGGirno:25515.
UCSCiRGD:3352. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10188 mRNA. Translation: AAA18885.1.
BC083926 mRNA. Translation: AAH83926.1.
RefSeqiNP_058796.1. NM_017100.1.
UniGeneiRn.11034.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4565080.
STRINGi10116.ENSRNOP00000025629.

PTM databases

iPTMnetiQ62673.
PhosphoSiteiQ62673.

Proteomic databases

PaxDbiQ62673.
PRIDEiQ62673.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25515.
KEGGirno:25515.
UCSCiRGD:3352. rat.

Organism-specific databases

CTDi5347.
RGDi3352. Plk1.

Phylogenomic databases

eggNOGiKOG0575. Eukaryota.
ENOG410XQBP. LUCA.
HOGENOMiHOG000248546.
HOVERGENiHBG001843.
InParanoidiQ62673.
KOiK06631.
OrthoDBiEOG78M01K.

Enzyme and pathway databases

BRENDAi2.7.11.21. 5301.

Miscellaneous databases

PROiQ62673.

Family and domain databases

Gene3Di3.30.1120.30. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR000959. POLO_box_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00659. POLO_box. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50078. POLO_BOX. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Amstrup J., Hansen J.A., Hxirlis Nielsen J.
    Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pancreas.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.

Entry informationi

Entry nameiPLK1_RAT
AccessioniPrimary (citable) accession number: Q62673
Secondary accession number(s): F1LNH6, Q5XHX4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: December 14, 2011
Last modified: July 6, 2016
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.