Q07832 (PLK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 141. History...
Names and origin
|Protein names||Recommended name:|
Serine/threonine-protein kinase PLK1
Polo-like kinase 1
Serine/threonine-protein kinase 13
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||603 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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, 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, 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 SGOL1: required for spindle pole localization of isoform 3of 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 By similarity. Ref.8
ATP + a protein = ADP + a phosphoprotein.
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.
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 3of SGOL1. 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 SGOL2 By similarity. Interacts with BIRC6/bruce By similarity. Interacts with CDK1-phosphorylated DCTN6 during mitotic prometaphase; the interaction facilitates recruitment to kinetochores By similarity. Interacts with CDK1-phosphorylated FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA-mediated PLK1 phosphorylation. Ref.7
Nucleus By similarity. Chromosome › centromere › kinetochore By similarity. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome By similarity. Cytoplasm › cytoskeleton › spindle 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 SGOL1 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.
Newborn and adult spleen, fetal and newborn kidney, liver, brain, thymus and adult bone marrow, thymus, ovary and testes.
In the thymus, levels increased during fetal development, were highest in newborn animals and decreased in the adult. In the testes, the PLK levels were higher in the adult than in prepubescent mice while in the ovary, the levels were higher in the prepubescent mice. Accumulates to a maximum during the G2 and M phases, declines to a nearly undetectable level following mitosis and throughout G1 phase, and then begins to accumulate again during S phase.
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.
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.
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.
Lethality: homozygous embryos do not develop beyond the eight cell stage. Heterozygous mice are healthy and fertile but frequently develop tumors, most frequently lung-invading and liver-invading lymphomas. Analysis of chromosome spreads of spleen-derived cells from 6-month-old mice show aneuploidy. Ref.6
Contains 2 POLO box domains.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 603||602||Serine/threonine-protein kinase PLK1||PRO_0000086557|
|Domain||53 – 305||253||Protein kinase|
|Domain||417 – 480||64||POLO box 1|
|Domain||515 – 584||70||POLO box 2|
|Nucleotide binding||59 – 67||9||ATP By similarity|
|Nucleotide binding||178 – 181||4||ATP By similarity|
|Region||194 – 221||28||Activation loop By similarity|
|Region||493 – 507||15||Linker By similarity|
|Region||538 – 540||3||Important for interaction with phosphorylated proteins By similarity|
|Motif||337 – 340||4||D-box that targets the protein for proteasomal degradation in anaphase By similarity|
|Active site||176||1||Proton acceptor By similarity|
|Binding site||82||1||ATP By similarity|
|Binding site||131||1||ATP; via carbonyl oxygen By similarity|
|Binding site||194||1||ATP By similarity|
Amino acid modifications
|Modified residue||103||1||Phosphoserine By similarity|
|Modified residue||210||1||Phosphothreonine; by AURKA By similarity|
|Modified residue||214||1||Phosphothreonine By similarity|
|Modified residue||269||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||335||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||375||1||Phosphoserine By similarity|
|Modified residue||450||1||Phosphoserine By similarity|
|Modified residue||498||1||Phosphothreonine By similarity|
|Cross-link||19||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||492||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Mutagenesis||82||1||K → M: Abolishes activity. Ref.5|
|Mutagenesis||194||1||D → N or R: Abolishes activity. Ref.5|
|Mutagenesis||206||1||E → D: No change in activity. Ref.5|
|Mutagenesis||206||1||E → V: Decreases activity three-fold. Ref.5|
|Mutagenesis||210||1||T → E: Increases activity four-fold. Ref.5|
|Mutagenesis||210||1||T → V: Decreases activity three-fold. Ref.5|
|Sequence conflict||4||1||A → V in AAA39948. Ref.1|
|Sequence conflict||15||1||A → T in AAA39948. Ref.1|
|Sequence conflict||23||1||P → L in AAA39948. Ref.1|
|Sequence conflict||27||1||V → A in AAA39948. Ref.1|
|Sequence conflict||29||1||G → S in AAA39948. Ref.1|
|Sequence conflict||41||1||P → L in AAA39948. Ref.1|
|Sequence conflict||54||1||V → I in AAA39948. Ref.1|
|Sequence conflict||495||1||A → R in AAA39948. Ref.1|
|||"Identification and cloning of a protein kinase-encoding mouse gene, Plk, related to the polo gene of Drosophila."|
Clay F.J., McEwen S.J., Bertoncello I., Wilks A.F., Dunn A.R.
Proc. Natl. Acad. Sci. U.S.A. 90:4882-4886(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Bone marrow.
|||"Cloning and characterization of human and murine homologues of the Drosophila polo serine-threonine kinase."|
Hamanaka R., Maloid S., Smith M.R., O'Connell C.D., Longo D.L., Ferris D.K.
Cell Growth Differ. 5:249-257(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6 X CBA.
|||"Cell cycle- and terminal differentiation-associated regulation of the mouse mRNA encoding a conserved mitotic protein kinase."|
Lake R.J., Jelinek W.R.
Mol. Cell. Biol. 13:7793-7801(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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: Mammary gland.
|||"Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk activity induces multiple septation structures."|
Lee K.S., Erikson R.L.
Mol. Cell. Biol. 17:3408-3417(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-82; ASP-194; GLU-206 AND THR-210.
|||"Polo-like kinase 1 is essential for early embryonic development and tumor suppression."|
Lu L.Y., Wood J.L., Minter-Dykhouse K., Ye L., Saunders T.L., Yu X., Chen J.
Mol. Cell. Biol. 28:6870-6876(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"Furry protein promotes Aurora A-mediated polo-like kinase 1 activation."|
Ikeda M., Chiba S., Ohashi K., Mizuno K.
J. Biol. Chem. 287:27670-27681(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FRY.
|||"Tex14, a plk1-regulated protein, is required for kinetochore-microtubule attachment and regulation of the spindle assembly checkpoint."|
Mondal G., Ohashi A., Yang L., Rowley M., Couch F.J.
Mol. Cell 45:680-695(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TEX14.
|+||Additional computationally mapped references.|
|L06144 mRNA. Translation: AAA39948.1.|
U01063 mRNA. Translation: AAA56635.1.
L19558 mRNA. Translation: AAA16071.1.
BC006880 mRNA. Translation: AAH06880.1.
|RefSeq||NP_035251.3. NM_011121.3. |
3D structure databases
|SMR||Q07832. Positions 39-328, 372-594. |
Protein-protein interaction databases
|BioGrid||202250. 30 interactions.|
|IntAct||Q07832. 27 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000033154; ENSMUSP00000033154; ENSMUSG00000030867. |
|UCSC||uc009joo.2. mouse. |
|MGI||MGI:97621. Plk1. |
Gene expression databases
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
PF00659. POLO_box. 2 hits.
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS50078. POLO_BOX. 2 hits. |
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: Q07832|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|