Q07832 (PLK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase PLK1
EC=2.7.11.21

Alternative name(s):
Polo-like kinase 1
Short name=PLK-1
Serine/threonine-protein kinase 13
Short name=STPK13

Gene names

Name:	Plk1
Synonyms:	Plk

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	603 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Ref.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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.
Subunit structure	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, MLF1IP and CDC25C. Interacts with isoform 3 of 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 FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA-mediated PLK1 phosphorylation. Ref.7
Subcellular location	Nucleus By similarity. Chromosome › centromere › kinetochore By similarity. Cytoplasm › cytoskeleton › 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.
Tissue specificity	Newborn and adult spleen, fetal and newborn kidney, liver, brain, thymus and adult bone marrow, thymus, ovary and testes.
Developmental stage	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.
Domain	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.
Post-translational modification	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.
Disruption phenotype	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
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily. Contains 2 POLO box domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Nucleus
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2 DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB G2/M transition of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB activation of mitotic anaphase-promoting complex activity Inferred from sequence or structural similarity. Source: UniProtKB centrosome organization Inferred from sequence or structural similarity. Source: UniProtKB cytokinesis Inferred from sequence or structural similarity. Source: UniProtKB microtubule bundle formation Inferred from sequence or structural similarity. Source: UniProtKB mitosis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-threonine phosphorylation Inferred from electronic annotation. Source: Compara protein destabilization Inferred from electronic annotation. Source: Compara protein localization to chromatin Inferred from sequence or structural similarity. Source: UniProtKB protein ubiquitination Inferred from electronic annotation. Source: Compara regulation of mitotic anaphase Inferred from electronic annotation. Source: Compara regulation of protein binding Inferred from electronic annotation. Source: Compara
Cellular_component	centrosome Inferred from sequence or structural similarity. Source: UniProtKB condensed nuclear chromosome outer kinetochore Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW kinetochore Inferred from sequence or structural similarity. Source: UniProtKB midbody Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB spindle microtubule Inferred from electronic annotation. Source: Compara spindle midzone Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW microtubule binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 603	603	Serine/threonine-protein kinase PLK1		PRO_0000086557
Regions
	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
Sites
	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
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Q07832 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 1B980646366EFA10	FASTA	603	68,301
	10 20 30 40 50 60 MNAAAKAGKL ARAPADLGKG GVPGDAVPGA PVAAPLAKEI PEVLVDPRSR RQYVRGRFLG 70 80 90 100 110 120 KGGFAKCFEI SDADTKEVFA GKIVPKSLLL KPHQKEKMSM EISIHRSLAH QHVVGFHDFF 130 140 150 160 170 180 EDSDFVFVVL ELCRRRSLLE LHKRRKALTE PEARYYLRQI VLGCQYLHRN QVIHRDLKLG 190 200 210 220 230 240 NLFLNEDLEV KIGDFGLATK VEYEGERKKT LCGTPNYIAP EVLSKKGHSF EVDVWSIGCI 250 260 270 280 290 300 MYTLLVGKPP FETSCLKETY LRIKKNEYSI PKHINPVAAS LIQKMLQTDP TARPTIHELL 310 320 330 340 350 360 NDEFFTSGYI PARLPITCLT IPPRFSIAPS SLDPSSRKPL KVLNKGVENP LPDRPREKEE 370 380 390 400 410 420 PVVRETNEAI ECHLSDLLQQ LTSVNASKPS ERGLVRQEEA EDPACIPIFW VSKWVDYSDK 430 440 450 460 470 480 YGLGYQLCDN SVGVLFNDST RLILYNDGDS LQYIERDGTE SYLTVSSHPN SLMKKITLLN 490 500 510 520 530 540 YFRNYMSEHL LKAGANITPR EGDELARLPY LRTWFRTRSA IILHLSNGTV QINFFQDHTK 550 560 570 580 590 600 LILCPLMAAV TYINEKRDFQ TYRLSLLEEY GCCKELASRL RYARTMVDKL LSSRSASNRL KAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]. Strain: C57BL/6. Tissue: Bone marrow.
[2]	"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. Tissue: Thymus.
[3]	"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]. Tissue: Testis.
[4]	"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]. Strain: FVB/N. Tissue: Mammary gland.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L06144 mRNA. Translation: AAA39948.1. U01063 mRNA. Translation: AAA56635.1. L19558 mRNA. Translation: AAA16071.1. BC006880 mRNA. Translation: AAH06880.1.
IPI	IPI00120767.
PIR	A47545. A54596.
RefSeq	NP_035251.3. NM_011121.3.
UniGene	Mm.16525.
3D structure databases
ProteinModelPortal	Q07832.
SMR	Q07832. Positions 39-328, 372-594.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q07832. 26 interactions.
MINT	MINT-4596676.
PTM databases
PhosphoSite	Q07832.
Proteomic databases
PaxDb	Q07832.
PRIDE	Q07832.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033154; ENSMUSP00000033154; ENSMUSG00000030867.
GeneID	18817.
KEGG	mmu:18817.
UCSC	uc009joo.2. mouse.
Organism-specific databases
CTD	5347.
MGI	MGI:97621. Plk1.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000248546.
HOVERGEN	HBG001843.
InParanoid	Q07832.
KO	K06631.
OMA	LCKKGHS.
OrthoDB	EOG4JDH6F.
Gene expression databases
ArrayExpress	Q07832.
Bgee	Q07832.
CleanEx	MM_PLK1.
Genevestigator	Q07832.
GermOnline	ENSMUSG00000030867. Mus musculus.
Family and domain databases
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. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. PF00659. POLO_box. 2 hits. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 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. [Graphical view]
ProtoNet	Search...
Other
NextBio	295174.
SOURCE	Search...

Entry information

Entry name

PLK1_MOUSE

Accession

Primary (citable) accession number: Q07832

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program