Reviewed, UniProtKB/Swiss-Prot P53350 (PLK1_HUMAN)

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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	603 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 APC/C inhibitors, and the regulation of mitotic exit and cytokinesis.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by serine and threonine phosphorylation.
Subunit structure	Interacts with CEP170 and EVI5. Interacts and phosphorylates ERCC6L. Interacts with FAM29A. Ref.11 Ref.12 Ref.13 Ref.14
Subcellular location	Nucleus.
Tissue specificity	Placenta and colon.
Developmental stage	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.
Induction	By growth-stimulating agents.
Post-translational modification	Catalytic activity is enhanced by phosphorylation of Thr-210 and/or Ser-137. Autophosphorylation and phosphorylation of Ser-137 are not significant events during activation of PLK1 in M phase.
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	Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Ref.4 Traceable author statement. Source: ProtInc mitosis Traceable author statement. Source: ProtInc positive regulation of ubiquitin-protein ligase activity during mitotic cell cycle Inferred from Experiment. Source: Reactome protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	centrosome Inferred from direct assay. Source: LIFEdb cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW polo kinase kinase activity Inferred from electronic annotation. Source: InterPro protein binding Ref.12 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIRC6	Q9NR09	1	EBI-476768,EBI-1765160
CHEK2	O96017	3	EBI-476768,EBI-1180783
EVI5	O60447	1	EBI-476768,EBI-852291
FBXO5	Q9UKT4	1	EBI-476768,EBI-852298
MCM2	P49736	1	EBI-476768,EBI-374819
MCM3	P25205	1	EBI-476768,EBI-355153
MCM7	P33993	3	EBI-476768,EBI-355924
WEE1	P30291	1	EBI-476768,EBI-914695

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_0000086556

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

Sites

Active site

176

1

Proton acceptor By similarity

Binding site

82

1

ATP By similarity

Amino acid modifications

Modified residue

6

1

Phosphothreonine Ref.15

Modified residue

103

1

Phosphoserine Ref.15

Modified residue

137

1

Phosphoserine Probable

Modified residue

210

1

Phosphothreonine Ref.15 Ref.9 Ref.16

Modified residue

214

1

Phosphothreonine Ref.15 Ref.16

Modified residue

269

1

Phosphoserine; by autocatalysis By similarity

Modified residue

335

1

Phosphoserine Ref.10

Modified residue

375

1

Phosphoserine Ref.15

Modified residue

450

1

Phosphoserine Ref.15

Modified residue

461

1

Phosphoserine Ref.15

Modified residue

464

1

Phosphothreonine Ref.15

Modified residue

498

1

Phosphothreonine Ref.15

Natural variations

Natural variant

12

1

R → L in a lung squamous cell carcinoma sample; somatic mutation. Ref.18

VAR_041018

Natural variant

261

1

L → F Ref.18

VAR_041019

Natural variant

297

1

N → D: dbSNP rs16972799.

VAR_051659

Natural variant

332

1

L → V Ref.18

VAR_041020

Natural variant

463

1

L → H Ref.18

VAR_041021

Natural variant

518

1

R → H Ref.18

VAR_041022

Natural variant

595

1

S → L: dbSNP rs34001032.

VAR_051660

Natural variant

599

1

R → H: dbSNP rs34954545.

VAR_051661

Experimental info

Mutagenesis

82

1

K → M: Abolishes activity. Ref.9

Mutagenesis

137

1

S → A: No change in activity. Ref.9

Mutagenesis

137

1

S → D: Increases activity. Results in a block in G1/S. Ref.9

Mutagenesis

194

1

D → N: Abolishes activity. Ref.8

Mutagenesis

194

1

D → R: Abolishes activity. Ref.8

Mutagenesis

206

1

E → D: No change in activity. Ref.8

Mutagenesis

206

1

E → V: Decreases activity. Ref.8

Mutagenesis

210

1

T → D: Increases activity. Ref.9 Ref.8

Mutagenesis

210

1

T → E: Slightly increases activity. Ref.9 Ref.8

Mutagenesis

210

1

T → V: Abolishes activity. Ref.9 Ref.8

Sequence conflict

2

1

S → T in AAA56634. Ref.1

Sequence conflict

11

1

A → P in AAA56634. Ref.1

Sequence conflict

58

1

F → L Ref.1

Sequence conflict

60

1

G → S Ref.1

Sequence conflict

73

1

A → V Ref.2

Sequence conflict

73

1

A → V Ref.7

Sequence conflict

123

1

N → T in CAA62260. Ref.6

Sequence conflict

141

1

L → P in CAA53536. Ref.4

Sequence conflict

227

1

G → E in CAA53536. Ref.4

Sequence conflict

301

1

N → G in AAA36659. Ref.2

Sequence conflict

495

1

A → G in AAA36659. Ref.2

Sequence conflict

501

1

E → Q in AAA36659. Ref.2

Secondary structure

1

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603

Helix Strand Turn

Details...

Beta strand

42 – 46

5

Turn

47 – 50

4

Beta strand

51 – 62

12

Beta strand

65 – 72

8

Turn

73 – 75

3

Beta strand

78 – 85

8

Helix

86 – 88

3

Helix

92 – 106

15

Beta strand

116 – 121

6

Beta strand

123 – 130

8

Helix

138 – 145

8

Helix

150 – 169

20

Helix

179 – 181

3

Beta strand

182 – 184

3

Beta strand

190 – 192

3

Helix

220 – 223

4

Helix

231 – 246

16

Helix

256 – 265

10

Helix

276 – 285

10

Helix

290 – 292

3

Turn

296 – 298

3

Helix

299 – 301

3

Helix

303 – 306

4

Helix

316 – 319

4

Helix

373 – 386

14

Beta strand

391 – 394

4

Helix

397 – 400

4

Helix

403 – 405

3

Beta strand

411 – 416

6

Turn

418 – 420

3

Beta strand

421 – 427

7

Beta strand

432 – 436

5

Beta strand

441 – 444

4

Beta strand

448 – 454

7

Beta strand

460 – 465

6

Helix

470 – 472

3

Helix

473 – 489

17

Turn

493 – 496

4

Beta strand

511 – 516

6

Beta strand

518 – 525

8

Beta strand

530 – 534

5

Turn

535 – 537

3

Beta strand

540 – 544

5

Turn

545 – 548

4

Beta strand

549 – 553

5

Beta strand

559 – 563

5

Helix

564 – 570

7

Helix

574 – 592

19

Sequences

	Sequence		Length	Mass (Da)
	P53350-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 178C2F13C10E8206	FASTA	603	68,255
	10 20 30 40 50 60 MSAAVTAGKL ARAPADPGKA GVPGVAAPGA PAAAPPAKEI PEVLVDPRSR RRYVRGRFLG 70 80 90 100 110 120 KGGFAKCFEI SDADTKEVFA GKIVPKSLLL KPHQREKMSM EISIHRSLAH QHVVGFHGFF 130 140 150 160 170 180 EDNDFVFVVL ELCRRRSLLE LHKRRKALTE PEARYYLRQI VLGCQYLHRN RVIHRDLKLG 190 200 210 220 230 240 NLFLNEDLEV KIGDFGLATK VEYDGERKKT LCGTPNYIAP EVLSKKGHSF EVDVWSIGCI 250 260 270 280 290 300 MYTLLVGKPP FETSCLKETY LRIKKNEYSI PKHINPVAAS LIQKMLQTDP TARPTINELL 310 320 330 340 350 360 NDEFFTSGYI PARLPITCLT IPPRFSIAPS SLDPSNRKPL TVLNKGLENP LPERPREKEE 370 380 390 400 410 420 PVVRETGEVV DCHLSDMLQQ LHSVNASKPS ERGLVRQEEA EDPACIPIFW VSKWVDYSDK 430 440 450 460 470 480 YGLGYQLCDN SVGVLFNDST RLILYNDGDS LQYIERDGTE SYLTVSSHPN SLMKKITLLK 490 500 510 520 530 540 YFRNYMSEHL LKAGANITPR EGDELARLPY LRTWFRTRSA IILHLSNGSV QINFFQDHTK 550 560 570 580 590 600 LILCPLMAAV TYIDEKRDFR TYRLSLLEEY GCCKELASRL RYARTMVDKL LSSRSASNRL KAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 8018557] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"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: 7902533] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5." Golsteyn R.M., Schultz S.J., Bartek J., Ziemiecki A., Ried T., Nigg E.A. J. Cell Sci. 107:1509-1517(1994) [PubMed: 7962193] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors." Holtrich U., Wolf G., Braeuninger A., Karn T., Boehme B., Ruebsamen-Waigmann H., Strebhardt K. Proc. Natl. Acad. Sci. U.S.A. 91:1736-1740(1994) [PubMed: 8127874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Lung.
[6]	"Identification and functional characterization of the human and murine polo-like kinase (Plk) promoter." Brauninger A., Strebhardt K., Rubsamen-Waigmann H. Oncogene 11:1793-1800(1995) [PubMed: 7478607] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-136.
[7]	"Cell cycle regulation of the human polo-like kinase (PLK) promoter." Uchiumi T., Longo D.L., Ferris D.K. J. Biol. Chem. 272:9166-9174(1997) [PubMed: 9083047] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-136.
[8]	"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: 9154840] [Abstract] Cited for: MUTAGENESIS OF ASP-194; GLU-206 AND THR-210.
[9]	"Phosphorylation of threonine 210 and the role of serine 137 in the regulation of mammalian polo-like kinase." Jang Y.-J., Ma S., Terada Y., Erikson R.L. J. Biol. Chem. 277:44115-44120(2002) [PubMed: 12207013] [Abstract] Cited for: PHOSPHORYLATION AT SER-137 AND THR-210, MUTAGENESIS OF LYS-82; SER-137 AND THR-210.
[10]	"Identification of phosphorylation sites in the polo-like kinases Plx1 and Plk1 by a novel strategy based on element and electrospray high resolution mass spectrometry." Wind M., Kelm O., Nigg E.A., Lehmann W.D. Proteomics 2:1516-1523(2002) [PubMed: 12442251] [Abstract] Cited for: PHOSPHORYLATION AT SER-335.
[11]	"The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles." Guarguaglini G., Duncan P.I., Stierhof Y.D., Holmstroem T., Duensing S., Nigg E.A. Mol. Biol. Cell 16:1095-1107(2005) [PubMed: 15616186] [Abstract] Cited for: INTERACTION WITH CEP170.
[12]	"The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1." Eldridge A.G., Loktev A.V., Hansen D.V., Verschuren E.W., Reimann J.D.R., Jackson P.K. Cell 124:367-380(2006) [PubMed: 16439210] [Abstract] Cited for: INTERACTION WITH EVI5.
[13]	"PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint." Baumann C., Koerner R., Hofmann K., Nigg E.A. Cell 128:101-114(2007) [PubMed: 17218258] [Abstract] Cited for: INTERACTION WITH ERCC6L.
[14]	"FAM29A promotes microtubule amplification via recruitment of the NEDD1-gamma-tubulin complex to the mitotic spindle." Zhu H., Coppinger J.A., Jang C.-Y., Yates J.R. III, Fang G. J. Cell Biol. 183:835-848(2008) [PubMed: 19029337] [Abstract] Cited for: INTERACTION WITH FAM29A.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-6; SER-103; THR-210; THR-214; SER-375; SER-450; SER-461; THR-464 AND THR-498, MASS SPECTROMETRY.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-210 AND THR-214, MASS SPECTROMETRY.
[17]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[18]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-12; PHE-261; VAL-332; HIS-463 AND HIS-518.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

U01038 mRNA. Translation: AAA56634.1.
L19559 mRNA. Translation: AAA36659.1.
X73458 mRNA. Translation: CAA51837.1.
X75932 mRNA. Translation: CAA53536.1.
BC002369 mRNA. Translation: AAH02369.1.
BC003002 mRNA. Translation: AAH03002.1.
BC014846 mRNA. Translation: AAH14846.1.
X90725 Genomic DNA. Translation: CAA62260.1.
U78073 Genomic DNA. Translation: AAB36946.1.

IPI

IPI00021248.

PIR

S34130.

RefSeq

NP_005021.2.

UniGene

Hs.592049

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q4K	X-ray	2.30	A/B/C	345-603	[»]
1Q4O	X-ray	2.20	A/B	367-603	[»]
1UMW	X-ray	1.90	A/B	367-603	[»]
2OGQ	X-ray	1.95	A	365-603	[»]
2OJX	X-ray	2.85	A	365-603	[»]
2OU7	X-ray	2.40	A	13-345	[»]
2OWB	X-ray	2.10	A	13-345	[»]
2RKU	X-ray	1.95	A	37-330	[»]
2V5Q	X-ray	2.30	A/B	33-345	[»]
3BZI	X-ray	2.10	A	365-603	[»]
3C5L	X-ray	2.33	A	373-593	[»]

DisProt

DP00428.

ModBase

Search...

Protein-protein interaction databases

IntAct

P53350. 15 interactions.

PTM databases

PhosphoSite

P53350.

Proteomic databases

PRIDE

P53350.

Genome annotation databases

Ensembl

ENSG00000166851. Homo sapiens. [Contig view]

GeneID

5347.

KEGG

hsa:5347.

Organism-specific databases

GeneCards

GC16P023597.

H-InvDB

HIX0012896.

HGNC

HGNC:9077. PLK1.

MIM

602098. gene.

PharmGKB

PA33410.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P53350.

HOVERGEN

P53350.

OMA

P53350. LCKKGHS.

Enzyme and pathway databases

BRENDA

2.7.11.21. 247.

Pathway_Interaction_DB

foxm1pathway. FOXM1 transcription factor network.
foxopathway. FoxO family signaling.

Reactome

REACT_152. Cell Cycle, Mitotic.

Gene expression databases

ArrayExpress

P53350.

Bgee

P53350.

CleanEx

HS_PLK1.

GermOnline

ENSG00000166851. Homo sapiens.

Family and domain databases

InterPro

IPR015728. Polo-like_kinase-related.
IPR017450. POLO_box.
IPR000959. POLO_box_duplicated.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

PANTHER

PTHR22982:SF10. Polo-like_kinase. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
PF00659. POLO_box. 2 hits.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

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 Resources

NextBio

20722.

SOURCE

Search...

Entry information

Entry name

PLK1_HUMAN

Accession

Primary (citable) accession number: P53350
Secondary accession number(s): Q15153, Q99746

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)