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Protein

Serine/threonine-protein kinase PLK3

Gene

PLK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1.25 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei91ATPPROSITE-ProRule annotation1
Active sitei185Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi68 – 76ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • p53 binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cytoplasmic microtubule organization Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • endomitotic cell cycle Source: UniProtKB
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • G2/M transition of mitotic cell cycle Source: UniProtKB
  • Golgi disassembly Source: UniProtKB
  • mitotic cell cycle checkpoint Source: UniProtKB
  • mitotic G1/S transition checkpoint Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of intracellular protein transport Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia Source: UniProtKB
  • protein kinase B signaling Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • regulation of cell division Source: UniProtKB
  • regulation of cytokinesis Source: UniProtKB
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • response to osmotic stress Source: UniProtKB
  • response to radiation Source: UniProtKB
  • response to reactive oxygen species Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle, DNA damage

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS10737-MONOMER.
BRENDAi2.7.11.21. 2681.
ReactomeiR-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ9H4B4.
SIGNORiQ9H4B4.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PLK3 (EC:2.7.11.21)
Alternative name(s):
Cytokine-inducible serine/threonine-protein kinase
FGF-inducible kinase
Polo-like kinase 3
Short name:
PLK-3
Proliferation-related kinase
Gene namesi
Name:PLK3
Synonyms:CNK, FNK, PRK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2154. PLK3.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • dendrite Source: Ensembl
  • Golgi stack Source: UniProtKB
  • neuronal cell body Source: Ensembl
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Golgi apparatus, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91K → R: Kinase defective mutant, abolishes activity. 7 Publications1
Mutagenesisi203D → A: Kinase defective mutant, abolishes activity. 1 Publication1
Mutagenesisi219T → E: Kinase-defective mutant. 1 Publication1
Mutagenesisi467 – 468WV → FA: Abolishes localization to the centrosome and ability to induce the G2/M arrest. 1 Publication2

Organism-specific databases

DisGeNETi1263.
OpenTargetsiENSG00000173846.
PharmGKBiPA26664.

Chemistry databases

ChEMBLiCHEMBL4897.
GuidetoPHARMACOLOGYi2170.

Polymorphism and mutation databases

BioMutaiPLK3.
DMDMi51338822.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000865641 – 646Serine/threonine-protein kinase PLK3Add BLAST646

Post-translational modificationi

Phosphorylated in an ATM-dependent manner following DNA damage. Phosphorylated as cells enter mitosis and dephosphorylated as cells exit mitosis.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9H4B4.
PaxDbiQ9H4B4.
PeptideAtlasiQ9H4B4.
PRIDEiQ9H4B4.

PTM databases

iPTMnetiQ9H4B4.
PhosphoSitePlusiQ9H4B4.

Expressioni

Tissue specificityi

Transcripts are highly detected in placenta, lung, followed by skeletal muscle, heart, pancreas, ovaries and kidney and weakly detected in liver and brain. May have a short half-live. In cells of hematopoietic origin, strongly and exclusively detected in terminally differentiated macrophages. Transcript expression appears to be down-regulated in primary lung tumor.

Developmental stagei

Expression is cell cycle regulated with a peak in G1 phase.1 Publication

Inductioni

Cytokine and cellular adhesion trigger induction. Down-regulated in a majority of lung carcinoma samples.1 Publication

Gene expression databases

BgeeiENSG00000173846.
CleanExiHS_PLK3.
GenevisibleiQ9H4B4. HS.

Organism-specific databases

HPAiHPA060318.

Interactioni

Subunit structurei

Interacts (via the POLO-box domain) with CIB1; leading to inhibit PLK3 kinase activity. Interacts with GOLGB1.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
POU2F1P148593EBI-751877,EBI-624770
PRNPP041564EBI-751877,EBI-977302
VRK1Q9998612EBI-751877,EBI-1769146

GO - Molecular functioni

  • p53 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107663. 13 interactors.
IntActiQ9H4B4. 5 interactors.
MINTiMINT-110679.
STRINGi9606.ENSP00000361275.

Chemistry databases

BindingDBiQ9H4B4.

Structurei

Secondary structure

1646
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi62 – 69Combined sources8
Beta strandi75 – 81Combined sources7
Turni82 – 84Combined sources3
Beta strandi87 – 94Combined sources8
Helixi95 – 98Combined sources4
Helixi101 – 114Combined sources14
Beta strandi125 – 130Combined sources6
Beta strandi132 – 139Combined sources8
Helixi147 – 154Combined sources8
Helixi159 – 178Combined sources20
Helixi188 – 190Combined sources3
Beta strandi191 – 193Combined sources3
Beta strandi199 – 201Combined sources3
Turni213 – 215Combined sources3
Turni224 – 226Combined sources3
Helixi229 – 232Combined sources4
Helixi239 – 255Combined sources17
Helixi265 – 273Combined sources9
Helixi285 – 294Combined sources10
Helixi299 – 301Combined sources3
Helixi305 – 309Combined sources5
Helixi312 – 315Combined sources4
Helixi325 – 328Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4B6LX-ray1.90A52-332[»]
ProteinModelPortaliQ9H4B4.
SMRiQ9H4B4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 314Protein kinasePROSITE-ProRule annotationAdd BLAST253
Domaini470 – 537POLO box 1PROSITE-ProRule annotationAdd BLAST68
Domaini567 – 637POLO box 2PROSITE-ProRule annotationAdd BLAST71

Domaini

The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK3 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them (By similarity). The POLO box domains mediates localization to the centrosome.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.
GeneTreeiENSGT00530000062954.
HOGENOMiHOG000248546.
HOVERGENiHBG001843.
InParanoidiQ9H4B4.
KOiK08862.
OMAiLCALRNC.
OrthoDBiEOG091G0D89.
PhylomeDBiQ9H4B4.
TreeFamiTF101089.

Family and domain databases

CDDicd13118. POLO_box_1. 1 hit.
cd13117. POLO_box_2. 1 hit.
Gene3Di3.30.1120.30. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR033701. POLO_box_1.
IPR033695. POLO_box_2.
IPR000959. POLO_box_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR020658. Ser/Thr_kinase_Plk3.
[Graphical view]
PANTHERiPTHR24345:SF42. PTHR24345:SF42. 1 hit.
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.

Q9H4B4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPAAGFLSP RPFQRAAAAP APPAGPGPPP SALRGPELEM LAGLPTSDPG
60 70 80 90 100
RLITDPRSGR TYLKGRLLGK GGFARCYEAT DTETGSAYAV KVIPQSRVAK
110 120 130 140 150
PHQREKILNE IELHRDLQHR HIVRFSHHFE DADNIYIFLE LCSRKSLAHI
160 170 180 190 200
WKARHTLLEP EVRYYLRQIL SGLKYLHQRG ILHRDLKLGN FFITENMELK
210 220 230 240 250
VGDFGLAARL EPPEQRKKTI CGTPNYVAPE VLLRQGHGPE ADVWSLGCVM
260 270 280 290 300
YTLLCGSPPF ETADLKETYR CIKQVHYTLP ASLSLPARQL LAAILRASPR
310 320 330 340 350
DRPSIDQILR HDFFTKGYTP DRLPISSCVT VPDLTPPNPA RSLFAKVTKS
360 370 380 390 400
LFGRKKKSKN HAQERDEVSG LVSGLMRTSV GHQDARPEAP AASGPAPVSL
410 420 430 440 450
VETAPEDSSP RGTLASSGDG FEEGLTVATV VESALCALRN CIAFMPPAEQ
460 470 480 490 500
NPAPLAQPEP LVWVSKWVDY SNKFGFGYQL SSRRVAVLFN DGTHMALSAN
510 520 530 540 550
RKTVHYNPTS TKHFSFSVGA VPRALQPQLG ILRYFASYME QHLMKGGDLP
560 570 580 590 600
SVEEVEVPAP PLLLQWVKTD QALLMLFSDG TVQVNFYGDH TKLILSGWEP
610 620 630 640
LLVTFVARNR SACTYLASHL RQLGCSPDLR QRLRYALRLL RDRSPA
Length:646
Mass (Da):71,629
Last modified:August 16, 2004 - v2
Checksum:i324CA3E9DE482514
GO

Sequence cautioni

The sequence AAC50637 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16A → T in CAC10659 (PubMed:11039900).Curated1
Sequence conflicti20P → T in CAC10659 (PubMed:11039900).Curated1
Sequence conflicti99A → V in CAC10659 (PubMed:11039900).Curated1
Sequence conflicti353G → V in CAC10659 (PubMed:11039900).Curated1
Sequence conflicti419D → H in CAC10659 (PubMed:11039900).Curated1
Sequence conflicti464 – 470VSKWVDY → FSEWVGF in CAC10659 (PubMed:11039900).Curated7
Sequence conflicti522P → R in CAC10659 (PubMed:11039900).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02109161T → S.1 PublicationCorresponds to variant rs17884581dbSNPEnsembl.1
Natural variantiVAR_02109268L → F.1 PublicationCorresponds to variant rs17884316dbSNPEnsembl.1
Natural variantiVAR_021093283L → F.1 PublicationCorresponds to variant rs17880471dbSNPEnsembl.1
Natural variantiVAR_021094483R → C.1 PublicationCorresponds to variant rs17884653dbSNPEnsembl.1
Natural variantiVAR_062384491D → N.1 PublicationCorresponds to variant rs17855444dbSNPEnsembl.1
Natural variantiVAR_021095498S → L.1 PublicationCorresponds to variant rs17880829dbSNPEnsembl.1
Natural variantiVAR_021096618S → P.1 PublicationCorresponds to variant rs17881786dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293866 mRNA. Translation: CAC10659.1.
AY764184 Genomic DNA. Translation: AAU88146.1.
AL592166 Genomic DNA. Translation: CAI13006.1.
CH471059 Genomic DNA. Translation: EAX07021.1.
BC013899 mRNA. Translation: AAH13899.1.
U56998 mRNA. Translation: AAC50637.1. Different initiation.
CCDSiCCDS515.1.
RefSeqiNP_004064.2. NM_004073.3.
UniGeneiHs.632415.

Genome annotation databases

EnsembliENST00000372201; ENSP00000361275; ENSG00000173846.
GeneIDi1263.
KEGGihsa:1263.
UCSCiuc001cmn.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293866 mRNA. Translation: CAC10659.1.
AY764184 Genomic DNA. Translation: AAU88146.1.
AL592166 Genomic DNA. Translation: CAI13006.1.
CH471059 Genomic DNA. Translation: EAX07021.1.
BC013899 mRNA. Translation: AAH13899.1.
U56998 mRNA. Translation: AAC50637.1. Different initiation.
CCDSiCCDS515.1.
RefSeqiNP_004064.2. NM_004073.3.
UniGeneiHs.632415.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4B6LX-ray1.90A52-332[»]
ProteinModelPortaliQ9H4B4.
SMRiQ9H4B4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107663. 13 interactors.
IntActiQ9H4B4. 5 interactors.
MINTiMINT-110679.
STRINGi9606.ENSP00000361275.

Chemistry databases

BindingDBiQ9H4B4.
ChEMBLiCHEMBL4897.
GuidetoPHARMACOLOGYi2170.

PTM databases

iPTMnetiQ9H4B4.
PhosphoSitePlusiQ9H4B4.

Polymorphism and mutation databases

BioMutaiPLK3.
DMDMi51338822.

Proteomic databases

MaxQBiQ9H4B4.
PaxDbiQ9H4B4.
PeptideAtlasiQ9H4B4.
PRIDEiQ9H4B4.

Protocols and materials databases

DNASUi1263.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372201; ENSP00000361275; ENSG00000173846.
GeneIDi1263.
KEGGihsa:1263.
UCSCiuc001cmn.4. human.

Organism-specific databases

CTDi1263.
DisGeNETi1263.
GeneCardsiPLK3.
H-InvDBHIX0199969.
HGNCiHGNC:2154. PLK3.
HPAiHPA060318.
MIMi602913. gene.
neXtProtiNX_Q9H4B4.
OpenTargetsiENSG00000173846.
PharmGKBiPA26664.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0575. Eukaryota.
ENOG410XQBP. LUCA.
GeneTreeiENSGT00530000062954.
HOGENOMiHOG000248546.
HOVERGENiHBG001843.
InParanoidiQ9H4B4.
KOiK08862.
OMAiLCALRNC.
OrthoDBiEOG091G0D89.
PhylomeDBiQ9H4B4.
TreeFamiTF101089.

Enzyme and pathway databases

BioCyciZFISH:HS10737-MONOMER.
BRENDAi2.7.11.21. 2681.
ReactomeiR-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ9H4B4.
SIGNORiQ9H4B4.

Miscellaneous databases

ChiTaRSiPLK3. human.
GeneWikiiPLK3.
GenomeRNAii1263.
PROiQ9H4B4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173846.
CleanExiHS_PLK3.
GenevisibleiQ9H4B4. HS.

Family and domain databases

CDDicd13118. POLO_box_1. 1 hit.
cd13117. POLO_box_2. 1 hit.
Gene3Di3.30.1120.30. 2 hits.
InterProiIPR011009. Kinase-like_dom.
IPR033701. POLO_box_1.
IPR033695. POLO_box_2.
IPR000959. POLO_box_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR020658. Ser/Thr_kinase_Plk3.
[Graphical view]
PANTHERiPTHR24345:SF42. PTHR24345:SF42. 1 hit.
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...

Entry informationi

Entry nameiPLK3_HUMAN
AccessioniPrimary (citable) accession number: Q9H4B4
Secondary accession number(s): Q15767, Q5JR99, Q96CV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 158 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.