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Protein

Serine/threonine-protein kinase PLK3

Gene

PLK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, DNA damage
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000173846.12
HGNCiHGNC:2154 PLK3
MIMi602913 gene
neXtProtiNX_Q9H4B4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi80817

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 Expressed in 146 organ(s), highest expression level in omental fat pad
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107663, 15 interactors
IntActiQ9H4B4, 8 interactors
STRINGi9606.ENSP00000361275

Chemistry databases

BindingDBiQ9H4B4

Structurei

Secondary structure

1646
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0575 Eukaryota
ENOG410XQBP LUCA
GeneTreeiENSGT00530000062954
HOGENOMiHOG000248546
HOVERGENiHBG001843
InParanoidiQ9H4B4
KOiK08862
OMAiNLMEGGD
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
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR033701 POLO_box_1
IPR033695 POLO_box_2
IPR000959 POLO_box_dom
IPR036947 POLO_box_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR020658 Ser/Thr_kinase_Plk3
PANTHERiPTHR24345:SF42 PTHR24345:SF42, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00659 POLO_box, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50078 POLO_BOX, 2 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

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 → S1 PublicationCorresponds to variant dbSNP:rs17884581Ensembl.1
Natural variantiVAR_02109268L → F1 PublicationCorresponds to variant dbSNP:rs17884316Ensembl.1
Natural variantiVAR_021093283L → F1 PublicationCorresponds to variant dbSNP:rs17880471Ensembl.1
Natural variantiVAR_021094483R → C1 PublicationCorresponds to variant dbSNP:rs17884653Ensembl.1
Natural variantiVAR_062384491D → N1 PublicationCorresponds to variant dbSNP:rs17855444Ensembl.1
Natural variantiVAR_021095498S → L1 PublicationCorresponds to variant dbSNP:rs17880829Ensembl.1
Natural variantiVAR_021096618S → P1 PublicationCorresponds to variant dbSNP:rs17881786Ensembl.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 No translation available.
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

Similar proteinsi

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 No translation available.
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, 15 interactors
IntActiQ9H4B4, 8 interactors
STRINGi9606.ENSP00000361275

Chemistry databases

BindingDBiQ9H4B4
ChEMBLiCHEMBL4897
GuidetoPHARMACOLOGYi2170

PTM databases

iPTMnetiQ9H4B4
PhosphoSitePlusiQ9H4B4

Polymorphism and mutation databases

BioMutaiPLK3
DMDMi51338822

Proteomic databases

MaxQBiQ9H4B4
PaxDbiQ9H4B4
PeptideAtlasiQ9H4B4
PRIDEiQ9H4B4
ProteomicsDBi80817

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
EuPathDBiHostDB:ENSG00000173846.12
GeneCardsiPLK3
H-InvDBiHIX0199969
HGNCiHGNC:2154 PLK3
HPAiHPA060318
MIMi602913 gene
neXtProtiNX_Q9H4B4
OpenTargetsiENSG00000173846
PharmGKBiPA26664
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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
PROiPR:Q9H4B4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173846 Expressed in 146 organ(s), highest expression level in omental fat pad
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
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR033701 POLO_box_1
IPR033695 POLO_box_2
IPR000959 POLO_box_dom
IPR036947 POLO_box_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR020658 Ser/Thr_kinase_Plk3
PANTHERiPTHR24345:SF42 PTHR24345:SF42, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00659 POLO_box, 2 hits
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50078 POLO_BOX, 2 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPLK3_HUMAN
AccessioniPrimary (citable) accession number: Q9H4B4
Secondary accession number(s): Q15767, Q5JR99, Q96CV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 16, 2004
Last modified: November 7, 2018
This is version 169 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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