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Protein

Serine/threonine-protein kinase PLK4

Gene

PLK4

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

Functioni

Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124).8 Publications

Caution

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei41ATPCurated1
Active sitei136Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi18 – 26ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.21 2681
ReactomeiR-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259 Loss of Nlp from mitotic centrosomes
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-8854518 AURKA Activation by TPX2
SignaLinkiO00444
SIGNORiO00444

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PLK4 (EC:2.7.11.213 Publications)
Alternative name(s):
Polo-like kinase 4
Short name:
PLK-4
Serine/threonine-protein kinase 18
Serine/threonine-protein kinase Sak
Gene namesi
Name:PLK4
Synonyms:SAK, STK18
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000142731.10
HGNCiHGNC:11397 PLK4
MIMi605031 gene
neXtProtiNX_O00444

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, Nucleus

Pathology & Biotechi

Involvement in diseasei

Microcephaly and chorioretinopathy, autosomal recessive, 2 (MCCRP2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe disorder characterized by microcephaly, delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities.
See also OMIM:616171

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41K → M: Abolishes ability to phosphorylate CDC25C and CHEK2. 2 Publications1
Mutagenesisi154D → A: Catalytically inactive mutant that causes some centrosome amplification above background levels when overexpressed. 1 Publication1
Mutagenesisi170T → D: Activating mutant. 2 Publications1

Keywords - Diseasei

Dwarfism

Organism-specific databases

DisGeNETi10733
MalaCardsiPLK4
MIMi616171 phenotype
OpenTargetsiENSG00000142731
PharmGKBiPA36205

Chemistry databases

ChEMBLiCHEMBL3788
GuidetoPHARMACOLOGYi2171

Polymorphism and mutation databases

BioMutaiPLK4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000865671 – 970Serine/threonine-protein kinase PLK4Add BLAST970

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei45N6-acetyllysine1 Publication1
Modified residuei46N6-acetyllysine1 Publication1
Modified residuei401PhosphoserineCombined sources1
Modified residuei665PhosphoserineCombined sources1
Modified residuei817PhosphoserineCombined sources1

Post-translational modificationi

Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation.1 Publication
Ubiquitinated; leading to its degradation by the proteasome.By similarity
Tyrosine-phosphorylated by TEC.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO00444
PaxDbiO00444
PeptideAtlasiO00444
PRIDEiO00444

PTM databases

iPTMnetiO00444
PhosphoSitePlusiO00444

Expressioni

Inductioni

Down-regulated in HCT 116 colorectal cancer cells, leading to aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. Down-regulated by p53/TP53.2 Publications

Gene expression databases

BgeeiENSG00000142731
CleanExiHS_PLK4
ExpressionAtlasiO00444 baseline and differential
GenevisibleiO00444 HS

Organism-specific databases

HPAiHPA017327
HPA035026

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with CEP152 (via N-terminus). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles (PubMed:27246242).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi11595652 interactors.
DIPiDIP-34467N
IntActiO00444 37 interactors.
MINTiO00444
STRINGi9606.ENSP00000270861

Chemistry databases

BindingDBiO00444

Structurei

Secondary structure

1970
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 5Combined sources4
Helixi9 – 11Combined sources3
Beta strandi12 – 20Combined sources9
Beta strandi22 – 31Combined sources10
Turni32 – 34Combined sources3
Beta strandi37 – 44Combined sources8
Helixi45 – 50Combined sources6
Helixi54 – 64Combined sources11
Beta strandi75 – 80Combined sources6
Beta strandi82 – 90Combined sources9
Helixi97 – 102Combined sources6
Beta strandi104 – 106Combined sources3
Helixi110 – 129Combined sources20
Helixi139 – 141Combined sources3
Beta strandi142 – 144Combined sources3
Beta strandi150 – 152Combined sources3
Turni158 – 161Combined sources4
Helixi193 – 206Combined sources14
Helixi217 – 225Combined sources9
Helixi236 – 245Combined sources10
Helixi250 – 252Combined sources3
Helixi256 – 259Combined sources4
Turni263 – 265Combined sources3
Helixi587 – 590Combined sources4
Beta strandi602 – 605Combined sources4
Beta strandi607 – 613Combined sources7
Beta strandi619 – 627Combined sources9
Beta strandi630 – 639Combined sources10
Beta strandi645 – 649Combined sources5
Helixi651 – 654Combined sources4
Beta strandi671 – 674Combined sources4
Helixi675 – 677Combined sources3
Helixi680 – 682Combined sources3
Helixi683 – 698Combined sources16
Beta strandi700 – 706Combined sources7
Beta strandi708 – 716Combined sources9
Beta strandi723 – 727Combined sources5
Beta strandi732 – 735Combined sources4
Beta strandi740 – 743Combined sources4
Beta strandi749 – 752Combined sources4
Helixi755 – 759Combined sources5
Helixi765 – 793Combined sources29
Beta strandi800 – 804Combined sources5
Beta strandi887 – 893Combined sources7
Turni894 – 896Combined sources3
Beta strandi897 – 902Combined sources6
Beta strandi905 – 911Combined sources7
Beta strandi916 – 922Combined sources7
Beta strandi924 – 929Combined sources6
Turni931 – 933Combined sources3
Beta strandi935 – 939Combined sources5
Helixi946 – 961Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N19NMR-A884-970[»]
3COKX-ray2.25A/B2-275[»]
4JXFX-ray2.40A4-269[»]
4N7VX-ray2.76A/B580-808[»]
4N7ZX-ray2.85A580-808[»]
4N9JX-ray2.60A/B581-808[»]
4YURX-ray2.65A2-275[»]
4YYPX-ray2.60A884-970[»]
5LHYX-ray3.311/2/3/4/5/6/7/8/9/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U884-970[»]
5LHZX-ray2.51A/B/C884-970[»]
ProteinModelPortaliO00444
SMRiO00444
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00444

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 265Protein kinasePROSITE-ProRule annotationAdd BLAST254
Domaini892 – 956POLO boxPROSITE-ProRule annotationAdd BLAST65

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0575 Eukaryota
ENOG410XQBP LUCA
GeneTreeiENSGT00530000062954
HOVERGENiHBG053617
InParanoidiO00444
KOiK08863
OMAiGADFEVW
OrthoDBiEOG091G05NQ
PhylomeDBiO00444
TreeFamiTF101090

Family and domain databases

CDDicd13114 POLO_box_Plk4_1, 1 hit
cd13115 POLO_box_Plk4_2, 1 hit
cd13116 POLO_box_Plk4_3, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR033700 Plk4
IPR000959 POLO_box_dom
IPR033699 POLO_box_Plk4_1
IPR033698 POLO_box_Plk4_2
IPR033696 POLO_box_Plk4_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008266 Tyr_kinase_AS
PANTHERiPTHR24345:SF50 PTHR24345:SF50, 1 hit
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF00659 POLO_box, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50078 POLO_BOX, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00444-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MATCIGEKIE DFKVGNLLGK GSFAGVYRAE SIHTGLEVAI KMIDKKAMYK
60 70 80 90 100
AGMVQRVQNE VKIHCQLKHP SILELYNYFE DSNYVYLVLE MCHNGEMNRY
110 120 130 140 150
LKNRVKPFSE NEARHFMHQI ITGMLYLHSH GILHRDLTLS NLLLTRNMNI
160 170 180 190 200
KIADFGLATQ LKMPHEKHYT LCGTPNYISP EIATRSAHGL ESDVWSLGCM
210 220 230 240 250
FYTLLIGRPP FDTDTVKNTL NKVVLADYEM PSFLSIEAKD LIHQLLRRNP
260 270 280 290 300
ADRLSLSSVL DHPFMSRNSS TKSKDLGTVE DSIDSGHATI STAITASSST
310 320 330 340 350
SISGSLFDKR RLLIGQPLPN KMTVFPKNKS STDFSSSGDG NSFYTQWGNQ
360 370 380 390 400
ETSNSGRGRV IQDAEERPHS RYLRRAYSSD RSGTSNSQSQ AKTYTMERCH
410 420 430 440 450
SAEMLSVSKR SGGGENEERY SPTDNNANIF NFFKEKTSSS SGSFERPDNN
460 470 480 490 500
QALSNHLCPG KTPFPFADPT PQTETVQQWF GNLQINAHLR KTTEYDSISP
510 520 530 540 550
NRDFQGHPDL QKDTSKNAWT DTKVKKNSDA SDNAHSVKQQ NTMKYMTALH
560 570 580 590 600
SKPEIIQQEC VFGSDPLSEQ SKTRGMEPPW GYQNRTLRSI TSPLVAHRLK
610 620 630 640 650
PIRQKTKKAV VSILDSEEVC VELVKEYASQ EYVKEVLQIS SDGNTITIYY
660 670 680 690 700
PNGGRGFPLA DRPPSPTDNI SRYSFDNLPE KYWRKYQYAS RFVQLVRSKS
710 720 730 740 750
PKITYFTRYA KCILMENSPG ADFEVWFYDG VKIHKTEDFI QVIEKTGKSY
760 770 780 790 800
TLKSESEVNS LKEEIKMYMD HANEGHRICL ALESIISEEE RKTRSAPFFP
810 820 830 840 850
IIIGRKPGST SSPKALSPPP SVDSNYPTRE RASFNRMVMH SAASPTQAPI
860 870 880 890 900
LNPSMVTNEG LGLTTTASGT DISSNSLKDC LPKSAQLLKS VFVKNVGWAT
910 920 930 940 950
QLTSGAVWVQ FNDGSQLVVQ AGVSSISYTS PNGQTTRYGE NEKLPDYIKQ
960 970
KLQCLSSILL MFSNPTPNFH
Length:970
Mass (Da):108,972
Last modified:November 13, 2007 - v3
Checksum:i4D56F5FD983211A6
GO
Isoform 2 (identifier: O00444-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     43-74: Missing.

Note: No experimental confirmation available.
Show »
Length:938
Mass (Da):105,253
Checksum:i3605FA717C82C2B7
GO
Isoform 3 (identifier: O00444-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: Missing.

Note: No experimental confirmation available.
Show »
Length:929
Mass (Da):104,636
Checksum:iECD6808B29B9D8D9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti34T → S in BAB69958 (PubMed:11489907).Curated1
Sequence conflicti58Q → K in CAA73575 (Ref. 1) Curated1
Sequence conflicti333D → N in BAH13823 (PubMed:14702039).Curated1
Sequence conflicti387S → R in BAB69958 (PubMed:11489907).Curated1
Sequence conflicti692F → S in BAH13823 (PubMed:14702039).Curated1
Sequence conflicti696V → L in BAB69958 (PubMed:11489907).Curated1
Sequence conflicti768Y → F in CAA73575 (Ref. 1) Curated1
Sequence conflicti842A → D in BAB69958 (PubMed:11489907).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04102786Y → C1 PublicationCorresponds to variant dbSNP:rs34156294Ensembl.1
Natural variantiVAR_041028146R → H1 PublicationCorresponds to variant dbSNP:rs35232579Ensembl.1
Natural variantiVAR_041029226A → T1 PublicationCorresponds to variant dbSNP:rs35448573Ensembl.1
Natural variantiVAR_019632232S → T4 PublicationsCorresponds to variant dbSNP:rs3811740Ensembl.1
Natural variantiVAR_041030317P → L1 PublicationCorresponds to variant dbSNP:rs35049837Ensembl.1
Natural variantiVAR_041031449N → D1 PublicationCorresponds to variant dbSNP:rs34906574Ensembl.1
Natural variantiVAR_041032519W → S1 PublicationCorresponds to variant dbSNP:rs56043017Ensembl.1
Natural variantiVAR_041033830E → D4 PublicationsCorresponds to variant dbSNP:rs17012739Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0381161 – 41Missing in isoform 3. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_03811743 – 74Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y13115 mRNA Translation: CAA73575.1
AB006972 mRNA Translation: BAB69958.1
AK302858 mRNA Translation: BAH13823.1
AK303399 mRNA Translation: BAH13953.1
AK314238 mRNA Translation: BAG36907.1
BC036023 mRNA Translation: AAH36023.1
CCDSiCCDS3735.1 [O00444-1]
CCDS54803.1 [O00444-2]
CCDS54804.1 [O00444-3]
RefSeqiNP_001177728.1, NM_001190799.1 [O00444-2]
NP_001177730.1, NM_001190801.1 [O00444-3]
NP_055079.3, NM_014264.4 [O00444-1]
UniGeneiHs.172052

Genome annotation databases

EnsembliENST00000270861; ENSP00000270861; ENSG00000142731 [O00444-1]
ENST00000513090; ENSP00000427554; ENSG00000142731 [O00444-2]
ENST00000514379; ENSP00000423582; ENSG00000142731 [O00444-3]
GeneIDi10733
KEGGihsa:10733
UCSCiuc003ifo.4 human [O00444-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPLK4_HUMAN
AccessioniPrimary (citable) accession number: O00444
Secondary accession number(s): B2RAL0
, B7Z837, B7Z8G7, Q8IYF0, Q96Q95, Q9UD84, Q9UDE2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: November 13, 2007
Last modified: March 28, 2018
This is version 169 of the entry and version 3 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