Details of the Target

General Information of Target

Target ID LDTP00276
Target Name Serine/threonine-protein kinase PLK4 (PLK4)
Gene Name PLK4
Gene ID 10733
Synonyms
SAK; STK18; Serine/threonine-protein kinase PLK4; EC 2.7.11.21; Polo-like kinase 4; PLK-4; Serine/threonine-protein kinase 18; Serine/threonine-protein kinase Sak
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MATCIGEKIEDFKVGNLLGKGSFAGVYRAESIHTGLEVAIKMIDKKAMYKAGMVQRVQNE
VKIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEMNRYLKNRVKPFSENEARHFMHQI
ITGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKMPHEKHYTLCGTPNYISP
EIATRSAHGLESDVWSLGCMFYTLLIGRPPFDTDTVKNTLNKVVLADYEMPSFLSIEAKD
LIHQLLRRNPADRLSLSSVLDHPFMSRNSSTKSKDLGTVEDSIDSGHATISTAITASSST
SISGSLFDKRRLLIGQPLPNKMTVFPKNKSSTDFSSSGDGNSFYTQWGNQETSNSGRGRV
IQDAEERPHSRYLRRAYSSDRSGTSNSQSQAKTYTMERCHSAEMLSVSKRSGGGENEERY
SPTDNNANIFNFFKEKTSSSSGSFERPDNNQALSNHLCPGKTPFPFADPTPQTETVQQWF
GNLQINAHLRKTTEYDSISPNRDFQGHPDLQKDTSKNAWTDTKVKKNSDASDNAHSVKQQ
NTMKYMTALHSKPEIIQQECVFGSDPLSEQSKTRGMEPPWGYQNRTLRSITSPLVAHRLK
PIRQKTKKAVVSILDSEEVCVELVKEYASQEYVKEVLQISSDGNTITIYYPNGGRGFPLA
DRPPSPTDNISRYSFDNLPEKYWRKYQYASRFVQLVRSKSPKITYFTRYAKCILMENSPG
ADFEVWFYDGVKIHKTEDFIQVIEKTGKSYTLKSESEVNSLKEEIKMYMDHANEGHRICL
ALESIISEEERKTRSAPFFPIIIGRKPGSTSSPKALSPPPSVDSNYPTRERASFNRMVMH
SAASPTQAPILNPSMVTNEGLGLTTTASGTDISSNSLKDCLPKSAQLLKSVFVKNVGWAT
QLTSGAVWVQFNDGSQLVVQAGVSSISYTSPNGQTTRYGENEKLPDYIKQKLQCLSSILL
MFSNPTPNFH
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Ser/Thr protein kinase family, CDC5/Polo subfamily
Subcellular location
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole
Function
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. Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites.
TTD ID
T71374
Uniprot ID
O00444
DrugMap ID
TTGPNZQ
Ensemble ID
ENST00000270861.10
HGNC ID
HGNC:11397
ChEMBL ID
CHEMBL3788

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A498 SNV: p.G6W .
HCT116 SNV: p.S884T .
Ishikawa (Heraklio) 02 ER SNV: p.G21Ter .
JURKAT Deletion: p.F562LfsTer26 .
MCC13 SNV: p.L959F .
NCIH3122 SNV: p.Q362E .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
ATP probe
 Probe Info  		K151(0.00); K162(0.00); K167(0.00)  LDD0199  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein disulfide-isomerase (P4HB) Protein disulfide isomerase family P07237
Serine/threonine-protein kinase PLK4 (PLK4) Ser/Thr protein kinase family O00444
Terminal nucleotidyltransferase 5B (TENT5B) TENT family Q96A09
Tripartite motif-containing protein 54 (TRIM54) . Q9BYV2
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger and BTB domain-containing protein 39 (ZBTB39) Krueppel C2H2-type zinc-finger protein family O15060
Other
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
14-3-3 protein sigma (SFN) 14-3-3 family P31947
Arrestin-C (ARR3) Arrestin family P36575
Centrosomal protein of 152 kDa (CEP152) CEP152 family O94986
Dynein regulatory complex subunit 4 (GAS8) DRC4 family O95995
Oxysterol-binding protein-related protein 3 (OSBPL3) OSBP family Q9H4L5
Tuftelin-interacting protein 11 (TFIP11) TFP11/STIP family Q9UBB9
AFG2-interacting ribosome maturation factor (AIRIM) . Q9NX04
Centrosomal protein of 192 kDa (CEP192) . Q8TEP8
DnaJ homolog subfamily B member 13 (DNAJB13) . P59910
Elongin-A (ELOA) . Q14241
F-box/WD repeat-containing protein 1A (BTRC) . Q9Y297
Protein ECT2 (ECT2) . Q9H8V3
SCL-interrupting locus protein (STIL) . Q15468
Sperm-associated antigen 5 (SPAG5) . Q96R06

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cfi-400945 Small molecular drug D0X2XZ
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Xmd8-92 Small molecular drug D0M0QQ

References

1 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.