Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PLK3 (Q9H4B4) - Overview - Molecular Target Synopsis

Protein


PLK3, Serine/threonine-protein kinase PLK3
Enzyme Classification 2.7.11.21
UniProt Q9H4B4

Also Known as PLK3_HUMAN, PLK3, CNK, FNK, PRK

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

4B6L
DISCOVERY OF ORAL POLO-LIKE KINASE (PLK) INHIBITORS WITH ENHANCED SELECTIVITY PROFILE USING RESIDUE TARGETED DRUG DESIGN
RCSB/PDB
Inspect Structure
See all 3D Structures for PLK3

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
646ENSG00000173846ENST00000372201ENSP00000361275Q9H4B4-1

Sub-cellular localization


UniProt: PLK3 is active in the following subcellular-locations: centrosome, cytoplasm, cytoskeleton, golgi apparatus, microtubule organizing center, nucleolus, nucleus.
GO terms: PLK3 is active in the following subcellular-locations: centrosome, cytoplasm, dendrite, Golgi stack, neuronal cell body, nucleolus, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PLK3 has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H226, UACC_257, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-74, OVCAR433, Hs 746T

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HMEC, HUVEC

(see details)

RNA Interference


PLK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HUO3N1, TE9. (see details)

3D Structures


For PLK3 there are:
1 structures (1 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PLK3 has been screened with 577 compounds (858 bioactivities), 70 compounds have bioactivities that show binding affinity of <= 500nM (92 bioactivities). (see details)