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
RNA Interference
Mutations

PLK4 (O00444) - Overview - Molecular Target Synopsis

Protein


PLK4, Serine/threonine-protein kinase PLK4
Enzyme Classification 2.7.11.21
UniProt O00444

Also Known as PLK4_HUMAN, PLK4, SAK, STK18

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). 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).

5LHY deposition date (13-JUL-16)
PB3 DOMAIN OF HUMAN PLK4 (APO)
RCSB/PDB
Inspect Structure
See all 3D Structures for PLK4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PLK4 is active in the following subcellular-locations: centriole, centrosome, cleavage furrow, cytoplasm, cytoskeleton, microtubule organizing center, nucleolus, nucleus.
GO terms: PLK4 is active in the following subcellular-locations: centriole, centrosome, cleavage furrow, cytosol, deuterosome, nucleolus, XY body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PLK4 has gain in 0 cell-lines, loss in 6 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, SR, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: WSU-FSCCL, OVCAR-8, LN-18

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: K562, MCF-7, HeLa-S3

(see details)

RNA Interference


PLK4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OVISE, HCH1. (see details)

3D Structures


There are 10 structures (35 chains) solved for PLK4
3 are solved in complex with at least one small molecule ligand

PLK4 is solved in complex with the approved drug(s):

ADN/ (1MUO_A, 4O0S_A, 4O0U_A, 4O0W_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PLK4 has been screened with 523 compounds (647 bioactivities), 107 compounds have bioactivities that show binding affinity of <= 500nM (157 bioactivities). (see details)