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

PKN2 (Q16513) - Overview - Molecular Target Synopsis

Protein


PKN2, Serine/threonine-protein kinase N2
Enzyme Classification 2.7.11.13
UniProt Q16513

Also Known as PKN2_HUMAN, PKN2, PRK2, PRKCL2

PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. Involved in the negative regulation of ciliogenesis (PubMed:27104747). Interacts (via the REM repeats) with RHOA (GTP-bound form preferentially) and interacts (via the REM repeats) with RAC1 (GTP-bound form preferentially); the interactions induce its autophosphorylation (PubMed:9121475, PubMed:20974804). Interacts with RHOC (PubMed:20974804). Interacts with NCK1 and NCK2 (PubMed:10026169). Interacts with NCK1 (via SH3 domains) (By similarity). Interacts with CD44 (By similarity). Interacts (via C-terminal kinase domain) with PDPK1; the interaction stimulates PDPK1 kinase activity (PubMed:10226025, PubMed:10792047, PubMed:11781095, PubMed:18835241). Interacts with MAP3K2; the interaction activates PRK2 kinase activity in a MAP3K2-independent kinase activity (PubMed:10818102). Interacts (via C-terminal domain) with AKT1; the interaction occurs with the C-terminal cleavage product of PRK2 in apoptotic cells (PubMed:10926925). Interacts (via C-terminus) with PTPN13 (via PDZ 3 domain) (PubMed:11356191). Interacts with HCV NS5B (via N-terminal finger domain) (PubMed:15364941). Interacts with CDK10 (PubMed:27104747).

6GBE
12 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE N2
IN THE STRUCTURE OF
MURINE PROTEIN TYROSINE PHOSPHATASE PTPN13 PDZ3 DOMAIN-PRK2 PEPTIDE COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for PKN2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PKN2 is active in the following subcellular-locations: cell junction, cell projection, cleavage furrow, cytoplasm, cytoskeleton, lamellipodium, membrane, midbody, nucleus.
GO terms: PKN2 is active in the following subcellular-locations: apical junction complex, centrosome, cleavage furrow, cytoplasm, cytosol, intermediate filament cytoskeleton, lamellipodium, midbody, nuclear body, nucleoplasm, nucleus, perinuclear region of cytoplasm, plasma membrane, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PKN2 has gain in 7 cell-lines, loss in 2 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, RXF_393, NCI_ADR_RES

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-74, OVCAR-8, BHY

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: NHLF, HMEC, HSMM

(see details)

RNA Interference


PKN2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: BT474, T47D. (see details)

3D Structures


For PKN2 there are:
4 structures (4 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PKN2 has been screened with 484 compounds (766 bioactivities), 10 compounds have bioactivities that show binding affinity of <= 500nM (15 bioactivities). (see details)