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

PKN1 (Q16512) - Overview - Molecular Target Synopsis

Protein


PKN1, Serine/threonine-protein kinase N1
Enzyme Classification 2.7.11.13
UniProt Q16512

Also Known as PKN1_HUMAN, PKN1, PAK1, PKN, PRK1, PRKCL1

PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. Interacts with ZFAND6 (By similarity). Interacts with ANDR (PubMed:12514133). Interacts with PRKCB (PubMed:20228790). Interacts (via REM 1 and REM 2 repeats) with RAC1 (PubMed:14514689, PubMed:18006505). Interacts (via REM 1 repeat) with RHOA (PubMed:10619026, PubMed:8571126). Interacts with RHOB (PubMed:9478917). Interacts (via C-terminus) with PDPK1 (PubMed:10792047). Interacts with CCNT2; enhances MYOD1-dependent transcription (PubMed:16331689). Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (PubMed:21224381).

4OTI
CRYSTAL STRUCTURE OF PRK1 CATALYTIC DOMAIN IN COMPLEX WITH TOFACITINIB
RCSB/PDB
Inspect Structure
See all 3D Structures for PKN1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PKN1 is active in the following subcellular-locations: cell membrane, cleavage furrow, cytoplasm, endosome, midbody, nucleus.
GO terms: PKN1 is active in the following subcellular-locations: cleavage furrow, cytoplasm, cytosol, endosome, midbody, nucleoplasm, nucleus, protein-containing complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PKN1 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: OVCAR_5, MDA_MB_231, RXF_393

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HEL, KG-1, HUP-T3

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, HUVEC, NHLF

(see details)

RNA Interference


PKN1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CROE33, H23. (see details)

3D Structures


For PKN1 there are:
8 structures (9 chains) solved
3 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

PKN1 is solved in complex with the approved drug(s):

MI1/TOFACITINIB (4OTI_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PKN1 has been screened with 227 compounds (278 bioactivities), 15 compounds have bioactivities that show binding affinity of <= 500nM (25 bioactivities). (see details)