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

ROCK2 (O75116) - Overview - Molecular Target Synopsis

Protein


ROCK2, Rho-associated protein kinase 2
Enzyme Classification 2.7.11.1
UniProt O75116

Also Known as ROCK2_HUMAN, ROCK2, KIAA0619

Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. Homodimer. Interacts with IRS1, RHOB and RHOC (By similarity). Interacts with RHOA (activated by GTP), PPP1R12A, CHORDC1, SORL1, EP300 and BRCA2. Interacts with NPM1 and this interaction enhances its activity. Interacts with RAF1 (By similarity).

6ED6
CRYSTAL STRUCTURE OF ROCK2 WITH A PYRIDINYLBENZAMIDE BASED INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for ROCK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: ROCK2 is active in the following subcellular-locations: cell membrane, centrosome, cytoplasm, cytoskeleton, microtubule organizing center, nucleus.
GO terms: ROCK2 is active in the following subcellular-locations: centrosome, cytoplasm, cytoplasmic ribonucleoprotein granule, cytoskeleton, cytosol, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ROCK2 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SW_620, A549, MDA_MB_435

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hep G2, HT-55, OCUM-1

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, AG445, HeLa-S3

(see details)

RNA Interference


ROCK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: 93VU, HCC1954. (see details)

3D Structures


For ROCK2 there are:
5 structures (16 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ROCK2 has been screened with 3516 compounds (4810 bioactivities), 1535 compounds have bioactivities that show binding affinity of <= 500nM (1977 bioactivities). (see details)